Past Questions: Difference between revisions

From Ethans Wiki
Newer edit →
Created page with "<span id="cicm-first-part-exam---ethans-answers"></span> = CICM First Part Exam - Ethan's answers = <span id="high-yield-topics"></span> === High yield topics === <blockquote>Topics with 5 or more past questions that are identical / very similar </blockquote> <span id="physiology"></span> === Physiology === * CNS ** CSF production, regulation, flow, content, physiological role (pretty much every year) * CVS ** Myocyte vs pacemaker action potentials * Renal/fluids..."
 
Tag: Replaced
Line 1: Line 1:
<span id="cicm-first-part-exam---ethans-answers"></span>
[[2022A]]
= CICM First Part Exam - Ethan's answers =
[[2021B]]
 
[[2021A]]
 
[[2020B]]
 
[[2020A]]
<span id="high-yield-topics"></span>
[[2019B]]
=== High yield topics  ===
[[2019A]]
 
[[2018B]]
<blockquote>Topics with 5 or more past questions that are identical / very similar
[[2018A]]
</blockquote>
[[2017B]]
 
[[2017A]]
 
[[2016B]]
<span id="physiology"></span>
[[2016A]]
=== Physiology ===
[[Pre-2016]]
 
* CNS
** CSF production, regulation, flow, content, physiological role (pretty much every year)
* CVS
** Myocyte vs pacemaker action potentials
* Renal/fluids/acids
** Renal blood flow + autoregulation
** Buffer systems of the body
* Resp
** Oxygen and carbon dioxide carriage in blood
** Control of breathing
** Respiratory/pulmonary compliance
** Functional residual capacity (FRC): define it, describe the factors effecting it, consequences of reducing it, measurement of it
* GIT
** Outline the functions of the liver
 
 
 
<span id="pharmacology"></span>
=== Pharmacology ===
 
* Amiodarone
* Vasopressors, inotropes
* GTN
* Pharmacology of NMBs (vec, sux, roc) - essentially a question every year-sitting
* Frusemide
* Ketamine
* Midazolam
* Magnesium sulfate
* Drugs to treat asthma (overview and MOA)
* Fractionated vs unfractionated heparin
 
 
 
<span id="measurement"></span>
=== Measurement ===
 
* Arterial lines and invasive BP
* Pulse oximetry / co-oximeter
* ETCO2 (differences between PaCO2, measurement, sources of error)
 
 
 
 
 
<span id="2022-1st-sitting"></span>
== 2022 (1st sitting) ==
 
 
 
<span id="question-1-1"></span>
=== Question 1 ===
 
 
 
<span id="question-1"></span>
==== Question ====
 
Outline the effects of critical illness on drug pharmacokinetics, including examples
 
 
 
<span id="example-answer-1"></span>
==== Example answer ====
 
 
 
Absorption
 
* Oral
** Decreased CO &gt; decreased GIT blood flow &gt; decreased absorption PO drugs
** Ileus + uraemia &gt; decreased gastric emptying &gt; decreased absorption of PO drugs
** Diarrhoea &gt; fast transit time &gt; decreased absorption
** Change in gastric pH (e.g. with PPI) alters drug absorption
** Decreased GIT blood flow (vasoconstrictors, barbiturates) &gt; decreased PO absorption
* Topical/IM/SC
** Vasoconstriction &gt; poor tissue perfusion &gt; decreased/slow absorption
* Inhalational
** Decreased MV / TV &gt; decreased delivery of aerosolised medications
 
 
 
Distribution
 
* Altered Vd
** Decreased CO (e.g. shock) &gt; slower redistribution
** Increased CO (e.g. hyperdynamic sepsis) &gt; faster residistribution
** Hypervolaemia (e.g. renal, cardiac, liver failure) &gt; increased Vd (vice versa)
** Critical illness &gt; muscle wasting &gt; alter lean mass percentage (alters Vd)
* Protein binding
** Decreased protein synthesis (e.g. decreased albumin) &gt; increased unbound fraction of drug &gt; increased Vd and drug activity
** Acid-base disturbances will alter free drug levels depending on drug pKa and the pH
* Inflammation &gt; impairs barrier function (e.g. BBB) &gt; increased penetration of meds (e.g. penicillins)
 
 
Metabolism
 
* Decreased CO &gt; decreased hepatic/renal blood flow &gt; decreased metabolism (e.g. propofol)
* Liver dysfunction &gt; Impaired phase 1 and 2 reactions and reduced 1st pass effect &gt; (e.g. labetalol, metoprolol)
* Renal dysfunction &gt; decreased renal metabolism &gt; prolonged drug effect (e.g. morphine)
* Hypothermia &gt; decreased metabolism &gt; Prolonged effect (e.g midazolam)
* Resp dysfunction &gt; Decreased resp metabolism of drugs (e.g. opioids) &gt; prolonged effect
 
 
 
Elimination
 
* Decreased CO (e.g. cardiogenic shock) = decreased GFR / HBF &gt; decreased clearance (e.g. gentamicin)
* Increased CO (e.g. hyperdynamic sepsis) &gt; increased GFR &gt; increased clearance
* Liver dysfunction &gt; impaired biliary excretion of drugs (e.g. vecuronium, rifampicin)
* Decreased GFR (e.g. AKI) &gt; decreased renal elimination drugs (e.g. Gentamicin, milrinone)
* Reduced MV &gt; decreased / slower clearance of volatile anaesthetics &gt; prolonged effect
 
 
 
<span id="examiner-comments-1"></span>
==== Examiner comments ====
 
<blockquote>
</blockquote>
 
 
<span id="online-resources-for-this-question-1"></span>
==== Online resources for this question ====
 
* Jenny's Jam Jar
* CICM Wrecks
* Deranged physiology
 
 
 
<span id="similar-questions-1"></span>
==== Similar questions ====
 
* Question 13, 2013 (1st sitting)
 
 
 
 
 
<span id="question-2-1"></span>
=== Question 2 ===
 
 
 
<span id="question-2"></span>
==== Question ====
 
Explain the mechanisms of transport of substances across cell membranes including appropriate examples (75%). Outline the structure of the Na<sup>+</sup>/K<sup>+</sup>-ATPase pump (25%)
 
 
 
<span id="example-answer-2"></span>
==== Example answer ====
 
 
 
Transport across cell membranes
 
{|
! Mode
! Mechanism
! Energy expenditure
! Electrochemical gradient
! Example
! Factors affecting
|-
| Passive (simple) diffusion
| Molecule passes through cell membrane
| No (passive)
| With/down
| CO2 and pulmonary vascular endothelium
| Fick's law of diffusion
|-
| Facilitated diffusion
| Molecule crosses membrane via transmembrane protein
| No (passive)
| With/down
| Glucose with the GLUT transporter
| Ficks law diffusion and number of carrier proteins
|-
| Ion channels
| Membrane spanning proteins (voltage, ligand or mechanical gated) &gt; conformational change &gt; opening of ion channel
| No (passive)
| With/down
| nACHR (Ach is ligand) with Na/K as ions
| Concentration gradient, number of channels
|-
| Primary active transport
| Molecule crosses membrane via carrier proteins
| Yes (active) requires ATP
| Against
| Na/K ATPase pump
| Availability of carrier, substrate and ATP
|-
| Secondary active transport (symport or antiport)
| Molecule crosses membrane via a carrier protein, with the energy being provided for the transport of another molecule
| Yes (but not directly)
| Against
| Na / H antiporter in principle cells of renal collecting ducts
| Availability of carrier, substrate and ATP
|-
| Endocytosis
| Cell membrane invaginates around a large molecule &gt; engulfs it &gt; contained within vesicle
| Yes
| Usually against
| Phagocytosis
| Poorly understood. ATP
|-
| Exocytosis
| Vesicle (containing molecule) fuses with cell membrane &gt; release of molecule
| Yes
| Usually against
| Exocytosis of ACh at the pre-synaptic cleft of the NMJ
| Poorly understood. ATP
|}
 
[[File:https://derangedphysiology.com/main/sites/default/files/sites/default/files/CICM Primary/E Cellular Physiology/cell transport across membranes2.JPG|thumb|none]]
 
 
 
Na/K-ATPase pump
 
* Membrane bound protein pump
* Structure
** Transmembrane protein, consists of two globular proteins
*** Large alpha subunit (MW = 105kDa)
*** Small beta subunit (MW 55kDa)
** Three binding sites for Na on internal surface, two binding sites for K on external surface
** ATPase activity at the Na binding site
* Function/Features
** Antiport --&gt; pumps 3 Na out and 2 K in
** Energy dependant (requires ATP)
* Process
** Once Na/K binding sites full, ATPase cleaves ATP &gt; release energy &gt; conformational change &gt; 3na out and 2K in
* Function
** Controls cell volume (prevents Gibbs Donnan equilibrium)
** Electrogenic (contributes to RMP)
 
 
 
<span id="examiner-comments-2"></span>
==== Examiner comments ====
 
<blockquote>
</blockquote>
 
 
<span id="online-resources-for-this-question-2"></span>
==== Online resources for this question ====
 
* Jenny's Jam Jar
* CICM Wrecks
* Deranged physiology
 
 
 
<span id="similar-questions-2"></span>
==== Similar questions ====
 
* Question 10, 2012 (2nd sitting)
 
 
 
 
 
<span id="question-3-1"></span>
=== Question 3 ===
 
 
 
<span id="question-3"></span>
==== Question ====
 
Define respiratory compliance, include its components and their normal values (25% marks). Explain the factors that affect respiratory compliance (75% of marks)
 
 
 
<span id="example-answer-3"></span>
==== Example answer ====
 
Respiratory compliance
 
* <math display="inline">Compliance \; = \; \frac{\Delta \;volume}{\Delta \;  pressure}</math>
* Compliance in the respiratory system (C<sub>RS</sub>) is a function of lung (C<sub>lung</sub>) and chest wall (C<sub>CW</sub>) compliance
** <math display="inline">\frac {1}{C_{RS}}\; = \; \frac {1}{C_{Lung}} \; + \; \frac {1}{C_{CW}}</math>
** Chest wall and lung compliance are roughly equal in healthy individual (~200mls.cmH2O)
** Thus normal compliance of the respiratory system is ~100mls.cmH2O
* Static compliance
** Compliance of the respiratory system at a given volume when there is no flow
* Dynamic compliance
** Compliance of the system when there is flow (respiration)
** Will always be less than static compliance due to airway resistance
** At a normal RR is approximately equal to static compliance
* Specific compliance
** The compliance of the system divided by the FRC
** Allows comparisons between patients which are independent of lung volumes
 
 
 
Factors effecting compliance
 
Chest wall
 
* Increased
** Collagen disorders (e.g. Ehlers-Danlos syndrome)
** Cachexia
** Rib resection, open chest
* Decreased
** Obesity
** Kyphosis / scoliosis / Pectus excavatum
** Circumferential burns
** Prone positioning
 
Lung compliance
 
<ul>
<li><p>Increased</p>
<ul>
<li><p>Normal ageing</p></li>
<li><p>Emphysema</p></li>
<li><p>Upright posture</p></li>
<li><p>Lung volume (highest compliance at FRC)</p></li></ul>
</li>
<li><p>Decreased</p>
<ul>
<li><p>Loss of surfactant (E.g. ARDS, hyaline membrane disease)</p></li>
<li><p>Loss of functional lung volume (e.g. pneumonia, lobectomy, pneumonectomy, atelectasis)</p></li>
<li><p>Pulmonary venous congestion (pHTN) and interstitial oedema (APO)</p></li>
<li><p>Reduced long elasticity (e.g. Pulmonary fibrosis)</p></li>
<li><p>Positioning (e.g. supine positioning)</p></li></ul>
 
<p></p></li></ul>
 
<span id="examiner-comments-3"></span>
==== Examiner comments ====
 
<blockquote>
</blockquote>
 
 
<span id="online-resources-for-this-question-3"></span>
==== Online resources for this question ====
 
* Jenny's Jam Jar
* CICM Wrecks
* Deranged physiology
 
 
 
<span id="similar-questions-3"></span>
==== Similar questions ====
 
* Question 17, 2019 (2nd sitting)
* Question 14, 2017 (1st sitting)
* Question 15, 2014 (1st sitting)
* Question 7, 2011 (2nd sitting)
* Question 13, 2007 (1st sitting)
 
 
 
 
 
<span id="question-4-1"></span>
=== Question 4 ===
 
 
 
<span id="question-4"></span>
==== Question ====
 
Describe the mechanisms of action and potential adverse effects of inhaled nitric oxide and prostacyclin
 
 
 
<span id="example-answer-4"></span>
==== Example answer ====
 
 
 
Nitric oxide MOA (inhaled)
 
* Pulmonary vasodilator
* Diffuses into smooth muscle cell &gt; activates guanyl cyclase &gt; increased conversion of GTP to cGMP &gt; decreased intracellular calcium &gt; relaxation of smooth muscle &gt; vasodilation
* As it is inhaled it selectively vasodilates well ventilated alveoli, which leads to improved V/Q matching &gt; decreased work of breathing and increased oxygenation
 
 
 
Prostacyclin MOA (inhaled)
 
* Pulmonary vasodilator
* Binds to prostacyclin receptor (IP receptor) &gt; active GPCR &gt; increased conversion of ATP to cAMP &gt; decreased intracellular calcium &gt; relaxation of smooth muscle &gt; vasodilation
* Improves V/Q matching by the same mechanism of NO
 
 
 
Adverse effects (NO)
 
* May exacerbate left ventricle heart failure
** Decreased pulmonary pressures &gt; increased RV SV &gt; increased LV preload
** Can overwhelm an impaired LV &gt; pulmonary oedema / worsening HF
* Vasodilatory effects
** Leads to flushing, headache, hypotension
** Less pronounced with inhaled therapy
* Rebound pulmonary hypertension and hypoxia
** Occurs following abrupt cessation
** Build up of vasoconstrictive molecules during therapy which are unopposed following cessation
* Thrombocytopaenia (up to 10%)
* Methaemaglobinaemia
** Relatively rare
** NO reacts with OxyHb to produce MetHb and nitrates
** Significant amounts &gt;5% only occurs at high doses e.g. &gt; 20ppm
* Tachyphylaxis (over days)
* AKI
** Usually with high doses &gt; 20ppm
** Relatively rare
 
 
 
Adverse effects (Prostacyclin)
 
* Inhibits platelet aggregation &gt; increased risk of bleeding
* Rebound pulmonary hypertension and hypoxia (same mechanism as above)
* Exacerbate LV heart failure (same mechanism as above)
* Vasodilatory effects &gt; flushing , headache, hypotension (less pronounced with inhaled)
 
 
 
<span id="examiner-comments-4"></span>
==== Examiner comments ====
 
<blockquote>
</blockquote>
 
 
<span id="online-resources-for-this-question-4"></span>
==== Online resources for this question ====
 
* Jenny's Jam Jar
* CICM Wrecks
* Deranged physiology
 
 
 
<span id="similar-questions-4"></span>
==== Similar questions ====
 
* Question 17, 2020 (2nd sitting)
* Question 14, 2011 (1st sitting)
 
 
 
 
 
<span id="question-5-1"></span>
=== Question 5 ===
 
 
 
<span id="question-5"></span>
==== Question ====
 
Write short notes on the pharmacology of labetalol and esmolol, highlighting their differences
 
 
 
<span id="example-answer-5"></span>
==== Example answer ====
 
{|
! Name
! Labetalol
! Esmolol
|-
| '''Class'''
| Alpha and beta blocker
| Beta blocker
|-
| '''Indications'''
| Hypertension
| ''Short term'' management of tachycardia/hypertension in hospital settings (e.g. OT)
|-
| '''Pharmaceutics'''
| 100/200mg tablets<br />
Clear solution (5mg.ml, 10ml ampoules)<br />
Mixture of stereoisomers
| Clear/slight yellow colourless solution 100mg/10ml
|-
| '''Routes'''
| IV, PO
| IV only
|-
| '''Dose'''
| IV: 5-20mg boluses, infusion 1-2mg.min<br />
PO: 100-800mg BD
| 10mg boluses / infusion titrated to effect
|-
| '''Pharmacodynamics'''
|
|
|-
| MOA
| a1 adrenergic antagonist <br />
Nonspecific Beta antagonist
| B1 selective antagonist
|-
| Effects
| CVS: decreased chronotropy, inotropy, dromotropy (beta effects), decreased SVR and afterload (alpha effects) &gt; decreased myocardial oxygen consumption + decreased BP<br />
RENAL: B1 blockage at JG cells &gt; decreased renin release &gt; decreased BP
| Same as labetalol (except no alpha mediated vasodilation)
|-
| Side effects
| CVS: bradycardia, hypotension (esp orthostatic), heart block <br />
RESP: dyspnoea, bronchospasm<br />
CNS: dizziness<br />
GIT: nausea, raised LFTs
| CVS: hypotension, bradycardia, heart block (B1 effects)<br />
RESP: NO bronchospasm or dyspnoea (no B2 effects)<br />
CNS: dizziness<br />
GIT: Nausea
|-
| '''Pharmacokinetics'''
|
|
|-
| Onset
| 1-2 hours (PO), &lt;5 mins (IV)
| Immediate (seconds-mins)
|-
| Absorption
| PO bioavailability 25%<br />
(extensive 1st pass metabolism)
| 0% oral bioavailability
|-
| Distribution
| 50% protein bound<br />
VOD = 8L/kg
| 60% protein bound <br />
VOD 3.5L/kg
|-
| Metabolism
| Hepatic (extensive)<br />
Glucuronide conjugation<br />
Inactive metabolites
| Rapid metabolism<br />
- Hydrolysis by RBC esterases<br />
Inactive metabolites
|-
| Elimination
| Renal (50%) / faecal (50%) elimination <br />
Inactive metabolites<br />
T 1/2 - 6 hours
| Renal<br />
Inactive metabolites<br />
T 1/2 = 10 mins (parent)
|}
 
 
 
<span id="examiner-comments-5"></span>
==== Examiner comments ====
 
<blockquote>
</blockquote>
 
 
<span id="online-resources-for-this-question-5"></span>
==== Online resources for this question ====
 
* Jenny's Jam Jar
* CICM Wrecks
* Deranged physiology
 
 
 
<span id="similar-questions-5"></span>
==== Similar questions ====
 
* Question 9, 2021 (2nd sitting)
* Question 14, 2019 (2nd sitting)
 
 
 
 
 
<span id="question-6-1"></span>
=== Question 6 ===
 
 
 
<span id="question-6"></span>
==== Question ====
 
Describe the cardiovascular changes seen throughout pregnancy
 
 
 
<span id="example-answer-6"></span>
==== Example answer ====
 
 
 
{|
! Factor
! Response during pregnancy
! Comments
|-
| HR
| Increases
| by up to 25%<br />
Peaks in 3rd trimester
|-
| SV
| Increases
| by up to 25% <br />
Predominately in 1st trimester
|-
| CO
| Increases
| - Up to 50%<br />
- Due to increased blood volume, increased HR/SV, increased VR and decreased SVR<br />
- Majority &gt; placenta (nutrient/gas to foetus), kidneys (80% increase, waste excretion), skin (regulates temp)
|-
| BP
| Decreases
| - By about 10%<br />
- Due to decreased SVR
|-
| Systemic vascular resistance
| Decreases
| - By up to 30%<br />
- Due to increased progesterone, PGs and downregulation of alpha receptors<br />
- Occurs predominately in 1st trimester
|-
| Blood volume
| Increases
| - By up to 40%<br />
- Due to stimulation of RAAS (oestrogen) and increased erythropoiesis (increased renal EPO) <br />
- Plasma volume increased &gt; RBC volume increase &gt; decreased HCT (dilutional anaemia)
|-
| CVP
| Unchanged
|
|-
| Oxygen delivery
| Increased
| Due to increased CO
|-
| Aorto-caval compression
| Increased
| Due to weight of the gravid uterus &gt; decreased VR
|-
| Colloid osmotic pressure
| Decreases
| Predisposes to oedema
|-
| '''Factor'''
| '''Response during delivery'''
| '''Comments'''
|-
| BP/VR/CO
| Uterine contraction
| By up to 50%<br />
Squeezes blood back into maternal circulation &gt; increases VR &gt; increased CO &gt; increased BP
|-
| '''Factor'''
| '''Response post partum'''
| '''Comments'''
|-
| CO
| Increased (immediately post)
| By up to 80%<br />
Due to autotransfusion of blood normally directed toward placenta/foetus
|-
| CO/ BP
| Decrease
| Return to normal ~2 weeks post delivery
|}
 
 
 
<span id="examiner-comments-6"></span>
==== Examiner comments ====
 
<blockquote>
</blockquote>
 
 
<span id="online-resources-for-this-question-6"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/16a/16b07/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2016-1-07.pdf CICM Wrecks]
* [https://derangedphysiology.com/main/required-reading/pregnancy-obstetrics-and-gynaecology/Chapter%201.1.3/circulatory-changes-pregnancy Deranged physiology]
 
 
 
<span id="similar-questions-6"></span>
==== Similar questions ====
 
<ul>
<li><p>Question 7, 2016 (first sitting)</p></li>
<li><p>Question 19, 2013 (second sitting)</p></li>
<li><p>Question 4, 2010 (second sitting)</p>
<p></p></li></ul>
 
 
 
<span id="question-7-1"></span>
=== Question 7 ===
 
 
 
<span id="question-7"></span>
==== Question ====
 
Write notes comparing the use of serum creatinine and creatinine clearance in the assessment of renal function in the critically ill
 
 
 
<span id="example-answer-7"></span>
==== Example answer ====
 
 
 
<ul>
<li><p>Creatinine </p>
<ul>
<li><p>Product of muscle metabolism</p></li>
<li><p>Freely filtered and not reabsorbed (but is partially secreted)</p>
<ul>
<li><p>Given this, it can be used to approximate GFR (decreased GFR is indicative of worsening renal function)</p></li></ul>
</li></ul>
 
<p></p></li></ul>
 
Creatinine clearance (CrCl)
 
<ul>
<li><p>CrCl = the volume of plasma cleared of creatinine per unit time</p></li>
<li><p>Measuring CrCl</p>
<ul>
<li><ol style="list-style-type: decimal;">
<li><p>Measure the plasma creatinine concentration</p></li></ol>
</li>
<li><ol style="list-style-type: decimal;">
<li><p>24 hour urine collection</p></li></ol>
</li>
<li><ol style="list-style-type: decimal;">
<li><p>Use the fick principle to calculate the CrCl </p></li></ol>
 
<ul>
<li><p>CrCl = urine volume x urine concentration / plasma concentration </p></li></ul>
</li></ul>
</li>
<li><p>Estimating CrCl</p>
<ul>
<li><p>Measuring urine concentrations is cumbersome</p></li>
<li><p>Can be estimated using various formula </p>
<ul>
<li><p>e.g. the Cockcroft-Gault equation and MDRD formulas</p></li>
<li><p>Uses Age, weight, gender and height to calculate CrCl from serum Cr</p></li>
<li><p>Not as accurate and makes several assumptions</p></li></ul>
</li></ul>
</li></ul>
 
 
 
Creatinine concentration
 
* Decreased renal function &gt; decreased CrCl &gt; increased Cr
* Therefore increased Cr is indicative of worsening renal function
* However
** The relationship is non linear
** Plasma creatinine concentration only begins to rise when ~50% of the renal function (GFR) is lost
** Thus there is a significant decrease in GFR before a noticeable rise in Cr
 
[[File:https://www.researchgate.net/profile/David-Johnson-103/publication/43449709/figure/fig1/AS:669059855183892@1536527708738/Normal-serum-creatinine-measurements-do-not-exclude-serious-loss-of-kidney-function.png|thumb|none|alt=Normal serum creatinine measurements do not exclude serious loss of... |  Download Scientific Diagram|Normal serum creatinine measurements do not exclude serious loss of... |  Download Scientific Diagram]]
 
 
 
Limitations of serum creatinine as biomarker of renal function
 
* Creatinine is partially secreted &gt; overestimates GFR
* Creatinine fluctuates
** Increased with: increased protein consumption, muscle injury, steroid use
** Decreased in: fasting, patients with low muscle mass, increased plasma volume (dilutional)
* Creatinine takes time to accumulate / only rises significantly following &gt;50% of loss of renal function
* Therefore
** Fluid resus or oedema &gt; falsely low creatinine &gt; falsely improving kidney injury
** Patients with low muscle mass may have low Cr &gt; masked kidney injury
** Extremes of age / weight / muscle mass &gt; unreliable results
** Cr and CrCl detect kidney injury late
* The level of inaccuracy increases with extremes of renal function
 
 
 
 
 
<span id="examiner-comments-7"></span>
==== Examiner comments ====
 
<blockquote>
</blockquote>
 
 
<span id="online-resources-for-this-question-7"></span>
==== Online resources for this question ====
 
* Jenny's Jam Jar
* [https://cicmwrecks.files.wordpress.com/2019/04/2013-2-11.pdf CICM Wrecks]
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2013-paper-2-saqs/question-11#answer-anchor Deranged physiology]
 
 
 
<span id="similar-questions-7"></span>
==== Similar questions ====
 
* Question 11, 2013 (second sitting)
 
 
 
 
 
<span id="question-8-1"></span>
=== Question 8 ===
 
 
 
<span id="question-8"></span>
==== Question ====
 
Describe the regulation of body water
 
 
 
<span id="example-answer-8"></span>
==== Example answer ====
 
 
 
Overview
 
* Water intake
** Approximately 25-30ml/kg of water is needed to be ingested for fluid/body homeostasis
*** ~2-2.5L per day for an average person
** Approximately half comes from drinking fluids, half from food and metabolic processes
* Water is lost through numerous ways
** Urine
*** ~1 - 1.5L / day
*** Obligatory loss is ~500mls to cover solute/waste clearance
** Insensible losses (skin, lungs etc)
*** ~900mls / day
** Faeces
*** ~100mls / day
* The body tightly regulates water balance to preserve plasma osmolality and intravascular volume status, but also allow waste clearance
** Note: Preservation of blood volume takes precedence over plasma osmolality
 
 
 
REGULATION
 
* Sensor
*# Osmoreceptors in hypothalamus detect increased (&gt;290mosm/L) osmolality with dehydration (major)
*# Low pressure baroreceptors (RA, great vessels) detect reduced pressure (stretch) with dehydration
*# High pressure baroreceptors (carotid sinus, aortic arch) detect reduced pressure (stretch) with dehydration
*# Macula densa (kidneys) detect reduced GFR (Na/Cl delivery) with dehydration
* Integrator
** Hypothalamus (anterior and lateral regions, predominately)
* Effector/effects
*# Release of ADH
*#* Synthesised in hypothalamus, transported to posterior pituitary for release
*#* ADH acts on collecting ducts in the kidney in to increase aquaporins on luminal wall --&gt; increased water reabsorption
*#* Released in response to increase osmolality and activation of RAAS
*# ANP/BNP
*#* Decreased stretch &gt; decreased ANP/BNP secretion --&gt; increased water reabsorption
*# RAAS
*#* Decreased baroreceptor activation --&gt; increased renin release
*#* Decreased GFR sensed by macula sensa &gt; increased renin release
*#* Renin &gt; activation of RAAS &gt; increased water reabsorption
*# Thirst centre (hypothalamus)
*#* Activation of thirst centre in the lateral hypothalamus (due to increased osmolality) &gt; behavioural change to increase water intake
* Feedback
** The above systems work predominately on a negative feedback system
 
 
 
<span id="examiner-comments-8"></span>
==== Examiner comments ====
 
<blockquote>
</blockquote>
 
 
<span id="online-resources-for-this-question-8"></span>
==== Online resources for this question ====
 
* Jenny's Jam Jar
* CICM Wrecks
* Deranged physiology
 
 
 
<span id="similar-questions-8"></span>
==== Similar questions ====
 
* Question 1, 2021 (2nd sitting)
* Question 8, 2008 (1st sitting)
* Question 4, 2015 (1st sitting)
* Question 9, 2018 (2nd sitting)
 
 
 
 
 
<span id="question-9-1"></span>
=== Question 9 ===
 
 
 
<span id="question-9"></span>
==== Question ====
 
Describe the pharmacology of 4% albumin
 
 
 
<span id="example-answer-9"></span>
==== Example answer ====
 
{|
! Name
! Albumin
|-
| '''Class'''
| Colloid (human plasma protein suspended in crytaloid sollution)
|-
| '''Indications'''
| Intravascular volume replacement<br />
Hypoalbuminaemia<br />
Plasma exchange<br />
Hepatorenal syndrome, pancreatitis, burns
|-
| '''Pharmaceutics'''
| 4% Albumin = 40g/L<br />
Contains Na 140mmols, Cl 128mmols, Octanoate 6.4mmols<br />
Hypotonic (260mOsm)<br />
-Albumin collected by blood donation (Whole blood &gt; plasmpheresis &gt; fractionated &gt; pasteurised &gt; partitioned &gt; stored)<br />
Stored at room temp (&lt;30 degrees)
|-
| '''Routes of administration'''
| IV
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Related to volume of fluid (i.e. volume expansion)<br />
Increase albumin concentration &gt; increase oncotic pressure / restores transport/drug binding function
|-
| Side effects
| No risk of bacteria/parasite infections (destroyed during processing), but risk of blood borne viruses (HIV, HepB, HCV) remains. <br />
Allergy, fluid overload, pulmonary oedema.
|-
| '''Pharmacokinetics'''
|
|-
| Absorption
| IV only (0% oral bioavailability)
|-
| Distribution
| Rapid distribution within intravascular space. <br />
Small Vd - about 5% leaves per hour
|-
| Metabolism
| Cellular proteolysis by cysteine protease
|-
| Elimination
| Degradation by liver and reticuloendothelial system<br />
Half life of ~20 days
|-
| '''Special points'''
| - Likely worsens outcomes in TBI <br />
- No need for blood cross matching
|}
 
 
 
<span id="examiner-comments-9"></span>
==== Examiner comments ====
 
<blockquote>
</blockquote>
 
 
<span id="online-resources-for-this-question-9"></span>
==== Online resources for this question ====
 
* Jenny's Jam Jar
* CICM Wrecks
* Deranged physiology
 
 
 
<span id="similar-questions-9"></span>
==== Similar questions ====
 
* Question 12, 2020 (2nd sitting)
* Question 1, 2015 (2nd sitting)
* Question 1, 2009 (2nd sitting)
 
 
 
 
 
 
 
<span id="question-10-1"></span>
=== Question 10 ===
 
 
 
<span id="question-10"></span>
==== Question ====
 
Describe the determinants of intracranial pressure (80% marks) and outline how it can be measured (20% marks)
 
 
 
<span id="example-answer-10"></span>
==== Example answer ====
 
 
 
Intracranial pressure (ICP)
 
* ICP = The pressure within the cranium, relative to atmospheric pressure
* Normal ICP is 5- 15 mmHg
* Governed by the Monro-Kellie doctrine (below)
* There is rhythmic variation in ICP due to variations in respiration and blood pressure
 
 
 
Monro-Kellie doctrine
 
<ul>
<li><p>The skull is a rigid container of fixed volume</p></li>
<li><p>The skull contents include: brain (~85%), CSF (~5-8%), blood (~5-8%)</p></li>
<li><p>Therefore any increase in volume of one substance must be met by a decrease in volume of another, or else there will be rise in the ICP</p>
<p></p></li></ul>
 
[[File:C:\Users\ethan\AppData\Roaming\Typora\typora-user-images\image-20211012142839178.png|thumb|none|alt=image-20211012142839178|image-20211012142839178]]
 
Determinants of ICP
 
* Brain tissue
** No capacity to alter volume under physiologically normal circumstances
** Increased volume in pathology: e.g. tumours, cerebral oedema &gt; increased ICP
* CSF
** Constantly produced (24mls/hr) and reabsorbed (24mls/hr), thus volume remains the same
** With increased ICP
*** CSF can be displaced from the cranium into the spinal subarachnoid space (as the spinal meninges have better compliance) &gt; decrease ICP
*** Increased ICP &gt; increased driving pressure for CSF reabsorption
** However if there is obstruction to CSF flow then there can be accumulation (e.g. hydrocephalus) &gt; increased ICP
* Blood
** Increased blood in cranium (e.g. cerbral vasodilation or haemorrhage) &gt; increased ICP
** With increased ICP &gt; Compression of the dural venous sinuses &gt; displace venous blood from the cranium &gt; lower ICP
** Blood flow is extensively autoregulated and effected by
*** MAP
*** PCO2
*** PO2
*** CMRO2
 
 
 
Measurement of ICP
 
<ul>
<li><p>Clinical</p>
<ul>
<li><p>Cannot be directly measured clinically</p></li>
<li><p>Though increased ICP may result in </p>
<ul>
<li><p>Headaches, nausea, vomiting</p></li>
<li><p>Papilledema </p></li>
<li><p>Decreased LOC</p></li>
<li><p>Cushing's reflex (critically high ICPs, very late)</p></li></ul>
</li>
<li><p>Optic nerve sheath diameter</p>
<ul>
<li><p>on US</p></li></ul>
</li>
<li><p>Lumbar puncture opening pressure</p>
<ul>
<li><p>Can approximate but not directly measure ICP</p></li>
<li><p>high CSF opening pressure may indicate high ICP</p></li>
<li><p>Numerous reasons why there would be a discrepancy in patients with pathology</p></li></ul>
</li></ul>
</li>
<li><p>Devices</p>
<ul>
<li><p>EVD (gold standard)</p>
<ul>
<li><p>Catheter which sits in the lateral ventricle</p></li>
<li><p>Pressure transmitted to wheatstone bridge via fluid filled tubing</p></li>
<li><p>Zeroed to atmospheric pressure</p></li></ul>
</li>
<li><p>Codmans / Intraparenchymal pressure monitor</p>
<ul>
<li><p>Sits in brain parenchyma (~2cm deep)</p></li>
<li><p>Pisoelectric strain gauge pressure sensor connected to a monitor via a fibreoptic cable</p></li>
<li><p>Only measures local ICP and cannot be re-zeroed</p></li></ul>
 
<p></p></li></ul>
</li></ul>
 
<span id="examiner-comments-10"></span>
==== Examiner comments ====
 
<blockquote>
</blockquote>
 
 
<span id="online-resources-for-this-question-10"></span>
==== Online resources for this question ====
 
* Jenny's Jam Jar
* CICM Wrecks
* Deranged physiology
 
 
 
<span id="similar-questions-10"></span>
==== Similar questions ====
 
* Question 7, 2020 (2nd sitting)
* Question 15, 2018 (1st sitting)
* Question 18, 2016 (2nd sitting)
* Question 14, 2016 (1st sitting)
* Question 18, 2010 (1st sitting)
 
 
 
 
 
 
 
<span id="question-11-1"></span>
=== Question 11 ===
 
 
 
<span id="question-11"></span>
==== Question ====
 
Outline the structure and function of the NMDA receptor (25% marks). Discuss the pharmacology of ketamine (75% marks)
 
 
 
<span id="example-answer-11"></span>
==== Example answer ====
 
 
 
NMDA receptor
 
* Structure
** Tetrameric (4 subunits), ligand gated, transmembrane receptor
* Location
** Abundant in the CNS (brain, spinal cord)
* Ion permeability
** Ca, Na, K
* Activated by
** Glutamate (excitatory neurotransmitter) and glycine
** Activation leads to removal of central Mg plug &gt; Na/Ca in, K out &gt; EPSP
* Blocked by
** Ketamine, Mg, memantidine
 
 
 
{|
! Name
! Ketamine
|-
| '''Class'''
| Anaesthetic (phencyclidine derivative)
|-
| '''Indications'''
| induction GA, conscious sedation, analgesia,
|-
| '''Pharmaceutics'''
| 10/50/100mg/ml.<br />
Clear colourless solution. <br />
Racemic mixture of S and R enantiomers, or S+ enantiomer alone. <br />
Water soluble.
|-
| '''Routes of administration'''
| IV/IM/PO/SC/PR
|-
| '''Dose'''
| 0-0.25mg/kg/hr (analgesia), 1-2mg/kg (GA), 0.5mg/kg (sedation)
|-
| pKa
| 7.5
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| NMDA antagonism, weak opioid receptor agonism, weak Ca ch inhibition
|-
| Effects
| CNS: dissociative anaesthesia and analgesia. <br />
CVS: increased HR/BPN (SNS stimulation), decreased pulmonary and systemic vascular resistance,<br />
Resp: bronchodilation
|-
| Side effects
| CNS: emergence reactions including hallucinations, unpleasant dreams. may increase ICP in non ventilated patients<br />
CVS: may increase HR/BP, increased myocardial O2 req.<br />
GIT: Nausea, vomiting, increased salivation<br />
RESP: apnoea
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| 30s IV, duration of effect 10-20mins
|-
| Absorption
| Lipid soluble &gt; readily absorbed. But poor OBA (16%) due to 1st pass metabolism
|-
| Distribution
| Large (~3L/kg) VOD<br />
Small protein binding (~30%).<br />
Crosses placenta.
|-
| Metabolism
| Hepatic (CYP450)<br />
Demethylation &gt; norketamine (30% potent) and inactive metabolites
|-
| Elimination
| Elimination T1/2 = 2 hours. <br />
Kidneys (95%), faeces (5%)
|-
| '''Special points'''
|
|}
 
 
 
<span id="examiner-comments-11"></span>
==== Examiner comments ====
 
<blockquote>
</blockquote>
 
 
<span id="online-resources-for-this-question-11"></span>
==== Online resources for this question ====
 
* Jenny's Jam Jar
* CICM Wrecks
* Deranged physiology
 
 
 
<span id="similar-questions-11"></span>
==== Similar questions ====
 
* Direct copy of Question 15, 2019 (1st sitting)
* Ketamine
** Question 4, 2018 (2nd sitting)
** Question 22, 2015 (1st sitting)
** Question 16, 2011 (2nd sitting)
** Question 7, 2010 (2nd sitting)
 
 
 
 
 
<span id="question-12-1"></span>
=== Question 12 ===
 
 
 
<span id="question-12"></span>
==== Question ====
 
Describe the process of excitation-contraction coupling and relaxation in smooth muscle
 
 
 
<span id="example-answer-12"></span>
==== Example answer ====
 
 
 
Excitation contraction coupling
 
* The process linking depolarisation (generated by an action potential) and initiation of muscle contraction
 
 
 
Process
 
* Calcium influx
** Voltage (from action potential) or ligands (e.g hormone, neurotransmitter) can open Ca channels &gt; calcium enters the cell
** The initial increase in calcium &gt; further release of Ca from the SR (calcium induced calcium release)
** Hormones/Neurotransmitters can also directly release calcium from the SR via IP3-DAG 2nd messenger pathway
* Calcium-calmodulin complex
** Calcium binds to calmodulin forming a complex
** The complex then activates myosin light chain kinase (MLCK)
* Activation of MLCK
** MLCK phosphorylates (activates) the myosin heads (requires ATP)
** Allows cross bridge formation between actin/myosin
* Relaxation
** Decrease in Ca (taken up in the SR by SERCA) leads to relaxation (no further MLCK activation)
** Myosin phosphatase dephosphorylates already active MLCK
 
 
 
[[File:C:\Users\ethan\AppData\Roaming\Typora\typora-user-images\image-20220531131819978.png|thumb|none|alt=image-20220531131819978|image-20220531131819978]]
 
 
 
 
 
Smooth muscle ECC vs skeletal/cardiac muscle ECC
 
* There are no t-tubules
** The AP propagates through gap junctions (unlike cardiac/skeletal muscle)
* There is no troponin
** They facilitate cross bridge formation via calmodulin instead (unlike cardiac/skeletal muscle)
* Smooth muscle cells have poorly developed sarcoplasmic reticulum
** Calcium influx is mainly from ECF and not from the SR (unlike cardiac/skeletal muscle)
* There is DHPR/ ryanodine receptor
** Calcium induced calcium release from the SR (unlike cardiac/skeletal muscle)
* 10x slower, lasts 30x longer
 
 
 
<span id="examiner-comments-12"></span>
==== Examiner comments ====
 
<blockquote>
</blockquote>
 
 
<span id="online-resources-for-this-question-12"></span>
==== Online resources for this question ====
 
* Jenny's Jam Jar
* CICM Wrecks
* Deranged physiology
 
 
 
<span id="similar-questions-12"></span>
==== Similar questions ====
 
*
 
 
 
 
 
<span id="question-13-1"></span>
=== Question 13 ===
 
 
 
<span id="question-13"></span>
==== Question ====
 
Compare and contrast the pharmacology of suxamethonium and rocuronium
 
 
 
<span id="example-answer-13"></span>
==== Example answer ====
 
{|
! Name
! Suxamethonium (succinylcholine)
! Rocuronium
|-
| '''Class'''
| Depolarising NMB
| Aminosteroid NMB / <br />
Non depolarising NMB
|-
| '''Indications'''
| Facilitate endotracheal intubation during anaesthesia (i.e. RSI)
| NMB (e.g. intubation, assist with difficult mechanical ventilation)
|-
| '''Pharmaceutics'''
| Clear colourless solution (50mg/ml)<br />
Refrigeration (4°C) - 2/52 at room temp<br />
Precipitates with thiopentone
| Clear colourless solution (10mg/ml, 5ml vial)<br />
Refrigeration (4°C) - 3/12 at room temp
|-
| '''Routes of administration'''
| IV, IM
| IV
|-
| '''Dose''' (RSI)
| 1-2 mg/kg (IV), 2-3 mg/kg (IM) <br />
Cant be given as infusion due to phase 2 block
| 0.6 - 1.2mg/kg <br />
Can be given as an infusion but variable offset
|-
| ED95
| 0.3mg/kg
| 0.3 mg/kg
|-
| '''Pharmacodynamics'''
|
|
|-
| MOA
| Binds to the nACh receptor on motor end plate &gt; depolarisation. Cannot be hydrolysed by Acetylcholinesterase in NMJ &gt; sustained depolarisation (i.e. Na channels remain in open-inactive state) &gt; muscle relaxation
| Inhibit the action of ACh at the NMJ by competitively binding to alpha subunit of nAChR on post junctional membrane
|-
| Effects
| NMB - paralysis.
| NMB - paralysis
|-
| Side effects
| Major: anaphylaxis, suxamethonium apnoea, malignant hyperthermia <br />
Minor: hyperkalaemia, myalgia, bradycardia/arrhythmia <br />
Pressure: increased IOP, ICP, intragastric pressure.
| CVS: tachycardia (in high doses, rare otherwise)<br />
IMMUNE: anaphylaxis (&lt;0.1%)
|-
| '''Pharmacokinetics'''
|
|
|-
| Onset/Duration
| Onset: 30s - 60s<br />
Duration &lt;10 mins
| Onset: 45-90s <br />
Duration: ~30-45 mins
|-
| Absorption
| -
| -
|-
| Distribution
| Protein binding = 30%<br />
Vd = 0.02 L/Kg
| Protein binding = 10%<br />
VOD = 0.2 L /kg<br />
|-
| Metabolism
| Rapid hydrolysis by plasma and liver pseudocholinesterase's (~20% reaches NMJ)
| Minimal hepatic metabolism (&lt;5%)
|-
| Elimination
| Minimal renal elimination (due to rapid metabolism)<br />
T 1/2 = 2 mins
| Bile 70%, Renal 30%<br />
Excreted unchanged<br />
T 1/2 - 1 - 1.5hrs
|-
| '''Special points'''
| May have prolonged duration of action with congenital or acquired (e.g. liver, renal, thyroid disease) pseudocholinesterase deficiency <br />
Treatment of malignant hyperthermia is with dantrolene (+ cooling + supportive care)
| Reversible with sugammadex and anticholinesterases (e.g. neostigmine)
|}
 
 
 
<span id="examiner-comments-13"></span>
==== Examiner comments ====
 
<blockquote>
</blockquote>
 
 
<span id="online-resources-for-this-question-13"></span>
==== Online resources for this question ====
 
* Jenny's Jam Jar
* CICM Wrecks
* Deranged physiology
 
 
 
<span id="similar-questions-13"></span>
==== Similar questions ====
 
* Rocuronium
** Question 13, 2018 (2nd sitting)
* Suxamethonium
** Question 6, 2011 (1st sitting)
** Question 2, 2012 (2nd sitting)
** Question 1, 2013 (2nd sitting)
** Question 10, 2018 (1st sitting)
** Question 10, 2020 (2nd sitting)
* Various other questions relating to properties of NMB more broadly
 
 
 
 
 
<span id="question-14-1"></span>
=== Question 14 ===
 
 
 
<span id="question-14"></span>
==== Question ====
 
Describe the neural integration of vomiting, highlighting the site and mechanism of action of antiemetics
 
 
 
<span id="example-answer-14"></span>
==== Example answer ====
 
 
 
Vomiting
 
* Involuntary, forceful and rapid expulsion of gastric contents via the mouth
 
 
 
Stages of vomiting
 
* Deep inspiration
* Closure of the nasopharynx and glottis
* Large retrograde contraction of intestines &gt; forces content into stomach
* Relaxation of the oesophagus, lower oesophageal sphincter and body of stomach
* Contraction of abdominal and thoracic muscles (including diaphragm)
* Increased intrabdominal pressure &gt; forces gastric contents into oesophagus and through the mouth
 
 
 
Neural integration
 
[[File:C:\Users\ethan\AppData\Roaming\Typora\typora-user-images\image-20220610194545783.png|thumb|none|alt=image-20220610194545783|image-20220610194545783]]
 
Anti-emetics
 
{|
! Class
! Example
! MOA
|-
| Serotonin antagonists
| Ondansetron
| Central and peripheral 5-HT3 receptor antagonism &gt; reduced afferent input to vomiting centre in medulla
|-
| Corticosteroids
| Dexamethasone
| MOA unclear. May involve: decreased peripheral 5HT release, PG antagonism
|-
| Dopamine antagonists
| Metoclopramide, Droperidol
| Central D2 antagonism at chemoreceptor trigger zone &gt; reduced afferent input to vomiting centre in medulla
|-
| Antihistamine
| Cyclizine
| Competitive H1 antagonism. Also has
|-
| NK1 antagonist
| Aprepitant
| Blocks action of substance P in brainstem vagal complexes involved in regulation of vomiting
|-
| Others
| Canabinoids
| Thought to act within the vomiting centre
|}
 
 
 
<span id="examiner-comments-14"></span>
==== Examiner comments ====
 
<blockquote>
</blockquote>
 
 
<span id="online-resources-for-this-question-14"></span>
==== Online resources for this question ====
 
* Jenny's Jam Jar
* CICM Wrecks
* Deranged physiology
 
 
 
<span id="similar-questions-14"></span>
==== Similar questions ====
 
* Question 3, 2014 (1st sitting)
 
 
 
 
 
 
 
<span id="question-15-1"></span>
=== Question 15 ===
 
 
 
<span id="question-15"></span>
==== Question ====
 
Describe the sequence of haemostatic events following injury to a blood vessel wall until clot stabilisation
 
 
 
<span id="example-answer-15"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-15"></span>
==== Examiner comments ====
 
<blockquote>
</blockquote>
 
 
<span id="online-resources-for-this-question-15"></span>
==== Online resources for this question ====
 
* Jenny's Jam Jar
* CICM Wrecks
* Deranged physiology
 
 
 
 
 
<span id="similar-questions-15"></span>
==== Similar questions ====
 
<ul>
<li><p>Question 10, 2019 (1st sitting)</p>
<p></p></li></ul>
 
 
 
 
 
<span id="question-16-1"></span>
=== Question 16 ===
 
 
 
<span id="question-16"></span>
==== Question ====
 
Outline the impact of sedative agents on thermoregulation (40% marks) and describe the physiological effects of a low body temperature (60% marks)
 
 
 
<span id="example-answer-16"></span>
==== Example answer ====
 
 
 
Core body temperature
 
* 37 degrees +/- 0.4 degrees
 
 
 
Effects of anaesthesia
 
<ul>
<li><p>The interthreshold range</p>
<ul>
<li><p>The range of core temps at which no autonomic thermoregulatory responses occurs</p></li>
<li><p>Normally 37 +/- 0.2 degrees</p></li>
<li><p>With general anaesthesia this is widened to 37 +/- 2 degrees </p></li></ul>
</li>
<li><p>Responses to general anaesthetic</p>
<ul>
<li><p>Behavioural responses completely abolished (seek warmth, clothing etc)</p></li>
<li><p>Volatile anaesthetics, opioids (e.g. morphine), IV sedatives (e.g. propofol) &gt; vasodilation &gt; increased heat loss.</p></li>
<li><p>Decreased responsiveness to temperature change (widened interthreshold range)</p></li>
<li><p>Opioids also decrease sympathetic outflow &gt; impaired vasoconstriction</p></li>
<li><p>If adjunct muscle relaxant used -&gt; shivering also prevented (decreased heat generation)</p></li>
<li><p>Therefore the only thermoregulatory responses available to anaesthetised/paralysed patient with hypothermia are vasoconstriction and non shivering thermogenesis. Hence body temperature changes passively in proportion to the difference in heat production and heat loss </p></li></ul>
 
<p></p></li></ul>
 
Mild hypothermia
 
* 34-36.5
* Common during anaesthesia
 
 
 
Effects of hypothermia
 
<ul>
<li><p>METABOLIC</p>
<ul>
<li><p>BMR drops 6% for every 1 degree in core temp --&gt; Decreased VO2</p></li>
<li><p>Hyperglycaemia (decreased cell uptake)</p></li></ul>
</li>
<li><p>CVS</p>
<ul>
<li><p>Decrease inotropy and chronotropy &gt; decreased CO</p></li>
<li><p>Arrhythmias (AF, VF)</p></li>
<li><p>QT prolongation, J wave</p></li>
<li><p>Resistance to DCCV</p></li>
<li><p>Peripheral vasoconstriction and blood redistribution</p></li>
<li><p>Increased risk of myocardial ischaemia</p></li></ul>
</li>
<li><p>CNS</p>
<ul>
<li><p>Confusion and decreasing LOC</p></li>
<li><p>Shivering</p></li>
<li><p>Seizures (increased seizure threshold)</p></li></ul>
</li>
<li><p>RESP</p>
<ul>
<li><p>Decreased RR</p></li>
<li><p>Left shift of O2 dissociation curve</p></li></ul>
</li>
<li><p>GIT</p>
<ul>
<li><p>Ileus</p></li>
<li><p>Decreased hepatic drug metabolism and clearance (slows enzymatic reactions, decreased blood flow)</p></li></ul>
</li>
<li><p>HAEM</p>
<ul>
<li><p>Increased HCT and blood viscosity</p></li>
<li><p>Coagulopathy,</p></li>
<li><p>Platelet dysfunction and sequestration</p></li></ul>
</li>
<li><p>RENAL</p>
<ul>
<li><p>Cold diuresis (decreased vasopressin synthesis)</p></li></ul>
</li>
<li><p>ENDO</p>
<ul>
<li><p>Decreased ACTH, TSH, vasopressin</p></li></ul>
</li>
<li><p>ACID-BASE</p>
<ul>
<li><p>Increased pH</p>
<p></p></li></ul>
</li></ul>
 
 
 
<span id="examiner-comments-16"></span>
==== Examiner comments ====
 
<blockquote>33% of candidates passed this question.<br />
Sedation reduces body temperature by interfering with heat production and increasing heat loss, along with widening of hypothalamic inter-threshold range. This portion of the question was generally well answered. The question asked to &quot;outline&quot; the answer. Many candidates actually &quot;described&quot; the thermoregulation process in general but were unable to relate those with the impact of sedation. The second part of the question (physiological effect of low body temperature) was answered by most of the candidates with the structure of organ-system wise description. A few candidates scored extra marks by relating these effects with degree of hypothermia and by describing how thermogenesis responses (including shivering) can influence those effects. Some candidates restricted their answers to the effect of thermogenesis in response hypothermia and did not include the overall physiological consequences of low body temperature. Better answers displayed an understanding of core temperature regulation, inter-threshold range and the effects of sedatives on thresholds for thermogenic responses, although only a few mentioned gain and maximal response. Better answers included specific detail (mentioned bradyarrhythmia, slow AF, VF, prolonged PR/QRS / J waves rather than just stating arrhythmia) across several organ systems. Marks were not awarded for generic statements such as 'decreased liver function' without some additional detail. Inadequate depth of knowledge was main reason behind overall poor scores.
</blockquote>
 
 
<span id="online-resources-for-this-question-16"></span>
==== Online resources for this question ====
 
* Jenny's Jam Jar
* CICM Wrecks
* Deranged physiology
 
 
 
 
 
<span id="similar-questions-16"></span>
==== Similar questions ====
 
* Question 9, 2021 (1st sitting)
 
 
 
 
 
 
 
<span id="question-17-1"></span>
=== Question 17 ===
 
 
 
<span id="question-17"></span>
==== Question ====
 
Write notes on:
 
* The principles of ultrasound
* Transducer properties and image resolution
* The doppler effect
 
 
 
<span id="example-answer-17"></span>
==== Example answer ====
 
 
 
Ultrasound = sound waves at higher frequencies then can be heard by humans (&gt;20kHz)
 
 
 
Sound wave generation
 
* Produced by piezoelectric effect
** Electrical voltage applied to quartz (piezoelectric) crystal &gt; vibrates &gt; sound emitted (Converts electrical energy to sound energy)
* Frequency of sound wave
** Different probes emit different frequencies of sound waves:
*** Liner = 15-6 MHz
*** Curved = 8-3 MHz
*** Cardiac = 5-1 MHz
** Effects
*** Higher frequency = shallower depth, better resolution
*** Lower frequency = better depth, less resolution
 
 
 
Sound wave effected by tissue and may be
 
* Absorbed
** Sound is absorbed, lost as heat
* Reflected
** Sound reflected off objected back to probe sensor
** Reflection occurs at interfaces of tissues with ''different'' densities (impedance)
* Refracted
** Change in direction (bending) of sound wave
* Scattered
** Sound reflected from tissue but not received by probe sensor
 
 
 
Detection of sound
 
* The probe spends 1% time emitting sound, 99% time listening for sound
* The crystals are vibrated by returning sound waves (echos) and generates a voltage (converse piezoelectric effect)
 
 
 
Processing
 
* Amplitude of the wave determines echogenicity
* Time taken for echo's to return determines depth
* Output mode
** B mode (brightness mode)
*** 2D crossection through tissue
*** Largest amplitude = brightest, smallest amplitude = darkest
** M mode (motion mode)
*** Movement of structures over time
* Resolution
** Spatial resolution
*** Dependant on axial (parallel to beam) and lateral (perpendicular to beam) resolution
*** Enhances by pulse wave and focusing
** Contrast resolution
*** Distinguish between two regions of similar echogenicitiy
** Temporal resolution
*** Distinguish change over time
*** Improved by framerate
 
 
 
Doppler effect
 
* The change in frequency of a wave in relation to an observer that is moving relative to the wave source.
* In medical ultrasound
** The change in frequency of ''sound'' waves reflected from moving tissue (e.g. erythrocytes)
*** Away from probe (lower frequency = blue colour)
*** Towards probe (higher frequency = red colour)
 
 
 
<span id="examiner-comments-17"></span>
==== Examiner comments ====
 
<blockquote>
</blockquote>
 
 
<span id="online-resources-for-this-question-17"></span>
==== Online resources for this question ====
 
* Jenny's Jam Jar
* CICM Wrecks
* Deranged physiology
 
 
 
 
 
<span id="similar-questions-17"></span>
==== Similar questions ====
 
*
 
 
 
 
 
 
 
<span id="question-18-1"></span>
=== Question 18 ===
 
 
 
<span id="question-18"></span>
==== Question ====
 
Describe the anatomy of the left subclavian vein
 
 
 
<span id="example-answer-18"></span>
==== Example answer ====
 
 
 
Course
 
* Continuation of the axillary vein (commences at the lateral border of the 1st rib)
* Travels medially, first arching cephalad before heading caudally toward the sternal notch
* Terminates by joining the internal jugular vein (IJV) and forming the brachiocephalic (innominate) vein behind the sternoclavicular joint
 
 
 
Tributaries
 
* External jugular vein
** Drains into the subclavian at the lateral border of anterior scalene muscle
* Thoracic duct
** Drains into either subclavian or innominate vein behind the sternoclavicular joint
 
 
 
Relationships
 
* Cephalad
** Skin, subcutaneous tissue, platysma
* Anterior
** Skin, clavicle, subclavius muscle
* Posterior
** Anterior scalene muscle which separates from the subclavian artery
* Posterior-inferiorly
** 1st rib, pleura, phrenic nerve
* Medial
** Brachiocephalic vein, mediastinal structures (vagus, trachea, aorta)
* Lateral
** Axillary vein, brachial plexus
 
 
 
Surface anatomy (infraclavicular approach)
 
* Needle is placed in the deltopectoral groove, inferior and lateral to the middle third of the clavicle.
* The needle is inserted at a shallow angle, passing under the middle third of the clavicle aiming at the sternal notch.
 
 
 
 
 
 
 
<span id="examiner-comments-18"></span>
==== Examiner comments ====
 
<blockquote>
</blockquote>
 
 
<span id="online-resources-for-this-question-18"></span>
==== Online resources for this question ====
 
* Jenny's Jam Jar
* CICM Wrecks
* Deranged physiology
 
 
 
 
 
<span id="similar-questions-18"></span>
==== Similar questions ====
 
*
 
 
 
 
 
 
 
<span id="question-19-1"></span>
=== Question 19 ===
 
 
 
<span id="question-19"></span>
==== Question ====
 
Describe the physiological factors that affect PaCO<sub>2</sub>
 
 
 
<span id="example-answer-19"></span>
==== Example answer ====
 
 
 
Overview
 
* PaCO<sub>2</sub> is normally 40mmHg +/- 3mmHg
* PaCO<sub>2</sub> is a balance between production and elimination
 
 
 
CO<sub>2</sub> production
 
* Metabolism
** CO<sub>2</sub> is the by-product of mitochondrial respiration via TCA cycle
** Increased metabolism &gt; increased CO<sub>2</sub> production
*** Metabolic rate is increased with
**** Exercise
**** Increased temp (e.g. infection)
**** Youth
**** Male sex
**** Pregnancy
**** Eating
* Energy source
** RQ = Ratio of Co2 produced: O2 consumed
*** Effected by the energy source utilised
*** Normally
**** Fats 0.7
**** Ketones/alcohols 0.7
**** Proteins 0.8
**** Carbohydrates 1.0
** Hence carbohydrates Increase CO2 production compared to lipids/proteins (though hot chips are delicious)
 
 
 
CO2 elimination
 
* Alveolar ventilaiton
** CO2 is a ventilation limited gas
** Increase minute ventilation (RR, TV) &gt; increase CO2 elimination via respiration &gt; decreased PaCO2
** Physiological factors that increase RR: Pain, anxiety, pregnancy, Hypoxia
* Tightly regulated
** Minute ventilation is increased by increased PaCo2
*** MV linearly increases 2L/min for every 1mmmHg increase in PaCo2
*** Due to the chemoreceptor responses
**** Central chemoreceptors
***** Located: Ventral medulla
***** CO2 diffuses across BBB &gt; increased H+ &gt; decreased pH &gt; detected by chemoreceptor &gt; stimulate dorsal resp group &gt; Increase MV
**** Peripheral chemoreceptors
***** Located: Carotid bodies, aortic bodies
***** Increased PaCo2 or decreased PaO2 &gt; stimulate the respiratory centre &gt; increased MV
 
 
 
<span id="examiner-comments-19"></span>
==== Examiner comments ====
 
<blockquote>33% of candidates passed this question.
 
Candidates who scored well generally defined PaCO2 and proceeded to describe factors in terms of those related to production and elimination. Good answers described the key production factor as being rate of production through aerobic metabolism which is in turn influenced by substrate and BMR. Those who scored well described elimination as being dependent upon minute ventilation, which in turn is influenced by CO2 detection by chemoreceptors, specifically detailing the difference between peripheral and central. Many candidates detailed pathophysiological factors which unfortunately did not gain any marks.
</blockquote>
 
 
<span id="online-resources-for-this-question-19"></span>
==== Online resources for this question ====
 
* Jenny's Jam Jar
* CICM Wrecks
* Deranged physiology
 
 
 
 
 
<span id="similar-questions-19"></span>
==== Similar questions ====
 
*
 
 
 
<span id="question-20-1"></span>
=== Question 20 ===
 
 
 
<span id="question-20"></span>
==== Question ====
 
Describe the physiological control of systemic vascular resistance (SVR)
 
 
 
<span id="example-answer-20"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-20"></span>
==== Examiner comments ====
 
<blockquote>
</blockquote>
 
 
<span id="online-resources-for-this-question-20"></span>
==== Online resources for this question ====
 
* Jenny's Jam Jar
* CICM Wrecks
* Deranged physiology
 
 
 
 
 
<span id="similar-questions-20"></span>
==== Similar questions ====
 
* Question 7, 2020 (1st sitting)
 
 
 
 
 
 
 
 
 
<span id="2021-2nd-sitting"></span>
== 2021 (2nd sitting) ==
 
<span id="question-1-2"></span>
=== Question 1 ===
 
 
 
<span id="question-21-1"></span>
==== Question ====
 
Describe the regulation of body water
 
 
 
<span id="example-answer-21"></span>
==== Example answer ====
 
 
 
Overview
 
* Water intake
** Approximately 30ml/kg of water is needed to be ingested for fluid/body homeostasis
*** Approx 2-2.5L per day for an average person
** Approximately half comes from drinking fluids, half from food and metabolic processes
* Water is lost through numerous ways
** Urine
*** Approx 1 - 1.5L / day
*** Obligatory loss is ~500mls to cover solute/waste clearance
** Insensible losses (skin, lungs etc)
*** Approx 900mls / day
** Faeces
*** Approx 100mls / day
* The body tightly regulates water balance to preserve plasma osmolality and intravascular volume status, but also allow waste clearance
** Preservation of blood volume takes precedence over plasma osmolality
 
 
 
REGULATION
 
* Sensors
*# Osmoreceptors in hypothalamus detect increased (&gt;290mosm/L) osmolality with dehydration (major)
*# Low pressure baroreceptors (RA, great vessels) detect reduced pressure (stretch) with dehydration
*# High pressure baroreceptors (carotid sinus, aortic arch) detect reduced pressure (stretch) with dehydration
*# Macula densa (kidneys) detect reduced GFR (Na/Cl delivery)
* Integrator
** Hypothalamus (anterior and lateral predominately)
* Effector/effects
*# Release of ADH
*#* Synthesised in hypothalamus transported to posterior pituitary for release
*#* ADH acts on collecting ducts in the kidney in to increase aquaporins on luminal wall --&gt; increased water reabsorption
*#* Released in response to increase osmolality and activation of RAAS
*# ANP/BNP
*#* Decreased stretch &gt; decreased ANP/BNP secretion --&gt; increased water reabsorption
*# RAAS
*#* Decreased baroreceptor activation --&gt; increased renin release
*#* Decreased GFR sensed by macula sensa &gt; increased renin release
*#* Renin &gt; activation of RAAS &gt; increased water reabsorption
*# Thirst centre (hypothalamus)
*#* Activation of thirst centre in the lateral hypothalamus (due to increased osmolality) &gt; behavioural change to increase water intake
* Feedback
** The above systems work predominately on a negative feedback system
 
 
 
<span id="examiner-comments-21"></span>
==== Examiner comments ====
 
<blockquote>28% of candidates passed this question.
 
This is a level 1 topic. An understanding as to how the body regulates water is crucial to the daily practice of critical care, this topic is well described in the major texts. This type of question lends itself to the basic template of sensor mechanisms, central processing and integration with effector limbs and feedback loops. However, high scoring answers require a quantification of responses and an introduction into how these processes are integrated and fine-tuned.
</blockquote>
 
 
<span id="online-resources-for-this-question-21"></span>
==== Online resources for this question ====
 
* CICM Wrecks
* Deranged Physiology
* Jenny's Jam Jar
 
 
 
<span id="similar-questions-21"></span>
==== Similar questions ====
 
* Question 8, 2008 (1st sitting)
* Question 4, 2015 (1st sitting)
* Question 9, 2018 (2nd sitting)
 
 
 
 
 
<span id="question-2-2"></span>
=== Question 2 ===
 
 
 
<span id="question-22-1"></span>
==== Question ====
 
Describe the pharmacology of lidocaine
 
 
 
<span id="example-answer-22"></span>
==== Example answer ====
 
{|
! Name
! Lidocaine (lignocaine)
|-
| '''Class'''
| Amide anaesthetic / Class 1b antiarrhythmic
|-
| '''Indications'''
| Local/regional/epidural anaesthesia, ventricular dysrhythmias, IV analgesia,
|-
| '''Pharmaceutics'''
| Clear colourless solution (1%, 2%, 4%). Can come with/without adrenaline. Also available as cream/spray
|-
| '''Routes of administration'''
| SC, IV, epidural, inhaled
|-
| '''Dose'''
| Regional Use: Toxic dose 3mg/kg (without adrenaline), 7mg/kg (with adrenaline)<br />
IV use: 1mg/kg initially, then ~1-2mg/kg/hr
|-
| pKA
| 7.9 (25% unionised at normal body fluid pH)
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Class 1b anti-arrhythmic: blocks Na channels, raising threshold potential + reducing slope of Phase 0 of action potential, shortened AP<br />
Local anaesthetic: binds to, and blocks, internal surface of Na channels
|-
| Effects
| Analgesic, anaesthetic, anti-arrhythmic
|-
| Side effects
| CNS: headache, dizziness, confusion, paraesthesia, reduced LOC, seizures<br />
CVS: hypotension, bradycardia, AV Block, arrhythmia<br />
CC/CNS ratio = 7 (lower number = more cardiotoxic)
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| Rapid onset (1-5 minutes)
|-
| Absorption
| IV &gt; Epidural &gt; subcut. <br />
Oral bioavailability 35%
|-
| Distribution
| 70% protein bound, <br />
Vd ~1L/kg.<br />
Crosses BBB
|-
| Metabolism
| Extensive hepatic metabolism with some active metabolites
|-
| Elimination
| Metabolites excreted in urine. <br />
Half life ~90mins. Increased with adrenaline (SC). Reduced in cardiac/hepatic failure.
|-
| '''Special points'''
|
|}
 
 
 
<span id="examiner-comments-22"></span>
==== Examiner comments ====
 
<blockquote>71% of candidates passed this question.
 
The answers for this question were generally of a good standard. Lidocaine is a core drug in intensive care practice and thus a high level of detail was expected. This question was best structured using a standard pharmacology template (pharmaceutics, pharmacokinetics and pharmacodynamics). A small number of answers omitted any pharmaceutic elements. Another common error was the use of vague and imprecise statements. For example, many answers stated that the maximum dose (without adrenaline) is 3 mg/kg, without specifying that this is subcutaneous. The concept of the ratio of the dose required to produce cardiovascular collapse to that required to induce seizures (CC/CNS ratio) was often mentioned. However, in many cases this was conveyed simply as an abbreviated statement without any additional explanation leaving the examiner unsure as to whether the candidate understood the concept (and thus unable to award any additional marks). In addition, many candidates confused the order of this ratio (incorrectly referring to it as a CNS/CC ratio of 7). Lastly, few answers made specific mention of the narrow therapeutic index and the associated implications for use in the ICU.
</blockquote>
 
 
<span id="online-resources-for-this-question-22"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/main/cicm-primary-exam/required-reading/nervous-system/Chapter%20326/lignocaine Deranged Physiology]
* [https://partone.litfl.com/local_anaesthetics.html Part One, LITFL] and [https://partone.litfl.com/sodium_channel_blockers.html Part One, LITFL]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-1-01.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-22"></span>
==== Similar questions ====
 
* Question 17, 2014 (1st sitting)
* Question 1, 2019 (1st sitting)
 
 
 
 
 
<span id="question-3-2"></span>
=== Question 3 ===
 
 
 
<span id="question-23-1"></span>
==== Question ====
 
Discuss the physiological determinants of cardiac output
 
 
 
<span id="example-answer-23"></span>
==== Example answer ====
 
 
 
Cardiac output
 
* The volume of blood ejected from the heart per unit time
* <math display="inline">CO = HR \; \times SV</math> and <math display="inline">CO \; = \; VR</math>
* CO is approximately 5L/min in the average person
 
 
 
Factors affecting CO
 
 
 
Heart rate
 
* If stroke volume remains the same, then increasing HR will increase CO
* However, in a healthy person within physiological HRs (60-150), if there is no increase in physiological demand, altering HR has limited effects on CO as the stroke volume reduces
* In extremes of HR, with increased metabolic demand, or pathology (e.g. poor contractility), altering HR will impact cardiac output
 
 
 
Stroke volume (SV)
 
* Stroke volume = EDV - ESV, Normally ~70mls
* Increased stroke volume = increased CO
* Factors affecting stroke volume include
** Preload
*** Myocardial sarcomere length just prior to contraction.
*** Cannot be measured, so approximated by EDV
*** Increased preload &gt; incre
*** Factors effecting preload include
**** Ventricular compliance
**** Venous return
**** Valvular disease
**** Heart rate
**** Myocardial wall thickness
**** Atrial contractility
** Afterload
*** External force required to be generated before the mycoardial sarcomere begins to shorten
*** Reduced afterload &gt; increased SV &gt; increased CO
*** Factors affecting afterload include:
**** Systemic vascular resistance
**** Outflow tract impedance
**** Transmural pressure
**** Myocardial wall thickness
** Contractility
*** Intrinsic ability of the myocardial fibres to shorten/contract
*** Increased contractility = increased SV = increased CO
*** Factors effecting contractility include
**** Bowditch effect
**** Anrep effect
**** Tone
**** Heart rate
**** Ischaemia/drugs.
 
 
 
<span id="examiner-comments-23"></span>
==== Examiner comments ====
 
<blockquote>65% of candidates passed this question.
 
Although the pass rate for this question was reasonably high the examiners commented on a lack of detailed knowledge within most answers for such a core component of our daily practice. Several candidates failed to provide a normal value and only few provided anything other than 5l/min. There was a general lack of detail, and at times, some confusion about the Frank Starling effect. Most candidates outlined the major determinants of stroke volume, although many were light on the determinants of each or incorporated incorrect facts. Several candidates did not mention HR as a determinant of CO
</blockquote>
 
 
<span id="online-resources-for-this-question-23"></span>
==== Online resources for this question ====
 
* CICM Wrecks
* Deranged Physiology
* [https://jennysjamjar.com.au/year/21b/21b03-discuss-the-physiological-determinants-of-cardiac-output/ Jenny's Jam Jar]
 
 
 
<span id="similar-questions-23"></span>
==== Similar questions ====
 
* Question 8, 2011 (1st sitting)
* Question 13, 2011 (2nd sitting)
* Question 19, 2014 (1st sitting)
 
 
 
 
 
<span id="question-4-2"></span>
=== Question 4 ===
 
 
 
<span id="question-24-1"></span>
==== Question ====
 
Compare the pharmacology of fluconazole and amphotericin
 
 
 
<span id="example-answer-24"></span>
==== Example answer ====
 
 
 
{|
! Name
! Fluconazole
! Amphotericin
|-
| '''Class'''
| Azole / antifungal
| Polyenes / antifungal
|-
| '''Indications'''
| Systemic fungal infections, prophylaxis fungal infections for immunocompromised
| Systemic fungal infections
|-
| '''Pharmaceutics'''
| Tablet (PO), White powder which is clear and colourless in solution (water, saline).
| Powder for reconstitution and injection
|-
| '''Routes of administration'''
| PO, IV
| IV, lozenges, inhalation
|-
| '''Dose'''
| Generally 200-800mg daily for systemic infections, reduced dose local infections or prophylaxis (e.g 50-200mg daily)
| ~1-5mg/kg daily
|-
| '''Pharmacodynamics'''
|
|
|-
| MOA
| Fungicidal. Disrupts ergosterol production (essential for cell membrane formation) leading to increased permeability.
| Fungicidal. Binds directly to ergosterol &gt; creates transmembrane channels &gt; permeability &gt; death
|-
| Coverage
| Covers: Candida albicans, Cryptococcus<br />
Doesnt: Most other fungi/yeast, aspergillus
| Good activity against almost all fungi/yeasts (inc. aspergillus, candida, crypto)
|-
| Side effects
| Liver: Potent CYP450 inhibitor &gt; many drug interactions, LFT derangement<br />
CNS: headache<br />
CVS: QT prolongation <br />
Derm: rash, alopecia<br />
GIT: N/V, diarrhoea, abdo pain
| Nephrotoxicity, hypokalaemia, infusion reactions , RTA
|-
| '''Pharmacokinetics'''
|
|
|-
| Onset
| Peak concentrations 1-2hours
|
|-
| Absorption
| Great oral bioavailability (&gt;90%)
| Poor oral bioavailability (hence only given IV)
|-
| Distribution
| Vd close to that of water ~0.7L/Kg. <br />
Good CSF, tissue, fluid penetration. <br />
Poorly protein bound (10%)
| Highly protein bound (90%). Negligible CSF/urine distribution.<br />
VOD = ~1L /Kg
|-
| Metabolism
| Not metabolised
| Minimal hepatic metabolism
|-
| Elimination
| Renal (unchanged 80%). <br />
T 1/2 ~30 hours
| Renal/faecal elimination. <br />
T 1/2 = 15 days.
|-
| '''Special points'''
| Monitoring: LFTs, drug interactions
| Monitoring: renal function
|}
 
 
 
<span id="examiner-comments-24"></span>
==== Examiner comments ====
 
<blockquote>6% of candidates passed this question.
 
This question exposed an area of the syllabus neglected by the candidates. Answers were generally vague in detail with lots of incorrect facts and generally displayed a very limited knowledge. Antifungal agents are regularly used in critically ill patients either as treatment or prophylaxis. An understanding of the aspects of these drugs with respect to spectrum of activity, mechanism of action, specific PK and PD properties as well as potential side effects would have been the basis for this compare and contrast question. Examiners want to be convinced that the candidates understand the strengths and weaknesses of each drug and in which circumstances one agent might be used in preference to the other.
</blockquote>
 
 
<span id="online-resources-for-this-question-24"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/syllabus/t/t2/t2ii-describe-the-pharmacology-of-antifungal-agents/ Jennys Jam Jar]
* [https://derangedphysiology.com/required-reading/infectious-diseases-antibiotics-and-sepsis/Chapter%202.2.3/pharmacology-antifungal-agents Deranged Physiology]
 
 
 
<span id="similar-questions-24"></span>
==== Similar questions ====
 
* ?Nil
 
 
 
 
 
<span id="question-5-2"></span>
=== Question 5 ===
 
 
 
<span id="question-25"></span>
==== Question ====
 
Write detailed notes on angiotensin, including its synthesis, role within the body and regulation
 
 
 
<span id="example-answer-25"></span>
==== Example answer ====
 
 
 
Synthesis and regulation
 
* Angiotensinogen
** Peptide hormone continuously synthesised in the liver and is a precursor to angiotensin
** Increased release in response to corticosteroids, oestrogens, thyroid hormones, AGT2 levels
* Renin converts angiotensinogen to Angiotensin I
** Renin is produced, stored, secreted from JG cells in kidney
** Stimulated by reduced GFR, decreased Na/CL delivery to MD, sympathetic innervation
** Inhibited by Angiotensin II (negative feedback)
* Angiotensin converting enzyme (ACE) converts Angiotensin I to Angiotensin II
** ACE is present in the capillary endothelial cells in the lungs (and renal endothelium)
* There is also angiotensin III and IV which are the product of further cleavage by peptidases
** These have similar effects to angiotensin II (but reduced potency)
* The renin-angiotensin-aldosterone system (RAAS) exerts negative feedback on the release of renin, additionally increased BP and Na/Cl delivery will decrease renin secretion
 
 
 
Effects of angiotensin
 
* Angiotensin I
** Thought to be physiologically inactive, but acts as a precursor to Angiotensin II
* Angiotensin II
** Renal effects
*** Increases Na-H antiporter activity in PCT &gt; increased Na/Water reabsorption
*** Vasoconstriction of afferent + efferent arterioles + contraction mesangial cells &gt; reduced GFR + urine output
** CVS effects
*** Binds AT1 receptors &gt; vasoconstriction &gt;increased SVR &gt; inc. BP
** Neurohormonal effects
*** Increases sensation of thirst through activation of hypothalamus &gt; increased blood volume
*** Increases the release of ADH from the pituitary gland
**** ADH Increases water reabsorption by inserting aquaporins in the collecting ducts
*** Increases production and release of aldosterone from adrenal cortex
**** Aldosterone increases blood volume: Increases Na/Water reabsorption in DCT
**** Aldosterone increases blood pressure: by increasing blood volume, but also by direct vasopressor effects
 
 
 
<span id="examiner-comments-25"></span>
==== Examiner comments ====
 
<blockquote>24% of candidates passed this question.
 
This question provided headings for the answer template. Good answers integrated the required facts from the appropriate chapters of the major texts. Most answers lacked detail surrounding the factors that increase or decrease angiotensin activity. Few answers provided any detail as to all the mechanisms through which angiotensin exerts it effects. A lot of answers focussed singularly on the vascular effects of angiotensin. Overall, there was often a paucity of detail, with vague statements and incorrect facts
</blockquote>
 
 
<span id="online-resources-for-this-question-25"></span>
==== Online resources for this question ====
 
* CICM Wrecks
* Deranged Physiology
* [https://jennysjamjar.com.au/year/21b/21b05-write-detailed-notes-on-angiotensin-including-its-synthesis-role-within-the-body-and-regulation/ Jenny's Jam Jar]
 
 
 
<span id="similar-questions-25"></span>
==== Similar questions ====
 
* Question 18, 2009 (2nd sitting)
* Question 6, 2011 (2nd sitting)
 
 
 
 
 
<span id="question-6-2"></span>
=== Question 6 ===
 
 
 
<span id="question-26"></span>
==== Question ====
 
Describe the functions of the placenta (80% marks). Outline the determinants of placental blood flow (20% marks).
 
 
 
<span id="example-answer-26"></span>
==== Example answer ====
 
 
 
FUNCTIONS OF PLACENTA
 
 
 
Nutrient/gas exchange
 
<ul>
<li><p>The foetus relies on maternal transfer of gasses, nutrients and wastes</p></li>
<li><p>Nutrients/wastes</p>
<ul>
<li><p>Active transport e.g Amino acids, calcium, some vitamins/minerals</p></li>
<li><p>Facilitated diffusion e.g. glucose (GLUT1 and GLUT3)</p></li>
<li><p>Simple diffusion e.g. Na, Cl, urea, creatinine based on Fick Principle</p></li></ul>
</li>
<li><p>Gasses</p>
<ul>
<li><p>Oxygen</p>
<ul>
<li><p>Passive diffusion</p></li>
<li><p>Facilitated by higher oxygen carrying capacity and affinity of foetal Hb as well as the Bohr/Double bohr effects</p></li></ul>
</li>
<li><p>Carbon dioxide</p>
<ul>
<li><p>Passive diffusion</p></li>
<li><p>Facilitated by the Haldane and double Haldane effects</p></li></ul>
</li></ul>
 
<p></p></li></ul>
 
Immunological function
 
* Foetus is genetically distinct with a non functioning immune system
* Trophoblast cells
** Lose MHC molecules and become coated in mucoprotein &gt; less immunogenic
* Chorionic cells
** Prevent maternal T cells and most immunoglobulins (except IgG) from entering &gt; less immunogenic
** Barrier to some bacteria/viruses and allows IgG across &gt; some immune protection
* Yolk sac
** a-fetoprotein and progesterone are immunosuppressive &gt; less immunogenic
 
 
 
Endocrine function
 
* Syncytiotrophoblast of placenta produces
** B-HCG - prolongs corpus luteum (prevents early miscarriage)
** Oestrogen - increases uteroplacental blood flow, stimulates uterine growth
** Progesterone - uterine relaxation, development of lactation glands
** hPL - maternal lipolysis, breath growth/development
 
 
 
PLACENTAL BLOOD FLOW
 
 
 
Flow
 
* Blood flow to the uterus in a non pregnant woman is normally around 200mls/min (~4% of CO)
* In a pregnant woman at term this increases to up to 750mls/min (~15% of CO)
* Majority of this &gt; placenta (~600mls/min), with some supplying the hypertrophied uterus.
* Foetal blood flow is approx half placental blood flow (~300mls/min, ~60%CO)
 
 
 
Determinants of flow
 
* No autoregulation of uteroplacental blood flow
* Most important factor governing flow is therefore perfusion pressure
** Increased uteroplacental perfusion pressure &gt; increase flow
* Uterine perfusion pressure is therefore effected by
** Maternal MAP
*** Effected by positioning (e.g. aortocaval compression), cardiac output, systemic vascular resistance
** Intrauterine pressure
*** Effected by contractions &gt; increased intrauterine pressure &gt; decreased flow
** Uterine vascular resistance
*** The radial arteries of the myometrium are modestly effected by exogenous vasopressors, catecholamines
* Compensates for the lack of autoregulation by increasing oxygen extraction
 
 
 
<span id="examiner-comments-26"></span>
==== Examiner comments ====
 
<blockquote>49% of candidates passed this question.
 
There was a wide range of marks for this question with a few candidates scoring excellent marks. Those answers that scored well provided a comprehensive list of functions as well as an explanation as to the what, how and/or why of these functions. Poorer answers omitted some of the functions or failed to elaborate on them by providing only a limited list. The second component of the question was generally well outlined, most candidates provided some estimate of normal values at term and a simple elaboration regarding the factors that affect placental blood flow.
</blockquote>
 
 
<span id="online-resources-for-this-question-26"></span>
==== Online resources for this question ====
 
* CICM Wrecks
* Deranged Physiology
* [https://jennysjamjar.com.au/year/21b/21b06-describe-the-functions-of-the-placenta-80-marks-outline-the-determinants-of-placental-blood-flow-20-marks/ Jenny's Jam Jar]
* [https://partone.litfl.com/the_placenta.html Part One, LITFL]
 
 
 
<span id="similar-questions-26"></span>
==== Similar questions ====
 
* Question 9, 2018 (1st sitting)
 
 
 
 
 
 
 
<span id="question-7-2"></span>
=== Question 7 ===
 
 
 
<span id="question-27"></span>
==== Question ====
 
Outline how the measurement of the following can be used in the assessment of liver function (25% marks of each): 1) Albumin 2) Prothrombin time 3) Glucose 4) Ammonia
 
 
 
<span id="example-answer-27"></span>
==== Example answer ====
 
 
 
<ol style="list-style-type: decimal;">
<li><p>Albumin</p>
<ul>
<li><p>Albumin is a protein synthesized in the liver (half life ~3 weeks)</p></li>
<li><p>Normally 34-45g/L in the blood</p></li>
<li><p>With chronic liver dysfunction there is reduced synthesis &gt; low albumin</p></li>
<li><p>More commonly related to other diseases</p>
<ul>
<li><p>Malnutrition</p></li>
<li><p>Protein loss (e.g. nephrotic syndrome)</p></li>
<li><p>Physiological dilution (e.g. pregnancy)</p></li>
<li><p>Inflammation/stress (negative acute phase reactant)</p></li></ul>
</li></ul>
 
<p></p></li>
<li><p>Prothrombin time</p>
<ul>
<li><p>Measures the rate of conversion of prothrombin to thrombin</p></li>
<li><p>Normal PT = 10-13 seconds</p></li>
<li><p>Most coagulation factors are synthesised by the liver</p></li>
<li><p>If synthetic function of the liver is impaired (e.g. by severe cirrhosis) there would be a prolonged prothrombin time. </p></li>
<li><p>If synthetic function of the liver is normal, but prothrombin time is prolonged, this would imply drug effect (eg. warfarin), consumptive coagulopathy, or VitK deficiency</p></li></ul>
</li></ol>
 
 
 
<ol style="list-style-type: decimal;">
<li><p>Glucose</p>
<ul>
<li><p>Essential energy substrate</p></li>
<li><p>Normal BGL = 4-6 for most people (physiologically varies with diet/time)</p></li>
<li><p>Liver is important for glucose homeostasis including glycolysis, glycogenolysis and gluconeogenesis</p></li>
<li><p>Liver failure may lead to both diabetes as well as hypoglycaemia</p></li>
<li><p>Blood glucose levels or neither sensitive, nor specific for liver dysfunction</p></li>
<li><p>Hypoglycaemia may be causes by numerous other conditions including pancreatic disorders, stress, drugs, diet/malnutrition, GIT absorption issues etc. </p>
<p></p></li></ul>
</li>
<li><p>Ammonia</p>
<ul>
<li><p>Ammonia is a nitrogenous waste product</p>
<ul>
<li><p>Produced by amino acid metabolism, urea hydrolysis in the GIT and renal synthe</p></li></ul>
</li>
<li><p>Normal level &lt;30ug/L in adults</p></li>
<li><p>Normally transported to liver for conversion to urea via urea cycle &gt; excreted kidneys</p></li>
<li><p>If liver is unable to metabolise ammonia &gt; accumulates</p></li>
<li><p>Hyperammonaemia is relatively specific to cirrhotic liver disease (90% of cases)</p></li>
<li><p>Other causes include</p>
<ul>
<li><p>Haematological disorders (e.g. myeloma)</p></li>
<li><p>Congenital defects in urea-cycle function</p></li>
<li><p>Drugs: e.g. valproate</p></li></ul>
</li></ul>
</li></ol>
 
 
 
<span id="examiner-comments-27"></span>
==== Examiner comments ====
 
<blockquote>54% of candidates passed this question.
 
This was a new question and overall, most candidates provided some detail on each component as requested. Those answers that used a simple template for each section generally scored better than those who wrote in a paragraph style for each section. Areas expected to be covered included the following; a definition of the variable to provide context, a normal value and the range of influences that effect the variable both related to liver function and or extrinsic to the liver (attempting to introduce the concepts of sensitivity and specificity for each test). Stronger answers provided some context as to whether the variable was sensitive to acute or chronic changes in liver function and which synthetic/metabolic component of the liver the variable represented
</blockquote>
 
 
<span id="online-resources-for-this-question-27"></span>
==== Online resources for this question ====
 
* CICM Wrecks
* Deranged Physiology
* Jenny's Jam Jar
 
 
 
<span id="similar-questions-27"></span>
==== Similar questions ====
 
* Nil
 
 
 
 
 
<span id="question-8-2"></span>
=== Question 8 ===
 
 
 
<span id="question-28"></span>
==== Question ====
 
Describe the anatomy of the internal jugular vein including surface anatomy landmarks relevant to central venous line insertion.
 
 
 
<span id="example-answer-28"></span>
==== Example answer ====
 
 
 
Internal jugular vein
 
* Originates at the jugular bulb (confluence of the inferior petrosal and sigmoid sinus')
* Exits skull via the jugular foramen with CN IX, X, XI
* Descends inferolaterally in the carotid sheath (initially posterior &gt; lateral to carotid artery with descent)
* Terminates behind the sternal end of the clavicle where it joins with the subclavian vein to form the brachiocephalic vein
* Tributaries: facial, thyroid, pharyngeal, lingual veins
* Right IJV usually larger then left
 
 
 
Relations
 
* Anterior to IJV: SCM, lymph nodes, CN XI
* Posterior to IJV: scalene muscles, lung pleura, lateral mass C1, vagus (poster-medial)
* Inferior/at termination: pleura (extends 2cm above clavicle)
* Medial: vagus, carotid artery
 
 
 
Variations
 
* Stenosis, complete occlusion, aneurysms, absence
* Variation in relation to carotid (e.g. anterior) in up to 1/4 cases
 
 
 
Ultrasound anatomy
 
* Often lateral to carotid (not always) and often larger than carotid
* Unlike carotid: Non pulsatile, thin walled, compressible
* Doppler flows can also be helpful.
 
 
 
Surface anatomy
 
* Identify triangle between the clavicle and two heads of SCM
* Palpate carotid
* Puncture lateral to carotid artery at 30 degree angle
* Aim caudally towards ipsilateral nipple
 
 
 
<span id="examiner-comments-28"></span>
==== Examiner comments ====
 
<blockquote>38% of candidates passed this question.
 
The overall pass rate for this question was poor considering how relevant this area of anatomy is in our daily practice. Better scoring answers used a template including a general description, origin, course and relations, tributaries and as requested in this question, the surface anatomy. Many answers that scored poorly only provided the briefest detail, were vague in their descriptions and incorrect with respect to the facts presented or imprecise with respect to the terminology used
</blockquote>
 
 
<span id="online-resources-for-this-question-28"></span>
==== Online resources for this question ====
 
* Deranged Physiology
* [https://jennysjamjar.com.au/year/21b/21b08-describe-the-anatomy-of-the-internal-jugular-vein-including-surface-anatomy-landmarks-relevant-to-central-venous-line-insertion/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-2-23.pdf CICM Wrecks]
* [https://partone.litfl.com/internal_jugular_vein.html Part One, LITFL]
 
 
 
<span id="similar-questions-28"></span>
==== Similar questions ====
 
* Question 23, 2017 (2nd sitting)
 
 
 
 
 
<span id="question-9-2"></span>
=== Question 9 ===
 
 
 
<span id="question-29"></span>
==== Question ====
 
Outline the classification and effects of beta-blocking drugs, including examples (50% marks). Compare and contrast the pharmacokinetics of metoprolol with esmolol (50% marks).
 
 
 
<span id="example-answer-29"></span>
==== Example answer ====
 
 
 
Classification of beta blockers
 
* All beta blockers are competitive antagnoists
* Can be classified according to
** Receptor selectivity
*** Non selective (B1 and B2) e.g. sotalol, propranolol
*** B1 selective e.g. metoprolol, esmolol, atenolol
*** A and B effects: labetalol, carvedilol
** Membrane stabilising effects (inhibit AP propagation)
*** Stabilising e.g. Propanolol, metoprolol
*** Non stabilising e.g. atenolol, esmolol, bisoprolol
** Intrinsic sympathomimetic activity
*** ISA e.g. labetalol, pindolol
*** Non ISA e.g. metoprolol, sotalol, propranolol, esmolol
 
 
 
Effects of beta blockers
 
* B1 antagonism
** Heart: decreased inotropy and chronotropy (decreased BP), decreased myocardial oxygen consumption, decreased AV nodal conduction
** Kidneys: decreased renin release &gt; decreased RAAS activation &gt; decreased BP
* B2 antagonism
** Respiratory: bronchoconstriction
** Circulation: vasoconstriction
** Skeletal muscle: reduced glucose uptake
** Eye: decreased aqueous humour production
* B3 antagonism
** Adipose tissue: reduced lipolysis
 
 
 
Compare/contrast metoprolol and esmolol pharmacokinetics
 
{|
! Name
! Metoprolol
! Esmolol
|-
| '''Pharmacokinetics'''
|
|
|-
| Onset
| Immediate when IV
| Immediate (only given IV)
|-
| Absorption
| 95% absorption, 50% oral bioavailability (1st pass effect)
| 0% oral bioavailability
|-
| Distribution
| VOD 5L/kg<br />
10% Protein bound<br />
High lipid solubility, readily crosses BBB
| VOD 3L/kg<br />
60% protein bound<br />
High lipid solubility, can cross BBB
|-
| Metabolism
| - Hepatic CYP450<br />
- Significant 1st pass metabolism. <br />
- Inactive metabolites
| - Blood<br />
- Hydrolysis by RBC esterase
|-
| Elimination
| Renal excretion<br />
T 1/2 approx 4 hours
| Minimal renal excretion <br />
T 1/2 = 10 mins
|}
 
 
 
<span id="examiner-comments-29"></span>
==== Examiner comments ====
 
<blockquote>59% of candidates passed this question.
 
This was a two-part question with marks and thus timing of the answers given as a percentage. There are generally many ways to classify drugs within the same class. These are usually well described in the relevant recommended pharmacological texts. Receptor distribution throughout the body and the effect of the drug-receptor interaction are useful ways to organise systemic pharmacodynamic responses, as opposed to a list of organ systems with associated vague statements of interaction
</blockquote>
 
 
<span id="online-resources-for-this-question-29"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2019-paper-2-saqs/question-14 Deranged Physiology]
* [https://jennysjamjar.com.au/year/19b/19b14-outline-the-classification-and-effects-of-beta-blocking-drugs-with-examples-505-of-marks-compare-and-contrast-the-pharmacokinetics-of-metoprolol-with-esmolol-50-of-marks/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-2-14.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-29"></span>
==== Similar questions ====
 
* Question 14, 2019 (2nd sitting)
 
 
 
 
 
<span id="question-10-2"></span>
=== Question 10 ===
 
 
 
<span id="question-30"></span>
==== Question ====
 
Describe the ventilation / perfusion (V/Q) relationships in the upright lung according to West’s zones (40%). Explain the physiological mechanisms responsible for these relationships (60%)
 
 
 
<span id="example-answer-30"></span>
==== Example answer ====
 
 
 
West zones
 
* A way of describing the regional differences in alveolar, arterial and venous pressures in the lung
* Initially Zones 1-3 described, with a 4th later added
 
 
 
West zone 1
 
* Pressure alveolus (PA) &gt; arterial pressure (Pa) &gt; venous pressure (Pv)
* Alveolus compresses arterial and venous flow. Hence there is ventilation but no perfusion
* Leads to infinite V/Q (dead space)
* Generally does occur under physiological conditions but can when
** Alveolar pressure is very high (very high PEEP)
** Arterial pressure is very low (shock)
 
 
 
West Zone 2
 
* Pa &gt; PA &gt; Pv
* Intermittent blood flow throughout cardiac cycle. PA acts as starling resistor
* Seen in the lung apex &gt; rib ~3
* V/Q As high as 3.0
 
 
 
West Zone 3
 
* Pa &gt; Pv &gt; PA
* Blood flows continuously throughout the cardiac cycle
* Majority of lung below ~Rib 3
* V/Q approaches 0.3
 
 
 
West zone 4
 
* Pa &gt; Pi (intersitital fluid) &gt; Pv &gt; PA
* With interstitial fluid acting as a starling resistor
* Seen in pathological states e.g. pulmonary oedema
 
 
 
V/Q ratio (in upright person)
 
* Perfusion (Q)
** Increases from apex &gt; base of lung
** Due to the effects of gravity &gt; increased hydrostatic pressure
* Ventilation
** Increases from apex &gt; base of lung
** Because of the vertical gradient of pleural pressure (-10cmH2O apex, -3cm base) the apices get less ventilation than the bases at normal lung volumes as they are less compliant
* V/Q ratio
** Because blood is denser than air, the effect of gravity is greater on perfusion than ventilation
** At about the level of rib 3: V/Q ratio is approx 1.
** Above rib 3 (West zone 1/2): V/Q &gt; 1.0
** Below rib 3 (West zone 3): V/Q &lt; 1.0
 
 
 
<span id="examiner-comments-30"></span>
==== Examiner comments ====
 
<blockquote>47% of candidates passed this question.
 
This is a core aspect of respiratory physiology, and a detailed understanding of this topic is crucial to the daily practise of intensive care. As such the answers were expected to be detailed. Strong answers included precise descriptions of the zones of the lung as described by West and related these to the V/Q relationship in the upright lung. Generally, most candidates scored well in this section. Diagrams were of varying value. However, an impression from the examiners was that candidates spent too much time on this first section and ran out of time for a detailed answer in the second section. The answers to the second section seemed rushed and were often lacking in detail with many incorrect facts. This question highlights the importance of exam technique preparation in the lead up to the written paper
</blockquote>
 
 
<span id="online-resources-for-this-question-30"></span>
==== Online resources for this question ====
 
* CICM Wrecks
* Deranged Physiology
* [https://jennysjamjar.com.au/year/21b/21b10-describe-the-ventilation-perfusion-v-q-relationships-in-the-upright-lung-according-to-wests-zones-40-explain-the-physiological-mechanisms-responsible-for-these-relationships-60/ Jenny's Jam Jar]
 
 
 
<span id="similar-questions-30"></span>
==== Similar questions ====
 
* Nil
 
 
 
 
 
<span id="question-11-2"></span>
=== Question 11 ===
 
 
 
<span id="question-31"></span>
==== Question ====
 
Provide a detailed account of the side-effects of amiodarone.
 
 
 
<span id="example-answer-31"></span>
==== Example answer ====
 
 
 
Overview
 
* Amiodarone is class III antiarrhythmic drug, which also has class I, II and IV activity
* It is predominately used for treatment of tachyarrhythmias
* It can be given PO or IV
* It has numerous side effects which increase in likelihood and severity with duration/dose of therapy.
* More than 50% patients will experience side effects with long term use.
* Most side effects are reversible if treatment is stopped
 
 
 
Side effects by organ/body system
 
* CNS
** Peripheral neuropathy and myopathy
** Sleep disturbance (10%)
* CVS
** Bradycardia and hypotension (esp. if given rapidly)
** QT prolongation
* RESP
** Pneumonitis, pulmonary fibrosis, pleuritis - all dose related
** High FiO2 requirement at time of therapy seems to be a risk factor
** Mortality for amiodarone induce lung toxicity is 10%
* GIT
** Can cause cirrhosis, hepatitis (&lt;5%), LFT derangement (15%), GIT upset
* OPHTHALMIC
** Corneal microdeposits (90%) &gt; blurring (10%)
* ENDOCRINE:
** Can cause both hypothyroidism (~5%) and hyperthyroidism (~1%)
* DERM:
** Photosensitivity (50%), skin discolouration (&lt;10%)
* PHARM
** Amiodarone can potentiate/interact with numerous other drugs, by displacing them from proteins, increasing their free fraction (e.g. phenytoin, warfarin)
* PREGNANCY
** Neurodevelopmental abnormalities
** Risk of congenital hypothyroidism
 
 
 
<span id="examiner-comments-31"></span>
==== Examiner comments ====
 
<blockquote>17% of candidates passed this question.
 
The question asked for a detailed account of the side effects of amiodarone, hence those candidates that just provided a list or outline scored less well. It was expected that candidates provide some detail of the side effect. Answers that scored well prioritised those relevant to ICU clinical practice. Many provided disorganised outlines of the side effects and frequently the cardiovascular side effects were poorly explained. Many candidates omitted the important drug interactions of amiodarone use and few candidates related the side effect profile to the duration of treatment
</blockquote>
 
 
<span id="online-resources-for-this-question-31"></span>
==== Online resources for this question ====
 
* CICM Wrecks
* [https://derangedphysiology.com/cicm-primary-exam/required-reading/cardiovascular-system/Chapter%20967/amiodarone Deranged Physiology]
* [https://jennysjamjar.com.au/year/21b/21b11-provide-a-detailed-account-of-the-side-effects-of-armiodarone/ Jenny's Jam Jar]
 
 
 
<span id="similar-questions-31"></span>
==== Similar questions ====
 
* Question 5, 2008 (2nd sitting)
* Question 22, 2010 (2nd sitting)
* Question 14, 2014 (2nd sitting)
* Question 11, 2016 (1st sitting)
* Question 2, 2018 (2nd sitting)
 
 
 
 
 
<span id="question-12-2"></span>
=== Question 12 ===
 
 
 
<span id="question-32"></span>
==== Question ====
 
Explain the physiological factors that affect airway resistance
 
 
 
<span id="example-answer-32"></span>
==== Example answer ====
 
 
 
Airway resistance
 
* Equal to the pressure difference between alveoli and the mouth divided by the flow rate
* Expressed as pressure per unit flow (cm.H2O.s)
 
 
 
FACTORS AFFECTING AIRWAY RESISTANCE
 
 
 
# Type of flow
#* Laminar flow produces less airway resistance than transitional or turbulent flow
#* The type of flow depends on Reynolds number (Re)
#** <math display="inline">Re \; = \; \frac {2 \; r \; v \; p} {n}</math> Where r = radius, v=velocity, p=density, n=viscosity
#* Hence
#** Increase in density, velocity or radius = increased Reynolds number = more likely turbulent
#** Increased viscosity (n) = decreased Re = more likely to be laminar flow
#* Laminar flow occurs typically with Re &lt;2000
 
 
 
<ol style="list-style-type: decimal;">
<li><p>Vessel (airway) radius</p>
<ul>
<li><p>Based off Hagen-Poiseuille equation (<math display="inline">Resistance \; = \; \frac {8nl}{\pi r^4}</math>) the smaller the calibre of the airway the increased resistance.</p></li>
<li><p>Factors which effect vessel radius</p>
<ul>
<li><p>Lung volume: </p>
<ul>
<li><p>increased lung volume = increased radius (radial traction pulling open bronchi)</p></li></ul>
</li>
<li><p>Smooth muscle tone</p>
<ul>
<li><p>Increased tone (e.g. bronchospasm or increased PSNS tone) narrows radius</p></li></ul>
</li>
<li><p>Decreased internal diameter</p>
<ul>
<li><p>E.g. due to sputum plugging/aspiration &gt; decreased effective radius</p></li></ul>
</li>
<li><p>External compression</p>
<ul>
<li><p>E.g. tumour, pneumothorax &gt; decreased radius </p>
<p></p></li></ul>
</li></ul>
</li></ul>
</li>
<li><p>Length</p>
<ul>
<li><p>Based off the H-P equation, increased length = increased resistance</p></li>
<li><p>Not seen in physiological conditions but can be altered for example with artificial ventilation</p>
<p></p></li></ul>
</li>
<li><p>Dynamic airway compression</p>
<ul>
<li><p>With forced expiration &gt; increased intrapleural pressure</p></li>
<li><p>If IP pressure &gt; airway pressure &gt; collapse &gt; decreased radius</p></li></ul>
</li></ol>
 
 
 
<span id="examiner-comments-32"></span>
==== Examiner comments ====
 
<blockquote>31% of candidates passed this question.
 
It was expected candidates cover the breadth of the factors that affect airway resistance. Generally, as a concept the type of flow (laminar vs turbulent) was answered well by most candidates, however many failed to mention the other factors that affect airway resistance. Airway diameter as a primary determinant of airway resistance was commonly omitted. Better answers which covered the factors affecting airway diameter classified them broadly and included examples such as physical compression/external obstruction, broncho-motor tone and local cellular mechanisms. Some answers did not explain these factors in enough detail and often with incorrect facts
</blockquote>
 
 
<span id="online-resources-for-this-question-32"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2017/04/2009-1-18-airway-resistance.pdf CICM Wrecks]
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2016-paper-2-saqs/question-6#answer-anchor Deranged Physiology]
* [https://jennysjamjar.com.au/year/21b/21b12-explain-the-physiological-factors-that-affect-airway-resistance/ Jenny's Jam Jar]
 
 
 
<span id="similar-questions-32"></span>
==== Similar questions ====
 
<ul>
<li><p>Question 18, 2009 (1st sitting)</p></li>
<li><p>Question 23, 2013 (2nd sitting)</p></li>
<li><p>Question 6, 2016 (2nd sitting)</p>
<p></p></li></ul>
 
 
 
 
 
<span id="question-13-2"></span>
=== Question 13 ===
 
 
 
<span id="question-33"></span>
==== Question ====
 
Describe the factors that affect mixed venous oxygen saturation
 
 
 
<span id="example-answer-33"></span>
==== Example answer ====
 
 
 
Mixed venous oxygen saturation (SmvO<sub>2</sub>)
 
<ul>
<li><p>The oxygen saturation of haemoglobin when measured in the pulmonary artery (after venous mixing in the right ventricle)</p></li>
<li><p>Measured using a pulmonary artery catheter</p></li>
<li><p>Normally ~75% </p></li>
<li><p>Provides better idea of whole body venous O2 sats (blood from SVC, IVC and coronary sinus)</p>
<p></p></li></ul>
 
Factors affecting SmvO<sub>2</sub>
 
* SmvO<sub>2</sub> is a balance between oxygen delivery and oxygen consumption
** Oxygen delivery (DO<sub>2</sub>) = cardiac output (CO) x oxygen content of arterial blood (CaO<sub>2</sub>)
** CaO<sub>2</sub> is dependant on the arterial oxygen saturation, partial pressure of oxygen and the loading ability of Hb (thus the PCO<sub>2</sub>, temperature, H+ concentration)
* Cardiac output
** Increased CO = increased oxygen delivery = increased SmvO<sub>2</sub> (vice versa)
* Hb concentration
** Increased Hb = increased DO<sub>2</sub> = increased SmvO<sub>2`</sub>
* Saturation of Hb
** Decreased arterial Hb saturation &gt; decreased DO<sub>2</sub> &gt; decreased SmvO<sub>2</sub>
* Loading of Hb with O<sub>2</sub>
** Left shift O2-Hb dissociated curve (Decreased H+, decreased PCO<sub>2</sub>, decreased temp) = increased SmvO<sub>2</sub>
* Oxygen consumption
** Increased oxygen consumption = decreased SmvO<sub>2</sub>
** Physiological conditions
*** e.g. exercise = increasing consumption = Decreased SmvO<sub>2</sub>
** Pathological conditions
*** e.g. fever/burns = increased consumption = decreased SmvO<sub>2</sub>
*** e.g. cyanide toxicity, hypothermia = decreased consumption/utilisation = increased SmvO<sub>2</sub>
 
 
 
Evidence
 
* No evidence to support targeting ScvO<sub>2</sub> or SmvO<sub>2</sub> saturations at present
 
 
 
<span id="examiner-comments-33"></span>
==== Examiner comments ====
 
<blockquote>49% of candidates passed this question.
 
Mixed venous oxygen saturation is used as a surrogate marker for the overall balance between oxygen delivery and oxygen consumption. A good answer stated this, described the importance of where it is measured and went on to describe the various factors that affect oxygen delivery and consumption. Descriptions of the factors that affect oxygen saturation of haemoglobin, partial pressure of oxygen in the blood and position of oxygen-haemoglobin dissociation curve were necessary to score well. Important omissions were factors that increased and decreased oxygen consumption. While many candidates were able to correctly write the equations for oxygen content and oxygen flux, they then failed to describe how the variables within these equations were related to mixed venous oxygen saturation.
</blockquote>
 
 
<span id="online-resources-for-this-question-33"></span>
==== Online resources for this question ====
 
* CICM Wrecks
* Deranged Physiology
* Jenny's Jam Jar
 
 
 
<span id="similar-questions-33"></span>
==== Similar questions ====
 
* Question 10, 2008 (1st sitting)
* Question 19, 2017 (1st sitting)
* Question 8, 2019 (1st sitting)
 
 
 
 
 
<span id="question-14-2"></span>
=== Question 14 ===
 
 
 
<span id="question-34"></span>
==== Question ====
 
Describe the production, action and regulation of thyroid hormones.
 
 
 
<span id="example-answer-34"></span>
==== Example answer ====
 
 
 
Overview
 
* Thyroid gland produces and secretes two hormones
** T<sub>4</sub> (thyroxine) = 93%
** T<sub>3</sub> (tri-iodothyronine) = 7%
 
 
 
Production and secretion
 
* T<sub>3</sub>/T<sub>4</sub> synthesised in thyroid follicles
* Iodide is taken into thyroid follicles via secondary active transport and oxidised to iodine by thyroperoxidase
* Thyroglobulin is synthesized in the follicular cell and is secreted into follicular cavity where it combines with iodine to form DIT and MIT, which subsequently couple to form T<sub>3</sub> or T<sub>4</sub>
* T<sub>3</sub>/T<sub>4</sub> are secreted from the vesicles (thyroglobulin is cleaved off in the process)
 
 
 
Regulation
 
* Increased production
** Increased TSH (from anterior pituitary) &gt; increased T<sub>3</sub>/T<sub>4</sub> production and release (from thyroid)
** TSH is increased by TRH (produced by paraventricular nucleus in hypothalamus)
** TRH is stimulated by numerous factors including low T3/4, cold, hypoglycaemia, pregnancy
* Decreased production
** Secretions are controlled via negative feedback loop on the hypothalamic-pituitary-thyroid axis
** Thus increased T3/T4 &gt; decreased TSH (from pituitary) and decreased TRH (from hypothalamus)
 
 
 
Transport / half life
 
* Transported in blood bound to albumin, thyroxine binding globulin
* Both are &gt;99% protein bound
* T3 has half life 24 hours
* T4 has half life 7 days
 
 
 
Functions
 
* T<sub>3</sub>/T<sub>4</sub> act on thyroid receptors in the cell nucleus &gt; increased gene transcription + protein synthesis
* T<sub>3</sub> is 3-5x more active than T<sub>4</sub> (though less abundant)
* Effects on organ system
** CVS
*** Increased HR, inotropy, CO
*** Decreased SVR
** RESP
*** Increased minute ventilation (due to increased CO<sub>2</sub> production)
** CNS
*** Increased: neuroexcitability, tremors
*** Decreased: depression, psychosis
** MSK
*** Increased osteoblast activity
** GIT
*** Increased GIT motility
** METABOLIC
*** Increased basal metabolic rate
*** Increased carbohydrate, fat and protein metabolism
 
 
 
 
 
<span id="examiner-comments-34"></span>
==== Examiner comments ====
 
<blockquote>81% of candidates passed this question.
 
This question was divided in three sections to help candidates formulate an answer template, which for the most part was answered well. Most answers included a detailed description of the production and regulation of thyroid hormones, including the importance of negative feedback. A brief description of the action of thyroid hormones on intracellular receptors, and a system-based description of physiological effects, including CHO, protein and fat metabolism was expected.
</blockquote>
 
 
<span id="online-resources-for-this-question-34"></span>
==== Online resources for this question ====
 
* CICM Wrecks
* Deranged Physiology
* [https://jennysjamjar.com.au/year/21b/21b14-describe-the-production-action-and-regulation-of-thyroid-hormones/ Jenny's Jam Jar]
 
 
 
<span id="similar-questions-34"></span>
==== Similar questions ====
 
<ul>
<li><p>Question 17, 2016 (1st sitting)</p>
<p></p></li></ul>
 
 
 
<span id="question-15-2"></span>
=== Question 15 ===
 
 
 
<span id="question-35"></span>
==== Question ====
 
Classify and describe the mechanisms of drug interactions with examples.
 
 
 
<span id="example-answer-35"></span>
==== Example answer ====
 
{|
! Classification of drug-drug interactions
! Example
|-
| '''BEHAVIOURAL'''
|
|-
| - One drug alters behaviour of patient for another
| - A depressed patient taking an antidepressant may be more compliant with other medications for unrelated conditions
|-
| '''PHARMACEUTIC'''
|
|-
| - Formulation of one drug is altered by another before administration
| - Precipitation of thiopentone (basic) and vecuronium (acidic) in a giving set
|-
| '''PHARMACOKINETIC'''
|
|-
| Absorption
| Bioavailability of bisphosphonates is reduced when co-administered with calcium as the drugs interact to form insoluble complexes
|-
| Distribution
| Valproate and phenytoin compete for the same transport protein binding sites &gt; decreased protein binding phenytoin &gt; increased effect
|-
| Metabolism
| Macrolides reduce metabolism of warfarin by outcompeting it for similar metabolic pathways (CYP450 enzymes) &gt; increased duration of effect
|-
| Elimination
| Probenecid decreases the active secretion of B-lactams and cephalosporins in renal tubular cells by competing for transport mechanisms &gt; decreased elimination of B-lactams / cephalosporins
|-
| '''PHARMACODYNAMIC'''
|
|-
| Homodynamic effects
| Drugs bind to the same receptor site (e.g. naloxone reverses the effects of opioids by outcompeting for the opioid receptor sites)
|-
| Allosteric modulation
| Drugs bind to the same receptor (GABA) but at different sites (e.g. barbiturates and benzodiazepines) &gt; increased effect
|-
| Heterodynamic modulation
| drugs bind to different receptors but affect the same second messenger system (e.g. glucagon reverses the effects of B-blockers by activating cAMP)
|-
| Drugs with opposing physiological actions (but different biological mechanisms)
| e.g. GTN vasodilates via guanyl cyclase-cGMP mediated vasodilation, while noradrenaline vasoconstricts via <math display="inline">\alpha</math> agonism
|}
 
 
 
<span id="examiner-comments-35"></span>
==== Examiner comments ====
 
<blockquote>54% of candidates passed this question.
 
This question has been asked previously, the answer template expected some description rather than a list of drug interactions. Generally, examples were provided for each type of interaction. The examiners reported too many vague, factually incorrect descriptions of the mechanisms and in some cases a very limited classification.
</blockquote>
 
 
<span id="online-resources-for-this-question-35"></span>
==== Online resources for this question ====
 
* CICM Wrecks
* Deranged Physiology
* [https://jennysjamjar.com.au/year/21b/21b15-classify-and-describe-the-mechanisms-of-drug-interactions-with-examples/ Jenny's Jam Jar]
 
 
 
<span id="similar-questions-35"></span>
==== Similar questions ====
 
* Question 3, 2017 (1st sitting)
* Question 9, 2015 (1st sitting)
 
 
 
 
 
<span id="question-16-2"></span>
=== Question 16 ===
 
 
 
<span id="question-36"></span>
==== Question ====
 
Classify the anti-psychotic drugs (25% marks). Outline the pharmacology of haloperidol (75% marks).
 
 
 
<span id="example-answer-36"></span>
==== Example answer ====
 
 
 
Classification of antipsychotics
 
* First generation (typical) antipsychotics
** Higher affinity for D2 receptors
** Leads to better effect on 'positive' symptoms (hallucinations, delusions, hyperactivity)
** Greater incidence of EPSE and less metabolic side effects
** Examples: haloperidol (Butyrophenones), chlorpromazine (Phenothiazines)
* Second generation (atypical) antipsychotics
** Block D2 as well as 5HT2A
** Greater effect on negative symptoms (apathy, lethargy etc)
** Fewer EPSE, but increased metabolic side effects (weight gain, diabetes, hyperChol etc)
** Examples: olanzapine, quetiapine, clozapine
 
 
 
Haloperidol
 
{|
! Name
! Haloperidol
|-
| '''Class'''
| Antipsychotic (1st generation)
|-
| '''Indications'''
| Behavioural emergencies, psychosis, intractable nausea/vomiting
|-
| '''Pharmaceutics'''
| PO tablets Clear solution for injection
|-
| '''Routes of administration'''
| PO, IM, IV
|-
| '''Dose'''
| 1-5mg IV, 2-30mg IM, 1-10mg PO
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Antipsychotic actions thought to be mediated by blockade of dopamine (D2 &gt; D1) receptors particularly in the limbic system. Also demonstrate weak antagonism of H1, mACh receptors
|-
| Effects
| CNS: apathy, decreased agitation, sedation<br />
CVS: QT prolongation / TdP<br />
GIT: anti-emetic <br />
MET: weight gain, diabetes, hyperChol<br />
Other: neuroepileptic malignant syndrome, extrapyramidal side effects (dystonia, akathisia, parkinsonism, TD) <br />
HAEM: leukopaenia<br />
RESP: respiratory depression in large enough doses
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| Peak effects after 3 hours (PO)
|-
| Absorption
| 80% PO bioavailability
|-
| Distribution
| &gt;90% protein bound<br />
VOD = 20L/kg
|-
| Metabolism
| Hepatic &gt; inactive metabolites
|-
| Elimination
| Renal (major) and faecal (minor) excretion of metabolites <br />
T 1/2 = ~24 hours (longer in IM, shorter in PO)
|-
| '''Special points'''
|
|}
 
 
 
<span id="examiner-comments-36"></span>
==== Examiner comments ====
 
<blockquote>28% of candidates passed this question.
 
Excellent answers were able to provide a classification of antipsychotics based on either typical/atypical or first/second generation categories, provide examples of each and identify key differences in mechanism and effects. They also distinguished between butyrophenones and phenothiazines within the typical antipsychotic group. Haloperidol was identified as a butyrophenone, with description of pharmaceutics, dose and route, as well as pharmacodynamics and pharmacokinetics. Key adverse effects were detailed, focusing on those specific to haloperidol, including a description of different types of extrapyramidal symptoms and QT prolongation/ torsades de pointes.
</blockquote>
 
 
<span id="online-resources-for-this-question-36"></span>
==== Online resources for this question ====
 
* CICM Wrecks
* Deranged Physiology
* [https://jennysjamjar.com.au/year/21b/21b16-classify-the-anti-psychotic-drugs-25-outline-the-pharmacology-of-haloperidol-75-marks/ Jenny's Jam Jar]
 
 
 
<span id="similar-questions-36"></span>
==== Similar questions ====
 
* Question 21, 2014 (2nd sitting)
 
 
 
 
 
<span id="question-17-2"></span>
=== Question 17 ===
 
 
 
<span id="question-37"></span>
==== Question ====
 
Explain the components of an ECG (electrocardiogram) monitor (70% marks). Outline the methods employed to reduce artefact (30% marks).
 
 
 
<span id="example-answer-37"></span>
==== Example answer ====
 
 
 
The ECG
 
* Myocyte action potentials sum to produce a voltage which can be measured as a potential difference between two electrodes on the skin
* ECG is therefore a graphical recording of the electrical events of the cardiac cycle
** P wave = atrial depolarisation
** P-R interval = av nodal conduction
** QRS = ventricular depolarisation
** T wave = ventricular repolarisation
* Useful in diagnosis of a range of cardiac conditions including arrhythmias, infarction, hypertrophy etc.
 
 
 
Components of ECG
 
# Electrodes
#* Sicky + conducting gel to ensure adequate skin contact
#* Silver chloride electrode to detect electrical potential differences
#* Earth lead - reduces interferance
#* Bipolar leads: 1, II and II. Unipolar: aVR, aVL, aVF, Praecordial V1-6
# Physical leads/cables (insulated)
#* Transmit the electrical signal
#* Insulation reduces interference / risk of harm from electrocution
# Processor/Amplifier
#* Processes augmented leads (creates 6 ecg leads from 3 physical limb leads)
#* Amplifies the low signal (~1mV) through differential amplification
#* Filters out noise/artefact
#** High input impedance - filters out EMG signal and mains interference
#** Low pass filtering - eliminates movement artefact
# Monitor/output device
#* Displays/prints/records the trace
 
 
 
Artefact and error
 
* Machine
** Incorrect filtering settings
*** ECG monitoring mode: Strong filter setting to focus on rhythm, reduces artefact
*** Diagnostic mode: Lower filtering setting to allow for subtle changes in ST segments (greater resolution at expense of noise)
* Cabling/Circuit
** Incorrect lead placement --&gt; errors with augmented leads, and interpretation --&gt; correct
** Interference with electronics (e.g. ventilators, dialysis machines) --&gt; limit exposure
** Damaged/broken cables --&gt; replaced
* Patient
** Excessive movement or motion artefact (movement, shivering, seizure)
*** Rewarm, low pass filtering, place over bony prominences
** Poor contact due to things such as hair, lotions, etc.
*** Cleaned with alcohol wipe / shaved to improve contact
 
 
 
 
 
<span id="examiner-comments-37"></span>
==== Examiner comments ====
 
<blockquote>46% of candidates passed this question.
 
Excellent answers described the function of the ECG device and its components. Components include electrodes, which form leads (unipolar and bipolar), the amplifier and an output device. The process of amplification and filtering (e.g., high and low pass filters), as well as monitoring and diagnostic ECG modes were described. A comprehensive list of ways to reduce artefacts, including strategies to address both patient and equipment factors was generally provided.
</blockquote>
 
 
<span id="online-resources-for-this-question-37"></span>
==== Online resources for this question ====
 
* CICM Wrecks
* Deranged Physiology
* [https://jennysjamjar.com.au/year/21b/21b17-explain-the-components-of-an-ecg-electrocardiogram-monitor-70-marks-outline-the-methods-employed-to-reduce-artefact-30-marks/ Jenny's Jam Jar]
 
 
 
<span id="similar-questions-37"></span>
==== Similar questions ====
 
* Question 5, 2011 (2nd sitting)
* Question 9, 2016 (1st sitting)
 
 
 
 
 
<span id="question-18-2"></span>
=== Question 18 ===
 
 
 
<span id="question-38"></span>
==== Question ====
 
Outline the neural pathways for the pupillary light, corneal, oculomotor and gag reflexes. The anatomical course of nerves is NOT required.
 
 
 
<span id="example-answer-38"></span>
==== Example answer ====
 
 
 
Pupillary light reflex
 
* Receptors: photoreceptors in retina
* Afferent: cranial nerve II
* Integrator/controller: pretectal nucleus in midbrain &gt; Edinger-Westphal nuclei
* Efferent: Cranial nerve III (preganglionic) &gt; ciliary ganglion
* Effector: iris via short ciliary nerves (postganglionic)
* Effect: direct + consensual pupillary constriction to light
 
 
 
Corneal reflex
 
* Receptors: free nerve endings / stretch receptors in epithelium of cornea
* Afferent: Ophthalmic division of cranial nerve V
* Integrator/controller: trigeminal nucleus &gt; facial nucleus
* Efferent: cranial nerve VII
* Effector: orbicularis oculi muscle
* Effect: ipsilateral eyelid movement (early response) followed by bilateral blink (late response)
 
 
 
Oculomotor reflex (Vestibulo–ocular reflex)
 
* Sensation: head rotation (angular acceleration)
* Sensor: semi-circular canals and otoliths in inner ear
* Afferent: cranial nerve VIII
* Integrator: vestibular nuclear complex (medulla and pons)
* Efferents: cranial nerves III, IV and VI
* Effect: activation of recti muscles (depending on rotation) to maintain visual focus
 
 
 
Gag reflex
 
* Stimulus: sensation to posterior pharyngeal wall
* Afferent: cranial nerve IX
* Integrator: NTS &gt; nucleus ambiguus
* Efferent: CN X
* Effects: Contraction of pharyngeal muscles
 
 
 
 
 
<span id="examiner-comments-38"></span>
==== Examiner comments ====
 
<blockquote>43% of candidates passed this question.
 
This is a fact-based question with little integration of knowledge required. Those candidates who synthesised their knowledge into a succinct and precise description of afferent and efferent pathways with a description of the various sensor and integrator components scored very high marks. A good working knowledge of all the cranial nerve reflex pathways are crucial to the practise of intensive care medicine. Marks were not awarded for any anatomical description related to these pathways.
</blockquote>
 
 
<span id="online-resources-for-this-question-38"></span>
==== Online resources for this question ====
 
* CICM Wrecks
* Deranged Physiology
* Jenny's Jam Jar
 
 
 
<span id="similar-questions-38"></span>
==== Similar questions ====
 
* ?Nil
 
 
 
 
 
<span id="question-19-2"></span>
=== Question 19 ===
 
 
 
<span id="question-39"></span>
==== Question ====
 
Outline the process of fibrinolysis (40% marks). Write short notes on the indications, mechanism of action, pharmacokinetics and side effects of tranexamic acid (60% marks).
 
 
 
<span id="example-answer-39"></span>
==== Example answer ====
 
 
 
Fibrinolysis
 
* Process by which fibrin (within blood clots) is broken down by plasmin into fibrin degradation products
* Normal physiological process as part of wound healing and is important for keeping vessels patent
* Steps
** Plasminogen (b-globulin) is produced in the liver
** Plasminogen is trapped in fibrin meshwork during initial clot formation
** Plasminogen can be converted by plasminogen activators (serum protease) into plasmin
** Plasmin subsequently cleaves fibrin &gt; fibrin degradation products
* Activation
** Intrinsic: Main physiological activator is tissue plasminogen activator which is released from injured endothelial cells (but is a slower process than coagulation to allow healing to take place)
** Extrinsic: urokinase, streptokinase, recombinant tPA can increase activation of plasminogen &gt; plasmin &gt; increased fibrinolysis
 
 
 
{|
! Name
! Tranexamic acid
|-
| '''Class'''
| Antifibrinolytic
|-
| '''Indications'''
| Trauma (within 3 hours), cardiac/obstetric/orthopaedic surgery, haemorrhage
|-
| '''Pharmaceutics'''
| 500mg Tablets (PO)<br />
Clear colourless solution (100mg/ml) for injection (IV)
|-
| '''Routes of administration'''
| PO, IV, IM
|-
| '''Dose'''
| 0.5 - 1 g (slow IV push), followed up by infusion of 1g over 8 hrs if needed
|-
| pKA
|
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Competitive inhibition of the activation of plasminogen into plasmin by binding to lysine binding sites on plasminogen
|-
| Effects
| Decreased fibrinolysis &gt; decreased bleeding
|-
| Side effects
| HAEM: Prothrombotic complications in those patients with risk factors<br />
GIT: nausea, vomiting CNS: seizures and dizziness (dose related)
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| Immediate (IV), 1 hour (IM), 2 hours (PO)
|-
| Absorption
| PO bioavailability = 50%, IM bioavailability 100%
|-
| Distribution
| Protein binding: very low (&lt;5%) <br />
VOD = 0.3L / kg
|-
| Metabolism
| Minimal hepatic metabolism
|-
| Elimination
| Renal elimination of active drug (95% unchanged)<br />
T 1/2 = 2hrs (IV), 10 hrs (PO)
|-
| '''Special points'''
| Dose reduce in renal failure
|}
 
 
 
<span id="examiner-comments-39"></span>
==== Examiner comments ====
 
<blockquote>30% of candidates passed this question.
 
The relative allocation of marks and thus time to be spent on each component was delineated by the relative percentages in the question. The first part of the question required a step-by-step outline of the fibrinolytic pathway with mention of the regulatory processes. Tranexamic acid is an important drug in the practice of intensive care and the question provided the headings under which to answer the question. The detail surrounding the keys aspects of this drug with respect to its use in critical care were often vague and underappreciated.
</blockquote>
 
 
<span id="online-resources-for-this-question-39"></span>
==== Online resources for this question ====
 
* CICM Wrecks
* Deranged Physiology
* [https://jennysjamjar.com.au/year/21b/21b19-outline-the-process-of-fibrinolysis-40-marks-write-short-notes-on-the-indications-mechanism-of-action-pharmacokinetics-and-side-effects-of-tranexamic-acid-60-marks/ Jenny's Jam Jar]
 
 
 
<span id="similar-questions-39"></span>
==== Similar questions ====
 
* Question 4, 2013 (1st sitting)
* Question 19, 2015 (2nd sitting)
 
 
 
 
 
<span id="question-20-2"></span>
=== Question 20 ===
 
 
 
<span id="question-40"></span>
==== Question ====
 
Describe the physical principles of haemodialysis and haemofiltration, including the factors affecting clearance (80% marks). Outline the key components of renal replacement fluids (20% marks).
 
 
 
<span id="example-answer-40"></span>
==== Example answer ====
 
 
 
Dialysis
 
* Separation of particles in a liquid, based on their differential ability to pass through a membrane
* Main mechanisms: haemodialysis, hemofiltration, combination of above
* Main indications: acidosis, electrolyte derangement, intoxication, fluid overload, ureamia,
 
 
 
Haemodialysis
 
* Utilises principle of diffusion
** Spontaneous movement of a substance from area of high &gt; low concentration
** Movement is dependant on Fick's law (thus temp, size, concentration, distance etc)
* Process
** Blood is pumped through an extracorporeal dialysis circuit
** Dialysate flows in a counter-current direction (maintains concentration gradient)
** Blood is separated from dialysate via semipermeable membrane (does not mix)
** Movement of molecules then diffuses according to Ficks law.
* Useful for clearance of small molecules, cannot clear larger molecules
 
 
 
Haemofiltration
 
* Uses principle of convection and solvent drag
** Elimination of materials is via bulk flow and independent of concentration
** Clearance is dependant on starling forces
* Process
** Blood is pumped through extracorporeal dialysis circuit
** A transmembrane pressure is applied to the blood side of a semi-permeable membrane
** Plasma is filtered across membrane and solutes (via drag) are eliminated as effluent.
** Renal replacement fluid is added to patient blood to restore volume, buffers, and normal haematocrit
* Can clear small-medium sized molecules
 
 
 
Factors effecting clearance
 
<ul>
<li><p>Drug factors</p>
<ul>
<li><p>Protein binding</p>
<ul>
<li><p>Small molecules bound to large proteins (e.g. aspirin bound to albumin) cannot be cleared</p></li></ul>
</li>
<li><p>Size/molecular weight</p>
<ul>
<li><p>Smaller molecules are more readily dialysed</p></li></ul>
</li>
<li><p>Volume of distribution</p>
<ul>
<li><p>Drugs with large Vd (e.g. barbituates) cannot readily be cleared as they rapidly redistribute</p></li></ul>
</li></ul>
</li>
<li><p>Dialysis factors</p>
<ul>
<li><p>Haemodialysis</p>
<ul>
<li><p>Blood / dialysate flow rate</p></li>
<li><p>Dialysate composition</p></li></ul>
</li>
<li><p>Haemofiltration</p>
<ul>
<li><p>Blood / effluent flow rate</p></li>
<li><p>Transmembrane pressure</p></li>
<li><p>Prefilter dilution</p></li>
<li><p>Sieving coefficient </p>
<p></p></li></ul>
</li></ul>
</li></ul>
 
Renal replacement fluids
 
* 5000ml bag, warmed to body temperature
* Contains
** Electrolytes
*** Na = isotonic
*** K, Mg, Phos, Ca = variable
** Buffers
*** Bicarbonate (predominately)
*** Can also use lactate, citrate
** Nutrients (i.e. gluc)
** Sterile water
* Osmolarity ~285
* Dose varied depending on degree of fluid removal desired
 
 
 
<span id="examiner-comments-40"></span>
==== Examiner comments ====
 
<blockquote>28% of candidates passed this question.
 
A brief description of the underlying mechanisms of dialysis and hemofiltration was required. Diffusion, the predominant mechanism in haemodialysis, involves movement of solute down the concentration gradient across the semipermeable membrane. This concentration gradient is generated and maintained by counter current movement of dialysate and blood. In hemofiltration the predominant mechanism is convection and solvent drag of the solute across the semipermeable membrane by application of transmembrane pressure. The filtrate is then replaced by replacement fluid. Small molecules are effectively removed by dialysis whereas hemofiltration can remove small and middle molecules. Various factors that impact clearance in haemodialysis and haemofiltration were expected separately. Constituents of replacement fluid should have included three broad headings of electrolytes, buffer and sterile water. Many answers lacked the details of how counter current mechanisms help, the difference in the two modalities in regard to clearance of molecules, how clearance is impacted by protein binding and volume distribution, sieving coefficient of the membrane and flow rates of blood and dialysate (or effluent) flow. The constituents of replacement fluid lacked details of various types of electrolytes, the common buffers and the strong ion difference.
</blockquote>
 
 
<span id="online-resources-for-this-question-40"></span>
==== Online resources for this question ====
 
* CICM Wrecks
* Deranged Physiology
* [https://jennysjamjar.com.au/year/21b/21b20-describe-the-physical-principles-of-haemodialysis-and-haemofiltration-including-the-factors-affecting-clearance-80-marks-outline-the-key-components-of-renal-replacement-fluids-20-marks/ Jenny's Jam Jar]
 
 
 
<span id="similar-questions-40"></span>
==== Similar questions ====
 
* Question 24, 2011 (1st sitting)
 
 
 
 
 
<span id="2021-1st-sitting"></span>
== 2021 (1st sitting) ==
 
 
 
<span id="question-1-3"></span>
=== Question 1 ===
 
 
 
<span id="question-41"></span>
==== Question ====
 
Describe the pharmacology of adrenaline.
 
 
 
<span id="example-answer-41"></span>
==== Example answer ====
 
{|
! Name
! Adrenaline
|-
| '''Class'''
| Naturally occurring catecholamine
|-
| '''Indications'''
| Haemodynamic support, anaphylaxis, bronchoconstriction/airway obstruction
|-
| '''Pharmaceutics'''
| Clear solution, light sensitive (brown glass), 1:1000 or 1:10,000
|-
| '''Routes of administration'''
| IV, IM, INH, ETT, Topical, subcut
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Non-selective adrenergic receptor agonist. <br />
At low doses B effects dominate, at high doses alpha dominate.<br />
Adrenaline &gt; a-1 receptor &gt; increased IP3 (2nd messenger) &gt; increased Ca <br />
Adrenaline &gt; B1,B2,B3 receptors &gt; increased cAMP (second messenger)
|-
| Effects
| CVS: vasoconstriction (high doses), vasodilation (low doses), increased inotropy + chronotropy<br />
RESP: bronchodilation, increased minute ventilation<br />
METABOLIC: hyperglycaemia (glycogenolysis, lipolysis, gluconeogenesis)<br />
CNS: increased MAC<br />
GIT: decreased intestinal tone/secretions
|-
| Side effects
| Extravasation &gt; tissue necrosis, pHTN due to increased PVR, hyperglycaemia, tachyarrhythmias,
|-
| '''Pharmacokinetics'''
|
|-
| Absorption
| Zero oral bioavailability due to GIT inactivation. variable/erratic ETT absorption.
|-
| Distribution
| Poor lipid solubility, doesn't cross BBB, crosses placenta
|-
| Metabolism
| Metabolised by MAO (mitochondria) and COMT (liver, blood, kidney) to VMA and metadrenaline
|-
| Elimination
| T 1/2: ~2 mins (due to rapid metabolism)<br />
Metabolites (above) are excreted in the urine
|}
 
 
 
<span id="examiner-comments-41"></span>
==== '''Examiner comments''' ====
 
<blockquote>90% of candidates passed this question.
 
Adrenaline is a level 1 drug and is commonly used in intensive care. A comprehensive explanation of the drugs MOA, PK, PD and side effect were expected. Candidates who scored well generally provided a factually accurate, detailed and well-structured answer. Overall, the quality of answer provided for this question was of a high standard.
</blockquote>
 
 
<span id="online-resources-for-this-question-41"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2021/05/2021-1-01.pdf CICM wrecks]
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2021-paper-1-saqs/question-1#answer-anchor Deranged Physiology]
* [https://partone.litfl.com/adrenergic_drugs.html Part 1]
 
 
 
<span id="similar-questions-41"></span>
==== Similar questions ====
 
* Question 2, 2018 (Paper 1)
* Question 15, 2017 (Paper 2)
* Question 18, 2012 (Paper 2)
* Question 8, 2012 (Paper 1)
 
 
 
 
 
 
 
 
 
<span id="question-2-3"></span>
=== Question 2 ===
 
 
 
<span id="question-42"></span>
==== Question ====
 
Describe the work of breathing and its components.
 
 
 
<span id="example-answer-42"></span>
==== Example answer ====
 
 
 
Work of breathing
 
* Energy used by the respiratory muscles during respiration
* Work of breathing (joules) = pressure x volume
* Normally ~0.35 J/L (approx 2% BMR)
* Can be represented using pressure-volume curves
 
 
 
Components
 
<ul>
<li><p>Elastic work (~70%)</p>
<ul>
<li><p>Force required to overcome the elastic forces of the chest wall, lung parenchyma, and alveoli surface tension</p></li>
<li><p>Elastic resistance increases with increasing tidal volumes</p></li>
<li><p>Energy is stored as elastic potential energy and used on expiration</p></li>
<li><p>Factors increasing elastic work: </p>
<p> e.g. obesity, chest wall deformities, circumfrential burns etc.</p>
<p> e.g. loss of surfactant in ARDS </p></li></ul>
</li>
<li><p>Non elastic (resistive) work (~30%)</p>
<ul>
<li><p>Derived from airway resistance (majority; 80% of non elastic work) and viscous tissue resistance (e.g. lung sliding over chest wall)</p></li>
<li><p>Airway resistance increases with increased RR (frequency dependence of work of breathing) or smaller airway diameter (e.g. bronchospasm)</p></li>
<li><p>Energy is lost as heat</p></li></ul>
</li></ul>
 
 
 
Work of breathing during a tidal volume breath (ref to fig below)
 
[[File:https://partone.litfl.com/resources/workofbreathing.svg|thumb|none|alt=img|img]]
 
 
 
 
 
 
 
<span id="examiner-comments-42"></span>
==== '''Examiner comments''' ====
 
<blockquote>24% of candidates passed this question.
 
This is a core topic within respiratory physiology. There was a very low pass rate for this question. Expected components of the answer included: a definition of WOB as a product of pressure and volume or force and distance including the units of measurement; followed by a detailed explanation of the following three broad components – elastic resistance, viscous resistance and airflow resistance. Further marks were awarded to situations where the energy for expiration increases beyond stored potential energy as well as the impact of respiratory rate and tidal volume on different aspects of the WOB. For example, the changes in TV will have relatively greater impact on the elastic component, whereas RR will impact the resistance component. Additional marks were awarded for describing the efficiency of breathing. A common area where candidates missed out on marks was producing a diagram of WOB without a description; many diagrams were often incorrectly drawn or had no axes labelled. There were many incorrect definitions or respiratory equations provided without any link to the written answer. Factual inaccuracy and limited depth of knowledge were also prevalent in poorly performing answers. Marks were not awarded for a description of the control of breathing.
</blockquote>
 
 
<span id="online-resources-for-this-question-42"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2021-paper-1-saqs/question-2#answer-anchor Deranged physiology]
* [https://cicmwrecks.files.wordpress.com/2021/05/2021-1-02.pdf CICM wrecks]
* [https://partone.litfl.com/work_of_breathing.html Part one LITFL]
 
 
 
<span id="similar-questions-42"></span>
==== Similar questions ====
 
* Nil
 
 
 
 
 
<span id="question-3-3"></span>
=== Question 3 ===
 
 
 
<span id="question-43"></span>
==== Question ====
 
Outline the formation, structure, and function of the platelet.
 
 
 
<span id="example-answer-43"></span>
==== Example answer ====
 
 
 
Formation/fate
 
* Produced via thrombopoiesis
** Within the bone marrow, common myeloid progenitor cells differentiate into megakaryocytes
** Megakaryocytes are the largest cell of the bone marrow (50-150um), have multiple (up to 8) nuclei. They produce pro-platelets in their cytoplasm which break up into numerous smaller functional platelets. Each megakaryocyte produces ~5000 platelets each
** Thrombopoiesis takes ~10 days
** Thrombopoietin (produced primarily in the liver) stimulates the differentiation and release of plts
** Process regulated by negative feedback loop based on platelet count
* Normally 150-400 x 10^9/L
* Lifespan is 7-10 days
* Utilised during clotting or removed by the reticuloendothelial system in the spleen or liver
 
 
 
Structure
 
* Not true cells, but fragments of the Megakaryocyte cytoplasm
* 1-4 um in size, Irregular, No nucleus.
* External glycocalyx later
* Contain:
** Mitochondria
** Dense granules (ATP, ADP, calcium)
** Alpha granules (vWF, thrombin)
** Contractile elements (microtubules)
 
 
 
Function
 
* Main function of platelets is haemostasis
* Platelets are important for formation of the platelet plug (primary haemostasis)
** Platelet adhesion
*** Damage to blood vessel wall exposes vWF in the subendothelium
*** Glycoprotein receptor complex (GP1b-IX) on platelets bind to vWF (adhesion)
** Platelet activation
*** When exposed to Tissue Factor, collagen, and vWF the platelets become activated
*** Activated platelets
**** Change shape (Swell, become irregular, develop pseudopods) to enable aggregation
**** Release molecules (Thromboxane A2, ADP, Serotonin) which activates further platelets + vasoconstricts
*** Platelet aggregation
**** Activated platelets bind to fibrinogen and vWF to form a soft platelet plug
* Platelets are also central to the cell based model of secondary haemostasis
** Initiation (less relevant to platelets)
** Amplification
*** Surface of activated platelets is primed with factors V, VIII, XI
*** Small amount of thrombin produced during initiation activates V, VIII and XI
*** XIa activates IX to IXa, which leads to formation of tenase complexes (accelerate thrombin production at platelet surface)
** Propagation
*** Begins with formation of tenase complexes on platelet surfaces (IXa-VIIIa)
*** Leads to increased rate of Factor X activation
*** The large amounts of Xa interacts with factor Va forming prothrombinase complex (Va-Xa)
*** Va-Xa catalyses the conversion of prothrombin to thrombin
 
 
 
 
 
<span id="examiner-comments-43"></span>
==== Examiner comments ====
 
<blockquote>79% of candidates passed this question.
 
This question was divided in three sections to help candidates formulate an answer template. The first section required a brief outline of the formation of platelets from pluripotent stem cells via megakaryocytes. The second section required an outline of platelet structure highlighting the special features such as, an absence of a nucleus, the presence of an external glycocalyx layer, specific surface receptors, contractile proteins, dense tubular system and granules. The third section was about platelet function where the expected focus was on the role of platelets in haemostasis. This required outlining the mechanism of platelet plug formation by adhesion-activation-aggregation, interactions with the coagulation cascade and role of platelets in clot contraction as well as fibroblast invasion. Although many candidates were able to answer the first section reasonably well, there was a noticeable knowledge deficit in the latter two sections. A significant proportion of answers had missing information on platelet structure and lack of structure in outlining platelet function
</blockquote>
 
 
<span id="online-resources-for-this-question-43"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2021/05/2021-1-03.pdf CICM Wrecks]
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2021-paper-1-saqs/question-3#answer-anchor Deranged physiology]
* [https://partone.litfl.com/platelets.html Part 1, LITFL]
 
 
 
<span id="similar-questions-43"></span>
==== Similar questions ====
 
* Question 6, 2016 (1st sitting)
* Question 20, 2011 (2nd sitting)
 
 
 
<span id="question-4-3"></span>
=== Question 4 ===
 
 
 
<span id="question-44"></span>
==== Question ====
 
Outline the dose (10% marks), composition (60% marks) and side effects (30% marks) of total parenteral nutrition (TPN).
 
 
 
<span id="example-answer-44"></span>
==== Example answer ====
 
 
 
Overview
 
<ul>
<li><p>TPN is the delivery of nutrients into the venous circulation to replace enteral requirements</p>
<p></p></li></ul>
 
Indications
 
* Patients who are unable to be fed via enteral route for prolonged periods of time (e.g. &gt;72 hours)
* May include patients who fail trial of enteral feeding or other contraindications (e.g. GI obstruction, severe pancreatitis, short gut syndromes)
 
 
 
Daily nutritional requirements (major)
 
{|
! Nutrient
! Requirement (kg/day)
|-
| H2O
| 30mls
|-
| Energy
| 25-30 kcal
|-
| Protein
| 1g (higher in critically ill, 1.5g)
|-
| Glucose
| 2g
|-
| Lipids
| 1g
|-
| Na
| 1-2 mmol
|-
| K
| 1mmol
|-
| Ca / Mg
| 0.1mmol
|-
| PO4
| 0.4 mmol
|}
 
'''Note'''
 
<ul>
<li><p>Requirements vary according to physiological (e.g. age, gender, body size, activity levels) and pathological (e.g. burns, sepsis, renal failure, hepatic failure) factors</p>
<p></p></li></ul>
 
Composition of TPN (note many formulations of this)
 
<ul>
<li><p>Glucose </p>
<ul>
<li><p>Typically supplies around 60-70% of daily caloric needs (~1400KCal)</p></li>
<li><p>Typically 50% dextrose used (3.4 kCal/mil - 824mls)</p></li></ul>
</li>
<li><p>Lipid</p>
<ul>
<li><p>Typically supplies around 30-40% daily caloric needs (~600Kcal)</p></li>
<li><p>Can be olive oil, soybean, fish oil based</p></li></ul>
</li>
<li><p>Protein (Amino acids)</p>
<ul>
<li><p>Will contribute to energy source + provides essential amino acids</p></li>
<li><p>L-amino acids used only</p></li>
<li><p>Typically 1.5g/kg/day in critically ill (~100g protein / day)</p></li></ul>
</li>
<li><p>Electrolytes (Na, K, Mg, Ca, Cl, PO4)</p>
<ul>
<li><p>TPN solutions can come with/without electrolytes and adjusted</p></li></ul>
</li>
<li><p>Vitamins, trace elements</p>
<ul>
<li><p>Micronutrients are added in appropriate amounts to the bag for adequate daily intake</p></li>
<li><p>Thiamine, folic acid and vitK are vulnerable to depletion and additional may be needed</p></li></ul>
</li>
<li><p>Water</p>
<ul>
<li><p>In solution, though insufficient for daily requirements</p></li>
<li><p>Hyperosmolar solution due to above nutrients</p></li></ul>
 
<p></p></li></ul>
 
Side effects / complications
 
* Delivery device / vascular access related
** Infection, pneumothorax, thrombosis, air embolism
* Fluid/elextrolyte disturbances
** Fluid overload
** Electrolyte derrangements, shifts and refeeding syndrome
** Acid base disturbances
* Metabolic disturbances
** Hypoglycaemia, hyperglycaemia (dose related issues due to over/under feeding)
** Hyperlipidaemia
 
 
 
<span id="examiner-comments-44"></span>
==== Examiner comments ====
 
<blockquote>59% of candidates passed this question.
 
The pharmacology of enteral and parenteral nutrition is a level 1 topic in the first part syllabus. The TPN dose in terms of daily calorie and other nutritional requirements were key expectations in first part of the question. A detailed list of all macro and micronutrients was required under TPN composition. Expected information about macronutrients were their forms in the TPN solution (e.g., carbohydrate in the form of glucose, protein in the form amino acids), their relative calorie contributions and their essential components (e.g., the names of the essential amino acids). Identification of potential variability in composition and dose based on specific patient factors scored extra marks. Side effects included metabolic derangements (refeeding syndrome, over or under-feeding, hyperglycaemia, hyperlipemia), biochemical disturbances (fluid and electrolyte imbalances), organ injury (liver, pancreas) and vascular access related complications. Limited breadth and depth of information as well as incorrect facts were prevalent in the answers that scored lower marks.
</blockquote>
 
 
<span id="online-resources-for-this-question-44"></span>
==== Online resources for this question ====
 
<ul>
<li><p>[https://cicmwrecks.files.wordpress.com/2021/05/2021-1-04.pdf CICM wrecks]</p></li>
<li><p>[https://derangedphysiology.com/required-reading/endocrinology-metabolism-and-nutrition/Chapter%205.3.3/contents-and-properties-parenteral-nutrition-mixture Deranged Physiology]</p></li>
<li><p>[https://derangedphysiology.com/main/cicm-fellowship-exam/past-papers/2015-paper-1-saqs/question-7#answer-anchor Deranged Physiology past paper]</p>
<p></p></li></ul>
 
<span id="similar-questions-44"></span>
==== Similar questions ====
 
* 2015 Fellowship paper
 
 
 
<span id="question-5-3"></span>
=== Question 5 ===
 
 
 
<span id="question-45"></span>
==== Question ====
 
Outline the factors that determine central venous pressure (60% marks) and explain how it is measured (40% marks).
 
 
 
<span id="example-answer-45"></span>
==== Example answer ====
 
 
 
Overview
 
* CVP is the venous blood pressure (of the great veins) measured at or near the right atrium
* Normally 0-6mmHg in spontaneously breathing non ventilated patient
 
 
 
Measurement
 
* Non invasive
** Echocardiography can provide non invasive estimations off the CVP
** Visual inspection of the height of the JVP can provide some bedside clinical insight
* Invasive
** Most commonly measured using central line
** Central line tip sits at or near the right atrium
** CVC is connected to a pressure transducer via incompressible tubing with flush solution
** Transducer is zeroed to the atmospheric pressure and levelled at the height of the right atrium
 
 
 
Factors determining CVP
 
* <math display="inline"> \Delta CVP \; = \; \frac {\Delta Volume}{\Delta Compliance}</math>
* Thus factors determining CVP related to those that influence compliance and volume
* Central venous blood volume
** Increased total blood volume (e.g. renal failure) = increased CVP
** Decreased CO (e.g. LV failure) &gt; blood backs up &gt; increased thoracic blood volume &gt; increased CVP
* Central venous vascular compliance
** Increased vascular tone central veins (e.g. noradrenaline) &gt; decreased compliance &gt; increased CVP
** Decreased myocardial/pericardial compliance &gt; increased CVP
** Decreased pulmonary arterial compliance (e.g. PAH) &gt; increased CVP
* Tricuspid valve function
** TV regurg &gt; increased CVP (retrograde transmission of RV systolic pressure)
** TV stenosis &gt; increased CVP (increased resistance to RV inflow)
* Intrathoracic pressure
** ITP is transmitted to the central venous compartment
** Thus, increased PEEP, IPPV, or a tension pneumothorax will lead to increased CVP
* Measurement technique
** Level of the transducer will clearly influence the CVP measured
 
 
 
<span id="examiner-comments-45"></span>
==== Examiner comments ====
 
<blockquote>57% of candidates passed this question.
 
This question examined a core area of cardiac physiology and measurement. Considering this, candidates overall, scored poorly in this section. There was a common misunderstanding around the relationship between cardiac output and CVP. A decrease in cardiac output (e.g. due to either decreased stroke volume or heart rate) will cause an increase in CVP as blood backs up in the venous circulation, increasing venous volume as less blood moves through to the arterial circulation; the resultant increase in thoracic volume increases central venous pressure. Several candidates confused the direction of their arrows, for example &quot;increased right atrial compliance increases CVP&quot;. Double negatives were used by several candidates which then resulted in the incorrect relationship described. (e.g., &quot;arrow down compliance and arrow down CVP&quot;). The measurement section should have included an explanation of the components of an invasive pressure monitoring system relevant to the measurement of CVP.
</blockquote>
 
 
<span id="online-resources-for-this-question-45"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2019-paper-2-saqs/question-6#answer-anchor Deranged Physiology]
* [https://jennysjamjar.com.au/year/21a/21a05-outline-the-factors-that-determine-central-venous-pressure-60-marks-and-explain-how-it-is-measured-40-marks/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2021/05/2021-1-05.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-45"></span>
==== Similar questions ====
 
* Question 6, 2019 (2nd sitting)
 
 
 
 
 
<span id="question-6-3"></span>
=== Question 6 ===
 
 
 
<span id="question-46"></span>
==== Question ====
 
Describe the pharmacology of vecuronium, including factors that prolong its action of neuromuscular blockade.
 
 
 
<span id="example-answer-46"></span>
==== Example answer ====
 
{|
! Name
! Vecuronium
|-
| '''Class'''
| Aminosteroid
|-
| '''Indications'''
| Muscle relaxant; intubation, control of ICP, assist ventilation,
|-
| '''Pharmaceutics'''
| Potentially unstable in solution<br />
Comes in powder (10mg), dissolved in water (5ml) for use
|-
| '''Routes of administration'''
| IV
|-
| '''Dose'''
| Intubation: 0.1mg/kg
|-
| ED95
|
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Non depolarising muscle relaxant;<br />
Competitive antagonism of ACh at N2 receptors on PSM of NMJ
|-
| Effects
| MSK: NMJ blockage (paralysis)<br />
CVS: nil<br />
RESP: Apnoea<br />
|-
| Side effects
| MSK: prolonged use can lead to myopathy<br />
Rare for histamine release (anaphylaxis, hypotension)
|-
| '''Pharmacokinetics'''
|
|-
| Onset/duration
| 90-120s; 30-45 minutes
|-
| Absorption
| IV only
|-
| Distribution
| Doesn't cross BBB; VD 0.23L/kg
|-
| Metabolism
| 20% hepatic de-acetylation
|-
| Elimination
| 70% biliary, 30% urinary
|-
| '''Reversal'''
| Can be reversed with sugammadex
|}
 
 
 
Factors prolonging action
 
* Electrolyte disturbances
** Hypokalaemia, Hypermagnesemia and hypocalcaemia potentiates non depolarising NMBA
* Acidosis
** Increased affinity for ACh receptor
* Hypothermia
** Reduced metabolism of muscle relaxant &gt; prolonged effects
* Hepatic/renal disease
** Prolonged metabolilsm/elimination of active metabolites
* Drug interactions
** e.g. lithium, diuretics, volatile anaesthetics, aminoglcosides
 
 
 
<span id="examiner-comments-46"></span>
==== Examiner comments ====
 
<blockquote>13% of candidates passed this question.
 
Vecuronium is a commonly available and regularly used amino-steroid neuromuscular blocking agent. It is a level 1 drug in the 2017 syllabus. A simple template utilising the headings; pharmaceutics, PK, PD, uses in ICU and adverse reactions with associated relevant important facts would have scored well. Expected information regarding the factors prolonging neuromuscular blockade included electrolyte abnormalities, drug interactions and patient factors. Overall, the level of understanding and knowledge demonstrated in the answers was below an expected standard for a level 1 drug.
</blockquote>
 
 
<span id="online-resources-for-this-question-46"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/21a/21a06-21a06-describe-the-pharmacology-of-vecuronium-including-factors-that-prolong-its-action-of-neuromuscular-blockade/ Jenny's Jam Jar]
* [https://partone.litfl.com/non-depolarising_nmbs.html Part One]
* [https://cicmwrecks.files.wordpress.com/2021/05/2021-1-06.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-46"></span>
==== Similar questions ====
 
* Question 1, 2008 (2nd sitting)
* Question 3, 2009 (2nd sitting)
* Question 7, 2015 (2nd sitting)
* Note: there has essentially been a question every year in relation to the pharmacology of one of the NMB drugs (sux, vec, roc) in one form of another.
 
 
 
 
 
<span id="question-7-3"></span>
=== Question 7 ===
 
 
 
<span id="question-47"></span>
==== Question ====
 
Outline the anatomy of the blood supply (arteries and veins) of the gastrointestinal system (oesophagus to anus)
 
 
 
<span id="example-answer-47"></span>
==== Example answer ====
 
 
 
Arterial supply
 
* The aorta (and its branches) supplies the entire arterial supply to the GIT
* The oesophagus is supplied by various arterial branches
** Cervical portion- inferior thyroid artery
** Thoracic portion - bronchial arteries
** Abdominal portion - left gastric, inferior phrenic arteries
* The abdominal aorta then has three main branches which supply the remainder of the GIT
** Celiac trunk
*** Arises from abdominal aorta immediately below aortic hiatus at T12/L1
*** Divides into left gastric artery, splenic artery, common hepatic artery
**** Left gastric a. (supplies stomach)
**** Splenic a. (supplies spleen, pancreas)
**** Common hepatic, divides into
***** Hepatic a. proper (supplies liver)
***** Gastroduodenal (supplies pancreas, duodenum, stomach)
***** Right gastric (supplies stomach)
** Superior mesenteric artery (SMA)
*** Arises from abdominal aorta immediately inferior to coeliac trunk (L1)
*** Multiple branches (15-20) which join in an arcade
*** Supplies the midgut structures (from duodenum to 2/3 transverse colon)
** Inferior mesenteric artery (IMA)
*** Arises from abdominal aorta ~L3
*** Multiple branches (including Left colic, sigmoid, superior rectal arteries), join in arcade
*** Supplies the hindgut (distal 1/3 transverse colon - rectum)
 
 
Venous drainage
 
<ul>
<li><p>For the most part, the venous drainage of the GIT is via veins which accompany the arterial system</p></li>
<li><p>They return via the portal vein</p>
<ul>
<li><p>Portal vein</p>
<ul>
<li><p>Combination SMV and splenic vein</p></li>
<li><p>Receives drainage from forgut structures</p></li></ul>
</li>
<li><p>Splenic vein</p>
<ul>
<li><p>Travels along with the splenic artery + drains corresponding regions (foregut)</p></li>
<li><p>Combines with SMV to form portal vein</p></li></ul>
</li>
<li><p>Superior mesenteric vein (SMV)</p>
<ul>
<li><p>Travels along with the SMA + drains corresponding regions (midgut)</p></li>
<li><p>Combines with splenic vein to form portal vein</p></li></ul>
</li>
<li><p>Inferior mesenteric vein (IMV)</p>
<ul>
<li><p>Travels along with the IMA + drains corresponding regions (hindgut)</p></li>
<li><p>Drains into the splenic vein</p></li></ul>
 
<p></p></li></ul>
</li></ul>
 
<span id="examiner-comments-47"></span>
==== Examiner comments ====
 
<blockquote>48% of candidates passed this question.
 
This question was answered best if the main arteries and veins were discussed first and then their corresponding supply outline in reasonable detail. Very few candidates were able to achieve this. Listing the names of vessels with no context and in a random non-sequential order did not attract many marks. The physiology of the blood supply to the liver also did not attract marks.
</blockquote>
 
 
<span id="online-resources-for-this-question-47"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/21a/21a07-outline-the-anatomy-of-the-blood-supply-arteries-and-veins-of-the-gastrointestinal-system-oesophagus-to-anus/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2021/05/2021-1-07.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-47"></span>
==== Similar questions ====
 
* Question 7, 2018 (1st sitting)
 
 
 
 
 
<span id="question-8-3"></span>
=== Question 8 ===
 
 
 
<span id="question-48"></span>
==== Question ====
 
Describe renal handling of potassium (60% marks), including factors that may influence it (40% marks).
 
 
 
<span id="example-answer-48"></span>
==== Example answer ====
 
 
 
Renal handling of potassium
 
* Potassium is freely filtered at the glomerulus
** Serum K = 4.2mmols/L, with 180L filtered / day (assuming GFR 125mls/min)
** Thus most of filtered K needs to be reabsorbed in the kidney
* Proximal convoluted tubule (PCT)
** ~60% of K reabsorbed
** Reabsorbed passively by solute drag (coupled to water reabsorption) + concentration gradient
** Water absorption is driven by the Na/K ATPAse on basolateral membrane &gt; drives Na reabsorption
* Loop of henle (LOH)
** 30% reabsorbed in thick ascending LOH
** NK2Cl cotransporter drives transcellular reabsorption (via basolateral K channels) + paracellular reabsorption (due to negative charge generated by Cl reabsorption)
** Active/secondary active transport
* DCT + CD
** 0-10% reabsorbed
** Secretion and absorption
*** Principle cells in DCT and CD: secrete potassium
*** Type A intercalated cells: reabsorb potassium
** Net effect depends on the K state at the time
*** With normal intake or excessive intake, net effect is secretion
*** With low intake the net effect is reabsorption
 
 
 
Regulation / factors influencing renal handling K
 
* Aldosterone
** Increases Na-K ATPase activity primarily in the principle cells &gt; increasing secretion of K
* Vasopressin
** Increases ROMK channels, increasing K secretion (balanced by decreased urinary flow rate)
* Acid base disturbances
** Metabolic alkalosis
*** Potassium secretion increases (increased Na/K ATPase activity due to low H+)
** Metabolic acidosis
*** Potassium secretion decreases (opposite of above)
* K intake
** Increased intake &gt; Increases ROMK channels &gt; increasing K secretion
 
 
 
<span id="examiner-comments-48"></span>
==== Examiner comments ====
 
<blockquote>33% of candidates passed this question.
 
This question covers a core physiology topic. The detail required is well described in the recommended reference texts. Generally, this question was poorly answered. From an answer template perspective, a &quot;describe question&quot; in this context involves both the stating the relevant potassium handling mechanism and then giving a description of how it occurs and how this system is regulated. Many answers that scored poorly simply listed sites of potassium handling but excluded the details surrounding the specific receptors and channels involved as well as the processes that exist to perpetuate and regulate these biological processes. Simple identification as to whether the potassium was being secreted or reabsorbed as well as the location as to where this may occur within the nephron, were often not specifically detailed or used interchangeably. Such answers scored poorly
</blockquote>
 
 
<span id="online-resources-for-this-question-48"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2021/05/2021-1-08.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/21a/21a08-describe-renal-handling-of-potassium-60-marks-including-factors-that-may-influence-it-40-marks/ Jenny's Jam Jar]
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2021-paper-1-saqs/question-8#answer-anchor Deranged Physiology]
 
 
 
<span id="similar-questions-48"></span>
==== Similar questions ====
 
* Question 16, 2010 (2nd sitting)
* Question 12, 2013 (1st sitting)
 
 
 
 
 
<span id="question-9-3"></span>
=== Question 9 ===
 
 
 
<span id="question-49"></span>
==== Question ====
 
Outline the mechanisms by which normal body temperature is maintained and regulated
 
 
 
<span id="example-answer-49"></span>
==== Example answer ====
 
 
 
Overview
 
* Human 'core temperature' is the 'deep body' temperature of the internal organs and viscera
** Core temperature ~ 37°C <math display="inline">\pm</math> 0.4°C, despite changes in ambient temperature
** Rectal, bladder, oesophageal, central vascular temperatures are often used as approximations.
* Peripheral temperatures are variable and generally less than the core temperature
* Significant hypothermia (e.g. &lt;35°C) or hyperthermia (e.g. &gt;40°C) can lead to multi-organ dysfunction
* Humans have multiple thermoregulatory mechanisms to resist change in core body temperature
** In general, heat is lost by 4 mechanism: conduction, convection, evaporation, radiation
** In general, heat is gained by 5 mechanisms: conduction, convection, evaporation, radiation, metabolism
 
 
 
 
 
Thermoregulatory system &amp; regulation
 
* Sensor
** Peripheral:
*** Skin thermoreceptors (cold= bulbs of Krause; warm=bulbs of Ruffini)
*** Travels via spinothalamic tract to hypothalamus
** Central:
*** Thermoreceptors (hypothalamus and spinal cord)
* Integrator/controller
** Hypothalamus
*** Functions as the thermostat (temperature kept around a thermoneutral zone, TNZ)
*** Stimulation of anterior hypothalamus leads to heat loss (temp above TNZ)
*** Stimulation of the posterior hypothalamus leads to heat conservation/generation (below TNZ)
* Effector/Response
** Response to cold
*** Shivering -&gt; involuntary muscle contractions that generate heat (ATP hydrolysis)
*** Peripheral vasoconstriction (ANS) --&gt; decreased cutaneous blood flow --&gt; decreased heat transfer from ambient air
*** Increase metabolic rate, thyroid hormone secretion, Non shivering thermogenesis (brown fat paeds, skeletal muscle adults) -&gt; increased heat generation
*** Behavioural changes (seek warmth)
*** Piloerection (unimportant in humans)
** Response to heat
*** Peripheral vasodilation (ANS) --&gt; increased cutaneous blood flow &gt; increased heat loss
*** Sweating --&gt; evaporative heat loss
*** Behavioural changes (seek cool)
 
 
 
<span id="examiner-comments-49"></span>
==== Examiner comments ====
 
<blockquote>59% of candidates passed this question. This question was relatively well answered by most candidates. There was significant variation in the temperatures expressed as normal and few candidates mentioned CORE temperature as a concept. Several candidates gave a detailed description of thermo-neutrality for which there were no marks.
</blockquote>
 
 
<span id="online-resources-for-this-question-49"></span>
==== Online resources for this question ====
 
<ul>
<li><p>[https://jennysjamjar.com.au/year/21a/21a09-outline-the-mechanisms-by-which-normal-body-temperature-is-maintained-and-regulated/ Jenny's Jam Jar]</p></li>
<li><p>[https://cicmwrecks.files.wordpress.com/2021/05/2021-1-09.pdf CICM Wrecks]</p></li>
<li><p>[https://icuprimaryprep.files.wordpress.com/2012/05/thermoregulation.pdf ICU Primary Prep]</p></li>
<li><p>[https://partone.litfl.com/regulation_of_body_temperature.html#id Part one LITFL]</p></li>
<li><p>Kerry brandis, page 285</p>
<p></p></li></ul>
 
<span id="similar-questions-49"></span>
==== Similar questions ====
 
* Question 6, 2007 (1st sitting)
* Question 4, 2009 (1st sitting)
* Question 19, 2018 (1st sitting)
 
 
 
 
 
<span id="question-10-3"></span>
=== Question 10 ===
 
 
 
<span id="question-50"></span>
==== Question ====
 
How does warfarin exert its pharmacological effect (40% marks)? Write brief notes on the pharmacology of the agents that can be used to reverse the effects of warfarin (60% marks).
 
 
 
<span id="example-answer-50"></span>
==== Example answer ====
 
{|
! Name
! Warfarin
|-
| '''Class'''
| Oral anticoagulant
|-
| '''Indications'''
| Systemic anticoagulation, e.g. in prophylaxis/treatment of thromboembolism
|-
| '''Pharmaceutics'''
| Racemic mixture of two enantiomers R and S, with the S isomer more biologically active.
|-
| '''Routes of administration'''
| Oral
|-
| '''Dose'''
| Varies; titrated to INR generally
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Inhibits the synthesis of vitamin K dependant clotting factors (II, VII, IX, X).<br />
Specifically, inhibits vitamin K epoxide reductase (VKORC1) from converting VitK from the oxidised to reduced form, which prevents carboxylation (activation) of clotting factors listed above (as well as protein C and S)
|-
| Effects
| Anticoagulation
|-
| Side effects
| Haemorrhage, teratogenicity (1st trimester), foetal haemorrhage (3rd trimester), drug interactions
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| Peak onset is 72 hours (as existing clotting factors not affected by warfarin)
|-
| Absorption
| 100% oral bioavailability
|-
| Distribution
| 99% protein bound, small VD 0.14L/Kg
|-
| Metabolism
| Complete hepatic metabolism
|-
| Elimination
| Renal elimination of metabolites
|-
| '''Reversal'''
| Vitamin K, FFP, Prothrombinex, cessation+time
|}
 
 
 
Reversal (in more detail)
 
* Cessation + time
** Stopping warfarin, will lead to normalisation of the INR generally in 4-5 days (but varies according to initial INR, comorbidities etc)
** Mechanism: drug washout
** Con: slow, risk of bleeding
** Pro: decreased risk thrombotic events from over/rapid correction
* Vitamin K
** can be given IV/IM/PO
** Higher doses, IV doses can reverse more rapidly
** Mechanism: replenishes the substrate
* Fresh frozen plasma
** Mechanism: Contains all necessary clotting factors - hence rapid reversal
** Blood product, with all the risks associated with this (fluid overload, infection, allergic responses)
** Dose: 2-4 units (varies)
** Con: require crossmatch, time for thawing etc
* Prothrombinex
** Mechanism: Contains factors II, IX, X (Aus) 500IU each- hence immediate reversal
** Dose: 25-50 u/kg
** Pro: immediate effects, smaller fluid volume, immediately available for use
** Con: Factor 7 absent, expensive
 
 
 
A general approach, adapted from Red Cross Blood Service
 
* Not bleeding
** INR not too high (&lt;4.5) and/or low bleeding risk = expectant management
** INR high &gt;4.5 and/or moderate-high bleeding risk = oral/IV Vit K
* Bleeding
** Life threatening: IV Vit K 10mg , Prothrombinex 50u/kg (or FFP if not available)
** Clinically significant: IV VitK 5-10mg, Prothrombinex 25u/kg (or FFP if not available)
** Minor bleeding: IV VIt K
 
 
 
<span id="examiner-comments-50"></span>
==== Examiner comments ====
 
<blockquote>43% of candidates passed this question.
 
Warfarin is listed as a level 1 drug in the 2017 syllabus and as such a detailed knowledge of its mechanism of action would be expected from candidates sitting the exam. The reversal agents for warfarin are collectively classed as level 2 drugs and hence the knowledge required would be at a write short notes level. The following topics were expected: what drugs may be used, how they work, in what dose, any common side effects, why/when would one be used in preference to others etc. The use of reversal agents for warfarin is a common practice in ICU. Generally, answers demonstrated a lack of a precise and detailed knowledge with respect to warfarin’s mechanism of action and had a very superficial knowledge with incorrect facts regarding the reversal agents
</blockquote>
 
 
<span id="online-resources-for-this-question-50"></span>
==== Online resources for this question ====
 
* [https://partone.litfl.com/anticoagulants.html#id Part One, LITFL] and [https://partone.litfl.com/exams/2020A/2020A06.html Part One LITFL]
* [https://cicmwrecks.files.wordpress.com/2021/05/2021-1-10.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/21a/21a10-how-does-warfarin-exert-its-pharmacological-effect-40-marks-write-brief-notes-on-the-pharmacology-of-the-agents-that-can-be-used-to-reverse-the-effects-of-warfarin-60-marks/ Jenny's Jam Jar]
* [https://www.ncbi.nlm.nih.gov/books/NBK470313/ StatPearls]
 
 
 
<span id="similar-questions-50"></span>
==== Similar questions ====
 
* Question 21, 2014 (1st sitting)
* Question 8, 2015 (1st sitting)
* Question 10, 2016 (1st sitting)
 
 
 
<span id="question-11-3"></span>
=== Question 11 ===
 
 
 
<span id="question-51"></span>
==== Question ====
 
Describe the buffer systems in the body
 
 
 
<span id="example-answer-51"></span>
==== Example answer ====
 
 
 
Buffers
 
* A solution consisting of a weak acid and its conjugate base
* Main function is to resist change to pH, with the addition of stronger acids/bases, through reversible binding of H+ ions
* Effectiveness depends on the buffer pKa, the pH of the solution, the amount of buffer present, whether the system is open or closed
* All buffers participate in equilibrium with each other in defence of pH (Isohydric principle)
 
 
 
Main buffering systems in ECF
 
* Bicarbonate-carbonic acid buffering system
* Protein buffering system (includes Hb buffering system)
* Phosphate buffering system
 
 
 
Bicarbonate-carbonic acid system
 
* pKa of 6.1
* Weak acid (H<sub>2</sub>CO3) and base (HCO<sub>3</sub> salt)
* Via reaction: <math display="inline"> CO_2 \; + H_2O \; \leftrightarrow \; H_2CO_3 \; \leftrightarrow \; HCO_3^- \; + H^+</math>
* Increased acid &gt; increased CO<sub>2</sub> (excreted via lungs)
* Increased base &gt; increased HCO<sub>3</sub> (excreted via kidneys)
* OPEN system - hence most important - responsible for 80% of the ECF buffering
 
 
 
Protein buffering system
 
* Include haemoglobin (150g/L) and plasma proteins (70g/L)
** Hb has pKa of 6.8. Weak acid (HHb) and weak base (KHb)
* H+ binds to the histadine residues on imadazole side chains, the HCO3 diffuses down concentration gradient into ECF
* Hb is quantitatively 6 times more important than plasma proteins, as the concentration is double and there are three times as many histadine residues in Hb
 
Phosphate buffering system
 
* Overall pKa 6.8
* Tribasic (HPO<sub>4</sub>, H<sub>2</sub>PO<sub>4</sub>, H<sub>3</sub>PO<sub>4</sub>) though only the H<sub>2</sub>PO<sub>4</sub> has a physiological pKa to be useful
* Overall contribution is minimal to the blood due to the low concentration of phosphate. However more important in the urine where the concentration is higher
* closed system
 
 
 
<span id="examiner-comments-51"></span>
==== Examiner comments ====
 
<blockquote>57% of candidates passed this question.
 
This is a core physiology topic; a detailed knowledge of buffering and the available buffer systems is crucial to ICU practice. A candidate presenting for the first part exam should have a detailed understanding of all aspects of the buffer systems. Higher scoring answers provided both technical details of the buffer systems, the context for their normal function and their relative importance. Efficient answers dealt with the buffers by chemical rather than by site, but many answers categorising buffers by site also scored well. Many low scoring answers simply failed to provide detail, some provided incorrect information. Very few candidates demonstrated an understanding of the isohydric principle
</blockquote>
 
 
<span id="online-resources-for-this-question-51"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/21a/21a11-describe-the-buffer-systems-in-the-body/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2021/05/2021-1-11.pdf CICM Wrecks]
* [https://partone.litfl.com/buffers.html Part One LITFL]
 
 
 
<span id="similar-questions-51"></span>
==== Similar questions ====
 
* Question 3, 2008 (2nd sitting)
* Question 19, 2011 (1st sitting)
* Question 22, 2014 (1st sitting)
* Question 6, 2018 (1st sitting)
 
 
 
<span id="question-12-3"></span>
=== Question 12 ===
 
 
 
<span id="question-52"></span>
==== Question ====
 
Describe the pharmacology of oxycodone.
 
 
 
<span id="example-answer-52"></span>
==== Example answer ====
 
{|
! Name
! Oxycodone
|-
| '''Class'''
| Semi-synthetic opioid (phenanthrene)
|-
| '''Indications'''
| Analgesia
|-
| '''Pharmaceutics'''
| White tablet (IR, MR) +/- naloxone - various conc<br />
Oral solution (1mg/ml)<br />
Clear, colourless, solution (10mg/ml)
|-
| '''Routes of administration'''
| PO, IV, SC, IM
|-
| '''Dose'''
| Depends<br />
- Example: PO 5-10mg PRN 4hrly, IV 1mg 5 minutes PRN
|-
| '''Morphine equivalence'''
| 1.5 x morphine <br />
(10mg oxycodone = 15mg morphine )
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| MOP receptor (Gi PCR) in cerebral cortex, basal ganglia, periaqueductal grey<br />
Weak KOP / DOP receptor activity
|-
| Effects
| CNS: Analgesia, sedation, euphoria, dyspho<br />
CVS: bradycardia, hypotension<br />
RESP: respiratory depression (reduces chemoreceptor sensitivity to CO2), depressed cough reflex<br />
GIT: decreased peristalsis &gt; constipation, nausea, vomiting<br />
MSK: pruritis, muscle rigidity<br />
GU: urinary retention<br />
EYE: miosis
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| Peak 5 mins, duration 4 hrs
|-
| Absorption
| 80% oral bioavailability
|-
| Distribution
| ~50% protein bound<br />
VOD = 3L/Kg<br />
Crosses placenta
|-
| Metabolism
| Hepatic metabolism (CYP3A4) - extensive<br />
Oxidation &gt; demethylation<br />
Active metabolites: noroxycodone, oxymorphone
|-
| Elimination
| Renal elimination <br />
Active metabolites<br />
T <sub>1/2</sub> = 2-4hrs (IR)
|-
| '''Reversal'''
| Naloxone (100mcg IV boluses, PRN 3 minutely)
|}
 
 
 
<span id="examiner-comments-52"></span>
==== Examiner comments ====
 
<blockquote>54% of candidates passed this question.
 
There were many exceptional answers which provided extensive detail on the drug. The best of these gave context for the drug characteristics, such as by referring to oxycodone relative to other opioid drugs that might be chosen, or to considerations for safe and effective administration. Some answers, however, provided generic information on opioid drugs, which could not gain all the available marks.
</blockquote>
 
 
<span id="online-resources-for-this-question-52"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2021/05/2021-1-12.pdf CICM wrecks]
* [https://jennysjamjar.com.au/year/21a/21a12-describe-the-pharmacology-of-oxycodone/ Jenny's Jam Jar]
* [https://partone.litfl.com/opioids.html#id Part one, LITFL]
 
 
 
<span id="similar-questions-52"></span>
==== Similar questions ====
 
<ul>
<li><p>Question 12, 2017 (1st sitting)</p>
<p></p></li></ul>
 
 
 
<span id="question-13-3"></span>
=== Question 13 ===
 
 
 
<span id="question-53"></span>
==== Question ====
 
List the cell types in the anterior pituitary gland. Outline their secretions, control and target organ effects.
 
 
 
<span id="example-answer-53"></span>
==== Example answer ====
 
 
 
Anterior pituitary connected to the hypothalamus via the hypophyseal portal system
 
 
 
Anterior pituitary cell types
 
* Chromophils (granular secretory cells)
** Acidophils (80%)
*** Red staining
*** Includes lactotropes (prolactin) and somatotropes (GH)
** Basophils (20%)
*** Blue staining
*** Includes gonadotropes (FSH, LH), thyrotropes (TSH) and corticotropes (ACTH)
* Chromophobes (agranular secretory cells)
** inactive/degranulated secretory cells
** Weakly staining, no longer secrete hormones
 
 
 
Anterior pituitary hormones and their effects
 
{|
! Hormone
! Increased release (stimulation)
! Decreased release (inhibition)
! Effects
|-
| ACTH
| Corticotrophin releasing hormone (CRH): stress, catecholamines, ADH
| Cortisol (negative feedback)
| Acts on adrenal cortex to increase release and synthesis of glucocorticoids and androgens
|-
| TSH
| Thyrotropin releasing hormone (TRH) from hypothalamus
| Negative feedback (T3/T4), somatostatin
| Increased synthesis and secretion of T3/T4 from thyroid cells<br />
Hyperplasia and hypertrophy of thyroid follicular cells
|-
| GH (somatotropin)
| Somatotropin releasing hormone from hypothalamus. Stress, starvation, hypoglycaemia
| - Somatostatin<br />
- Negative feedback (IGF-1)
| - Releases IGFs (anabolic action; growth and differentiation of cells)<br />
- Increases protein, fat, carbohydrate metabolism/utilisation in liver, adipose/muscle tissues.
|-
| FSH, LH
| Gonadotropin releasing hormone from hypothalamus
| Negative feedback (FSH, LH)
| LH: ovulation (females), testosterone secretion (males)<br />
FSH: ovarian follicle development (females), spermatogenesis (males)
|-
| Prolactin
| Thyrotropin releasing hormone (TRH), suckling
| Prolactin inhibiting hormone, dopamine, negative feedback
| Promotes mammary gland and ductal development (during pregnancy)<br />
Promotes lactation, amenorrhoea (following delivery)
|}
 
 
 
 
 
<span id="examiner-comments-53"></span>
==== Examiner comments ====
 
<blockquote>40% of candidates passed this question.
 
Few candidates described cell types as chromophils and chromophobes. There were many errant references to chromaffin cells which are found mainly in the adrenal medulla, and to staining on H&amp;E. Chromophil cells stain by absorbing chromium salts. Few candidates mentioned that the hormones secreted by the anterior pituitary are peptides. Most candidates outlined the hypophyseal-portal system well. Knowledge of TSH and ACTH control and target organ effects were good. Similar knowledge for LH, FSH, PRL and GH was much more sporadic.
</blockquote>
 
 
<span id="online-resources-for-this-question-53"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/21a/21a13-list-the-cell-types-in-the-anterior-pituitary-gland-outline-their-secretions-control-and-target-organ-effects/ Jenny's jam Jar]
* [https://cicmwrecks.files.wordpress.com/2021/05/2021-1-13.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-53"></span>
==== Similar questions ====
 
* None?
 
 
 
<span id="question-14-3"></span>
=== Question 14 ===
 
 
 
<span id="question-54"></span>
==== Question ====
 
Describe the pharmacology of sodium bicarbonate.
 
 
 
<span id="example-answer-54"></span>
==== Example answer ====
 
{|
! Name
! Sodium Bicarbonate
|-
| '''Class'''
|
|-
| '''Indications'''
| Severe NAGMA, alkalinisation of urine (salicylate toxicity), hyperkalaemia, TCA overdose (Na channel blocking effects)
|-
| '''Pharmaceutics'''
| Tablet (varying doses e.g. 300mg)<br />
Clear colourless solution (various concentrations e.g, 4.2%, 8.4%) which can be given hypertonic or isotonic
|-
| '''Routes of administration'''
| PO, IV
|-
| '''Dose'''
| 1mmol/kg IV = 1ml/kg of 8.4% (cardiac arrest due to hyperK)
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Dissociates into Na and HCO3. The HCO3 functions as a buffer in the bicarbonate-carbonic acid buffering system (raising pH). The Na increases the strong ion difference in plasma (raising pH)
|-
| Effects
| Increases pH, alkalinisation of urine
|-
| Side effects
| Hypokalaemia, hypocalcaemia, hypernatremia<br />
Fluid overload (Large doses IV)<br />
Extravasation tissue injury (IV)<br />
Metabolic alkalosis (overdose)
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| Immediate
|-
| Absorption
| NA
|-
| Distribution
| Intravascular space
|-
| Metabolism
| <math display="inline"> CO_2 \; + H_2O \; \leftrightarrow \; H_2CO_3 \; \leftrightarrow \; HCO_3^- \; + H^+</math>
|-
| Elimination
| Renal (bicarbonate), lungs (as CO<sub>2</sub>)
|-
| '''Special points'''
| Incompatible with calcium /magnesium salts (precipitates)
|}
 
 
 
<span id="examiner-comments-54"></span>
==== Examiner comments ====
 
<blockquote>29% of candidates passed this question.
 
This question was best answered with a structured approach as per any pharmacology question. It nonetheless required good understanding of various aspects of physiology. Many candidates failed to gain marks by omitting to mention facts which could have been prompted by a defined structure. A good response mentioned the pharmaceutic features including formulation and the hypertonicity of IV bicarbonate, pharmacodynamics including indications for use, mode of action, adverse effects (systemic and local), pharmacokinetics and dose. Pleasingly a few candidates stated that sodium bicarbonate’s mechanism of action to cause alkalosis involved increasing the strong ion difference in plasma. Credit was also given for stating the mechanism of action as providing bicarbonate ions to augment the extracellular buffer system
</blockquote>
 
 
<span id="online-resources-for-this-question-54"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2021/05/2021-1-14.pdf CICM Wrecks ]
* [https://jennysjamjar.com.au/year/21a/21a14-describe-the-pharmacology-of-sodium-bicarbonate/ Jenny's Jam Jar ]
* [https://litfl.com/sodium-bicarbonate-use/ LITFL]
* [https://www.ncbi.nlm.nih.gov/books/NBK559139/ StatPearls]
 
 
 
<span id="similar-questions-54"></span>
==== Similar questions ====
 
* None?
 
 
 
<span id="question-15-3"></span>
=== Question 15 ===
 
 
 
<span id="question-55"></span>
==== Question ====
 
Explain perfusion limited and diffusion limited transfer of gases in the alveolus.
 
 
 
<span id="example-answer-55"></span>
==== Example answer ====
 
 
 
Gas diffusion
 
* Rate of diffusion of gasses is given by Fick's Law
 
<math display="block">Diffusion = \frac {A \times D \; \times \Delta P}{T }</math>
Where: A= lung area, D = diffusion constant of the gas, <math display="inline">\Delta</math>P = partial pressure gradient of gas, T=thickness of membrane. Diffusion constant is influence by the Temperature of the gas, the density of the gas and the size of the molecules
 
* Gas diffusion at the level of the alveolus can either be perfusion or diffusion limited.
 
 
 
Perfusion limited gases
 
* Rapidly equilibrates between alveolus and capillary
* Equilibration time is less than the capillary transit time
* Thus for the majority of the RBCs time travelling through the capillary, there is no further diffusion
* As a result this gas is 'perfusion limited' because increasing the blood flow (perfusion) will increase gas transfer, but increasing the rate of diffusion will not
* Examples
** Oxygen (under normal conditions)
*** Due to the large partial pressure gradient (100 &gt; 40)
*** Equilibrates within 0.25s (pulmonary capillary transit time 0.75s)
** Carbon dioxide
*** While a smaller partial pressure gradient (46 &gt; 40), the diffusivity of CO<sub>2</sub> is 20 X greater than O<sub>2</sub>
*** Equilibrates within 0.25s
*** Actually ventilation limited - as you need to blow off CO2 to ensure gradient
** Nitrous oxide
*** Relatively insoluble and doesn't bind to Hb, therefore struggles to equilibrate
 
 
 
Diffusion limited gasses
 
* Does not rapidly equilibrate between alveolus and capillary
* Equilibration time is greater than the capillary transit time
* Thus for the entirety of the RBCs time in the capillary there is ongoing diffusion occurring
* As a result this gas is 'diffusion limited' because increasing the rate of diffusion will increase the rate of gas transfer, but increasing the blood flow (perfusion) will not.
* Examples
** Carbon monoxide
*** Slowly diffuses
*** CO binds to Hb so avidly that there is virtually none in the plasma
*** Therefore the equilibrium is never reached and further gas exchange could occur with a greater diffusivity
** Oxygen
*** Typically perfusion limited under normal circumstances.
*** Under extreme conditions it may become diffusion limited
**** Increase altitude &gt; decreased PAO2
**** High cardiac output &gt; reduced capillary transit time
**** Alveolar membrane disease &gt; decreases rate of diffusion
 
 
 
<span id="examiner-comments-55"></span>
==== Examiner comments ====
 
<blockquote>36% of candidates passed this question.
 
This question required detail on those factors affecting gas exchange at the level of the alveolus. A description of the components of the Fick equation was expected - and how this related to oxygen and carbon dioxide transfer at the alveolar capillary membrane. The rapid rate of equilibration (developed tension) was the limiting factor in of blood/alveolar exchange that rendered some gases perfusion limited (examples - N2O, O2 under usual conditions but not all) and the slower rate of others diffusion limited (examples CO and O2 under extreme conditions e.g., exercise, altitude). Estimates of time taken for each gas to equilibrate relative to the time taken for the RBC to travel across the interface was also expected for full marks. CO2 despite rapid equilibration and higher solubility was correctly described as perfusion limited (unless in disease states). Better answers described CO2 as ventilation limited. Some answers also correctly included the component of interaction with the RBC and haemoglobin. Ventilation/perfusion inequalities over the whole lung were not asked for and scored no marks
</blockquote>
 
 
<span id="online-resources-for-this-question-55"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2021/05/2021-1-15.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/21a/21a15-explain-perfusion-limited-and-diffusion-limited-transfer-of-gases-in-the-alveolus/ Jenny's Jam Jar]
* [https://partone.litfl.com/diffusing_capacity_and_limitation.html Part One, LITFL]
 
 
 
<span id="similar-questions-55"></span>
==== Similar questions ====
 
* None
 
 
 
<span id="question-16-3"></span>
=== Question 16 ===
 
 
 
<span id="question-56"></span>
==== Question ====
 
Describe the pharmacology of piperacillin-tazobactam
 
 
 
<span id="example-answer-56"></span>
==== Example answer ====
 
{|
! Name
! Piperacillin-tazobactam
|-
| '''Class'''
| Semi-synthetic penicillin (piperacillin)<br />
B-lactamase inhibitor (tazobactam)
|-
| '''Indications'''
| Pseudomonal infection<br />
Broad spectrum antimicrobial cover of severe infections/sepsis
|-
| '''Pharmaceutics'''
| Powder, reconstitutes in water/NaCl/glucose
|-
| '''Routes of administration'''
| IV/IM
|-
| '''Dose'''
| 4g/0.5g 8hrly<br />
4g/0.5g 6hrly (pseudomonas cover); dose reduced renal failure
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Piperacillin: bactericidal - inhibits cell wall synthesis by preventing cross linking of peptidoglycans by replacing the natural substrate (D-ala-D-ala) with their B-lactam ring<br />
Tazobactam: B lactamase inhibitor (prevents piperacillin degradation)
|-
| Antimicrobial cover
| Broad spectrum coverage of gram positive bacteria, gram negative bacteria, anaerobes. Covers pseudomonas.<br />
Doesn't cover: MRSA, VRE, ESBL, atypical
|-
| Side effects
| GIT: diarrhoea, nausea, vomiting<br />
Renal: AKI<br />
Allergy (up to 10%), rash most common, skin eruptions/SJS and anaphylaxis (&lt;1/10,000)
|-
| '''Pharmacokinetics'''
|
|-
| Absorption
| Minimal oral absorption &gt; IV<br />
Peak concentrations immediately after dose.
|-
| Distribution
| Very good tissue penetration (minimal CNS without active inflammation)<br />
Low protein binding (&lt;30%)
|-
| Metabolism
| Piperacillin: not metabolised<br />
Tazobactam: metabolised to M1, an inactive metabolite
|-
| Elimination
| Renal (80% unchanged)
|-
| '''Special points'''
| Removed by haemodialysis
|}
 
 
 
<span id="examiner-comments-56"></span>
==== Examiner comments ====
 
<blockquote>62% of candidates passed this question.
 
Most candidates used a structured approach with the usual major pharmacology headings. Mechanism of action was well described by most, with better answers including mechanisms of resistance. Higher scoring candidates included an explanation as to the combination of the drugs. Likewise, better answers included detailed information on spectrum of activity beyond “gram positive and gram negative”, including relevant groups of organisms which are not covered. There also seemed to be some confusion about coverage for anaerobes, which piperacillin tazobactam covers well. Specific detail about adverse reactions, other than ‘allergy, rash, GI upset, phlebitis, etc’, is expected for commonly used antibiotics.
</blockquote>
 
 
<span id="online-resources-for-this-question-56"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/21a/21a16-describe-the-pharmacology-of-piperacillin-tazobactam/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2021/05/2021-1-16.pdf CICM Wrecks]
* MIMS
 
 
 
<span id="similar-questions-56"></span>
==== Similar questions ====
 
* Question 20, 2019 (2nd sitting)
 
 
 
<span id="question-17-3"></span>
=== Question 17 ===
 
 
 
<span id="question-57"></span>
==== Question ====
 
Describe the principles of measurement of arterial haemoglobin O2 saturation using a pulse oximeter (60% marks). Outline the limitations of this technique (40% marks).
 
 
 
<span id="example-answer-57"></span>
==== Example answer ====
 
 
 
Definition
 
* Non invasive spectrophotometric technique to measure O2 saturation in arterial blood
* Normal: typically 95-100% (for young health individuals)
 
 
 
Components
 
* Two light sources (LEDs): emit light at 660nm and 940nm
* Light detector (photodiode)
* Opaque housing unit (minimises ambient light)
* Signal amplifier, noise filter
* Microprocessor
* Connectors , user interface and alarm system
 
 
 
Physical principles
 
# Utilises the principles of the Beer-Lambert law: <math display="inline">A = ε \; l \; c</math>
#* Absorption (A) of light passing through a substance is directly proportional to
#** The optical path length (Lambert's law; l)
#** The concentration of attenuating species within the substance (Beers Law; c)
#** The absorptivity of the attenuating species ( ε )
 
# Utilises the different absorption spectra of Oxy- and deoxy-Hb
#* Deoxy-Hb absorbs far more light in the ''red'' spectra (660nm)
#* Oxy-Hb absorbs far more light in the ''near-infrared'' spectra (940nm)
 
 
 
How it works
 
# Pulsatile blood (arterial) is isolated and Hb saturation calculated
#* During pulsatile flow, there is expansion and contraction of the blood vessels
#* This alters the optical distance (Lamberts law), changing the absorption spectra
#* Non pulsatile elements (e.g. venous blood) are excluded from the pulsatile elements (arterial blood) by creating a ratio of absorbances (R)
#* Whereas the ratio of absorbances at different spectra (660nm vs 940nm) utilised to calculate saturation of Hb
 
<math display="block">R = \frac {Pulsatile_{660} \; / \; Non-pulsatile_{660}}{Pulsatile_{940} \; / \; Non-pulsatile_{940}}</math>
# Empirical correlation with SaO2
#* The relationship between R and SpO2 was derived empirically by comparing arterial oxygen saturations (from ABGs) at different R values in healthy volunteers
# There are important corrections in modern pulse oximeters
#* Correction for Hb concentration using isosbestic points
#* Correction for ambient light using rapid cycling of the light source (up to 1000 hz)
 
 
 
Limitations
 
* Requires detectable pulsatile flow (shock, poor perfusion, hypothermia, ECMO, CPB)
* Bodily movements (e.g. shivering, seizure) confound readings
* Not accurate nor calibrated at low saturations (progressive decline in accuracy as SaO2 decreases)
* Not all devices are created equal (device accuracy ranges; generally within 1-5% of ABGs)
* Ambient light contamination (effects minimal due to rapid cycling as described above)
* Interference: nail polish, oedema, intravascular dyes (methylene blue)
* False readings: carbon monoxide poisoning, MetHb
* Racial bias in pulse oximetry: tested predominately on white population. [https://www.nejm.org/doi/full/10.1056/NEJMc2029240 A study] demonstrated 3x as many black patients had occult hypoxemia compared to white patients.
 
 
 
<span id="examiner-comments-57"></span>
==== Examiner comments ====
 
<blockquote>74% of candidates passed this question.
 
Most candidates provided a reasonable structured sequence of how a pulse oximeter generates a value. Nearly all candidates described the Beer-Lambert laws correctly, but few specifically described the basic principles of absorption spectrophotometry. Most candidates had a reasonable list of extrinsic factors that can interfere with pulse oximeter performance, but few described the intrinsic/inherent limitations of the device that can cause SpO2 to be different to SaO2, such as functional versus fractional saturation.
</blockquote>
 
 
<span id="online-resources-for-this-question-57"></span>
==== Online resources for this question ====
 
<ul>
<li><p>[https://ketaminenightmares.com/pex/saqs/other/clinical_measurement/2019A15_pulse_oximetry_sources_of_inaccuracy.htm Ketamine Nightmares]</p></li>
<li><p>[https://partone.litfl.com/pulse_oximetry.html Part One, LITFL]</p></li>
<li><p>[https://cicmwrecks.files.wordpress.com/2021/05/2021-1-17.pdf CICM Wrecks] and [https://cicmwrecks.files.wordpress.com/2019/04/2018-1-08.pdf CICM Wrecks]</p></li>
<li><p>[https://jennysjamjar.com.au/year/21a/21a17-describe-the-principles-of-measurement-of-arterial-haemoglobin-o2-saturation-using-a-pulse-oximeter-60-marks-outline-the-limitations-of-this-technique-40-marks/ Jenny's Jam Jar]</p></li>
<li><p>[https://derangedphysiology.com/cicm-primary-exam/past-papers/2021-paper-1-saqs/question-17#answer-anchor Deranged Physiology]</p>
<p></p></li></ul>
 
<span id="similar-questions-57"></span>
==== Similar questions ====
 
* Question 3, 2008 (1st sitting)
* Question 5, 2013 (2nd sitting)
* Question 7, 2014 (1st sitting)
* Question 8, 2018 (1st sitting)
 
 
 
<span id="question-18-3"></span>
=== Question 18 ===
 
 
 
<span id="question-58"></span>
==== Question ====
 
Outline the pharmacology of intravenous magnesium sulphate
 
 
 
<span id="example-answer-58"></span>
==== Example answer ====
 
{|
! Name
! Magnesium sulphate
|-
| '''Indications'''
| HypoMg, eclampsia/pre-eclampsia, severe asthma, arrhythmias (including TdP), analgesia
|-
| '''Pharmaceutics'''
| Clear colourless solution, various concentrations
|-
| '''Routes of administration'''
| IV, IM
|-
| '''Dose'''
| 5mmol bolus (torsade's). <br />
4g (16mmols) bolus &gt; 1g/hr thereafter (eclampsia, PET)
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Essential cation<br />
- Essential cofactor in hundreds of enzymatic reactions<br />
- Necessary in several steps of glycolysis (ATP production)<br />
- NMDA receptor antagonism (increasing seizure threshold)<br />
- Inhibits Ach release at NMJ (muscle relaxation)<br />
- Smooth muscle relaxation (Inhibits Ca L-type channels)
|-
| Effects
| CNS: anticonvulsant (NMDA effect)<br />
Resp: Bronchodilation (CCB effect &gt; SM relaxation)<br />
CVS: Anti-arrhythmic ( decreased conduction velocity due to CCB effect)
|-
| Side effects
| Related to speed of administration + degree of HyperMg <br />
Toxicity generally occurs &gt; 4mmol/L<br />
CVS: Hypotension, bradycardia<br />
CNS/MSK: hyporeflexia, muscle weakness, CNS depression, potentiates NMBs<br />
RESP: respiratory depression<br />
GIT: Nausea, vomiting
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| Immediate
|-
| Absorption
| N/A
|-
| Distribution
| 30% protein bound
|-
| Metabolism
| Not metabolised
|-
| Elimination
| Urine; clearance is proportional to GFR and plasma concentration
|-
| '''Special points'''
| Incompatible with calcium salts &gt; precipitation<br />
Drug interaction with NMB agents (potentiation)
|}
 
 
 
<span id="examiner-comments-58"></span>
==== Examiner comments ====
 
<blockquote>57% of candidates passed this question.
 
The best answers appropriately addressed the pharmacology of magnesium sulphate, rather than diverting into physiology. They noted that the question concerned intravenous magnesium sulphate and did not discuss other routes. They included pharmaceutics, important examples of the wide-ranging indications, listed potential modes of action and considered the full range of body systems affected including potential adverse effects. Drug interactions, such as potentiation of neuromuscular blocking agents, and pharmacokinetics (including stating that magnesium is not metabolised) were described
</blockquote>
 
 
<span id="online-resources-for-this-question-58"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/21a/21a18-outline-the-pharmacology-of-intravenous-magnesium-sulphate/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2021/05/2021-1-18.pdf CICM Wrecks] and [https://cicmwrecks.files.wordpress.com/2017/04/2014-2-20-pharmacology-mgso4.pdf CICM Wrecks]
* [https://partone.litfl.com/magnesium.html PartOne, LITFL]
* [https://www.ncbi.nlm.nih.gov/books/NBK554553/ StatPearls]
* MIMS
 
 
 
<span id="similar-questions-58"></span>
==== Similar questions ====
 
* Question 10, 2011 (2nd sitting)
* Question 20, 2014 (2nd sitting)
* Question 10, 2015 (2nd sitting)
* Question 4, 2019 (2nd sitting)
 
 
 
<span id="question-19-3"></span>
=== Question 19 ===
 
 
 
<span id="question-59"></span>
==== Question ====
 
Describe the adult coronary circulation (50% marks) and its regulation (50% marks)
 
 
 
<span id="example-answer-59"></span>
==== Example answer ====
 
 
 
Vascular anatomy
 
* Coronary arteries arise from the sinuses of valsalva at the aortic root
** Left coronary artery (LCA)
*** LAD
**** Branches: D1, D2 arteries
**** Supplies: anterior 2/3 of the IV septum, anterior LV, LA
*** LCx
**** Branches: OM1, OM2
**** Supplies: inferolateral LV wall, SA node (40%), AV node (20%)
** Right coronary artery
*** Branches: Right marginal branches
*** Supplies: RA, RV, SA node (60%), AV node (80%)
** PDA
*** Continuation of RCA (~70%), LCx (~15%), or both (~15%)
*** Supplies: posterior inferior LV
* Coronary veins
** Majority (85%) of venous drainage is via the coronary sinus
*** Great cardiac vein (follows LAD)
*** Middle cardiac vein (follows PDA)
*** Small cardiac vein (follows RCA)
** Remainder (15%)
*** Anterior cardiac veins --&gt; RA
*** Thebesian veins (drains into cardiac chamber directly)
 
 
 
Coronary blood flow
 
* CBF ~250mls/min (5% CO)
* Oxygen extraction near maximal (70%) --&gt; Increased CBF is needed for increased O2 demand.
* RCA: blood flow is constant, pulsatile and higher flow rate during systole
* LCA: blood flow is intermittent, pulsatile, and higher flow rate during diastole
 
 
 
Regulation of flow
 
* Autoregulation
** Metabolic autoregulation
*** Anaerobic metabolism &gt; increased vasoactive substances (lactate, adenosine, CO2, NO) &gt; vasodilation &gt; increased flow
*** Predominant means of autoregulation
** Myogenic autoregulation
*** CBF is autoregulated over a wide range of BPs (perfusion pressure 50-120mmhg)
*** Increased transmural pressure &gt; vasoconstriction &gt; flow reduction
*** Modest means of autoregulation
* Direct autonomic control
** Weak effect
** a1 activation &gt; vasoconstriction; B/muscarinic activation &gt; vasodilation
* Indirect autonomic control
** Increase / decrease HR to alter time in diastole/systole which will lead to increased/decreased flow
** i.e. Increased PSNS activity &gt; decreased HR &gt; increased diastolic time &gt; increased CBF
 
 
 
<span id="examiner-comments-59"></span>
==== Examiner comments ====
 
<blockquote>62% of candidates passed this question.
 
Good candidates described normal blood flow to the coronary circulation, including differences between the right and left ventricles. Coronary artery anatomy was outlined, including the regions of the heart supplied and the concept of dominance. In addition to epicardial vessels, strong answers also outlined penetrating arteries, subendocardial supply and venous drainage. Regulation of coronary blood flow required an explanation of flow-dependence of the heart given its high oxygen extraction rate. Metabolic autoregulation and its mediators needed to be described, along with the physical factors driving coronary blood flow. Less important mechanisms such as the role of the autonomic nervous system were also described, with an emphasis on indirect effects over direct effects.
</blockquote>
 
 
<span id="online-resources-for-this-question-59"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2021/05/2021-1-19.pdf CICM Wrecks] and [https://cicmwrecks.files.wordpress.com/2017/04/2014-2-10-coronary-circ.pdf CICM Wrecks]
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2021-paper-1-saqs/question-19#answer-anchor Deranged Physiology]
* [https://partone.litfl.com/coronary_circulation.html Part One, LITFL]
* [https://jennysjamjar.com.au/year/21a/21a19-describe-the-adult-coronary-circulation-50-marks-and-its-regulation-50-marks/ Jenny's Jam Jar]
* [https://ketaminenightmares.com/pex/saqs/physiology/cardiovascular/2010B10_myocardial_oxygen_supply_and_demand_determinants_of_coronary_blood_flow.htm Ketamine Nightmares]
 
 
 
<span id="similar-questions-59"></span>
==== Similar questions ====
 
<ul>
<li><p>Question 11, 2008 (2nd sitting)</p></li>
<li><p>Question 10, 2014 (2nd sitting)</p></li>
<li><p>Question 11, 2018 (1st sitting)</p>
<p></p></li></ul>
 
<span id="question-20-3"></span>
=== Question 20 ===
 
 
 
<span id="question-60"></span>
==== Question ====
 
Outline the physiological factors that influence cerebral blood flow
 
 
 
<span id="example-answer-60"></span>
==== Example answer ====
 
 
 
Cerebral blood flow (CBF)
 
* ~15% CO (~750mls/min) under normal resting conditions
* High demand due to high metabolic rate
* Brain is very sensitive to interruptions (due to high demand and inability to store energy)
 
 
 
Factors effecting CBF
 
* Related to blood pressure, vessel characteristics, rheological factors per Hagan-Poiseuille eqn.
** <math display="inline">CBF \; = \; \frac {\Delta P \pi R^4}{8 \eta L}</math>
** Where: ΔP represents the driving pressure (i.e. CPP), R is the radius of the blood vessels, η is blood viscosity, L is the length of the tube.
 
 
 
<ol style="list-style-type: decimal;">
<li><p>Pressure effects</p>
<ul>
<li><p>Cerebral perfusion pressure (CPP) = MAP - ICP (or CVP whichever is higher)</p></li>
<li><p>Normally CBF is kept constant across a wide range of CPP (approx 50-150mmHg)</p></li>
<li><p>Able to do this via cerebral autoregulation</p>
<ul>
<li><p>Predominant means is myogenic autoregulation</p>
<ul>
<li><p>Increased CPP &gt; Inc. stretch &gt; inc. wall tension &gt; vasoconstriction &gt; decreased CBF</p></li></ul>
</li></ul>
</li>
<li><p>Outside autoregulatory ranges (e.g. MAP &lt;50mmhg or &gt;150mmHg)</p>
<ul>
<li><p>CBF becomes pressure passive (any increase in CPP = increase CBF, vice versa)</p></li></ul>
 
<p></p></li></ul>
</li>
<li><p>Vessel radius effects</p>
<ul>
<li><p>Myogenic autoregulation (per above)</p></li>
<li><p>PaCO<sub>2</sub></p>
<ul>
<li><p>CO2 is a cerebral vasodilator = increased CBF</p></li>
<li><p>Linear increase in CBF for increase CO2 between 20-80mmHg</p></li></ul>
</li>
<li><p>PaO2</p>
<ul>
<li><p>Within normal physiological limits does not effect CBF</p></li>
<li><p>Exponential increase in CBF with hypoxia (e.g. PaO2 &lt;50-60) due to vasodilation</p></li></ul>
</li>
<li><p>Metabolism/metabolic autoregulation</p>
<ul>
<li><p>Linear increase in CBF for any increase in mebtaolism (flow metabolism coupling)</p></li>
<li><p>Controlled by local vasoactive mediators (H+, adenosine, NO)</p></li></ul>
</li>
<li><p>Neurohormonal</p>
<ul>
<li><p>Minimal impact of hormones (e.g. adrenaline) on vessel radius</p></li>
<li><p>Minimal impact of ANS mediated vasoconstriction</p></li></ul>
 
<p></p></li></ul>
</li>
<li><p>Rheological factors</p>
<ul>
<li><p>Minimal effect, does not rapidly change</p></li>
<li><p>Mostly dependant upon HCT</p></li>
<li><p>Increased HCT = increased resistance = reduced blood flow</p></li></ul>
 
<p></p></li>
<li><p>Vessel length</p>
<ul>
<li><p>Would not change = no effect</p></li></ul>
</li></ol>
 
 
 
<span id="examiner-comments-60"></span>
==== Examiner comments ====
 
<blockquote>19% of candidates passed this question. Overall, this question was poorly answered with a high failure rate. A good answer gave a normal value, iterated that CBF is held relatively constant by autoregulation, and proceeded to divide factors affecting CBF into categories with an explanation/description of each. Those factors with the greatest influence were expected to have more accompanying information (e.g., pressure/myogenic autoregulation, metabolic). Systemic factors such as MAP, O2, CO2 were expected to be mentioned with detail of the impact (i.e., key values, relationships demonstrated with a description and/or labelled graph). Local factors within the brain such as H+ concentration/pH, metabolic activity (including the impact of temperature, inclusion of mediators, regional variation based on activity &amp; grey versus white matter) were also expected to be mentioned. Few answers mentioned impact of pH change independently of CO2. Few answers mentioned how CO2 changes the pH of CSF and that over time, this impact is buffered/reduces. The role of the sympathetic nervous system was required to be mentioned although not explored in detail (although many answers overstated the importance of the SNS on CBF or gave a simplistic concept such as increased SNS activity increases CBF). Many answers focussed on descriptions of the Monro-Kelly doctrine and ICP to the exclusion of the aforementioned factors or included detail on factors influencing MAP which were not required (and irrelevant when within the autoregulation range). Many answers were simplistic: e.g., increase MAP increase CPP therefore increase CBF, or by stating CO2/O2 without mentioning a relationship or the limits/patterns of the relationship. Many answers failed to separate the effect of systemic PaO2 and PaCO2 from metabolic autoregulation.
</blockquote>
 
 
<span id="online-resources-for-this-question-60"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2021-paper-1-saqs/question-20#answer-anchor Deranged Physiology]
* [https://jennysjamjar.com.au/year/21a/21a20-outline-the-physiological-factors-that-influence-cerebral-blood-flow/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2021/05/2021-1-20.pdf CICM Wrecks]
* [https://partone.litfl.com/cerebral_blood_flow.html Part One, LITFL]
* [https://ketaminenightmares.com/pex/saqs/physiology/neurophysiology/2021B07_cerebral_blood_flow_regulation.htm Ketamine Nightmares]
 
 
 
<span id="similar-questions-60"></span>
==== Similar questions ====
 
* Question 11, 2009 (1st sitting)
* Question 5, 2008 (1st sitting)
 
 
 
 
 
<span id="2020-2nd-sitting"></span>
== 2020 (2nd sitting) ==
 
 
 
<span id="question-1-4"></span>
=== Question 1 ===
 
 
 
<span id="question-61"></span>
==== Question ====
 
Describe and compare the action potentials from cardiac ventricular muscle cells and the sino-atrial node.
 
 
 
<span id="example-answer-61"></span>
==== Example answer ====
 
 
 
Pacemaker vs myocyte action potential
 
{|
!
! Myocyte
! Pacemaker
|-
| '''Resting potential'''
| -90 mV
| No set RMP but minimum potential is around -60 mV
|-
| '''Threshold potential'''
| -70 mV
| -40 mV
|-
| '''Phases of AP'''
|
|
|-
| '''Phase 4'''
| - Resting membrane potential (-90mV)<br />
- Maintained by inward rectifying K current
| - Slow depolarisation (drift) to threshold (-40mv)<br />
-Funny current Na influx, slowing K efflux
|-
| '''Phase 0'''
| - Rapid depolarisation at threshold (-70mV)<br />
- Fast voltage gated Na opens (influx) &gt; depolarisation<br />
-Peak around +40mV
| - Depolarisation (slower relative) <br />
- L type Ca channels open (influx)<br />
-Peak around +20mV
|-
| '''Phase 1'''
| - Partial repolarisation<br />
- Na close (stops influx), K opens (efflux)
| No Phase 1
|-
| '''Phase 2'''
| - Long Plateau (100-200ms) <br />
- L type Ca channels opens (influx) which balances K efflux
| No phase 2, no plateau
|-
| '''Phase 3'''
| - Rapid repolarisation to membrane potential (~-90mv)<br />
- L type Ca channels close, continued K efflux
| - Rapid repolarisation <br />
-K open (efflux), Ca close (stops influx)
|-
|
|
|
|}
 
[[File:https://derangedphysiology.com/main/sites/default/files/sites/default/files/old image pile/Neurocritical-care/images/comparison of ventricular myocyte and pacemaker action potentials 3.jpg|thumb|none]]
 
[[File:C:\Users\ethan\AppData\Roaming\Typora\typora-user-images\image-20220202114143450.png|image-20220202114143450]][[File:C:\Users\ethan\AppData\Roaming\Typora\typora-user-images\image-20220202114127372.png|image-20220202114127372]]
 
 
 
<span id="examiner-comments-61"></span>
==== Examiner comments ====
 
<blockquote>72% of candidates passed this question.<br />
This question details an aspect of cardiac physiology which is well described in multiple texts. Comprehensive answers included both a detailed description of each action potential and a comparison highlighting and explaining any pertinent differences. The question lends itself to well-drawn, appropriately labelled diagrams and further explanations expressed in a tabular form. Better answers included a comparison table with points of comparison such as the relevant RMP, threshold value, overshoot value, duration, conduction velocity, automaticity, ion movements for each phase (including the direction of movement) providing a useful structure to the table. Incorrect numbering of the phases (0 – 4) and incorrect values for essential information (such as resting membrane potential) detracted from some responses
</blockquote>
 
 
<span id="online-resources-for-this-question-61"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-21#answer-anchor Deranged Physiology]
* [https://jennysjamjar.com.au/year/20b/20b01-describe-and-compare-the-action-potentials-from-cardiac-ventricular-muscle-cells-and-the-sino-atrial-node/ Jenny's Jam Jar]
* [https://ketaminenightmares.com/pex/saqs/physiology/cardiovascular/2016B02_action_potentials_pacemaker_cell_vs_ventricular_myocyte.htm Ketamine Nightmares]
* [https://cicmwrecks.files.wordpress.com/2021/05/2020-2-01.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-61"></span>
==== Similar questions ====
 
* Question 23, 2010 (2nd sitting)
* Question 19, 2013 (1st sitting)
* Question 11, 2016 (2nd sitting)
* Question 21, 2017 (2nd sitting)
 
 
 
 
 
<span id="question-2-4"></span>
=== Question 2 ===
 
 
 
<span id="question-62"></span>
==== Question ====
 
Define functional residual capacity (10% marks). Outline the functions (70% marks) of the functional residual capacity and the factors affecting it (20% marks).
 
 
 
<span id="example-answer-62"></span>
==== Example answer ====
 
 
 
Functional residual capacity
 
* The volume of gas in the lungs at end-expiration during tidal breathing
* Typically ~30mls/kg (or ~2.1L in 70kg adult)
* Sum of the residual volume and expiratory reserve volume
* Represents the point at which the elastic recoil force of lung, and the expanding elastic force of the chest wall are equal
 
 
 
Functions/role of FRC
 
* Oxygen reservoir
** Maintains an oxygen reservoir &gt; maintains oxygenation between breaths / periods of apnoea
** Prevents rapid changes in PaO2
* Maintains small airway patency
** At FRC, the airway resistance is low
** Normally FRC &gt; closing capacity (prevents atelectasis)
* Reduces work of breathing
** At FRC, lung compliance is maximal and airway resistance is low
* Minimises cardiac workload
** At FRC, pulmonary vascular resistance is minimal
* Important starting point for measuring lung volumes
 
 
 
Factors effecting FRC
 
* Lung size
** Increasing lung size = increasing FRC
** Thus affected by
*** Height (Taller FRC &gt; shorter)
*** Age (adult FRC &gt; children)
*** Gender (Male FRC &gt; female)
* Respiratory compliance
** Increase in compliance
*** e.g. emphysema, increased PEEP
*** Leads to increased FRC
** Decrease in compliance
*** E.g. ARDS, obesity, pregnancy
*** Leads to reduction in FRC
* Age (increasing age generally increases FRC)
* Anaesthesia
** Reduces FRC (multifactorial)
* Posture
** FRC decreases when going from erect to supine position
 
 
 
Thus if FRC is reduced we will get
 
* Reduction in
** Lung compliance
** oxygen reserves
** tidal volumes
* Increase in
** airway resistance
** pulmonary vascular resistance
** atelectasis
** work of breathing
** V/Q mismatch
 
 
 
<span id="examiner-comments-62"></span>
==== Examiner comments ====
 
<blockquote>79% of candidates passed this question.<br />
This question was in two parts with the percentage of marks allocated an indication of the relevant time or detail expected per part. The second part of the question also contained two distinct headings which should have been used in the answer. As an outline question, dot points with a brief explanation of each point were expected. Most candidates drew diagrams, few of which added value. For a diagram to add value it should be accurate, have labelled axes, a scale with numerical values and units. As a general rule, diagrams should also be explained and help to illustrate or relate to a written point.<br />
For factors affecting FRC, to score full marks, it should be clearly stated if the factor causes an increase or decrease in FRC. This topic is well covered in the recommended respiratory texts.
</blockquote>
 
 
<span id="online-resources-for-this-question-62"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2020-paper-2-saqs/question-2#answer-anchor Deranged Physiology]
* [https://cicmwrecks.files.wordpress.com/2021/05/2020-2-02.pdf CICM Wrecks]
* [https://ketaminenightmares.com/pex/saqs/physiology/respiratory/2015A09_functional_residual_capacity.htm Ketamine Nightmares]
 
 
 
<span id="similar-questions-62"></span>
==== Similar questions ====
 
* Question 15, 2010 (2nd sitting)
* Question 4, 2015 (2nd sitting)
* Question 8, 2017 (1st sitting)
* Question 24, 2017 (2nd sitting)
 
 
 
<span id="question-3-4"></span>
=== Question 3 ===
 
 
 
<span id="question-63"></span>
==== Question ====
 
Describe the pharmacology of hydrocortisone.
 
 
 
<span id="example-answer-63"></span>
==== Example answer ====
 
{|
! Name
! Hydrocortisone
|-
| '''Class'''
| Glucocorticoid (endogenous)
|-
| '''Indications'''
| Glucocorticoid insufficiency, allergy/anaphylaxis/asthma, severe septic shock, immunosuppression (e.g. transplant, autoimmune dz)
|-
| '''Pharmaceutics'''
| Tablet, white powder diluted in water
|-
| '''Routes of administration'''
| IV, PO
|-
| '''Dose'''
| 50-200mg QID (commonly in ICU population)
|-
| '''Bio-equivalence'''
| 100mg hydrocort = 25mg pred = 20mg methypred = 4mg dex
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Lipid soluble &gt; crosses cell membrane &gt; binds to intracellular steroid receptors &gt; alters gene transcription &gt; metabolic, anti-inflammatory &amp; immunosuppressive effects in tissue-specific manner
|-
| Effects
| CNS: sleep disturbance, psychosis, mood changes<br />
CVS: Increased BP (mineralocorticoid effect + increased vascular smooth muscle receptor expression to catecholamines)<br />
RESP: decreased airway oedema, increased SM response to catecholamines<br />
RENAL: Na + water retention (mineralocorticoid effect)<br />
Metabolic: Hyperglycaemia, gluconeogenesis, protein catabolism, fat lipolysis and redistribution, adrenal suppression<br />
MSK: Osteoporosis, skin thinning<br />
Immune: immunosuppression + anti-inflammatory effects (decreased phospholipase, interleukins, WBC migration and function)<br />
GIT: Increased risk of peptic ulcers<br />
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| Peak effect 1-2 hours, duration of action 8-12 hours
|-
| Absorption
| 50% oral bioavailability
|-
| Distribution
| 90% protein bound, small Vd (0.5L/kg)
|-
| Metabolism
| Hepatic &gt; inactive metabolites
|-
| Elimination
| Metabolites excreted renally. Elimination T/12 = ~1 hour
|-
| '''Special points'''
| Risk of reactivation of latent TB / other infections
|}
 
 
 
<span id="examiner-comments-63"></span>
==== Examiner comments ====
 
<blockquote>69% of candidates passed this question.<br />
Hydrocortisone is a level 1 drug in the syllabus. Most answers were well structured, many used key headings. In general, detailed information specific to hydrocortisone was lacking. Answers that focused on the mechanism of action, pharmacodynamic effects and pharmacokinetics effects which were detailed and accurate scored well. It was expected that significant detail be included in the sections with relevance to clinical practice for example, the mechanism of action and pharmacodynamic effects including the side effect profile. An indication/appreciation of the timelines of such was also represented in the marking template.
</blockquote>
 
 
<span id="online-resources-for-this-question-63"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2021/05/2020-2-03.pdf CICM Wrecks]
* [https://partone.litfl.com/corticosteroids.html Part One, LITFL]
* [https://jennysjamjar.com.au/year/20b/20b03-describe-the-pharmacology-of-hydrocortisone/ CICM Wrecks]
 
 
 
<span id="similar-questions-63"></span>
==== Similar questions ====
 
* Question 10, 2017 (1st sitting)
 
 
 
<span id="question-4-4"></span>
=== Question 4 ===
 
 
 
<span id="question-64"></span>
==== Question ====
 
Outline the role of the liver in the metabolism of fat (â…“ marks), carbohydrate (â…“ marks) and proteins (â…“ marks).
 
 
 
<span id="example-answer-64"></span>
==== Example answer ====
 
 
 
Carbohydrate metabolism
 
* Glycolysis
** Metabolises glucose to generates ATP + pyruvate.
** Pyruvate is converted to Acetyl Coa and enters the TCA cycle (aerobic) or is converted to lactate (anaerobic)
** Catabolic role
* Glycogenesis
** The liver can store up to a 100g of glucose in the form of glycogen
** Stimulated by insulin (released from the pancreas) when BSLs are HIGH
** Anabolic role
* Glycogenolysis
** Liver can mobilise stored glycogen to produce glucose via glycogenolysis
** Stimulated by glucagon (released from pancreas) when BSLs are LOW
** Catabolic role
* Gluconeogenesis
** Liver can synthesise glucose from non-carbohydrate precursors (amino acids, lactate, glycerol)
** Stimulated by glucagon (released from pancreas) when BSLs are LOW
** Anabolic role
 
 
 
Fat metabolism
 
* Lipid breakdown (B oxidation)
** In the liver, free fatty acids undergo B-oxidation to Acetyl CoA
** Acetyl Coa then enables energy production by entering Krebs Cycle
** Catabolic role
* Lipid synthesis
** Lipids, including cholesterol, are synthesised in liver from Acetyl CoA
** Anabolic role
* Lipid processing
** Apolipoproteins are synthesised in the liver and are responsible for processing of VLDL, LDL, HDL
 
 
 
Protein metabolism
 
* Protein synthesis
** Liver is responsible for synthesis of most plasma proteins (except immunoglobulins)
** Anabolic role
* Deamination
** Individual amino acids have their amino groups removed by liver &gt; a keto acids &gt; TCA cycle
** Catabolic role
* Amino acid synthesis
** Keto-acids can be transformed into non-essential amino acids by transamination, forming new amino acids.
* Urea formation
** Ammonia (end product of amino acid degradation) is converted to urea &gt; excretion in urine
 
 
 
<span id="examiner-comments-64"></span>
==== Examiner comments ====
 
<blockquote>54% of candidates passed this question.<br />
This question relates to basic hepatic physiology and is well described in the recommended texts. The mark allocation and division of time was indicated in the question. Better answers used the categorisation in the question as an answer structure. Many candidates gave a good description of beta oxidation, the formation of Acetyl Co A and ketone synthesis. A description of the synthesis of cholesterol, phospholipids, lipoproteins and fatty acid synthesis from proteins and carbohydrates mainly using glycogen, glucose and lactate also received marks. Candidates seem to have a better understanding of fat and glucose metabolism than protein metabolism. Higher scoring candidates appreciated the anabolic and catabolic processes of each component.
</blockquote>
 
 
<span id="online-resources-for-this-question-64"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/20b/20b04-outline-the-role-of-the-liver-in-the-metabolism-of-fat-1%e2%81%843-marks-carbohydrate-1%e2%81%843-marks-and-proteins-1%e2%81%843-marks/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2021/05/2020-2-04.pdf CICM Wrecks]
* Basic Physiology for the Anaesthetist (simplest overview)
 
 
 
<span id="similar-questions-64"></span>
==== Similar questions ====
 
* Question 18, 2015 (1st sitting)
 
 
 
<span id="question-5-4"></span>
=== Question 5 ===
 
 
 
<span id="question-65"></span>
==== Question ====
 
Describe the anatomy (70% marks) and effects (30% marks) of the sympathetic nervous system.
 
 
 
<span id="example-answer-65"></span>
==== Example answer ====
 
 
 
Sympathetic nervous system (SNS)
 
* Portion of the autonomic nervous
* Provides involuntary control of many bodily functions
 
 
 
Anatomy of SNS
 
* Preganglionic component
** Short, myelinated, preganglionic neurons
** Originate in the lateral horn of the spinal cord between T1 and L3 (thoracolumbar outflow)
** Travel via ventral roots and white rami communicantes to synapse in the ganglia
** Neurotransmitter is acetylcholine &gt; nicotinic receptor
* Ganglionic component
** Two types (prevertebral ganglia and paravertebral ganglia)
*** Paravertebral ganglia form the two sympathetic chains which extend along the vertebral column
*** Prevertebral ganglia are located in abdominal cavity around branches of aorta (e.g.. coeliac ganglia)
** Preganglionic neurons can synapse at ganglia above, below, at same level or directly to prevertebral ganglia
* Post ganglionic component
** Long, unmyelinated, postganglionic neurons
** Leave the ganglia through the grey matter communicantes &gt; effector tissue/organ
** Neurotransmitter is noradrenaline &gt; adrenergic receptor
** There are exceptions e.g. Adrenal medulla: directly innervated by preganglionic neurons (ACh)
 
 
 
Effects of SNS
 
{|
! Organ
! SNS
|-
| Heart
| Increased chronotropy (B1) and inotropy (B1), increased lusitropy
|-
| Arterioles
| Vasoconstrict (a1, a2)
|-
| Lung
| Bronchodilation (B2)
|-
| GIT
| Inhibition of peristalsis (predominately a1,a2)
|-
| Liver
| Glycogenolysis (B2)
|-
| Renal
| Increased renin release (B1)
|-
| Pupils
| Dilation (a1)
|-
| Salivary glands
| Inhibition of salivation
|-
| Adrenal gland
| Release of norad and adrenaline
|-
| Bladder
| Detrusor relaxation (B2), sphincter contraction (a1)
|-
| Sweat gland
| Sweat (ACh)
|}
 
 
 
<span id="examiner-comments-65"></span>
==== Examiner comments ====
 
<blockquote>51% of candidates passed this question.<br />
Most candidates had a suitable structure to their answers, those without a clear organisation of thought tended to gain fewer marks. In many cases incorrect information or limited detail, particularly around the anatomical organisation prevented higher marks.
</blockquote>
 
 
<span id="online-resources-for-this-question-65"></span>
==== Online resources for this question ====
 
* [https://www.kenhub.com/en/library/anatomy/sympathetic-nervous-system Kenhub - best source]
* [https://cicmwrecks.files.wordpress.com/2021/05/2020-2-05.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/20b/20b05-describe-the-anatomy-70-marks-and-effects-30-marks-of-the-sympathetic-nervous-system/ Jennys Jam Jar]
* [https://partone.litfl.com/autonomic_nervous_system.html Part One, LITFL]
 
 
 
<span id="similar-questions-65"></span>
==== Similar questions ====
 
* Question 17, 2013 (2nd sitting)
* Question 20, 2015 (1st sitting)
 
 
 
 
 
<span id="question-6-4"></span>
=== Question 6 ===
 
 
 
<span id="question-66"></span>
==== Question ====
 
Classify the oral hypoglycaemic drugs (20% marks); include their mechanism of action (40% marks) and their most significant side effects (40% marks).
 
 
 
<span id="example-answer-66"></span>
==== Example answer ====
 
 
 
Hypoglycaemic agents
 
{|
! Drug class
! Example
! Mechanism of action
! Important side effects
|-
| '''Commonly used'''
|
|
|
|-
| Biguanides
| Metformin
| Multiple mechanisms of action.<br />
1) Inhibits hepatic+renal gluconeogenesis<br />
2) increases insulin sensitivity (increases GLUT4 receptors to increase peripheral utilisation),<br />
3) Delayed glucose uptake from GIT
| Lactic acidosis (higher risk with renal/liver impairment) due to increased glycolysis and impaired gluconeogenesis leading to lactatemia<br />
GIT upset (diarrhoea, nausea, vomiting)
|-
| Sulfonylureas
| Gliclazide
| Increase insulin secretion from pancreatic B cells , reduce insulin sensitivity
| Risk of hypoglycaemia, GIT upset, blood dyscrasias
|-
| DPP-4 inhibitors
| Sitagliptin
| Inhibit DPP-4 (which normally breaks down GLP-1). GLP-1 stimulates insulin release from pancreas, reduces appetite, delays gastric emptying
| Risk of hypoglycaemia<br />
Risk of pancreatitis
|-
| SGLT-2 inhibitors
| Empagliflozin
| Inhibits SGLT-2 receptors &gt; decrease glucose reabsorption in the PCT
| Osmotic diuresis (Polyuria, polydipsia, dehydration), euglycemic diabetic ketoacidosis, risk of hypoglycaemia, UTIs
|-
| '''Not commonly used'''
|
|
|
|-
| Alpha glucosidase inhibitors
| Acarbose
| Slows/prevents carbohydrate breakdown and absorption
| GIT upset
|-
| Thiazolidineodiones
| Pioglitazone
| Increases insulin sensitivity via PPAR receptors in fat cells
| Increased risk of heart failure
|-
| Meglitinides
| Repaglinide
| Similar to sulfonureas, though different receptor
| Hypoglycaemia, sig. interaction with antifungals &gt; high levels &gt; hypos
|}
 
 
 
GLP-1 agonists
 
* Commonly given S/C
* New oral agents are becoming available - not yet widely used in AUS
 
 
 
<span id="examiner-comments-66"></span>
==== Examiner comments ====
 
<blockquote>37% of candidates passed this question.<br />
High scoring answers most often started with a strong and logical structure and focused on the requested categories of information. Many candidates gave good answers across the wide range of drugs. Several candidates could have scored more highly by giving more correct information on biguanides and sulphonylureas.
</blockquote>
 
 
<span id="online-resources-for-this-question-66"></span>
==== Online resources for this question ====
 
* [https://icuprimaryprep.files.wordpress.com/2015/01/q6-classify-the-oral-hypoglycaemic-drugs_-include-their-mechanism-of-action-and-their-most-significant-side-effects-march-2013.pdf ICU Primary Prep]
* [https://cicmwrecks.files.wordpress.com/2021/05/2020-2-06.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-66"></span>
==== Similar questions ====
 
* Question 6, 2013 (1st sitting)
 
 
 
 
 
<span id="question-7-4"></span>
=== Question 7 ===
 
 
 
<span id="question-67"></span>
==== Question ====
 
Compare and contrast external ventricular drains and intraparenchymal fibreoptic pressure monitors.
 
 
 
<span id="example-answer-67"></span>
==== Example answer ====
 
{|
!
! External ventricular drain (EVD)
! intraparenchymal catheter (e.g. codman)
|-
| Location/anatomy
| Sits in the lateral ventricle. Inserted 2-3cm lateral midline ~10cm posterior to the nasion (Kochers point) aiming away from motor cortex
| Sits in the brain parenchyma (2cm depth)
|-
| Method of measurement
| Pressure transmitted to wheatstone bridge via fluid filled non compressible tubing.
| Pisoelectric strain gauge pressure sensor, connected to monitor via fibreoptic cable
|-
| Calibration
| Yes, can be zero'd post insertion to atmosphere
| No, cannot be zeroed post insertion
|-
| Diagnostic (ICP)
| Yes, gold standard.
| Yes
|-
| Diagnostic (CSF sample)
| Yes, can sample CSF
| No, cannot sample CSF
|-
| Therapeutic<br />
(drain CSF)
| Yes
| No, cannot drain CSF
|-
| Sources of error
| Migration of catheter tip, blockage of EVD, incorrect levelling to tragus, damping/resonance
| Drift, only measures local ICP (not global ICP)
|-
| Advantages
| Diagnostic (CSF sample, ICP) and therapeutic (high ICP), can be re-zeroed, cheaper
| Easier to insert with less expertise, less complications (infection, haemorrhage)
|-
| Disadvantages
| Increased risk of: trauma, infection, misplacement
| Decreased risk of trauma, infection, haemorrhage. Not therapeutic. Cannot be recalibrated and prone to drift. More expensive. measures local ICP only
|}
 
 
 
<span id="examiner-comments-67"></span>
==== Examiner comments ====
 
<blockquote>22% of candidates passed this question.<br />
This question is ideally suited to a tabular format, where candidates are expected to highlight the significant similarities and differences as well as why a certain monitor may be chosen in preference to another rather than compile two lists written next to each other. To score well in this question, a statement of what could be measured (ICP: global vs local), a description of the measurement principles, along with other measurement related information like calibration and sources of error was required. Also sought was information regarding anatomical placement (e.g., lateral ventricle for EVD) and method of placement.<br />
Furthermore, a comparison with each other (e.g., higher infection/bleeding risk with EVD, greater risk of trauma due to size and insertion, expertise to insert, cost, therapeutic benefit, risk of blocking) was required for completion. Candidates who structured these elements into advantages and disadvantages were generally able to elucidate this information and score better.
</blockquote>
 
 
<span id="online-resources-for-this-question-67"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/20b/20b07-compare-and-contrast-external-ventricular-drains-and-intraparenchymal-fibreoptic-pressure-monitors/ Jennys Jam Jar]
* [chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/viewer.html?pdfurl=https%3A%2F%2Fcicmwrecks.files.wordpress.com%2F2021%2F05%2F2020-2-07.pdf&clen=256304&chunk=true CICM Wrecks]
* [https://derangedphysiology.com/main/cicm-fellowship-exam/past-papers/2010-paper-1-saqs/question-8#answer-anchor Deranged Physiology]
 
 
 
<span id="similar-questions-67"></span>
==== Similar questions ====
 
* ?None so far as I can tell
 
 
 
 
 
<span id="question-8-4"></span>
=== Question 8 ===
 
 
 
<span id="question-68"></span>
==== Question ====
 
Describe the cough reflex.
 
 
 
<span id="example-answer-68"></span>
==== Example answer ====
 
 
 
Cough
 
* Complex, sudden expulsion of air from the airways
** Can voluntarily cough, however the cough reflex = involuntary
 
 
 
Purpose of cough reflex
 
* Airway protective function
** Helps clear foreign material/noxious stimuli from the airway
* N.B: Useful clinically in brain death testing
 
 
 
COUGH REFLEX
 
 
 
Sensors
 
* Rapidly adapting mechanoreceptors, slowly adapting mechanoreceptors, and c-fibres
 
 
 
Stimulus for cough
 
* Chemical, mechanical, noxious stimuli in the airways (larynx, trachea, carina, bronchi)
** e.g. leukotrienes, histamine, bradykinin, foreign bodies
 
 
 
Afferents
 
* Afferents from the internal laryngeal nerve (br. of vagus nerve)
 
 
 
Integrator/controller
 
* Vagal afferents synapse in the medullary respiratory centre (NTS)
 
 
 
Efferents
 
* Diaphragm (via phrenic nerve)
* Abdominal muscles (via spinal motor nerves)
* Larynx (via laryngeal branch of vagus nerve)
 
 
 
Effector / mechanism
 
<ul>
<li><p>Coordinated action of respiratory, pharyngeal, abdominal muscles</p></li>
<li><p>Phase 1: inspiratory phase</p>
<ul>
<li><p>Deep inspiration to near vital capacity (muscles of inspiration, including diaphragm)</p></li></ul>
</li>
<li><p>Phase 2: compressive phase</p>
<ul>
<li><p>Closure of the cords+epiglottis, contraction of the abdominal and intercostal muscles </p></li>
<li><p>Leads to dramatic rise in intrapleural pressure (&gt;100cmH<sub>2</sub>O)</p></li></ul>
</li>
<li><p>Phase 3: expulsive phase</p>
<ul>
<li><p>Sudden ''partial'' opening of the cords and epiglottis </p></li>
<li><p>Leads to ''violent'' expiration of turbulent air removing foreign material</p></li></ul>
 
<p></p></li></ul>
 
<span id="examiner-comments-68"></span>
==== Examiner comments ====
 
<blockquote>62% of candidates passed this question.<br />
Overall, this question was reasonably well answered. Those that performed well had suitably detailed knowledge and structured their responses which generally included a definition and purpose of the reflex as well as the identification and a description of the afferent, integrator/controller, and efferent limbs of the reflex. This structure allowed a logical platform for the elucidation of the detail required in the answer, including types of stimulus, receptors, nerves (for both limbs of the reflex) and the muscles used in the phasic response to be clearly articulated.
</blockquote>
 
 
<span id="online-resources-for-this-question-68"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/main/cicm-primary-exam/required-reading/respiratory-system/Chapter%200204/pathways-and-importance-cough-reflex Deranged Physiology]
* [https://jennysjamjar.com.au/year/20b/20b08-describe-the-cough-reflex/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2021/05/2020-2-08.pdf CICM Wrecks]
* [https://partone.litfl.com/cough_reflex.html Part One, LITFL]
 
 
 
<span id="similar-questions-68"></span>
==== Similar questions ====
 
<ul>
<li><p>Question 13, 2014 (1st sitting)</p></li>
<li><p>Question 8, 2020 (2nd sitting) of the Fellowship exam</p>
<p></p></li></ul>
 
 
 
<span id="question-9-4"></span>
=== Question 9 ===
 
 
 
<span id="question-69"></span>
==== Question ====
 
Outline the daily nutritional requirements, including electrolytes, for a normal 70 kg adult.
 
 
 
<span id="example-answer-69"></span>
==== Example answer ====
 
 
 
Energy intake
 
* Most guidelines recommend around 25-30 kcal/kg of energy / day
** Approx 2000 kcal / day for average adult
* Met with a combination of carbohydrates, protein, fats
* Critically unwell patients, may need more due to increased energy expenditure.
 
 
 
Carbohydrates
 
* Preferred substate for energy production
* Average intake (adult) ~350g / day
** Minimum recommended intake &gt;2g.kg.day
* 1g carbs = 4 kCal energy
 
 
 
Fats
 
* Provides essential fatty acids (e.g. Omega 6 + 3 fatty acids)
* Essential for synthesis of cell membranes and for fat soluble vitamins (A,D,E,K)
* Recommended intake = 1g.kg.day (i.e. ~70g / day)
* 1g fat = 9kCal energy
* Ideal carb : fat ratio not empirically known, but in practice we use ~70:30
 
 
 
Protein
 
* Replaces essential amino acids (e.g. phenylalanine, valine, leucine) which cannot be produced in vivo
* Recommended intake (healthy adult) = 1g.kg.day
** Critically ill patients will need more (1.5- 2g.kg.day - i.e. 100-140g/day)
* 1g protein = 4 kCal energy
* Not typically included in the resting energy expenditure
 
 
 
Water / electrolytes
 
* Water: 30ml/kg/day
* Sodium: 1-2mmol/kg/day
* Potassium: 1mmol/kg/day
* Calcium: 0.1mmol/kg/day
* Magnesium: 0.1 mmol/kg/day
* Phosphate 0.4mmol/kg/day
 
 
 
Vitamins
 
<ul>
<li><p>Organic compounds that the body is unable to synthesise, though needs for cellular function</p>
<ul>
<li><p>Commonly enzyme cofactors, antioxidants, metabolic regulators</p></li>
<li><p>Required in small amounts</p></li></ul>
</li>
<li><p>Fat soluble</p>
<ul>
<li><p>A,D,E,K</p></li>
<li><p>Excessive intake &gt; toxicity</p></li>
<li><p>Stored largely in liver</p></li></ul>
</li>
<li><p>Water soluble</p>
<ul>
<li><p>E.g. vitamin C, B1, nicotinic acid, B12, folate</p></li>
<li><p>Not readily stored - readily excreted in urine &gt; less likely to be toxic</p></li></ul>
 
<p></p></li></ul>
 
Trace elements
 
* E.g. zinc, copper, iron, selenium, iodine
* Needed for daily functioning in trace amounts
 
 
 
<span id="examiner-comments-69"></span>
==== Examiner comments ====
 
<blockquote>40% of candidates passed this question.<br />
This topic is well covered in the recommended physiology textbooks. Many answers unfortunately simply listed the various components without providing sufficient detail; outline questions require some context around the key points as opposed to just a list.<br />
Most candidates had a good estimate for the basal energy requirements of a resting adult. Good candidates were able to outline the g/kg daily protein requirements and the distribution of remaining energy intake between carbohydrates and lipids and included how this may change during periods of stress. They also stated the energy derived per gram of each of those food groups. Few candidates mentioned the need to include essential amino acids. Similarly, with fat intake, few candidates mentioned the need for essential fatty acids. A definition of “vitamin” would have received credit. Most candidates were able to classify vitamins as water soluble or fat soluble. Most candidates mentioned trace elements (with an abbreviated list) and mentioned bone minerals. A daily intake requirement for Na and K was expected, though not for bone minerals or trace elements.
</blockquote>
 
 
<span id="online-resources-for-this-question-69"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/20b/20b09-outline-the-daily-nutritional-requirements-including-electrolytes-for-a-normal-70-kg-adult/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2021/05/2020-2-09.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-69"></span>
==== Similar questions ====
 
* Question 2, 2017 (2nd sitting)
 
 
 
 
 
<span id="question-10-4"></span>
=== Question 10 ===
 
 
 
<span id="question-70"></span>
==== Question ====
 
Describe the pharmacology of suxamethonium.
 
 
 
<span id="example-answer-70"></span>
==== Example answer ====
 
{|
! Name
! Suxamethonium (succinylcholine)
|-
| '''Class'''
| Depolarising muscle relaxant
|-
| '''Indications'''
| Facilitate endotracheal intubation during anaesthesia (i.e. RSI)
|-
| '''Pharmaceutics'''
| Clear colourless solution (50mg/ml), needs refrigeration (4°C) or else lasts only a couple of weeks at room temp
|-
| '''Routes of administration'''
| IV, IM
|-
| '''Dose'''
| 1-2 mg/kg (IV), 2-3 mg/kg (IM)
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Binds to the nACh receptor on motor end plate &gt; depolarisation. Cannot be hydrolyed by Acetylcholinesterase in NMJ &gt; sustained depolarisation (i.e. Na channels remain in open-inactive state) &gt; muscle relaxation
|-
| Effects
| Flaccid paralysis.
|-
| Side effects
| Major: anaphylaxis, suxamethonium apnoea, malignant hyperthermia<br />
Minor: hyperkalaemia, myalgia, bradycardia/arrhythmia<br />
Pressure: increased IOP, ICP, intragastric pressure.
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| Onset 30s - 60s, duration &lt;10 mins
|-
| Absorption
| -
|-
| Distribution
| 30% protein bound<br />
Vd = 0.02 L/Kg
|-
| Metabolism
| Rapid hydrolysis by plasma cholinesterase's (~20% reaches NMJ)
|-
| Elimination
| Minimal renal elimination (due to rapid metabolism)
|-
| '''Special points'''
| May have prolonged duration of action with congenital or acquired (e.g. liver, renal, thyroid disease) pseudocholinesterase deficiency <br />
Treatment of malignant hyperthermia is with dantrolene (+ cooling + supportive care)
|}
 
 
 
<span id="examiner-comments-70"></span>
==== Examiner comments ====
 
<blockquote>63% of candidates passed this question.<br />
This was a level 1 pharmacology question, and it represents core knowledge. The mechanism of action of suxamethonium and the interactions at the neuromuscular junction as well as pharmaceutics were areas that often required further detail. Few candidates mentioned the effects of suxamethonium on the autonomic nervous system. Another common omission related to the factors that reduce plasma cholinesterase activity beyond genetic deficiency (such as liver disease, renal failure, thyrotoxicosis). Pleasingly, there was generally a good understanding of role, dosing, side effect profile, pharmacokinetics and of special situations and limitations of use pertinent to this drug.
</blockquote>
 
 
<span id="online-resources-for-this-question-70"></span>
==== Online resources for this question ====
 
<ul>
<li><p>[https://partone.litfl.com/depolarising_nmbs.html Part One, LITFL]</p></li>
<li><p>[https://jennysjamjar.com.au/year/20b/20b10-describe-the-pharmacology-of-suxamethonium/ Jennys Jam Jar]</p></li>
<li><p>[https://cicmwrecks.files.wordpress.com/2021/05/2020-2-10.pdf CICM Wrecks]</p></li>
<li><p>[https://ketaminenightmares.com/pex/saqs/pharmacology/muscle_relaxants/2018B04_suxamethonium_vs_rocuronium.htm Ketamine Nightmares]</p>
<p></p></li></ul>
 
<span id="similar-questions-70"></span>
==== Similar questions ====
 
* Question 6, 2011 (1st sitting)
* Question 2, 2012 (2nd sitting)
* Question 1, 2013 (2nd sitting)
* Question 10, 2018 (1st sitting)
* Various other questions relating to properties of NMB more broadly
 
 
 
 
 
<span id="question-11-4"></span>
=== Question 11 ===
 
 
 
<span id="question-71"></span>
==== Question ====
 
Describe the changes in the circulatory system that occur during exercise.
 
 
 
<span id="example-answer-71"></span>
==== Example answer ====
 
 
 
Exercise
 
* Leads to increased oxygen demand (predominately skeletal muscle) and increased metabolic waste products which need to be cleared
* Leads to many circulatory changes:
 
 
 
Cardiac output
 
* Increased oxygen demand &gt; increased CO (as CO is the main modifiable component of the oxygen delivery equation - Hb, Sats, PaO2 not readily changeable)
* Most of the increased CO goes to skeletal muscle beds
* Due to a combination of increased HR/SV
* Increases 5-6x - from 5L/min up to 30L/min
 
 
 
Heart rate
 
* Increased HR due to SNS mediated chronotropy
* Max = 220-age
 
 
 
Stroke volume
 
* Increased SV initially is due to
** Reduced afterload (skeletal muscle vasodilation &gt; decreased peripheral vascular resistance)
** Increased preload (peripheral venoconstriction &gt; increased venous return)
** SNS mediated inotropy
 
<ul>
<li><p>With increasing HR, SV will begin to decrease (due to reduced diastolic filling time)</p>
<ul>
<li><p>Plateaus at ~50% VO2max</p>
<p></p></li></ul>
</li></ul>
 
Redistribution of blood flow
 
* Vasodilation in skeletal muscle beds
** Mediated by local factors (hypoxia, CO2, Lactate, adenosine) which lead to vasodilation (to decrease resistance, thus increase blood flow)
** Also mediated by autonomic factors: SNS activation &gt; B2 stimulation &gt; vasodilation
* Vasoconstriction of non working tissues
** SNS mediated vasoconstriction of GIT, Kidneys &gt; blood flow directed to &quot;working tissues&quot;
* Coronary blood flow
** Increases by metabolic autoregulation due to increased demand from increased inotropy/chronotropy
* Cerebral blood flow
** Remains constant (autoregulation) - no increase in metabolic demand. Increased BP &gt; myogenic vasoconstriction.
 
 
 
Increased oxygen extraction
 
* Increased CO<sub>2</sub> and H+ and temperature in working skeletal muscle beds &gt; right shift of the oxygen-Hb dissociation curve &gt; increased O2 extraction (Bohr effect)
 
 
 
Blood pressure/s
 
* Increased SBP (due to increased inotropy &gt; increased CO)
* Decreased DBP (due to reduced SVR from skeletal vasodilation)
* Widened pulse pressure (increased SBP, decreased DBP)
* Overall increase in MAP (increase in CO is greater than reduction in PVR)
 
 
 
Other haemodynamics
 
* Increased venous return &gt; increased CVP and PCWP
 
 
 
<span id="examiner-comments-71"></span>
==== Examiner comments ====
 
<blockquote>22% of candidates passed this question.<br />
This is an applied physiology question. Better answers categorised the changes in some manner and included a measure of the degree of change as applicable (e.g., what increases, what decreases and what may stay the same). The question was to describe the changes so that the detail behind the mechanisms enabling these changes to occur was expected (e.g., neurohumoral, local factors). Marks were also awarded for any regional variation that occurs
</blockquote>
 
 
<span id="online-resources-for-this-question-71"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2021/05/2020-2-11.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/20b/20b11-describe-the-changes-in-the-circulatory-system-that-occur-during-exercise/ Jennys Jam Jar]
* [https://derangedphysiology.com/main/cicm-primary-exam/required-reading/cardiovascular-system/Chapter%20504/cardiovascular-response-exercise Deranged Physiology]
 
 
 
<span id="similar-questions-71"></span>
==== Similar questions ====
 
* ? none
 
 
 
 
 
<span id="question-12-4"></span>
=== Question 12 ===
 
 
 
<span id="question-72"></span>
==== Question ====
 
Describe the physiology (50% marks) and pharmacology (50% marks) of albumin.
 
 
 
<span id="example-answer-72"></span>
==== Example answer ====
 
 
 
Albumin physiology
 
* Structure
** Human plasma protein
** 69kDa
* Synthesis
** Synthesised in the liver (~10-15g/day)
** Decreased synthesis: liver disease, protein malnutrition, sepsis/infection (prioritises other Acute Phase Reactants)
* Distribution
** Accounts for ~50% plasma proteins
** 40% intravascular, 60% extravascular (skin, muscle, liver)
* Functions
** Osmotic pressure - accounts for majority (80%) of plasma oncotic pressure
** Transport / drug binding (mainly acidic drugs)
** Acid-base buffer (protein-buffering system)
** Detoxification role
* Breakdown
** Broken down by cysteine protease into amino acids
** Half life ~20 days
* Elimination
** Elimination half life 16 hours
** Increased loss with renal dysfunction (e.g. nephropathy)
 
 
 
Albumin Pharmacology
 
{|
! Name
! Albumin
|-
| '''Class'''
| colloid (human plasma protein)
|-
| '''Indications'''
| Intravascular volume replacement, low albumin, hepatorenal syndrome, SBP
|-
| '''Pharmaceutics'''
| 4% or 20% concentrations. Hypotonic <br />
-Collected by blood donation (whole blood, plasma apheresis) &gt; fractionated &gt; pasteurised &gt; partitioned &gt; stored.
|-
| '''Routes of administration'''
| IV
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Related to volume of fluid (i.e. volume expansion) and role of albumin (oncotic, transport, etc)
|-
| Side effects
| No risk of bacteria/parasite infections (destroyed during processing), but risk of blood borne viruses (HIV, HepB, HCV) remains.<br />
Allergy, fluid overload.
|-
| '''Pharmacokinetics'''
|
|-
| Absorption
| IV only (0% oral bioavailability)
|-
| Distribution
| Rapid distribution within intravascular space. <br />
Small Vd - about 5% leaves per hour
|-
| Metabolism
| Cellular proteolysis by cysteine protease
|-
| Elimination
| Degradation by liver and reticuloendothelial system
|-
| '''Special points'''
| - May worsen outcomes in TBI<br />
- No need for blood cross matching
|}
 
 
 
<span id="examiner-comments-72"></span>
==== Examiner comments ====
 
<blockquote>19% of candidates passed this question.<br />
The question required an equal treatment of the physiology and pharmacology of albumin. The physiology discussion needed to include synthesis, factors affecting synthesis, distribution in the body (including the proportion divided between the plasma and interstitial space), functions, breakdown, and elimination half-life. Discussion of the pharmacology should have included available preparations (4% and 20% Albumin) and pharmaceutics, distribution, elimination (both the protein and crystalloid components), mechanism of action to expand the plasma compartment, longevity in the plasma compartment, indications, and adverse effects. Oedema, circulatory overload, immunological reactions, and relative contraindication in brain injury were important to mention. There was some confusion regarding the infectious risks of albumin. An outline of the manufacturing process from donated plasma and pasteurisation was expected.
</blockquote>
 
 
<span id="online-resources-for-this-question-72"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/required-reading/haematological-system/Chapter%20337/physiology-and-pharmacology-albumin Deranged Physiology]
* [https://jennysjamjar.com.au/year/20b/20b12-describe-the-physiology-50-marks-and-pharmacology-50-marks-of-albumin/ Jennys Jam Jar]
* [chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/viewer.html?pdfurl=https%3A%2F%2Fcicmwrecks.files.wordpress.com%2F2021%2F05%2F2020-2-12.pdf&clen=247533&chunk=true CICM Wrecks]
 
 
 
<span id="similar-questions-72"></span>
==== Similar questions ====
 
* Question 1, 2015 (2nd sitting)
* Question 1, 2009 (2nd sitting)
 
 
 
<span id="question-13-4"></span>
=== Question 13 ===
 
 
 
<span id="question-73"></span>
==== Question ====
 
Describe the anatomical (20% marks) and physiological (80% marks) features of the pulmonary circulation.
 
 
 
<span id="example-answer-73"></span>
==== Example answer ====
 
 
 
Anatomical features (pulmonary circulation)
 
* Low pressure, low resistance, high capacitance, high flow system
** Thus --&gt; vessel walls are highly elastic + have less muscle + much thinner than systemic circulation
* Circulation
** RV &gt; Pulmonary trunk &gt; R/L pulmonary artery &gt; progressively smaller pulmonary arteries &gt; capillaries &gt; progressively larger pulmonary veins &gt; pulmonary veins x4 &gt; LA
** Arteries and veins travel with respective bronchi, nerves and lymphatics in bronchovascular bundle
 
 
 
Physiological features (pulmonary circulation)
 
<ul>
<li><p>Low pressure system</p>
<ul>
<li><p>Normal PA</p>
<ul>
<li><p>Systolic pressure 15-25mmHg</p></li>
<li><p>Diastolic pressure 8-15mmHg</p></li>
<li><p>Mean pressure 10-15mmHg</p></li></ul>
</li>
<li><p>Pulmonary venous pressure ~8-10mmHg</p></li></ul>
</li>
<li><p>Low resistance system</p>
<ul>
<li><p>~100-200dynes/sec/cm-5 </p></li>
<li><p>~10% of systemic circulation</p></li>
<li><p>With further flow (e.g. increased CO during exercise) can maintain low resistance by recruitment of additional capillaries </p></li></ul>
</li>
<li><p>High flow system</p>
<ul>
<li><p>Pulmonary arterial flow = cardiac output</p></li>
<li><p>Needs capacity to expand (highly elastic) with increasing CO</p></li></ul>
</li>
<li><p>Volume</p>
<ul>
<li><p>Contains ~10% circulating blood volume (~500mls)</p></li>
<li><p>Has capacity to expand (highly elastic, recruit additional capillaries)</p></li></ul>
</li>
<li><p>Regional distribution of blood flow</p>
<ul>
<li><p>Right lung receives 55% CO, left lung 45% CO</p></li>
<li><p>Flow distributed according to hydrostatic and alveolar pressure (west zones)</p></li>
<li><p>Hypoxic pulmonary vasoconstriction can redirect blood flow away from poorly ventilated regions</p></li></ul>
</li>
<li><p>Regulation</p>
<ul>
<li><p>Minimal capacity to self regulate (except for hypoxic vasoconstriction) with weak autonomic activity</p></li>
<li><p>Response to hypoxia: vasoconstriction</p></li>
<li><p>Response to hypercapnia: vasoconstriction</p></li></ul>
</li>
<li><p>Functions</p>
<ul>
<li><p>Main function is gas exchange: Absorbs O2, releases Co2</p></li>
<li><p>Other functions: filtration clots/debris, source of ACE, metabolism of PGs</p></li></ul>
 
<p></p></li></ul>
 
<span id="examiner-comments-73"></span>
==== Examiner comments ====
 
<blockquote>25% of candidates passed this question.<br />
The examiners consider that an understanding of the pulmonary circulation is core area of the syllabus. In general, the anatomy section was better answered than the physiological features. As well as a description of the gross anatomy of the pulmonary circulation tracking it from the pulmonary valve to the left atrium, some mention of the microscopic anatomy was required (e.g., that the pulmonary arteries are thin walled with little smooth muscle).<br />
For the second part of the question, a breadth of knowledge was required. Candidates were expected to address the following physiological features of the pulmonary circulation: volume, pressure, resistance, regulation and regional distribution and function. Marks were apportioned to each section, so it was important to write something on each section. Focussing on one section in detail (e.g., a very detailed description of West’s Zones) usually came at the expense of missing one or more of the other sections, most commonly the functions of the pulmonary circulation. Indeed, candidates that scored well provided information on each section and for the functions of the pulmonary circulation mentioned more than gas exchange.
</blockquote>
 
 
<span id="online-resources-for-this-question-73"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2021/05/2020-2-13.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/20b/20b13-describe-the-anatomical-20-marks-and-physiological-80-marks-features-of-the-pulmonary-circulation/ Jenny's Jam Jar]
* [https://derangedphysiology.com/main/cicm-primary-exam/required-reading/respiratory-system/Chapter%20062/physiological-characteristics-pulmonary-blood-vessels Deranged Physiology] and [https://derangedphysiology.com/main/cicm-primary-exam/required-reading/respiratory-system/Chapter%200112/anatomy-pulmonary-and-bronchial-circulation Deranged Physiology]
 
 
 
<span id="similar-questions-73"></span>
==== Similar questions ====
 
* Question 7, 2017 (1st sitting)
 
 
 
 
 
<span id="question-14-4"></span>
=== Question 14 ===
 
 
 
<span id="question-74"></span>
==== Question ====
 
Describe the anatomy of the larynx.
 
 
 
<span id="example-answer-74"></span>
==== Example answer ====
 
* General anatomy
** Located at the levels of C3- C6
** Serves as a connection between the oropharynx and the trachea
** Lined by pseudostratified columnar ciliated epithelium below cords, stratified square epithelium above
* General functions
** Respiration (conductive airway)
** Swallowing and protection of airway from GI tract
** Phonation
** Cough reflex
* Cartilages
** 3 Paired: arytenoid, corniculate, cuneiform
** 3 unpaired: thyroid, cricoid, epiglottis
* Extrinsic muscles
** Infrahyoid and suprahyoid muscles
** move the larynx as a whole (elevates, depresses)
* Intrinsic muscles
** Move individual laryngeal components
** Grouped into: adductors/abductors (e.g. cricoarytenoids, oblique arytenoids), tensors/relaxors (e.g. cricothyroid, thyroarytenoid) and the vocalis muscle (minute adjustments vocal cord)
* Vocal ligament
** Attaches to thyroid cartilage (ant) to arytenoid cartilage (post)
** Opening forms the Rima Glottis
** Produces phonation
* relations
** Skin/fascia (anterior)
** Thyroid gland (anterior, lateral and inf.)
** pharynx/oesophagus (posterior)
** Carotid arteries (lateral), jugular veins (lateral)
** Vagus and laryngeal nerves (lateral)
* Innervation
** Motor: All laryngeal muscles are supplied by the RLN except the cricothyroid which is supplied by the External branch of the superior laryngeal nerve
** Sensory: internal branch of the superior laryngeal nerve (above cords), RLN (below cords)
* Arterial supply
** Upper half: Superior laryngeal artery (br. from the superior thyroid artery)
** Lower half: Inferior laryngeal artery (br. of the inferior thyroid artery)
* Venous drainage
** Superior and inferior laryngeal veins which drain into respective thyroid veins
* Lymphatics
** Above the vocal cords: superior deep cervical LNs
** Below the vocal cords: inferior deep cervical LNs
 
 
 
<span id="examiner-comments-74"></span>
==== Examiner comments ====
 
<blockquote>40% of candidates passed this question.<br />
For this question, candidates were expected to address the location of the larynx, its relations, the cartilages (single and paired), ligaments, muscles (intrinsic and extrinsic), innervation (sensory and muscular) and blood supply (including venous drainage). Marks were apportioned to each section, so whilst some detail was required, breadth of knowledge was also important. Most candidates had a grasp of the gross anatomy, the main relations and at least the innervation provided by the recurrent laryngeal nerve. However, an understanding of the functional anatomy of the cartilages was not always apparent. It should be noted that not every single muscle needed to be named (especially for the extrinsic muscles), but an understanding of the major muscle groups should have been included
</blockquote>
 
 
<span id="online-resources-for-this-question-74"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/20b/20b14-outline-the-anatomy-of-the-larynx/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2021/05/2020-2-14.pdf CICM Wrecks]
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2020-paper-2-saqs/question-14#answer-anchor Deranged Physiology]
 
 
 
<span id="similar-questions-74"></span>
==== Similar questions ====
 
* Question 24, 2015 (1st sitting)
 
 
 
 
 
<span id="question-15-4"></span>
=== Question 15 ===
 
 
 
<span id="question-75"></span>
==== Question ====
 
Compare and contrast the pharmacology of dobutamine and levosimendan.
 
 
 
<span id="example-answer-75"></span>
==== Example answer ====
 
{|
! Name
! Dobutamine
! Levosimendan
|-
| '''Class'''
| Synthetic catecholamine (inodilator)
| Calcium sensitizer (Inodilator)
|-
| '''Indications'''
| Increase inotropy in cardiogenic shock, cardiac stress testing
| Increase inotropy in cardiogenic shock
|-
| '''Pharmaceutics'''
| Clear colourless solution (12.5mg/ml)<br />
Diluted in water
| Diluted in glucose, clear-yellow
|-
| '''Routes of administration'''
| IV
| IV, PO
|-
| '''Dose'''
| Infusion (0.5-20 ug/kg/min)
| Load, then infusion
|-
| pKA
| 10.4
| 6.3
|-
| '''Pharmacodynamics'''
|
|
|-
| MOA
| B1 and B2 agonist (B1&gt;&gt; B2)
| - Sensitises troponin C to calcium &gt; increases contractility (without impairing relaxation) <br />
- Activates ATP-sensitive K channels in smooth muscle &gt; vasodilation
|-
| Effects
| CVS: increased inotropy, increased chronotropy, increased lusitropy, increased dromotropy, decreased SVR, increased BP, increased risk arrhythmias, increased myocardial oxygen requirement<br />
RESP: bronchodilation, <br />
CNS: Increased CBF<br />
RENAL: Increased RBF
| Increased chronotropy, increased inotropy, coronary vasodilation, decreased afterload, increased SV and CO, decreased SVR, decreased blood pressure and myocardial oxygen consumption, hypotension, arrhythmias, GIT upset, dizziness
|-
| '''Pharmacokinetics'''
|
|
|-
| Onset
| Immediate
| 1 hour
|-
| Absorption
| 0% oral bioavailability
| 85% oral bioavailability
|-
| Distribution
| Small Vd (0.2L/Kg)<br />
Unknown protein binding
| Small Vd (0.3L/kg)<br />
99% protein bound
|-
| Metabolism
| Hepatic and tissue metabolism<br />
COMT/MAO &gt; inactive metabolites
| By liver into inactive metabolites (95%) and active metabolites (5%)
|-
| Elimination
| Renal (70%) and faecal (20%) excretion of metabolites <br />
T 1/2 = 2mins
| Renal elimination of metabolites (active metabolites last as long as 80 hours)
|-
| '''Special points'''
| Does not require SAS approval
| Requires SAS approval in AUS
|}
 
 
 
<span id="examiner-comments-75"></span>
==== Examiner comments ====
 
<blockquote>41% of candidates passed this question.<br />
The objective of this question was that candidates relay a detailed knowledge of both drugs with respect to their individual pharmacology highlighting the important clinical aspects of each drug (e.g., mechanism of action, metabolism, duration of effect). Then an integration of this knowledge was in the contrast section where the better candidates highlighted features of the drug that would influence when or why one may use it with respect to the second agent. Tabular answers of the pharmacology of each drug without any integration or comparison scored less well. A detailed knowledge of both agents was expected to score well.
</blockquote>
 
 
<span id="online-resources-for-this-question-75"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2021/05/2020-2-15.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/20b/20b15-compare-and-contrast-the-pharmacology-of-dobutamine-and-levosimendan/ Jenny's Jam jar]
* [https://partone.litfl.com/non-adrenergic_drugs.html Part One, LITFL] and [https://partone.litfl.com/adrenergic_drugs.html#id Part One, LITFL]
* [https://derangedphysiology.com/main/cicm-primary-exam/required-reading/cardiovascular-system/Chapter%20974/dobutamine Deranged Physiology] and [https://derangedphysiology.com/main/cicm-primary-exam/required-reading/cardiovascular-system/Chapter%20978/levosimendan Deranged Physiology]
 
 
 
<span id="similar-questions-75"></span>
==== Similar questions ====
 
* Dobutamine
** Question 14, 2011 (2nd sitting)
** Question15, 2016 (2nd sitting)
* Levosimendan
** Question 8, 2012 (1st sitting)
** Question 10, 2013 (2nd sitting)
 
 
 
 
 
<span id="question-16-4"></span>
=== Question 16 ===
 
 
 
<span id="question-76"></span>
==== Question ====
 
Describe the formation of gastric acid (50% marks) and the regulation of gastric acid secretion (50% marks).
 
 
 
<span id="example-answer-76"></span>
==== Example answer ====
 
 
 
Gastric acid
 
* Gastric acid (HCl, pH 1.6) is one component of gastric secretions
* Other components include: Gastrin, pepsinogen, IF, mucous
* ~2L of gastric secretions produced per day
* Gastric acid is important for innate immunity, pepsin activity, iron absorption etc.
 
 
 
Formation of gastric acid
 
<ul>
<li><p>Produced by the parietal cells in the stomach</p></li>
<li><p>Mechanism of HCl production</p>
<ul>
<li><p>CO2 diffuses into parietal cells from blood</p></li>
<li><p>CO2 reacts with water to give H2CO3 (catalysed by CA)</p></li>
<li><p>H2CO3 dissociates into H+ and HCO3</p></li>
<li><p>At the basolateral membrane: HCO3 is exchanged for Cl (Cl in, HCO3 out)</p></li>
<li><p>Cl then passively diffuses down concentration gradient into secretory canaliculi</p></li>
<li><p>At the apical membrane: H-K ATPase pumps H+ into secretory canaliculi (against concentration gradient)</p></li></ul>
 
<p></p></li></ul>
 
Stages of secretion
 
* Cephalic
** ~30% of gastric secretions as a result of this phase
** Due to thought / taste / sight / smell of food
** Leads to increased PSNS (vagal) activity
* Gastric
** ~60% of gastric secretions during this phase
** Due to the mechanical stretch of the stomach by the food
** Leads to increased PSNS activity and gastrin release
* Intestinal
** &lt;10% of gastric secretions during this phase
** Distention of small intestine --&gt; release of secretin
** Increased acid load in duodenum --&gt; release of somatosatin
 
 
 
Regulation of gastric acid secretion
 
* Histamine
** Most important stimulus for gastric acid secretion
** Synthesised and stored in neighbouring ECL cells
** Binds to H2 receptors on parietal calls &gt; HCl release
** Stimuli: PSNS activity + gastrin
* PSNS (vagal) activity
** Vagal nerve stimulation of M3 receptors (Ach) on parietal cells &gt; increased release HCl
** Vagal stimulation of ECL cells &gt; increased release histamine
* Gastrin
** Released from G cells
** Indirectly leads to increased release of histamine from ECL cells
** Activated by vagus, Inhibited by secretin
* Somatostatin
** Released from D cells
** Inhibits gastrin
* Secretin
** Released from S cells
** Inhibits gastrin
 
 
 
<span id="examiner-comments-76"></span>
==== Examiner comments ====
 
<blockquote>26% of candidates passed this question.<br />
The is question was divided into two sections offering equal marks. The first section required a description of the generation and transport of both H+ and Cl- into the stomach lumen by the parietal cell. The contributions of basolateral and luminal ion channels, the role of carbonic anhydrase and accurate description of the net flux was expected for full marks. The second section required comments on the roles of neural and endocrine regulation. Increased acid secretion via acetylcholine (via muscarinic M3), histamine (via H2) and gastrin were expected as was reduced secretion via secretin and somatostatin. Better responses were able to combine and integrate these into cephalic, gastric, and intestinal phases. The nature and function of other gastric secretions and the role of pharmacologic agents was not asked for and therefore not awarded any marks.
</blockquote>
 
 
<span id="online-resources-for-this-question-76"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2021/05/2020-2-16.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/20b/20b16-describe-the-formation-of-gastric-acid-50-marks-and-the-regulation-of-gastric-acid-secretion-50-marks/ Jennys jam Jar]
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2020-paper-2-saqs/question-16#answer-anchor Deranged Physiology]
 
 
 
<span id="similar-questions-76"></span>
==== Similar questions ====
 
* None
 
 
 
 
 
<span id="question-17-4"></span>
=== Question 17 ===
 
 
 
<span id="question-77"></span>
==== Question ====
 
Describe the pharmacology of inhaled nitric oxide (NO).
 
 
 
<span id="example-answer-77"></span>
==== Example answer ====
 
{|
! Name
! Nitric oxide
|-
| '''Class'''
| Inorganic gas / inhaled pulmonary vasodilator
|-
| '''Indications'''
| ARDS, Right heart failure, pHTN
|-
| '''Pharmaceutics'''
| Colourless gas (100ppm NO, 800ppm N2) in aluminium cylinders
|-
| '''Routes of administration'''
| Inhaled (via the inspiratory limb of an ETT)
|-
| '''Dose'''
| Typically 5-20ppm - titrated to minimal effective dose
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Stimulates cGMP &gt; reduction in intracellular Ca &gt; relaxation of SM. <br />
As inhaled &gt; selectively vasodilates well ventilated alveoli
|-
| Effects
| RESP: Inhibits HPV, improves V/Q matching, <br />
CVS: decreased pulmonary vascular resistance, <br />
CNS: Increased CBF
|-
| Side effects
| Methaemoglobinaemia<br />
hypotension<br />
Rebound pHTN following abrupt cessation<br />
Thrombocytopaenia
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| Seconds
|-
| Absorption
| Rapidly absorbed in pulmonary circulation due to high lipid solubility
|-
| Distribution
| Minimal systemic distribution
|-
| Metabolism
| Reacts with oxyHb to produce methaemaglobin and nitrates.<br />
T 1/2 5 seconds
|-
| Elimination
| Metabolites (main metabolite = nitrate) are renally excreted
|-
| '''Special points'''
|
|}
 
 
 
<span id="examiner-comments-77"></span>
==== Examiner comments ====
 
<blockquote>24% of candidates passed this question.<br />
Nitric Oxide (NO) is an inorganic colourless and odourless gas presented in cylinders containing 100/800 ppm of NO and nitrogen. Many candidates mentioned oxygen instead of nitrogen. The exposure of NO to oxygen is minimized to reduce formation of nitrogen dioxide and free radicals. Hence it is administered in inspiratory limb close to the endotracheal tube. Many candidates did not mention the contraindications/caution for NO use. Candidates generally did well in mentioning the impact on improving V/Q mismatch by promoting vasodilatation only in the ventilated alveoli and reducing RV afterload. Many candidates did not mention the extra cardio-respiratory effects. The expected adverse effects of NO were nitrogen dioxide related pulmonary toxicity, methemoglobinemia and rebound pulmonary hypertension on abrupt cessation. Pharmacokinetics of NO carried a significant proportion of marks. It was expected that the answers would involve mention of location of delivery of NO in inspiratory limb and reason behind it, the high lipid solubility and diffusion, the dose (5-20ppm), very short half-life of &lt; 5 seconds and combination with oxyhemoglobin to produce methaemoglobin and nitrate. The main metabolite is nitrate which is excreted in urine.
</blockquote>
 
 
<span id="online-resources-for-this-question-77"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2021/05/2020-2-17.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/20b/20b17-describe-the-pharmacology-of-inhaled-nitric-oxide-no/ Jennys Jam Jar]
* [https://derangedphysiology.com/main/cicm-primary-exam/required-reading/respiratory-system/Chapter%20313/pharmacology-pulmonary-vasodilators Deranged Physiology]
* [https://partone.litfl.com/pulmonary_vasodilators.html Part One, LITFL]
 
 
 
<span id="similar-questions-77"></span>
==== Similar questions ====
 
* Question 14, 2011 (1st sitting)
 
 
 
 
 
<span id="question-18-4"></span>
=== Question 18 ===
 
 
 
<span id="question-78"></span>
==== Question ====
 
Define afterload (10% marks) and describe the physiological factors that may affect afterload on the left ventricle (90% marks).
 
 
 
<span id="example-answer-78"></span>
==== Example answer ====
 
 
 
Afterload
 
* Isolated muscle: The external force required to be generated before the myocardial sarcomere can begin to shorten in the isolated muscle.
* Intact heart: the forces impeding ejection of blood from the ventricle during contraction
 
 
 
Change in afterload
 
* Decreased afterload --&gt; increased LV stroke volume --&gt; increased CO
* Increased afterload --&gt; reduced LV stroke volume --&gt; reduced CO
 
 
 
Factors effecting afterload
 
* Broadly, the factors effecting afterload can be broken up into factors effecting
** Mycocardial wall stress
** Impedance to flow
 
 
 
MYOCARDIAL WALL STRESS (governed by the law of LaPlace)
 
* Transmural pressure
** Negative intrathoracic pressure &gt; increased transmural pressure &gt; increased afterload
** e.g. inhalation (more pronounced in asthma)
* Ventricular size
** Increased radius of ventricle &gt; increased wall stress &gt; increased afterload
** e.g. ventricular dilation
* Myocardial wall thickness
** Increased thickness &gt; reduced wall stress (more sarcomeres share tension) &gt; reduced afterload
** e.g. LV hypertrophy
 
 
 
IMPEDENCE TO FLOW
 
* Arterial compliance
** Poorly compliance vessels &gt; increased afterload
** e.g. in pathology such as atherosclerosis
* Arterial resistance/impedance
** Related to (Hagen-Poiseuille equation)
*** the length of the arterial system (fixed)
*** blood viscosity (e.g. HCT, changes slowly)
*** Vessel radius (most important factor, changes readily)
** E.g. profound vasoconstriction of capacitance vessels (e.g. norad infusion) &gt; increased resistance &gt; increased afterload
* Outflow tract impedance
** Leads to increased afterload (increased forced required for ejection)
** E.g. valvular disease (AS), SAM, LVOT
 
 
 
<span id="examiner-comments-78"></span>
==== Examiner comments ====
 
<blockquote>53% of candidates passed this question.<br />
Afterload can be defined as factors resisting ventricular ejection and contributing to myocardial wall stress during systole. Most answers utilised the law of Laplace to expand upon factors affecting ventricular wall tension. Systemic vascular resistance was commonly mentioned, but less frequently defined. Aortic and left ventricular outflow tract impedance were commonly referred to. Effects of preload and neurohumoral stimuli were less well outlined. Description of factors affecting right ventricular afterload and depictions of left ventricular pressure volume loops earned no extra marks unless directly referenced to the question.
</blockquote>
 
 
<span id="online-resources-for-this-question-78"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2021/05/2020-2-18.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/20b/20b18-define-afterload-10-marks-and-describe-the-physiological-factors-that-may-affect-afterload-on-the-left-ventricle-90-marks/ Jennys Jam Jar]
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2020-paper-2-saqs/question-18#answer-anchor Deranged Physiology]
 
 
 
<span id="similar-questions-78"></span>
==== Similar questions ====
 
* Question 7, 2009 (1st sitting)
* Question 17, 2012 (1st sitting)
* Question 19, 2014 (2nd sitting)
 
 
 
 
 
<span id="question-19-4"></span>
=== Question 19 ===
 
 
 
<span id="question-79"></span>
==== Question ====
 
Explain how the kidney handles an acid load.
 
 
 
<span id="example-answer-79"></span>
==== Example answer ====
 
 
 
Acid production
 
* Normal biproducts of cellular function and metabolism
* 'Fixed acids'
** Body produces ~1mmol/kg/day
** Fixed acids, except for lactate, are eliminated by the kidneys
* 'volatie acids' (i.e. CO2)
** Body produces ~15-20moles/day
** Eliminated by the lungs
 
 
 
Mechanisms of acid-base regulation by kidneys
 
 
 
# Secretion of H+ / Reabsorption of HCO3
#* H+ activately secreted into the urine
#** Na-H exchanger (PCT, LOH)
#** H+ ATPase (DCT)
#** H-K ATPase (CD)
#* HCO3 is freely filtered at glomerulus (needs to be reabsorbed)
#* H+ and HCO3 combine to form H2CO3
#* H2CO3 converted to H2O and CO2 (by apical carbonic anhydrase)
#* H2O aand CO2 diffuse into cell and converted back to H2CO3 by CA
#* H2CO3 then dissociates into HCO3 and H+ (HCO3 reabsorbed, H+ is secreted once more)
#* This allows for all HCO3 to be reabsorbed
 
 
 
<ol style="list-style-type: decimal;">
<li><p>Combination with titratable acids</p>
<ul>
<li><p>Excess H+ combines with filtered buffers (e.g. phosphate, sulphate)</p></li>
<li><p>Phosphate is most important and is responsible for eliminating ~40% of excess fixed acid load / day </p>
<ul>
<li><p>H+ combines with HPO4 &gt; H2PO4 (ionised, not reabsorbed)</p></li></ul>
</li>
<li><p>Minimal capacity to increase </p></li></ul>
 
<p></p></li>
<li><p>Ammonium mechanism</p>
<ul>
<li><p>Excess H+ can bind to ammonia &gt; excreted</p>
<ul>
<li><p>in PCT/DCT: metabolism of glutamine &gt; releases new HCO3 and excess NH4</p></li>
<li><p>In CD: secretion of NH3 binds to H+ &gt; NH4 (ionised and cannot be reabsorbed)</p></li></ul>
</li>
<li><p>Accounts for remainder of excess fixed acid load,</p></li>
<li><p>Has capacity to greatly expand when there is excess H+</p></li></ul>
</li></ol>
 
 
 
<span id="examiner-comments-79"></span>
==== Examiner comments ====
 
<blockquote>51% of candidates passed this question.<br />
This question required candidates to understand the renal response to an acid load. It was expected that candidates would answer with regard to recycling of bicarbonate in the proximal tubule, excretion of titratable acid via the phosphate buffer system and generation of ammonium and its role in acid secretion. Many candidates had a good understanding of the bicarbonate system but used this to explain the secretion of new acid.
</blockquote>
 
 
<span id="online-resources-for-this-question-79"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2021/05/2020-2-19.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/20b/20b19-explain-how-the-kidney-handles-an-acid-load/ Jennys Jam Jar]
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2020-paper-2-saqs/question-19#answer-anchor Deranged Physiology]
 
 
 
<span id="similar-questions-79"></span>
==== Similar questions ====
 
* Question 12, 2014 (2nd sitting)
 
 
 
 
 
<span id="question-20-4"></span>
=== Question 20 ===
 
 
 
<span id="question-80"></span>
==== Question ====
 
Describe the pharmacology of intravenous sodium nitroprusside.
 
 
 
<span id="example-answer-80"></span>
==== Example answer ====
 
{|
! Name
! Sodium nitroprusside
|-
| '''Class'''
| Nitrate vasodilator
|-
| '''Indications'''
| Hypertensive emergencies (or need for strict BP control)
|-
| '''Pharmaceutics'''
| IV solution (50mg/2mL)<br />
Light sensitive
|-
| '''Routes of administration'''
| IV only
|-
| '''Dose'''
| Titrated to effect (0-2mcg/kg/min)
|-
| pKA
| 3.3
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Prodrug<br />
Diffuses into RBCs and reacts with Oxy-Hb to produce NO<br />
NO diffuses into cell &gt; incr cGMP &gt; decreased Ca &gt; SM relaxation
|-
| Effects
| CVS: decreased BP, afterload<br />
RESP: impairs HPVC<br />
CNS: cerebral vasodilation<br />
GI: ileus<br />
metabolic: acidosis
|-
| Side effects
| headache, hypotension, rebound hypertension (abrupt withdrawal), cyanide toxicity (high doses), metabolic acidosis, hypoxia, raised ICP
|-
| '''Pharmacokinetics'''
|
|-
| Onset/offset
| Immediate onset + offset
|-
| Absorption
| 0% oral bioavailability
|-
| Distribution
| VOD 0.25L/Kg (confined intravasc).<br />
Nil protein binding
|-
| Metabolism
| Nitroprusside &gt; cyanide &gt; prussic acid &gt; thiocyanate
|-
| Elimination
| Metabolites via urine
|-
| '''Special points'''
|
|}
 
 
 
<span id="examiner-comments-80"></span>
==== Examiner comments ====
 
<blockquote>49% of candidates passed this question.<br />
This was a straightforward pharmacology question relating to a relatively common and archetypal intensive care medication. The structure of the question was well handled by most of the candidates; easily falling into the classic pharmaceutics, pharmacokinetic and pharmacodynamics framework. Many candidates had a superficial knowledge of the presentation and formulation of the drug, aside from its light sensitivity. Better answers detailed the drug according to the above-mentioned framework but also accurately highlighted specific points relevant to the ICU practise such as the metabolic handling of sodium nitroprusside and relating this to the consequences of the various metabolic products.
</blockquote>
 
 
<span id="online-resources-for-this-question-80"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2021/05/2020-2-20.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/20b/20b20-describe-the-pharmacology-of-intravenous-sodium-nitroprusside/ Jennys Jam Jar]
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2020-paper-2-saqs/question-20#answer-anchor Deranged Physiology]
 
 
 
<span id="similar-questions-80"></span>
==== Similar questions ====
 
* Question 11, 2015 (1st sitting)
 
 
 
 
 
 
 
<span id="2020-1st-sitting"></span>
== 2020 (1st sitting) ==
 
 
 
<span id="question-1-5"></span>
=== Question 1 ===
 
 
 
<span id="question-81"></span>
==== Question ====
 
Describe the carriage of carbon dioxide in blood.
 
 
 
<span id="example-answer-81"></span>
==== Example answer ====
 
 
 
Overview
 
* CO<sub>2</sub> is constantly produced as a by-product of metabolism and needs to be cleared
* CO<sub>2</sub> content of blood
** Mixed venous: 52mls/100mls blood, at PaCO<sub>2</sub> of ~45mmHg
** Arterial: 48mls/100mls blood, at PaCO<sub>2</sub> of ~40mmHg
* CO<sub>2</sub> is transported in three main forms in the blood
** Dissolved
** As bicarbonate
** In combination with proteins (carbamino compounds)
 
 
 
Dissolved CO<sub>2</sub>
 
* Accounts for
** ~5% of the total carbon dioxide in the blood
** ~10% of the CO<sub>2</sub> evolved by the lung
* The amount dissolved is proportional to the partial pressure (Henry's Law)
* 20x more soluble than O<sub>2</sub>, so dissolved CO<sub>2</sub> plays a more significant role in transport
 
 
 
Bicarbonate
 
<ul>
<li><p>Accounts for </p>
<ul>
<li><p>~90% of the carbon dioxide in the blood</p></li>
<li><p>~60% of the CO<sub>2</sub> evolved by the lung</p></li></ul>
</li>
<li><p>Bicarbonate is formed by the following sequence </p>
<math display="block">CO_2 + H_{2}O \leftrightarrow H_{2}CO_{3} \leftrightarrow H^+  + HCO_3^-</math></li>
<li><p>Process</p>
<ul>
<li><p>CO2 dissolves into RBC and leads to H+ and HCO3 (per above equation)</p></li>
<li><p>HCO3 moves into plasma, H+ binds to reduced (deoxy) Hb</p>
<ul>
<li><p>KHb + H+ &lt;-&gt; HHb + K+</p></li></ul>
</li>
<li><p>Cl moves into the cell to maintain electroneutrality (chloride shift)</p></li>
<li><p>When Hb is oxygenated in the lungs, H+ dissociates and converted back to CO2 by the above equation and is exhaled</p></li>
<li><p>Haldane effect accounts for the increased capacity of Hb to carry CO2 when poorly oxygenated</p></li></ul>
</li></ul>
 
 
 
Carbamino compounds
 
* Accounts for
** ~5% of the CO<sub>2</sub> in the blood
** ~30% of the CO<sub>2</sub> evolved by the lung
* Formed by the combination of CO<sub>2</sub> with terminal amine groups in blood proteins
** NH2 + CO2 &lt;-&gt; NHCOO- + H+
* Haemoglobin is the most abundant protein and has most imadazole side chains (greatest carrier capacity)
** The reaction occurs faster with deoxHb than oxy-Hb (Haldane effect)
 
 
 
<span id="examiner-comments-81"></span>
==== Examiner comments ====
 
<blockquote>68% of candidates passed this question.<br />
A detailed understanding of the carriage of carbon dioxide (CO2) in the blood is essential to the<br />
practice of intensive care medicine. Comprehensive answers classified and quantified the<br />
mechanisms of CO2 carriage in the blood and highlighted the differences between the arterial and<br />
venous systems. An explanation of the physiological principles surrounding these differences and<br />
the factors which may affect them was expected. The changes that occur at the alveolar and<br />
peripheral tissue interfaces with a similar explanation of process was also required. Candidate<br />
answers were often at the depth of knowledge required for an ‘outline question’ and a more<br />
detailed explanation was required to score well.
</blockquote>
 
 
<span id="online-resources-for-this-question-81"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2020-paper-1-saqs/question-1#answer-anchor Deranged Physiology]
* [https://cicmwrecks.files.wordpress.com/2020/07/2020-1-01.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/20a/20a01-describe-the-carriage-of-carbon-dioxide-in-blood/ Jenny's Jam Jar]
* [https://partone.litfl.com/carbon_dioxide_transport.html Part One, LITL]
* [https://propofoldreams.files.wordpress.com/2015/04/resp-co2-carriage.pdf Propofol dreams]
* [https://ketaminenightmares.com/pex/saqs/physiology/respiratory/2019A04_co2_carriage_in_blood.htm Ketamine Nightmares]
 
 
 
<span id="similar-questions-81"></span>
==== Similar questions ====
 
* Question 6, 2012 (1st sitting)
* Question 1, 2012 (2nd sitting)
* Question 13, 2015 (1st sitting)
* Question 5, 2018 (2nd sitting)
* Question 1, 2020 (1st sitting)
 
 
 
<span id="question-2-5"></span>
=== Question 2 ===
 
 
 
<span id="question-82"></span>
==== Question ====
 
Describe the pharmacology of glyceryl trinitrate (GTN)
 
 
 
<span id="example-answer-82"></span>
==== Example answer ====
 
{|
! Name
! Glyceryl trinitrate (GTN)
|-
| '''Class'''
| Organic nitrate
|-
| '''Indications'''
| Hypertension, acute pulmonary oedema, angina, ACS/LV failure,
|-
| '''Pharmaceutics'''
| Clear liquid (IV), Patch (transdermal), tablet (SL), spray (SL)
|-
| '''Routes of administration'''
| Sublingual, intravenous, transdermal, PO
|-
| '''Dose'''
| Patch: 5/15mg/24hr SL: 400mcg PRN IV: titrated to effect
|-
| pKA
| 5.6
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Prodrug, which is dinitrated to produce active nitric oxide (NO). NO diffuses into smooth muscle cell &gt; binds to guanylyl cyclase &gt; increased cGMP &gt; decreased intracellular Ca &gt; smooth muscle relaxation &gt; vasodilation
|-
| Effects
| CVS: systemic vasodilation (preferentially venodilation, coronary arterial dilation) &gt; decreased SVR &gt; decreased BP + VR, decreased myocardial O2 consumption (decreased VR &gt; decreased preload), reflex tachycardia CNS: Increased CBF &gt; inc ICP, headache RESP: Bronchodilation (weak), decreased PVR OTHER: flushing, methaemaglobinaemia
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| 1-3 mins (SL), &lt;1 min (IV), Patch variable.
|-
| Absorption
| Oral bioavailability &lt;5% (hepatic high first pass effect) Sublingual spray 40% Sublingual tablet 60%
|-
| Distribution
| 60% protein bound. Vd 3L/kg
|-
| Metabolism
| Hydrolysis Site: liver + RBC cell wall + vascular cell walls. Active metabolites
|-
| Elimination
| Renal T 1/2 B = 5 minutes (parent compound).
|-
| '''Special points'''
| Can develop tachyphylaxis (depletion of sulfhydryl groups)
|}
 
 
 
<span id="examiner-comments-82"></span>
==== Examiner comments ====
 
<blockquote>69% of candidates passed this question.<br />
GTN is a commonly used ‘level 1’ drug. The most comprehensive answers included information<br />
on available drug preparations, indications, mechanism of action, pharmacodynamics and<br />
pharmacokinetics and its side-effect profile. It was expected that significant detail be included in<br />
the pharmacodynamic section (e.g. preferential venodilation, reflex tachycardia, effects on<br />
myocardial oxygen demand etc). Common omissions included tachyphylaxis, dosing and its<br />
metabolism. Many answers didn’t mention the first pass effect.
</blockquote>
 
 
<span id="online-resources-for-this-question-82"></span>
==== Online resources for this question ====
 
* [https://ketaminenightmares.com/pex/saqs/pharmacology/cardiovascular_drugs/2004A06_glyceryl_trinitrate.htm Ketamine Nightmares]
* [https://jennysjamjar.com.au/year/20a/20a02-describe-the-pharmacology-of-glyceryl-trinitrate-gtn/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/07/2020-1-02.pdf CICM Wrecks]
* [https://derangedphysiology.com/cicm-primary-exam/required-reading/cardiovascular-system/Chapter%20954/nitrate-vasodilators-and-sodium-nitroprusside Deranged Physiology]
 
 
 
<span id="similar-questions-82"></span>
==== Similar questions ====
 
* Question 15, 2008 (1st sitting)
* Question 20, 2008 (2nd sitting)
* Question 16, 2010 (1st sitting)
* Question 2, 2016 (2nd sitting)
 
 
 
 
 
<span id="question-3-5"></span>
=== Question 3 ===
 
 
 
<span id="question-83"></span>
==== Question ====
 
Outline the potential adverse consequences of blood transfusion.
 
 
 
<span id="example-answer-83"></span>
==== Example answer ====
 
 
 
Immunological (acute &lt; 24 hours)
 
{|
! Adverse event
! Incidence
! Mechanism
|-
| Acute haemolytic transfusion reaction
| 1 : 75,000<br />
(Death 1:2 mil)
| E.g. ABO incompatibility. Immunological destruction of transfused cells (Type II hypersensitivity).
|-
| Febrile non-haemolytic transfusion reaction
| ~1%
| Cytokine release from stored cells causing a mild inflammatory reaction with recipient alloantibodies
|-
| Mild allergic reactions (e.g. urticaria)
| ~1-5%
| Hypersensitivity to plasma proteins in the transfused unit
|-
| Severe allergic reactions (i.e. anaphylaxis)
| ~ 1 : 50,000
| Type I hypersensitivity reaction to plasma protein in transfused unit
|-
| Transfusion related acute lung injury (TRALI)
| Variable
| Donor plasma HLA activates recipient pulmonary neutrophils, causing fever, shock, and non-cardiogenic pulmonary oedema
|}
 
 
 
Immunological (delayed &gt; 24 hours)
 
{|
! Adverse event
! Incidence
! Mechanism
|-
| Delayed haemolytic transfusion reaction
| 1: 5,000
| Alloimmunized to minor RBC antigens (kidd, duffy, Kell) during previous transfusions which is not detected due to low levels in pre-transfusion screening. Reaction if re-exposed
|-
| Transfusion associated graft versus host disease
| Rare
| Transfused lymphocytes recognise host HLA as positive causing marrow aplasia (rare now with leukodepletion)
|-
| Alloimmunisation
| ~1-10%
| Previous sensitisation leading to antibody production on re-exposure.
|}
 
 
 
Non-immunological (acute &lt; 24 hours)
 
{|
! Adverse event
! Incidence
! Mechanism
|-
| Non immune mediated haemolysis
| Rare
| Due to physicochemical damage to RBCs
|-
| Transfusion transmitted bacterial infections
| 1:250,000 - 2.5 million
| Contamination during collection or processing. Most common organisms are those which use iron as a nutrient and reproduce at low temperatures, e.g. ''Yersinia Pestis''.
|-
| Transfusion associated circulatory overload
| 1%
| Rapid increase in intravascular volume in patients with poor circulatory compliance or chronic anaemia. May result in pulmonary oedema and be confused with TRALI.
|-
| Others
| Variable
| Hypothermia, coagulopathies, electrolytes disturbance, metabolic derangements
|}
 
 
 
Non-immunological (delayed &gt; 24 hours)
 
{|
! Adverse event
! Incidence
! Mechanism
|-
| Iron overload
| Rare (unless massive transfusion e.g. &gt;20 units)
| Each unit of PRBC contains ~250mg of iron, whilst average excretion is 1mg.day-1.
|-
| Infections
| Less than 1:1 million
| From donor
|}
 
 
 
<span id="examiner-comments-83"></span>
==== Examiner comments ====
 
<blockquote>43% of candidates passed this question.<br />
As only an outline was asked for, a brief statement about each complication was sufficient. Better answers were structured using a classification of: Acute Immunological, Acute Non- Immunological, Delayed Immunological and Delayed Non-immunological. Examples of expected detail would include the following: E.g. Bacterial infection – a statement outlining the incidence of bacterial infection, a common causative organism or why bacterial infections are more commonly associated with platelet transfusions than red cells would have scored the marks allocated to ‘bacterial infection’. E.g. Acute Haemolytic Transfusion Reaction – a statement about red cells being destroyed due to incompatibility of antigen on transfused cells with antibody of the recipient and an approximate incidence scored the marks allocated to AHTR. An excellent resource is the Australian Red Cross transfusion website as listed in the suggested reading section of the syllabus.
</blockquote>
 
 
<span id="online-resources-for-this-question-83"></span>
==== Online resources for this question ====
 
* [https://partone.litfl.com/transfusion_reactions.html#transfusion-reactions Part One, LITFL]
* [https://www.lifeblood.com.au/health-professionals/clinical-practice/adverse-events/classification-incidence Lifeblood, red cross blood service]
* [https://jennysjamjar.com.au/year/20a/20a03-outline-the-potential-adverse-consequences-of-blood-transfusion/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/07/2020-1-03.pdf CICM Wrecks]
* [https://derangedphysiology.com/main/cicm-primary-exam/required-reading/haematological-system/Chapter%20335/adverse-effects-blood-transfusion Deranged Physiology]
* [https://ketaminenightmares.com/pex/saqs/physiology/haematology/2018B06_blood_transfusion_adverse_effects.htm Ketamine Nightmares]
 
 
 
<span id="similar-questions-83"></span>
==== Similar questions ====
 
<ul>
<li><p>Question 13, 2013 (2nd sitting)</p></li>
<li><p>Question 16, 2017 (1st sitting)</p>
<p></p></li></ul>
 
 
 
<span id="question-4-5"></span>
=== Question 4 ===
 
 
 
<span id="question-84"></span>
==== Question ====
 
Explain the counter-current mechanism in the kidney.
 
 
 
<span id="example-answer-84"></span>
==== Example answer ====
 
 
 
Purpose
 
* The counter current mechanism of the kidney is important for establishing the osmotic gradient necessary for forming concentrated urine (thus preserving water)
 
 
 
Formation
 
* Formed by the loop of henle
* Assuming a naïve system. Iso-osmolar fluid (300mosm) arrives at the aLOH.
** This is because water/solutes are absorbed in equal amounts in the PCT.
* In the aLOH the Na-K-2Cl transporter reabsorbs these ions. Water is impermeable. Interstitium becomes hyperosmotic (now 400mosm)
* When the next iso-osmotic fluid arrives (300sm), there is a concentration gradient (water leaves through permeable dLOH) leading to hypertonic filtrate
* The hypertonic filtrate then arrives in the aLOH and the Na-K-2Cl pump works again.
* The interititum becomes further hypertonic (e.g. 400mosm).
* Process repeats until a maximal concentration gradient of around 600mosm exists between inner medulla and cortex
* Finally, through urea trapping from the collecting ducts (facilitated diffusion via UTA1 and UTA3 receptors), the osmotic gradient in the inner medulla is increased to approximately 1200mosm
 
 
 
Maintenance
 
* Vasa recta is organised in such a way that it does not wash away the established concentration gradient (close proximity, in parallel, opposite direction of flow)
* Achieves this by also looping down into the inner medulla (water lost, solute gained) then back up (water gained, solute lost)
* The slow nature of this flow in combination with its anatomy (parallel + close proximity) prevents the washing away of the concentration gradient
* This is known as the counter current exchanger
 
 
 
<span id="examiner-comments-84"></span>
==== Examiner comments ====
 
<blockquote>63% of candidates passed this question.<br />
Higher scoring candidates described the counter-current multiplier mechanism, the countercurrent<br />
exchanger and the contribution of urea cycling to the medullary osmotic gradient. Detailing<br />
the mechanisms as to how they may be established, maintained and or regulated. Descriptions<br />
of the multiplier (LOH) alone did not constitute a passing score. Values for osmolality at the cortex<br />
&amp; medulla and within the different parts of the LOH was required. A description of the countercurrent<br />
exchanger system where inflow runs parallel to, counter to and in close proximity to the<br />
outflow was expected. This could have been achieved by describing the anatomical layout of the<br />
loop of Henle and the vasa recta.
</blockquote>
 
 
<span id="online-resources-for-this-question-84"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2020/07/2020-1-04.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/20a/17a18-2/ Jenny's Jam Jar]
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2020-paper-1-saqs/question-4#answer-anchor Deranged Physiology]
 
 
 
<span id="similar-questions-84"></span>
==== Similar questions ====
 
* Question 9, 2011 (1st sitting)
* Question 22, 2015 (2nd sitting)
 
 
 
 
 
<span id="question-5-5"></span>
=== Question 5 ===
 
 
 
<span id="question-85"></span>
==== Question ====
 
Outline the mechanisms of antimicrobial resistance (50% of marks). Briefly outline the pharmacology of ciprofloxacin (50% of marks).
 
 
 
<span id="example-answer-85"></span>
==== Example answer ====
 
 
 
Antimicrobial resistance
 
* Occurs when the maximal level of drug tolerated in insufficient to inhibit growth
* Broadly occurs via genetic alteration or changes to protein expression
 
 
 
Mechanisms of resistance
 
# Prevent access to drug target
#* Decrease permeability
#** E.g. pseudomonas resistance to carbapenems due to reduction in porins
#* Active efflux of drug
#** Efflux pumps &gt; extrude antibiotics e.g. fluoroquinolone resistance
# Alter antibiotic target site
#* e.g. VRE - Alteration to Peptidoglycan binding site protein, reducing affinity of drug.
# Modification / inactivation of drug
#* E.g. ESBL and penicillins/cephalosporins whereby b-lactamases hydrolyse B-lactam rings
# Modification of metabolic pathways
#* E.g. Bactrim resistance. Metabolic pathways bypass site of antibiotic action
 
 
 
{|
! Name
! Ciprofloxacin
|-
| '''Class'''
| Quinolone
|-
| '''Indications'''
| Prostatitis, complicated UTIs, bone/joint infections
|-
| '''Pharmaceutics'''
| Oral tablet, light-yellow power for injection (water diluent)
|-
| '''Routes of administration'''
| IV, PO
|-
| '''Dose'''
| 250-750mg BD (PO), 200-400mg BD/TDS (IV)
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Bactericidal; inhibit bacterial DNA synthesis by blocking DNA gyrase and topoisomerase IV.
|-
| Spectrum
| Broad spectrum (GN+ MSSA). Effective against pseudomonas + anthrax (lol)<br />
Effective against some atypicals (legionella).<br />
No anaerobe cover.
|-
| Side effects
| GIT: nausea, vomiting<br />
CNS: dizziness, headache<br />
CVS: prolonged QT interval, arrhythmias <br />
MSK: Myopathy, tendonitis + rupture, arthropathy
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| 1-2 hours (PO) for peak effect. Immediately (IV)
|-
| Absorption
| Oral bioavailability 70%
|-
| Distribution
| Vd 2.5L/kg. Protein binding 25%, good tissue penetration (except for poor CSF penetration)
|-
| Metabolism
| Partially hepatic
|-
| Elimination
| Renal excretion of metabolites. T1/2 3-5 hours.
|-
| '''Special points'''
| Increasing world wide resistance to quinolones.
|}
 
 
 
<span id="examiner-comments-85"></span>
==== Examiner comments ====
 
<blockquote>71% of candidates passed this question.<br />
Most candidates had a structured answer to mechanisms of resistance that covered the major categories (alter target protein, prevent entry, efflux, degrade drug) and provided an example of a bacteria and the affected antibiotic, as was required to answer the question in full. Ciprofloxacin, whilst perhaps not a first line drug in the ICU, was not well known by many candidates. Better answers included a brief outline of class, mechanism of action (action on DNA gyrase to inhibit replication), spectrum (Gram negatives particularly mentioning Pseudomonas, lesser Gram positive cover, not anaerobes, some atypical), PK (with correct dose, wide penetration into tissues including bone/prostate etc., predominantly renal excretion), side effects/toxicity (common or specific to cipro e.g. QT, tendinitis, arthropathy) and an example of resistance.
</blockquote>
 
 
<span id="online-resources-for-this-question-85"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2020/07/2020-1-05.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/20a/20a05/ Jennys Jam Jar]
* AMH/MIMS
* [https://partone.litfl.com/antimicrobial_resistance.html Part One, LITFL]
 
 
 
<span id="similar-questions-85"></span>
==== Similar questions ====
 
* Question 9, 2019 (1st sitting)
 
 
 
 
 
<span id="question-6-5"></span>
=== Question 6 ===
 
 
 
<span id="question-86"></span>
==== Question ====
 
Outline how the respiratory system of a neonate differs from that of an adult.
 
 
 
<span id="example-answer-86"></span>
==== Example answer ====
 
 
 
Anatomical differences in neonates (with respect to adults)
 
* Head
** Larger head and occiput
** Smaller mandible
** Larger tongue, tonsils, adenoids.
* Neck
** Shorter neck with higher laryngeal position
** Larger, less rigid epiglottis
* Larynx/trachea/bronchi
** Shorter, narrower and softer trachea
** Main Bronchi angle equal L-R for neonate (adults right is more vertical)
** Reduced bronchial smooth muscle &gt; less bronchospasm (but bronchodilators less effective)
* Alveoli
** Fewer (and more immature) alveoli
* Reduced type 1 muscle fibres in diaphragm (25% neonates, 55% in adults) - more susceptible to fatigue
 
 
 
Physiological differences in neonates (with respect to adults)
 
* Volumes/capacities
** Similar FRC (30ml/kg), and TV (7mls/kg) to adults
** Lower vital capacity (45mls/kg) and TLC (65mls/kg)
** Increased minute ventilation (generated by increased RR, as TV proportionally similar)
** Increased physiological deadspace (3mls vs 2 mls)
** Increased closing capacity &gt; increased shunt
* Compliance
** Increased chest wall compliance (proportionally more cartilage)
** Decreased lung compliance (less surfactant)
* Resistance
** Respiratory resistance is increased at birth: bronchi are smaller and lung volumes are smaller
* Mechanics
** Obligate nose breathers
** More susceptible to fatigue (Reduced type 1 muscle fibres in diaphragm)
** Increased work of breathing overall (increased MV, increased dead space, increased shunt)
* Gas exchange
** Increased oxygen consumption (6mls/kg/min)
** Increased shunt (10-25%, due to patent ductus arteriosus)
** Foetal haemoglobin = increased oxygen affinity (left shift oxy curve)
* Control
** Immature respiratory centre - decreased response to hypercapnia, periodic apnoea,
 
 
 
<span id="examiner-comments-86"></span>
==== Examiner comments ====
 
<blockquote>20% of candidates passed this question.<br />
This question required an outline of the anatomical, mechanical and functional differences. It was expected that factors leading to an increased work of breathing and oxygen cost would be mentioned. The mechanics of expiration were not often included in candidates’ answers. Immaturity of the alveoli and peripheral chemoreceptors were common omissions. Inaccuracies regarding upper airway anatomy and compliance of the chest wall cost some candidates marks. The question did not call for an explanation of the relative difficulty of intubation. Discussion of pathophysiology due to airway obstruction, causes of central apnoea or sensitivity to drugs was not required. Many answers included inaccurate information. Points which were often missed were difference in bronchial angles, number of alveoli, number of type 1 fibres in diaphragm, ciliary function and peripheral chemoreceptors.
</blockquote>
 
 
<span id="online-resources-for-this-question-86"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2021/05/2020-1-06.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/20a/20a06-outline-how-the-respiratory-system-of-a-neonate-differs-from-that-of-an-adult/ Jenny's Jam Jar]
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2013-paper-1-saqs/question-7#answer-anchor Deranged Physiology]
 
 
 
<span id="similar-questions-86"></span>
==== Similar questions ====
 
* Question 7, 2017 (1st sitting)
 
 
 
 
 
<span id="question-7-5"></span>
=== Question 7 ===
 
 
 
<span id="question-87"></span>
==== Question ====
 
Describe the physiological control of systemic vascular resistance (SVR).
 
 
 
<span id="example-answer-87"></span>
==== Example answer ====
 
 
 
Overview
 
* SVR is the impediment to flow generated by the systemic vasculature (excluding pulmonary) and can be defined according to ohms law (SVR = (MAP-CVP) / CO)
* The main determinants of SVR is conceptualised by the Hagen-Poiseuille equation
** <math display="inline">SVR = { 8l. \eta \over \pi r^4}</math>
** Length (l), and viscosity of blood (n) does not readily change, hence the most significant determinant of SVR is the vessel radius (R)
* Control of radius
** Majority of this control occurs at the level of the arteriole (sig. amount of smooth muscle in wall - can readily alter calibre)
 
 
 
Systemic control of vessel radius
 
* SNS
** Activation of the SNS (pain, emotion, exercise, fear etc) &gt; release of NA from the post ganglionic neurons &gt; activates alpha-1 receptors &gt; vasoconstriction &gt; increased SVR
** Alpha-1 receptors are plentiful in the skin, kidneys, GIT (but minimal in the heart and brain, leading to preferential flow to these organs)
* PSNS
** Much less important (external genitalia)
** Activation leads to vasodilation (decreased SVR)
* Arterial baroreflex control
** Increased BP &gt; increased arterial wall stretch &gt; increased firing of aortic and carotid sinus baroreceptors &gt; decreased sympathetic tone &gt; vasodilation &gt; decreased SVR (vice versa)
* Chemoreceptor reflex
** Peripheral and central chemoreceptors activated by hypoxia &gt; increased SVR
* Hormonal control
** Numerous endocrine mediators affect SVR
** E.g. Angiotensin (AT1 receptors) and vasopressin (V1 receptors) increase SVR
* Temperature
** Heat causes vasodilation &gt; decreased SVR (and vice versa)
 
 
 
Regional/local control of vessel radius
 
* Myogenic autoregulation
** e.g. brain, kidneys, can alter vessel radius via myogenic means. Less important peripherally.
** Incr. pressure &gt; incr. stretch &gt; release of vasoactive mediators &gt; constriction &gt; increased SVR
* Metabolic autoregulation
** e.g. brain, coronary vasculature
** Decreased oxygen delivery / increased utilisation &gt; increased metabolites (CO2, H, lactate, NO, adenosine) &gt; vasodilation &gt; decreased SVR
 
 
 
<span id="examiner-comments-87"></span>
==== Examiner comments ====
 
<blockquote>21% of candidates passed this question.<br />
This question invited a detailed discussion of the physiological control mechanisms in health, not<br />
pathophysiology nor drug-mediated effects. The central and reflex control mechanisms that regulate SVR over time are distinct from the local determinants of SVR. There was often confusion between dependent and independent variables. Cardiac output is generally depended upon SVR, not vice versa, even though SVR can be mathematically calculated from CO and driving pressures. The question asked about systemic vascular resistance and did not require a discussion of individual organs except for a general understanding that local autoregulation versus central neurogenic control predominates in different tissues. Emotional state, temperature, pain and pulmonary reflexes were frequently omitted. Peripheral and central chemoreceptors and low-pressure baroreceptors were relevant to include along with high pressure baroreceptors.
</blockquote>
 
 
<span id="online-resources-for-this-question-87"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2020-paper-1-saqs/question-7#answer-anchor Deranged Physiology]
* [https://jennysjamjar.com.au/year/20a/20a07-describe-the-physiological-control-of-systemic-vascular-resistance-svr/ Jenny's Jam Jar]
 
 
 
<span id="similar-questions-87"></span>
==== Similar questions ====
 
* None so far as I can tell..
 
 
 
 
 
<span id="question-8-5"></span>
=== Question 8 ===
 
 
 
<span id="question-88"></span>
==== Question ====
 
Describe the production, metabolism and role of lactate.
 
 
 
<span id="example-answer-88"></span>
==== Example answer ====
 
 
 
Production
 
* Lactate is a product of anaerobic metabolism
** Glucose is converted to pyruvate via glycolysis
*** Aerobic metabolism: Pyruvate is converted to Acetyl Coa and enters the TCA cycle &gt; oxidative phosphorylation (38 ATP per glucose)
*** Anaerobic metabolism: pyruvate is unable to be converted to Acetyl CoA and enter the TCA cycle. Instead it is converted into lactate (producing 2 ATP and regenerates NAD+ to allow glycolysis to continue)
* Lactate is produced mainly in skin, muscle, RBCs, brain, intestines
* Normal plasma levels are ~0.5-2mmols
* Increased lactate (&gt;2 mmols) may be due to numerous causes
** Physiological causes: E.g. exercise
** Hypoxaemia: e.g. Shock, anaemia, CO poisoning, hypoxia
** Disease: e.g. Sepsis, liver failure, thiamine def.
** Drugs/toxins: e.g. adrenaline, salbutamol, ethanol, biguanides, cyanide
** Congenital errors in metabolism: e.g. G6PD deficiency
 
 
 
Metabolism/fate
 
* Lactate produced intracellulary diffuses out of the cell
* Majority (80%) of circulating lactate is then metabolised in the liver via the cori-cycle
** Lactate is converted back to glucose via gluconeogenesis (consumes 6ATP), and can undergo glycolysis again
* Lactate can also be used as a fuel source, for example in the heart
 
 
 
Role
 
* Lactate sink
** Allows a period of ongoing ATP production from glycolysis during periods of hypoxia, TCA inhibition, pyruvate accumulation
* Lactate shuttle hypothesis
** Lactate is produced under aerobic+anaerobic conditions and may shuttle intra-cellularly and inter-cellularly to be used as sources of energy via gluconeogenesis
* Signalling molecule
** Emerging evidence that lactate
*** alters gene expression
*** may be involved in redox signalling
*** Mediate control of lipolysis
 
 
 
<span id="examiner-comments-88"></span>
==== Examiner comments ====
 
<blockquote>16% of candidates passed this question.<br />
Better answers used the categorisation in the question as a structure for their answer. Many candidates gave a good description of lactate production from glycolysis, increasing with accumulation of NADH and pyruvate, when these are unable to enter Krebs cycle. There were however, many vague and incorrect descriptions as to what lactate is and its physiological role. Many candidates suggested that its presence is abnormal or pathological. Most answers demonstrated a superficial understanding and physiological detail of lactate’s role as an energy currency in times of oxygen debt. Higher scoring candidates often mentioned non-hypoxic causes of pyruvate accumulation which include; circulating catecholamines, exercise, sepsis or lack or mitochondria (RBCs). Mention of the relative ATP production of the two fates of pyruvate was also noted in more complete answers. The Cori cycle was generally superficially described. A key role of lactate is the ‘lactate sink’, allowing a period of ongoing ATP production from glycolysis when cells become oxygen deplete or the Kreb’s cycle is inhibited; few candidates detailed or highlighted this.
</blockquote>
 
 
<span id="online-resources-for-this-question-88"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/20a/20a08-describe-the-production-metabolism-and-role-of-lactate/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2021/05/2020-1-08.pdf CICM Wrecks]
* Also used Ohs, LITFL, random websites
 
 
 
<span id="similar-questions-88"></span>
==== Similar questions ====
 
* Question 5, 2010 (1st sitting)
* Question 6, 2015 (2nd sitting)
 
 
 
 
 
<span id="question-9-5"></span>
=== Question 9 ===
 
 
 
<span id="question-89"></span>
==== Question ====
 
Outline the changes to drug pharmacokinetics and pharmacodynamics that occur at term in pregnancy.
 
 
 
<span id="example-answer-89"></span>
==== Example answer ====
 
 
 
Pharmakokinetics
 
* Absorption
** Oral
*** Nausea and vomiting in early preg &gt; reduced PO absorption
*** Increased intestinal blood flow (due to increased CO) &gt; increased PO absorption
*** Decreased gastric acid production &gt; increased pH &gt; unionised drugs absorbed more
*** Delayed gastric emptying peri-labour may increase/decrease absorption depending on drug
** IM / SC / Transdermal
*** Increased absorption due to increased CO + increased skin/muscle blood flow
** IV
*** Faster IV onset due to increased CO
** Neuraxial
*** Decreased peridural space &gt; decreased dose required
* Distribution
** Volume of distribution
*** Increased total body water &gt; increased Vd for hydrophilic drugs
*** Increased body fat &gt; increased Vd for lipophilic drugs
** Plasma proteins
*** Decreased protein binding (increased free fraction) due to reduced concentrations albumin and a-1 glycoprotein
* Metabolism
** Liver
*** Some metabolic enzymes reduced / some increased (due to progesterone/oestrogen ratio)
*** Leads to variable drug responses
**** E.g. increased metabolism of midazolam, phenytoin, but decreased caffeine.
** Placenta metabolises some drugs (?sig of effect)
** Decreased plasma cholinesterase (though no change in Succinylcholine effect)
* Elimination
** Renal
*** Increased clearance due to increased GFR (e.g. cefazolin)
** Hepatobiliary
*** Decreased clearance due to cholestatic effects of oestrogen (e.g. rifampacin)
** Resp
*** Increased volatile washout due to increased minute ventilation
 
 
 
Pharmacodynamics
 
* Increased sensitivity to volatile anaesthetics (decreased MAC)
* Increased sensitivity to IV anaesthetics
* Increased sensitivity to local anaesthetics
* Changed therapeutic indices due to risk of teratogenicity / fetal damage
 
 
 
<span id="examiner-comments-89"></span>
==== Examiner comments ====
 
<blockquote>7% of candidates passed this question.<br />
Answers framed around absorption, distribution, metabolism and excretion performed better. Some brief comments on physiology are required as the basis for pharmacokinetic change, but discussion of physiology that was not then specifically related to pharmacology did not score marks. Specific ‘real life’ examples necessitating change in practice or prescribing were well regarded e.g. reduction in spinal/epidural local anaesthetic dosing. Vague statements about possible or theoretical changes were less well regarded.
</blockquote>
 
 
<span id="online-resources-for-this-question-89"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2020/07/2020-1-09.pdf CICM Wrecks]
* [https://derangedphysiology.com/cicm-primary-exam/required-reading/variability-drug-response/Chapter%20241/changes-drug-response-during-pregnancy Deranged Physiology]
* [https://jennysjamjar.com.au/year/20a/20a09-outline-the-changes-to-drug-pharmacokinetics-and-pharmacodynamics-that-occur-at-term-in-pregnancy/ Jenny's Jam Jar]
* [https://journals.lww.com/anesthesia-analgesia/fulltext/2016/03000/pharmacokinetics_and_pharmacodynamics_of_drugs.26.aspx#:~:text=Increased%20plasma%20volume%20increases%20the,if%20the%20dosing%20is%20unchanged.&text=Albumin%20concentration%20decreases%20during%20the%20second%20trimester%20and%20declines%20further%20throughout%20pregnancy. Random journal article] and [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195457/ Another one]
 
 
 
<span id="similar-questions-89"></span>
==== Similar questions ====
 
* Question 11, 2011 (1st sitting)
* Question 16, 2016 (2nd sitting)
 
 
 
<span id="question-10-5"></span>
=== Question 10 ===
 
 
 
<span id="question-90"></span>
==== Question ====
 
Compare and contrast the pharmacology of noradrenaline and vasopressin.
 
 
 
<span id="example-answer-90"></span>
==== Example answer ====
 
{|
! Name
! Noradrenaline
! Argipressin
|-
| '''Class'''
| Endogenous catecholamine
| Endogenous nonapeptide
|-
| '''Indications'''
| Vasopressor (Hypotension/shock)
| Platelet dysfunction (vWD), hypotension/shock (catecholamine sparing), CNS diabetes insipidus
|-
| '''Pharmaceutics'''
| Clear solution. 1:1000. Brown ampule (prevent light oxidation). Diluted in dextrose.
| Clear colourless solution
|-
| '''Routes of administration'''
| IV only (central vein)
| IV infusion (central vein) for vasopressor support. Given IN/SC for other indications.
|-
| '''Dose'''
| Infusion titrated to effect (generally 0 - 0.5 mcg/kg/min)
| 2.4 units/hr (for vasopressor support)<br />
- At lower doses has predominant V1 activity, V2 activity at higher doses
|-
| pKA
|
|
|-
| '''Pharmacodynamics'''
|
|
|-
| MOA
| Predominately Alpha 1 agonism. Some beta adrenergic receptor agonism. a1 &gt; B1 &gt; B2
| Physiologically secreted by PVN of hypothalamus &gt; stored in posterior pituitary &gt; secreted in response to hypovolaemia + increased osmolality<br />
→ V1 receptor (blood vessels) agonism &gt; Vasoconstriction &gt; increased SVR &gt; increased BP <br />
→ V2 receptor (collecting ducts of nephrons) agonism &gt; increased water reabsorption &gt; increased BP<br />
→ V2 receptor (endothelial cells) agonism &gt; increased vWF release and Factor VIII activity
|-
| Effects
| CVS: peripheral vasoconstriction &gt; increased SVR &gt; inc. BP, reflex bradycardia, increased afterload (from SVR) &gt; decreased CO (minor), increased myocardial O2 consumption, no sig. change in dromotropy, lusitropy or inotropy<br />
CNS: decreased CBF (depending on BP), headache<br />
RESP: increased PVR, bronchodilation <br />
GIT/RENAL/uterine: vasoconstriction &gt; decreased BF<br />
MSK: extravasation &gt; necrosis <br />
| CVS: ACS, angina, arrhythmias<br />
HAEM: Excessive platelet aggregation / thrombosis <br />
RENAL: Hyponatraemia (increased water reabsorption &gt; Na reabsorption)<br />
GIT: abdominal pain , nausea, vomiting<br />
DERM: Ischaemia from vasoconstriction<br />
Allergic reactions (bronchospasm, urticarial rash, anaphylaxis)
|-
| '''Pharmacokinetics'''
|
|
|-
| Onset
| Immediate
| Fast (not as fast as noradrenaline)
|-
| Absorption
| IV only (0% oral bioavailability)
| IV only (0% oral bioavailability)
|-
| Distribution
| Does not cross BBB.<br />
Vd = 0.1L/kg <br />
Protein binding = 25%
| 20% protein bound, Vd 0.2L/Kg
|-
| Metabolism
| Readily metabolised by MAO and COMT into inactive metabolites (VMA, normetadrenaline). 25% taken up in lungs.
| Extensive hepatic and renal metabolism by serine proteases and oxido-reductase enzymes &gt; inactive metabolites
|-
| Elimination
| Excreted in urine as inactive metabolites (&gt;85%).<br />
Half life ~2 mins
| Renal elimination <br />
T <sub>1/2</sub> &lt;10 minutes
|-
| '''Special points'''
| Tachyphylaxis (slow)<br />
Effect exaggerated in patients taking MAOI (less breakdown)
|
|}
 
 
 
<span id="examiner-comments-90"></span>
==== Examiner comments ====
 
<blockquote>49% of candidates passed this question.<br />
These are both level 1 drugs regularly used in intensive care. Significant depth and detail of each<br />
drug were expected. Overall knowledge was deemed to be superficial and lacked integration.<br />
Better answers identified key points of difference and overlap in areas such as structure, pharmaceutics, pharmacokinetics, pharmacodynamics, mechanism of action, adverse effects<br />
and contraindications. A tabular list of individual drug pharmacological properties alongside each<br />
other did not score as well as answers which highlighted key areas of difference and similarities.
</blockquote>
 
 
<span id="online-resources-for-this-question-90"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/20a/20a10-compare-and-contrast-the-pharmacology-of-noradrenaline-and-vasopressin/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/07/2020-1-10.pdf CICM Wrecks]
* [https://derangedphysiology.com/required-reading/pharmacology-and-toxicology/Chapter%201.3.2/comparative-pharmacology-inotropes-and-vasopressors Deranged Physiology]
* [https://ketaminenightmares.com/pex/saqs/pharmacology/cardiovascular_drugs/2002B08_vasopressin.htm Ketamine nightmares] and [https://ketaminenightmares.com/pex/saqs/pharmacology/cardiovascular_drugs/2017B07_ephedrine_vs_noradrenaline.htm Ketamine Nightmares]
 
 
 
<span id="similar-questions-90"></span>
==== Similar questions ====
 
* None directly comparing these. Some a while back on norad or vaso individually
 
 
 
<span id="question-11-5"></span>
=== Question 11 ===
 
 
 
<span id="question-91"></span>
==== Question ====
 
Describe the structure and function of adult haemoglobin
 
 
 
<span id="example-answer-91"></span>
==== Example answer ====
 
 
 
Haemoglobin
 
* Metalloprotein found within erythrocytes (RBCs)
* 200-300 million molecules of Hb within each RBC
 
 
 
Structure
 
* Hb molecules are tetramer's consisting of four globular protein subunits
** Majority of adult blood contains 2x alpha and 2x beta globular subunits (HbA)
** Various other forms of Hb: HbA2 (adult), HbF (fetal), HbS (Sickle cell disease), etc.
** The make up of these subunits effects their capacity to bind + transport O2
* Each globular subunit is attached to one Haem group
* Each haem group contains:
** A protoporphyrin ring
** A central ion molecule in ferrous state (Fe2+)
 
 
 
Function
 
<ul>
<li><p>Oxygen transport</p>
<ul>
<li><p>Reversibly binds to oxygen and transports it around the body in the blood</p></li>
<li><p>One haem group can bind one O<sub>2</sub> molecule (each Hb molecule binds four O2 molecules), exhibits positive cooperativity.</p></li>
<li><p>Amount of binding is related to PAO2 (98% at 100mmHg, 75% at 40mmhg)</p></li>
<li><p>98% of oxygen in the blood is carried by Hb</p></li></ul>
</li>
<li><p>Carbon dioxide transport</p>
<ul>
<li><p>Reversibly binds to carbon dioxide to transport it away from the tissues to the lungs</p></li>
<li><p>Hb contributes to the CO2 transport by 2 mechanisms</p>
<ul>
<li><p>By directly forming carbo-amino compounds (30% CO2 evolved from lung)</p></li>
<li><p>As a proton acceptor for the RBC bicarbonate transport system (60% of CO2 evolved from lung)</p></li></ul>
</li></ul>
</li>
<li><p>Buffer</p>
<ul>
<li><p>Haemoglobin is the primary protein buffering system in the blood</p></li>
<li><p>It exists as a weak acid (HHb) and Base (KHb)</p></li>
<li><p>Buffers by binding excess H+ ions to the imidazole side chains of the histidine residues</p></li></ul>
</li>
<li><p>Nitric oxide regulation</p>
<ul>
<li><p>Hb is important in regulating NO function</p></li>
<li><p>Hb readily binds NO and can inactivate or transport it, thus regulating its activity.</p></li></ul>
 
<p></p></li></ul>
 
<span id="examiner-comments-91"></span>
==== Examiner comments ====
 
<blockquote>57% of candidates passed this question.<br />
Marks were awarded for the two components of this question – structure and function. The<br />
structure component was often only briefly described with a cursory overview provided; however,<br />
this component contributed around half of the available marks. Many candidates were unable to<br />
accurately describe the structural components of the haemoglobin molecule. The functional<br />
component was handled better – however much time was wasted with detailed drawings of the<br />
oxyhemoglobin curve (not many marks awarded for this). The basic function of haemoglobin<br />
carriage of oxygen and carbon dioxide was known, but detail was often missing about its role as<br />
a buffer or its role in the metabolism of nitric oxide.
</blockquote>
 
 
<span id="online-resources-for-this-question-91"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/20a/20a11-describe-the-structure-and-function-of-adult-haemoglobin/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/07/2020-1-11.pdf CICM Wrecks]
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2020-paper-1-saqs/question-11 Deranged Physiology]
 
 
 
<span id="similar-questions-91"></span>
==== Similar questions ====
 
<ul>
<li><p>Question 11, 2014 (1st sitting)</p></li>
<li><p>Question 14, 2016 (2nd sitting)</p>
<p></p></li></ul>
 
 
 
<span id="question-12-5"></span>
=== Question 12 ===
 
 
 
<span id="question-92"></span>
==== Question ====
 
Explain resonance and its significance and the effects of damping on invasive arterial blood pressure measurement.
 
 
 
<span id="example-answer-92"></span>
==== Example answer ====
 
 
 
Resonance
 
* Increase in the oscillations of a vibrating system when energy is applied to the system in harmonic proportions to the natural frequency of the system
 
 
 
Natural frequency
 
* Frequency at which a system oscillates when not subjected to repeated/continuous external forces, in the absence of damping
 
 
 
Resonance and IABP
 
<ul>
<li><p>An arterial waveform is the composite of many wave forms of increasing frequencies (harmonics)</p></li>
<li><p>At least 8 harmonics must be analysed to have sufficient resolution in the waveform</p></li>
<li><p>We do not want the arterial line system to oscillate at a frequency close to the heart rate</p></li>
<li><p>Commonly measured HR ranges 30 to 180/min = 0.5Hz to 3Hz </p></li>
<li><p>To minimise effects of resonance, the natural system of our arterial system must therefore be 8 harmonics above the frequency we are measuring (3Hz)</p></li>
<li><p>If 3Hz is the fastest HR we are measuring then 8x3 = 24Hz. Thus our system must be &gt;24Hz</p></li>
<li><p>To increase the natural frequency of the arterial line system we can use a short, wide, stiff catheter with no bubbles in tube</p>
<p></p></li></ul>
 
Damping
 
* Loss of energy in the system, which gradually reduces amplitude of oscillations
* Dampening is used to prevent large amplitude changes due to resonance when the natural frequency of the system is close to the transducers natural frequency
* There is an optimal level of damping (damping coefficient 0.64)which maximises frequency responsiveness
* Degree of damping can be assessed using the square wave (fast flush) test
 
 
 
Overdamped (coefficient &gt;0.7)
 
* Falsely low SBP
* Falsely high DBP
* Loss of fine waveforms
* MAP remains fairly accurate
 
 
 
Underdamped (coefficient &lt;0.6)
 
* Falsely high SBP
* Falsely low DBP
* MAP remains fairly accurate
 
 
 
<span id="examiner-comments-92"></span>
==== Examiner comments ====
 
<blockquote>23% of candidates passed this question.<br />
Many candidates gave detailed answers that involved the set up and components of the arterial<br />
line system that was not asked for in the question and did not attract marks. There was confusion<br />
around the correct use of the terms natural frequency, resonance frequency and harmonics –<br />
candidates that were able to describe these frequencies correctly went on to achieve a good mark<br />
– the graphs and discussion around optimal dampening, over and underdamped traces were<br />
often drawn poorly or without sufficient detail, and at times were not used within in the context of<br />
the answer. Descriptions of the clinical effect seen with over / under dampened traces on blood<br />
pressure was well described.
</blockquote>
 
 
<span id="online-resources-for-this-question-92"></span>
==== Online resources for this question ====
 
<ul>
<li><p>[https://intensiveblog.com/invasive-arterial-blood-pressure-measurement/ Intensive Blog]</p></li>
<li><p>[https://derangedphysiology.com/cicm-primary-exam/past-papers/2020-paper-1-saqs/question-12#answer-anchor Deranged Physiology] and [https://derangedphysiology.com/cicm-primary-exam/required-reading/cardiovascular-system/Chapter%20734/resonance-damping-and-frequency-response Deranged Physiology]</p></li>
<li><p>[chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/viewer.html?pdfurl=http%3A%2F%2Fwww.anaesthesia.uct.ac.za%2Fsites%2Fdefault%2Ffiles%2Fimage_tool%2Fimages%2F93%2F05-Arterial%2520Transducers%2520and%2520Damping%2520%2528G%2520Davies%2529.pdf&clen=592839&chunk=true Anaesthesia course]</p></li>
<li><p>[https://jennysjamjar.com.au/year/20a/20a12-explain-resonance-and-its-significance-and-the-effects-of-damping-on-invasive-arterial-blood-pressure-measurement/ Jenny's Jam Jar]</p></li>
<li><p>[chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/viewer.html?pdfurl=https%3A%2F%2Fcicmwrecks.files.wordpress.com%2F2020%2F07%2F2020-1-12.pdf&clen=388609&chunk=true CICM wrecks] and [chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/viewer.html?pdfurl=https%3A%2F%2Fcicmwrecks.files.wordpress.com%2F2017%2F04%2F2015-1-12-resonance-and-damping.pdf&clen=226337&chunk=true CICM Wrecks]</p>
<p></p></li></ul>
 
<span id="similar-questions-92"></span>
==== Similar questions ====
 
<ul>
<li><p>Question 24, 2012 (1st sitting)</p></li>
<li><p>Question 12, 2015 (1st sitting)</p></li>
<li><p>Question 17, 2017 (2nd sitting)</p>
<p></p></li></ul>
 
<span id="question-13-5"></span>
=== Question 13 ===
 
 
 
<span id="question-93"></span>
==== Question ====
 
Explain the control of breathing
 
 
 
<span id="example-answer-93"></span>
==== Example answer ====
 
 
 
Normal respiration
 
* 12-20 / min
* Normal tidal volumes ~6-8mls/kg (~500mls in 70kg adult)
* Normal minute ventilation ~6-10L/min
 
 
 
Voluntary control of respiration
 
* Mediated via the cerebral cortex via the corticospinal tracts and motor neurons of the muscle of respiration
 
 
 
Involuntary control of respiration
 
* Adjusts ventilation to adapt to the needs of the body
 
 
 
Sensors + afferents
 
* Peripheral chemoreceptors
** Located in carotid and aortic bodies
** Stimulated by fall in PaO2, rise in PaCO2, or fall in pH
** Afferents CN IX (carotid body) and CN X (aortic body)
* Central chemomreceptors
** Located at ventral medulla near the respiratory centre
** Detects change in CSF pH (due to CO2 diffusion across BBB)
* Mechanoreceptors
** Slow stretch receptors in the bronchial and lung tissue
** Activated by stretch
** Afferent is CN X
* Other inputs:
** Temperature (thalamus)
** Emotion (limbic system)
** Hormones (adrenaline)
** Lung water (J receptors in the lung)
** Baroreceptor reflex
 
 
 
Integrator/controller + efferents
 
* Respiratory centre in the medulla and pons
* Nucleus retroambiugualis (controls expiratory muscle group via UMN)
* Nucleus parambigualis (controls inspiratory muscle group via UMN)
* Nucleus ambigualis (pharyngeal muscle dilator function)
* Pre-botsinger complex (respiratory pacemaker &gt; phrenic nerve)
* Pontine respiratory group (prevents over expansion of the lung)
 
 
 
Effectors
 
* Muscles of respiration
** Pharyngeal muscles - dilate airway
** Laryngeal muscles - abduct vocal cords
** External intercostals - elevate ribs, move sternum forward &gt; increase AP + lateral diameter thoracic cavity
** Diaphragm = main inspiratory muscle &gt; increases intrathoracic volume
** Accessory muscles = SCM, pecs, scalene, abdominal muscles
 
 
 
<span id="examiner-comments-93"></span>
==== Examiner comments ====
 
<blockquote>53% of candidates passed this question.<br />
Most candidates provided a structured answer based around a sensor / central integration /<br />
effector model with appropriate weighting towards the sensor / integration component. Better<br />
answers provided an understanding of details of receptor function, roles of the medullary and<br />
pontine nuclei and how these are thought to integrate input from sensors. Marks were awarded<br />
to PaCO2 ventilation and PaO2 ventilation response when accurate, correctly labelled diagrams<br />
or descriptions were provided.
</blockquote>
 
 
<span id="online-resources-for-this-question-93"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2020-paper-1-saqs/question-13#answer-anchor Deranged Physiology]
* [https://cicmwrecks.files.wordpress.com/2020/07/2020-1-13.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/20a/20a13-explain-the-control-of-breathing/ Jennys Jam Jar]
 
 
 
<span id="similar-questions-93"></span>
==== Similar questions ====
 
<ul>
<li><p>Question 21, 2013 (1st sitting)</p></li>
<li><p>Question 2, 2015 (1st sitting)</p></li>
<li><p>Question 13, 2015 (2nd sitting)</p>
<p></p></li></ul>
 
 
 
<span id="question-14-5"></span>
=== Question 14 ===
 
 
 
<span id="question-94"></span>
==== Question ====
 
Describe the pharmacology of frusemide.
 
 
 
<span id="example-answer-94"></span>
==== Example answer ====
 
{|
! Name
! Furosemide
|-
| '''Class'''
| Loop diuretic
|-
| '''Indications'''
| Oedema/fluid overload, renal insufficiency, hypertension
|-
| '''Pharmaceutics'''
| Tablet, clear colourless solution (light sensitive),
|-
| '''Routes of administration'''
| IV, PO,
|-
| '''Dose'''
| Varies (~40mg daily commonly used for well patients, can be sig. increased)
|-
| pKA
| 3.6 (highly ionised; poorly lipid soluble)
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Binds to NK2Cl transporter in the thick ascending limb LOH, leads to decreased Na,K, Cl reabsorption &gt; decreased medullary tonicity + Inc Na/Cl delivery to distal tubules &gt; decreased water reabsorption &gt; diuresis
|-
| Effects
| Renal: diuresis<br />
CVS: hypovolaemia, arteriolar vasodilation + decreased preload (=mechanism for improvement of dyspnoea before diuretic effect)<br />
Renal: increase in RBF
|-
| Side effects
| CVS: hypovolaemia, hypotension<br />
Renal/metabolic: Metabolic alkalosis, LOW Na, K, Mg, Cl, Ca, increased Cr<br />
Ototoxicity, tinnitus, deafness
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| 5 mins (IV), 30-60 mins (PO), Effect lasts 6 hours.
|-
| Absorption
| Bioavailability varies person-person (40-80%)
|-
| Distribution
| Vd = 0.1L/Kg, 95% protein bound (albumin)
|-
| Metabolism
| &lt; 50% metabolised renally into active metabolite
|-
| Elimination
| Renally cleared (predominately unchanged). T1/2 ~90 mins.
|-
| '''Special points'''
| Deafness can occur with rapid adminsitration in large doses
|}
 
 
 
<span id="examiner-comments-94"></span>
==== Examiner comments ====
 
<blockquote>51% of candidates passed this question.<br />
Most candidates presented a well-structured answer and provided a basic understanding.<br />
Answers that provided accurate indications and details of the mechanism underlying the actions<br />
of frusemide attracted more marks. Those recognising the increased delivery of sodium and<br />
chloride to the distal tubule (exceeding resorptive capacity) were awarded more marks that those<br />
answers that attributed the diuretic action solely to reduction in the medullary gradient. Frusemide<br />
has many potential adverse effects and a reasonable list was expected. Conflicting information<br />
was common (e.g. highly bound to albumin – Vd 4 L/kg) and better answers avoided this.
</blockquote>
 
 
<span id="online-resources-for-this-question-94"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/required-reading/renal-system/Chapter%20022/furosemide Deranged Physiology]
* [https://partone.litfl.com/diuretics.html#id Part One, LITFL]
* [https://jennysjamjar.com.au/year/20a/20a14/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/07/2020-1-14.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-94"></span>
==== Similar questions ====
 
* Question 20, 2013 (1st sitting)
* Question 16, 2018 (1st sitting)
* Question 18, 2019 (1st sitting)
 
 
 
<span id="question-15-5"></span>
=== Question 15 ===
 
 
 
<span id="question-95"></span>
==== Question ====
 
Define bioavailability (10% of marks). Outline the factors which affect it (90% of marks).
 
 
 
<span id="example-answer-95"></span>
==== Example answer ====
 
 
 
Bioavailability
 
* The fraction of the drug dose reaching the systemic circulation, compared to an equivalent dose given intravenously.
* Can be calculated from the area under the concentration time curves for an identical bolus dose given non-intravenously (e.g. orally) and intravenously at the same time.
 
<math display="block">{Bioavailability} = \frac{AUC_{oral}}{AUC_{IV}}</math>
[[File:C:\Users\ethan\AppData\Roaming\Typora\typora-user-images\image-20210305141509389.png|thumb|none]]
 
 
 
Factors influencing bioavailability
 
* Preparation of the drug
** Preparation (e.g. solution &gt; capsule &gt; tablet &gt; coated tablet)
* Drug properties
** Molecular size (increase = decreased absorption)
** Degree of ionisation (non ionised - increased bioavailability)
** Lipid solubility (increased solubility = increased bioavailability)
* Route of administration
** Oral, transdermal, Subcutaneous, intramuscular, intranasal, inhaled etc.
* Drug interactions
** Drugs/food may interact/inactivate/bind to the drug
** e.g. absorption of tetracyclines reduced with concurrent administration of calcium such as in milk
* Patient factors
** Oral: Malabsorption syndromes (e.g. coeliac disease), gastric stasis (e.g. postop),
** IM/SC/Topical: Degree of tissue perfusion
** Pregnancy - alters gastric pH, intestinal motility
** Pharmacogenetic differences in absorption, metabolism of drugs (e.g. isoniazid)
* First pass metabolism
** Drugs absorbed via GIT pass via portal vein to liver and are subject to first pass metabolism (metabolised prior to reaching systemic circulation).
** May be impaired with hepatic insufficiency (increased bioavailability)
 
 
 
<span id="examiner-comments-95"></span>
==== Examiner comments ====
 
<blockquote>49% of candidates passed this question.<br />
Many candidates spent time defining and describing aspects of pharmacokinetics which were not<br />
relevant to the question. E.g. clearance, volume of distribution and half-life. Candidates who<br />
scored well utilised a structure which incorporated the headings of the factors which affect the<br />
bioavailability of medications with a simple description as to the nature of the effect. These factors<br />
included: the physical properties of the drug, the preparation, patient factors, the route of<br />
administration and metabolism amongst others.
</blockquote>
 
 
<span id="online-resources-for-this-question-95"></span>
==== Online resources for this question ====
 
<ul>
<li><p>[https://jennysjamjar.com.au/year/20a/20a15-define-bioavailability-10-of-marks-outline-the-factors-which-affect-it-90-of-marks-2/ Jennys Jam Jar]</p></li>
<li><p>[https://cicmwrecks.files.wordpress.com/2020/07/2020-1-15.pdf CICM Wrecks]</p></li>
<li><p>[https://derangedphysiology.com/cicm-primary-exam/past-papers/2020-paper-1-saqs/question-15#answer-anchor Deranged physiology]</p>
<p></p></li></ul>
 
<span id="similar-questions-95"></span>
==== Similar questions ====
 
* Question 22, 2017 (2nd sitting)
 
 
 
<span id="question-16-5"></span>
=== Question 16 ===
 
 
 
<span id="question-96"></span>
==== Question ====
 
Outline the formation, circulation and functions of cerebrospinal fluid
 
 
 
<span id="example-answer-96"></span>
==== Example answer ====
 
 
 
CSF
 
* ECF located in the ventricles and subarachnoid space
* ~2ml/kg
* Divided evenly between the cranium and spinal column
 
 
 
Formation
 
* Constantly produced
* ~550ml produced per day (~24mls/hr)
* Produced by
** Choroid plexus (70%) - located in ventricles of brain
** Capillary endothelial cells (30%)
* Produced by a combination of ultrafiltration (via fenestrated choroidal capillaries) and active secretion
** Na actively transported out. Gradient drives co-transport of HCO3 + Cl
** Glucose via facilitated diffusion, water by osmosis
 
 
 
Circulation
 
<ul>
<li><p>Circulation is driven by</p>
<ul>
<li><p>Ciliary movement of ependymal cells</p></li>
<li><p>Respiratory oscillations and arterial pulsations</p></li>
<li><p>Constant production and absorption</p></li></ul>
</li>
<li><p>CSF flows from </p>
<ul>
<li><p>Lateral ventricles &gt; foramen of Monro &gt; 3rd ventricle &gt; Sylvian aqueduct &gt; 4th ventricle &gt; cisterna magna (via foramen megendie and luschka) &gt; spreads between spinal/cranial subarachnoid spaces</p></li></ul>
</li>
<li><p>Reabsorption by the arachnoid villi</p>
<ul>
<li><p>Rate of ~24mls/hr</p></li>
<li><p>Located predominately in the dural walls of the sagittal + sigmoid sinuses</p></li>
<li><p>Function as one way valves, with driving pressure leading to absorption.</p>
<p></p></li></ul>
</li></ul>
 
Functions
 
* Mechanical protection
** The low specific gravity of CSF &gt; decreased effective weight of the brain (1500g &gt; 50g)
** With the reduced weight
*** Less inertia = less acceleration/deceleration forces
*** Suspended &gt; no contact with the rigid skull base
* Buffering of ICP
** CSF can be displaced / reabsorbed to offset any increase in ICP
* Stable extracellular environment
** Provides a constant, tightly controlled, ionic environment for normal neuronal activity
* Control of respiration
** The pH of CSF is important in the control of respiration (CO2 freely diffuses into CSF and can activate central chemoreceptors)
* Nutrition
** Provides a supply of oxygen, sugars, amino acids to supply the brain
 
 
 
<span id="examiner-comments-96"></span>
==== Examiner comments ====
 
<blockquote>81% of candidates passed this question.<br />
This is a three-part question and was marked as such. The circulation and functions of CSF was<br />
generally well answered. Formation of CSF, however, was answered poorly, with many candidates listing its composition instead. The examiners were looking for an understanding of the physiological processes of formation not the composition
</blockquote>
 
 
<span id="online-resources-for-this-question-96"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2020/07/2020-1-16.pdf CICM Wrecks]
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2020-paper-1-saqs/question-16#answer-anchor Deranged Physiology]
* [https://ketaminenightmares.com/pex/saqs/physiology/neurophysiology/2011B13_cerebrospinal_fluid.htm Ketamine Nightmares]
* [https://jennysjamjar.com.au/year/20a/20a16-outline-the-formation-circulation-and-functions-of-cerebrospinal-fluid/ Jenny's Jam Jar]
 
 
 
<span id="similar-questions-96"></span>
==== Similar questions ====
 
* Question 22, 2007 (1st sitting)
* Question 6, 2008 (2nd sitting)
* Question 2, 2013 (1st sitting)
* Question 16, 2015 (1st sitting)
* Question 24, 2017 (1st sitting)
* Question 15, 2018 (2nd sitting)
* Question 11, 2019 (1st sitting)
 
 
 
<span id="question-17-5"></span>
=== Question 17 ===
 
 
 
<span id="question-97"></span>
==== Question ====
 
Discuss the advantages and disadvantages of the use of an intravenous infusion of fentanyl in comparison to morphine.
 
 
 
<span id="example-answer-97"></span>
==== Example answer ====
 
 
 
Distribution
 
* Fentanyl
** Widely and rapidly distributed in tissues
** Thus will accumulate in tissues with sustained infusions
* Morphine
** Relatively less widely distribute and thus less likely to accumulate in tissues
 
 
 
Context sensitive half time (CSHT)
 
* due to the differences in distribution, fentanyl has an increased CSHT relative to morphine
* Therefore, the effects of morphine are less likely to be effected by the duration of infusions, whereas with fentanyl, increasing infusions will lead to longer time to wear off and in a less predictable manner
 
 
 
Metabolism
 
* Morphine
** Metabolised hepatically (hepatic insufficiency - prolonged effect)
** Active metabolites (accumulate in renal failure - prolonged effect)
* Fentanyl
** Metabolised by liver (thus hepatic insufficiency = prolonged effect)
** Does not have active metabolites
 
 
 
Lipid solubility
 
* Morphine = poor lipid solubility = prolonged CNS effect
* Fentanyl = good lipid solubility = reduced CNS effect
 
 
 
Protein binding
 
* Fentanyl has 90% protein binding, morphine 30%
* Thus low protein in critical ilness = increased effect of fentanyl (morphine less effected)
 
 
 
Other pharmocodynamics
 
* Morphine is a vasodilator (helpful in CCF, less so in septic shock)
* Fentanyl has no direct cardiovascular effects
* Fentanyl has a fast onset of action
 
 
 
Other
 
<ul>
<li><p>Fentanyl more expensive than morphine</p>
<p></p></li></ul>
 
<span id="examiner-comments-97"></span>
==== Examiner comments ====
 
<blockquote>27% of candidates passed this question.<br />
These are both level 1 drugs commonly used as an infusion in daily practice. This question specifically asked the candidates to frame their answers around an intravenous infusion of fentanyl in comparison to morphine. A tabular listing of general properties of the two drugs highlighting the differences between the drugs would not score well. The question asks for a considered response that should focus on context sensitive half-life, compartments and metabolism, instead many focused on the speed of onset and potency, which are minor considerations when drugs are given for long periods by infusion. Candidates often demonstrated a superficial knowledge of key pharmacokinetic concepts with limited application of these principles in the context of an intravenous infusion. Better answers also related the above to various relevant pharmacodynamic influences such as age, liver and renal impairment.
</blockquote>
 
 
<span id="online-resources-for-this-question-97"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/main/cicm-primary-exam/required-reading/nervous-system/Chapter%20334/pharmacology-opioids Deranged physiology]
* [https://jennysjamjar.com.au/year/20a/20a17-discuss-the-advantages-and-disadvantages-of-the-use-of-an-intravenous-infusion-of-fentanyl-in-comparison-to-morphine/ Jennys Jam Jar]
* [https://ccr.cicm.org.au/file/download-article?id=f0b726e8-fd2d-459a-84a5-49822f92d11e&settings=litnzgC1RAsiHS43rCo4xgM%2BVt2H30uE0mydKdrFKC4%3D Bellomo's paper]
 
 
 
<span id="similar-questions-97"></span>
==== Similar questions ====
 
* Question 16, 2011 (1st sitting)
* Question 12, 2016 (2nd sitting)
* Question 13, 2017 (2nd sitting)
 
 
 
<span id="question-18-5"></span>
=== Question 18 ===
 
 
 
<span id="question-98"></span>
==== Question ====
 
Describe the respiratory changes that occur throughout pregnancy
 
 
 
<span id="example-answer-98"></span>
==== Example answer ====
 
 
 
Anatomical changes
 
<ul>
<li><p>Diaphragm</p>
<ul>
<li><p>Ascends progressively (up to 4cm) throughout pregnancy due to mass effect from the foetus</p></li></ul>
</li>
<li><p>Chest wall</p>
<ul>
<li><p>Increased AP + Lateral chest wall diameters</p></li>
<li><p>Thoracic circumfrence increases</p></li>
<li><p>Due to effect of relaxin </p></li></ul>
</li>
<li><p>Increased oropharyngeal oedema (increased oestrogen)</p>
<p></p></li></ul>
 
Lung volumes
 
* Lung volume changes occur after trimester 1
* Mostly due to mass effect of pregnancy
** TLC decreases ~5%
** FRC decreases ~20%
** IC increases by 10%
** FRC decreased by 20%
** No change to closing capacity
 
 
 
Breathing + Mechanics
 
* Minute ventilation
** Increases by 50% (Due to increased TV and RR) - trimester 1
** Due to left shift of PaCO2 curve by progesterone
** Increases during labour due to pain
* Compliance
** chest wall compliance decreases due to increased abdominal contents (Trimester 1)
** Lung compliance stays the same
* Resistance
** Increased upper airway resistance due to mucosal oedema (due to oestrogen, progesterone)
 
 
 
Gas exchange / tension
 
* PaO2 increases
* PaCO2 decreases (increased minute ventilation) due to progesterone induced sensitivity to CO2
* Leads to compensated respiratory alkalosis (progesterone)
 
 
 
VO2
 
* Increased oxygen consumption (~20%) due to increased body mass + fetus
* Increases by up to 60% in labour
 
 
 
Post delivery
 
* FRC and TV return to normal within 5 days
 
 
 
<span id="examiner-comments-98"></span>
==== Examiner comments ====
 
<blockquote>31% of candidates passed this question.<br />
The question asked for a description of the respiratory changes throughout pregnancy, which includes labour. Simple lists of changes did not score highly. A straightforward structure including; first, second and third trimester delineation would have elevated many answers from below par to a pass. Many good answers gave succinct detail on both mechanical respiratory changes and the hormonal mechanisms behind them. Higher scoring answers also described the overall effect of individual changes to spirometry, geometry or respiratory control.
</blockquote>
 
 
<span id="online-resources-for-this-question-98"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/main/required-reading/pregnancy-obstetrics-and-gynaecology/Chapter%20114/respiratory-changes-during-pregnancy Deranged Physiology]
* [https://cicmwrecks.files.wordpress.com/2020/07/2020-1-18.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/20a/20a18-describe-the-respiratory-changes-that-occur-throughout-pregnancy/ Jennys Jam Jar]
* [https://ketaminenightmares.com/pex/saqs/physiology/obstetrics/2019A03_pregnancy_respiratory_effects.htm Ketamine Nightmares]
 
 
 
<span id="similar-questions-98"></span>
==== Similar questions ====
 
* Question 4, 2014 (1st sitting)
 
 
 
<span id="question-19-5"></span>
=== Question 19 ===
 
 
 
<span id="question-99"></span>
==== Question ====
 
Discuss the determinants of venous return to the heart.
 
 
 
<span id="example-answer-99"></span>
==== Example answer ====
 
 
 
Venous return
 
* Rate of blood flow back to the right atrium
* In healthy state: venous return = cardiac output (else pathological pooling of blood occurs)
* Can be defined by
** VR = MSFP - RAP / resistance to venous return
* Therefore factors effecting venous return are those that affect
** MSFP
** RAP
** Resistance to venous return
** Cardiac output
 
 
 
Cardiac output
 
* Increased CO = increased venous reutn
* CO is effected by
** Afterload (reduced afterload = increased cardiac output = increased VR)
** Contractility (increased contractility = increased CO = increased VR)
 
 
 
MSFP
 
* Normally ~7mmHg
* Increased MSFP = increased VR
* Affected by venomotor tone and blood volume
* Increased VR (= increased blood volume and increased venomotor tone)
 
 
 
RAP
 
* Increased RAP = reduced driving pressure = reduced venous return
* Factors which increase RAP
** Positive intrathoracic pressure (e.g. PPV)
** Reduced pericardial compliance (e.g. effusion)
** Reduced RA compliance/contractility (e.g. AF)
** TVR
 
 
 
Resistance to venous return
 
* Increased RVR = reduced VR (due to ohms law)
* Factors effecting RVR
** Autonomic tone
** Intrabdominal pressure
** IVC Obstruction (e.g. pregnancy) reduces VR
** Posture (decreased VR with erect posture)
** Vasoactive drugs
** skeletal muscle pump
 
 
 
<span id="examiner-comments-99"></span>
==== Examiner comments ====
 
<blockquote>67% of candidates passed this question.<br />
The factors that influence VR are captured in 2 formulae; VR = CO, and VR = (MSFP-RAP) / Venous Resistance. Candidates that used these as the backbone structure of their answer scored well. Quite a few candidates failed to consider factors that affect left heart CO also effect VR. Recognising that CO does = VR appeared to elude some candidates.
</blockquote>
 
 
<span id="online-resources-for-this-question-99"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/main/cicm-primary-exam/required-reading/cardiovascular-system/Chapter%200282/concept-venous-return Deranged physiology]
* [https://cicmwrecks.files.wordpress.com/2021/05/2020-1-19.pdf CICM wrecks]
* [https://jennysjamjar.com.au/year/20a/20a19/ Jenny's Jam Jar]
 
 
 
<span id="similar-questions-99"></span>
==== Similar questions ====
 
* Question 6, 2018 (2nd sitting)
 
 
 
<span id="question-20-5"></span>
=== Question 20 ===
 
 
 
<span id="question-100"></span>
==== Question ====
 
Outline the distribution, absorption, elimination, regulation and physiological role of phosphate.
 
 
 
<span id="example-answer-100"></span>
==== Example answer ====
 
 
 
Absorption
 
* Normal intake = ~0.5mmols/kg/day
* Absorbed in the intestine (duodenum, jejunum)
** Passive mechanism = paracellular = not regulated
** Active mechanism = cotransport with sodium = regulated
 
 
 
Distribution
 
* 85% = stored in bone/teeth
* 14% = intracellular
* 1% = extracellular fluid (half ionised, other half forms complexes/proteins)
** Normal serum level = 0.8-1.2 mmol/L
 
 
 
Elimination
 
* Renal
** Freely filtered in kidney
** Most is reabsorbed in proximal and distal tubules
** 2/3 of phosphate that is lost, is lost renally
* Stool
** 1/3 lost in stools
 
 
 
Regulation
 
<ul>
<li><p>Calcitriol</p>
<ul>
<li><p>Increased bone reabsorption</p></li>
<li><p>Increased Intestinal absorption</p></li>
<li><p>Increased Renal reabsorption</p></li></ul>
</li>
<li><p>PTH</p>
<ul>
<li><p>Decreased renal reabsorption</p></li>
<li><p>Increased bone resorption</p></li>
<li><p>Net effect =decrease in serum phosphate</p></li></ul>
</li>
<li><p>Thyroxine</p>
<ul>
<li><p>Increased renal reabsorption</p></li></ul>
</li>
<li><p>Glucocorticoids</p>
<ul>
<li><p>Decreased renal reabsorption</p></li></ul>
 
<p></p></li></ul>
 
Role
 
* Structural role
** bone and teeth formation
** Phospholipids of cell membranes, DNA, RNA
* Regulatory role
** Second messenger (IP3)
* Metabolic role
** Synthesis of ATP
** Acid base regulation (urinary and intracellular buffering)
** cofactor in oxygen transport (2-3 DPG)
 
 
 
<span id="examiner-comments-100"></span>
==== Examiner comments ====
 
<blockquote>29% of candidates passed this question.<br />
The answer structure should have utilized the headings provided in the question. Many candidates described the physiology of calcium, which while related, did not attract marks. The distribution section required not only the sites of distribution but also the percentages found in each. The regulation should have included both primary and secondary mechanisms and an outline on the factors affecting renal excretion, intestinal absorption and release from bone etc. An outline of the physiological role of phosphate required a broad knowledge of physiological processes.
</blockquote>
 
 
<span id="online-resources-for-this-question-100"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/20a/20a20-outline-the-distribution-absorption-elimination-regulation-and-physiological-role-of-phosphate/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/07/2020-1-20.pdf CICM Wrecks]
* [https://derangedphysiology.com/main/cicm-primary-exam/required-reading/body-fluids-and-electrolytes/Chapter%20122/distribution-phosphate-body-fluid-compartments Deranged physiology]
 
 
 
<span id="similar-questions-100"></span>
==== Similar questions ====
 
* ?None
 
 
 
 
 
 
 
<span id="2019-2nd-sitting"></span>
== 2019 (2nd sitting) ==
 
 
 
<span id="question-1-6"></span>
=== Question 1 ===
 
 
 
<span id="question-101"></span>
==== Question ====
 
Describe the physiological consequences of the oral ingestion of 1 litre of water in a young adult.
 
 
 
<span id="example-answer-101"></span>
==== Example answer ====
 
 
 
Handling of oral water ingestion
 
* Absorption
** Near complete absorption of water occurs in the proximal small intestine (85%), with 10% in large bowel, 5% in rectum.
** Most of the diffusion is transcellular and driven by osmosis (due to active absorption of other electrolytes, including sodium)
* Distribution
** Absorbed water distributes equally amongst all body fluid compartments, proportional to size
*** ~66% into the ICF (~667mls)
*** ~33% into the ECF (~333mls)
**** ~75% of which is interstitial fluid
**** ~21% of which is intravascular
**** ~4% of which is transcellular fluid
* Elimination
** Water is eliminated predominately by renal excretion
** Filtered water at the glomerulus is highly regulated
 
 
 
Physiological consequences of oral water ingestion
 
* Decrease in osmolality
** ~2.5% decrease in osmolality for 1L of oral water
** Sensed by osmoreceptors (hypothalamus) which have sensitivity of ~2% &gt; decrease in secretion of vasopressin from the posterior pituitary gland
** Decreased vasopressin &gt; decreased luminal aquaporin channel insertion in collecting ducts of nephrons &gt; decreased water reabsorption &gt; diuresis
* Decrease in plasma Na concentration
** Leads to release of angiotensin and aldosterone &gt; increased Na reabsorption in nephron
* Small increase in blood volume
** For 1L oral ingestion of water &gt; leads to ~70mls of intravascular water (33% of 1L goes to ECF, 21% of which is intravascular)
** This change is below the sensitivity threshold of the cardiovascular regulatory reflexes &gt; no change in blood pressure/HR of a normal healthy individual
 
 
 
<span id="examiner-comments-101"></span>
==== Examiner comments ====
 
<blockquote>28% of candidates passed this question.<br />
It was expected candidates would provide details the consequences of water ingestion from its rapid absorption in the small intestine to the resultant impact on plasma osmolarity and the minimal impact of plasma volume of this volume. Some detail on the mechanisms of absorption (transcellular vs osmosis) was expected and the distribution of water across body fluid spaces. Many candidates accurately described the small drop in plasma osmolarity that is sufficient to trigger osmoreceptors with better answers providing details of the locations and mechanisms involved. The physiological consequences of inhibition of ADH, including the renal effects of decreased water permeability in distal renal tubules and collecting ducts. The volume load after distribution would be lower than the plasma volume triggers for the circulatory reflex responses.
</blockquote>
 
 
<span id="online-resources-for-this-question-101"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/syllabus/i/i1/i1i-19b01-describe-the-physiological-consequences-of-the-oral-ingestion-of-1-litre-water-in-a-young-adult/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-2-01.pdf CICM Wrecks]
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2019-paper-2-saqs/question-1#answer-anchor Deranged Physiology]
 
 
 
<span id="similar-questions-101"></span>
==== Similar questions ====
 
* ? None
 
 
 
 
 
<span id="question-2-6"></span>
=== Question 2 ===
 
 
 
<span id="question-102"></span>
==== Question ====
 
Describe renal blood flow and its regulation (80% of marks). Outline the impact of adrenoreceptor agonists on renal blood flow (20% of marks).
 
 
 
<span id="example-answer-102"></span>
==== Example answer ====
 
 
 
Renal blood flow (RBF)
 
* Approximately 20-25% of cardiac output (1-1.25L/min)
* Majority of blood flow is distributed to the renal cortex (95%) compared to renal medulla (5%)
* Renal blood flow far exceeds metabolic requirements --&gt; to support the filter function of th ekidney
 
 
 
Anatomy of RBF
 
* Renal arteries &gt; interlobar arteries &gt; arcuate arteries &gt; interlobular arteries &gt; afferent arterioles &gt; glomerulus &gt; efferent arterioles &gt; peritubular capillaries &gt; venous system
* Venous system similarly named in reverse
 
 
 
Regulation of RBF
 
* Autoregulation
** Kidneys have the capacity to autoregulate (cortical nephrons can, juxtamedullary nephrons cant)
** Can maintain a constant RBF across a wide range in MAP (70-170mmHg)
** Two main mechanisms: myogenic autoregulation, tubuloglomerular feedback
** Myogenic autoregulation
*** Intrinsic contraction of the afferent arterioles in response to increased transmural pressures via release of vasoactive mediators
** Tubuloglomerular feedback
*** Increased RBF &gt; increased GFR &gt; increased Na/Cl sensed by macula densa &gt; releases adenosine &gt; constriction of afferent arterioles &gt; decreased RBF
*** Decreased RBF &gt; decreased GFR &gt; decreased Na/Cl at macula densa &gt; releases NO &gt; dilation &gt; increased RBF
* SNS
** Activation of adrenoreceptors &gt; constriction of arterioles &gt; decreased RBF
* Hormonal response
** Renin is released by B1 stimulation and decreased GFR
** AG2 constricts afferent and efferent arterioles &gt; decreased flow
 
 
 
Impact of adrenoreceptor agonists on RBF
 
* As mentioned, kidneys are innervated by SNS (adrenergic receptors)
* Massive SNS stimulus (e.g. shock, high dose adrenergic agonists) can override autoregulation
* Efferent arterioles constrict greater than afferent arterioles &gt; decrease in RBF, but the GFR is proportionally less effected (greater perfusion pressure)
* Effect of alpha adrenergic agonists
** Will act as renal vasoconstrictors &gt; decrease renal blood flow / GFR
** Examples: phenylephrine, metaraminol
* Effect of beta adrenergic agonists
** Will lead to increased RBF (vasodilator)
** Example: isoprenaline
* Non-selective adreneergic agonists
** Greater proportion of alpha &gt; beta receptors.
** Mixed agonists (e.g. adrenaline) will predominately lead to decreased flow (alpha predominance)
 
 
 
<span id="examiner-comments-102"></span>
==== Examiner comments ====
 
<blockquote>64% of candidates passed this question.<br />
This question was well answered by most candidates. The description of renal flow involves a brief comment of the anatomy including interlobar, arcuate, interlobular arteries, then afferent and efferent arterioles – 2 sets of capillaries and then corresponding veins and better answers made the distinction better cortical and medullary flow and went on to detail the consequence of this. Renal blood flow is autoregulated and most candidates describe well the various mechanisms around myogenic and tubuloglomerular feedback. Additional marks were gained with by discussing renal vascular resistance and how this may be varied. The impact of adrenoreceptor agonists is varied but generally sympathomimetic agents will vasoconstrict and therefore increase renovascular resistance and result in a decrease renal blood flow. The relative impact on afferent vs efferent arteriolar tone may alter glomerular perfusion pressure.
</blockquote>
 
 
<span id="online-resources-for-this-question-102"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2019-paper-2-saqs/question-2#answer-anchor Deranged Physiology]
* [https://jennysjamjar.com.au/year/19b/19b02/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-2-02.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-102"></span>
==== Similar questions ====
 
* Question 4, 2019 (1st sitting)
* Question 18, 2017 (1st sitting)
* Question 3, 2015 (2nd sitting)
* Question 11, 2012 (1st sitting)
* Question 21, 2011 (2nd sitting)
* Question 12, 2008 (2nd sitting)
 
 
 
 
 
<span id="question-3-6"></span>
=== Question 3 ===
 
 
 
<span id="question-103"></span>
==== Question ====
 
Describe the relationship between muscle length and tension (50% of marks). Outline the physiologic significance of this relationship in cardiac muscle (50% of marks).
 
 
 
<span id="example-answer-103"></span>
==== Example answer ====
 
 
 
Length-tension relationship
 
<ul>
<li><p>The tension generated within a single muscle fibre is related to its length</p></li>
<li><p>Total tension = passive tension + active tension</p></li>
<li><p>Passive tension</p>
<ul>
<li><p>Increases with increasing muscle length (modelled as a non-linear spring)</p></li></ul>
</li>
<li><p>Active tension</p>
<ul>
<li><p>Also varies with muscle length, but is described by the sliding filament model and has an optimal length at which maximal tension is generated</p></li>
<li><p>The physiological basis of this is due to different number of actin-myosin cross bridges formed at the different muscle lengths</p></li>
<li><p>The optimal myocardial sarcomere length is ~2.2 um (greatest overlap of actin-myosin filaments)</p></li></ul>
</li>
<li><p>The resting muscle length is often close to the optimal length for active tension</p>
<p></p></li></ul>
 
Cardiac muscle
 
* The muscle length-tension relationship forms an important part of the Frank-Starling law (strength of myocardial contraction is dependant on the initial muscle fibre length)
* With increase in diastolic filling of the heart &gt; increase stretch (preload) &gt; increased muscle length (increased cross bridge formation) &gt; increased force of contraction &gt; increased stroke volume
** Note: this mechanism is within limits. When the muscle length is too great, there is actually a reduction in cross bridge formation &gt; decreased SV
* Importance
** Ensures venous return = cardiac output (else pooling would occur)
** Allows beat-beat adjustments to variation in preload
 
 
 
<span id="examiner-comments-103"></span>
==== Examiner comments ====
 
<blockquote>41% of candidates passed this question.<br />
Some detail was expected on a general description that tension is variable with the length of muscle. It was expected answers would describe that there is a resting length at which tension developed on stimulation is maximal. Many candidates omitted that differences exist between muscle types with smooth muscle behaving differently. Additional credit was given for the distinction about active tension vs resting tension. It was expected a description of the potential mechanism would be included with discussion of sliding filament theory, overlapping fibres and optimal sarcomere length. Some candidates utilised a diagram effectively to convey understanding and more detail was rewarded with additional marks.<br />
The second half of the question involved describing how this relationship is particularly important in cardiac muscle and underpins the Frank Starling relationship and all the cardiac physiology that follows. Initial length of fibres is determined by the diastolic filling of the heart, so pressure developed is proportionate to the total tension developed. The developed tension increases as diastolic volume increases to a maximum (the concept of Heterometric regulation). Better answers appreciated that the physiology may be different for a whole heart rather than isolated muscle fibres.
</blockquote>
 
 
<span id="online-resources-for-this-question-103"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2019-paper-2-saqs/question-3 Deranged Physiology]
* [https://jennysjamjar.com.au/year/19b/19b03-describe-the-relationship-between-muscle-length-and-tension-50-of-marks-outline-the-physiologic-significance-of-this-relationship-in-cardiac-muscle-50-of-marks/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-2-03.pdf CICM Wrecks]
* [https://www.youtube.com/watch?v=4QM3v3gtP8o&ab_channel=CVPhysiologist CVS Physiology]
 
 
 
<span id="similar-questions-103"></span>
==== Similar questions ====
 
* ? None
 
 
 
 
 
<span id="question-4-6"></span>
=== Question 4 ===
 
 
 
<span id="question-104"></span>
==== Question ====
 
Outline the pharmacology of intravenously administered magnesium sulphate
 
 
 
<span id="example-answer-104"></span>
==== Example answer ====
 
{|
! Name
! Magnesium sulphate
|-
| '''Indications'''
| HypoMg, eclampsia/pre-eclampsia, severe asthma, arrhythmias (including TdP), analgesia
|-
| '''Pharmaceutics'''
| Clear colourless solution, various concentrations
|-
| '''Routes of administration'''
| IV, IO
|-
| '''Dose'''
| 10-20mmols
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Essential cation<br />
- Essential cofactor in hundreds of enzymatic reactions<br />
- Necessary in several steps of glycolysis (ATP production)<br />
- NMDA receptor antagonism (increasing seizure threshold)<br />
- Inhibits Ach release at NMJ<br />
- Smooth muscle relaxation (Inhibits Ca L-type channels)
|-
| Effects
| CNS: anticonvulsant<br />
Resp: Bronchodilation<br />
CVS: Anti-arrhythmic
|-
| Side effects
| Related to speed of administration + degree of HyperMg (dose dependant)<br />
CVS: Hypotension, bradycardia<br />
CNS/MSK: hyporeflexia, muscle weakness, CNS depression<br />
RESP: respiratory depression<br />
GIT: Nausea, vomiting
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| Immediate
|-
| Absorption
| N/A
|-
| Distribution
| 30% protein bound
|-
| Metabolism
| Nil
|-
| Elimination
| Urine; clearance is proportional to GFR and plasma concentration
|-
| '''Special points'''
| Incompatible with calcium salts &gt; precipitation<br />
Drug interaction with NMB agents (potentiation)
|}
 
 
 
<span id="examiner-comments-104"></span>
==== Examiner comments ====
 
<blockquote>55% of candidates passed this question.<br />
Overall answers were well structured. However, a lack of detail and inaccurate pharmacokinetics was common. Better answers included a discussion of the mechanism of action of Mg++ including Ca++ antagonism, presynaptic cholinergic effects and NMDA receptor antagonism. Adverse effects were not discussed in detail by many candidates and contraindications were commonly omitted.
</blockquote>
 
 
<span id="online-resources-for-this-question-104"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/21a/21a18-outline-the-pharmacology-of-intravenous-magnesium-sulphate/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2021/05/2021-1-18.pdf CICM Wrecks] and [https://cicmwrecks.files.wordpress.com/2017/04/2014-2-20-pharmacology-mgso4.pdf CICM Wrecks]
* [https://partone.litfl.com/magnesium.html PartOne, LITFL]
* [https://www.ncbi.nlm.nih.gov/books/NBK554553/ StatPearls]
* MIMS
 
 
 
<span id="similar-questions-104"></span>
==== Similar questions ====
 
* Question 10, 2011 (2nd sitting)
* Question 20, 2014 (2nd sitting)
* Question 10, 2015 (2nd sitting)
* Question 18, 2021 (1st sitting)
 
 
 
 
 
<span id="question-5-6"></span>
=== Question 5 ===
 
 
 
<span id="question-105"></span>
==== Question ====
 
Describe the anatomical course and relations of the trachea and bronchial tree (to the level of the segmental bronchi).
 
 
 
<span id="example-answer-105"></span>
==== Example answer ====
 
 
 
Trachea
 
* 10-12cm long fibromuscular tube
* Continuation of the larynx (at ~C6) and divides into the left and right main bronchi at the level of the carina (~T5)
* Relations
** Superior: larynx
** Anterior: manubrium, thyroid, brachiocephalic trunk, thymus
** Posteriorly: oesophagus, recurrent laryngeal nerve
** Right lateral: thyroid, right common carotid a., right vagus nerve, azygous vein. Eventually the right lung and pleura,
** Left lateral: thyroid, left common carotid, arch of aorta, left subclavian artery, left recurrent laryngeal nerve. Eventually the left lung and pleura,
 
 
 
Bronchi
 
* Left main bronchi
** 5cm long, courses leftward
** More horizontal and smaller diameter than right main bronchi
** Relations: azygos vein, right pulmonary artery (ant), pulmonary veins, oesophagus (post)
* Right main bronchi
** 2.5cm long, courses rightward
** More verticle and larger in diameter than left main bronchi
** Relations: pulmonary hilum - aortic arch, descending aorta, left pulmonary artery, left pulmonary veins
 
 
 
Lobar bronchi
 
* Each main bronchi gives rise to lobar bronchi
** Right: upper, middle and lower lobe bronchi
** Left: upper and lower lobe bronchi
* Each lobar bronchi gives rise to segmental bronchi
** 10 segmental bronchi on each side (left / right) corresponding to the 'bronchopulmonary segments'
** Left
*** LUL: Apical, Superior, Inferior, Anterior
*** LLL: Anterior, Lateral, Posterior, Superior
** Right
*** RUL: Apical, Posterior, Anterior
*** RML: Lateral, Medial,
*** RLL: Superior, Medial, Anterior, Lateral, Posterior
* Relations: predominately alveoli, pleura and accompanying pulmonary arteries/veins at this stage
 
 
 
Addit: mnemonics for remembering bronchopulmonary lung segments
 
* Right lung
** 'A PALM Seed Makes Another Little Palm'
*** RUL: Apical, Posterior, Anterior
*** RML: Lateral, Medial,
*** RLL: Superior, Medial, Anterior, Lateral, Posterior
* Left lung
** 'ASIA ALPS'
*** LUL: Apical, Superior, Inferior, Anterior
*** LLL: Anterior, Lateral, Posterior, Superior
 
<span id="examiner-comments-105"></span>
==== Examiner comments ====
 
<blockquote>24% of candidates passed this question.<br />
Better answers included details of the significant structures related to the cervical and mediastinal trachea and bronchi. The lobar branches and bronchopulmonary segments requiring naming to attract full marks. Many answers lacked sufficient detail or contained inaccuracies regarding vertebral levels and key structural relations. Some candidates discussed the general anatomy of the airway, including the larynx, structure of the airways, blood supply and innervation. This did not attract marks.
</blockquote>
 
 
<span id="online-resources-for-this-question-105"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2019-paper-2-saqs/question-5#answer-anchor Deranged Physiology]
* [https://jennysjamjar.com.au/year/19b/19b05/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-2-05.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-105"></span>
==== Similar questions ====
 
* Question 24, 2016 (2nd sitting)
 
 
 
 
 
<span id="question-6-6"></span>
=== Question 6 ===
 
 
 
<span id="question-106"></span>
==== Question ====
 
Outline the factors that determine central venous pressure and explain how it is measured.
 
 
 
<span id="example-answer-106"></span>
==== Example answer ====
 
 
 
Overview
 
* CVP is the venous blood pressure measured at or near the right atrium
* Normally 0-6mmHg in spontaneously breathing non-ventilated patient
* Measurement taken at end-expiration
 
 
 
Measurement
 
* Most commonly measured using central venous catheter (CVC)
** CVC tip sits at or near the right atrium
** CVC is connected to a pressure transducer via incompressible tubing with flush solution
** Transducer is zeroed to the atmospheric pressure and levelled at the height of the right atrium
* Echocardiography can provide non-invasive estimations off the CVP
* Visual inspection of the height of the JVP can provide some bedside clinical insight
 
 
 
Factors determining CVP
 
* Central venous blood volume
** Increased total blood volume (e.g. renal failure) = increased MSFP &gt; increased CVP
** Decreased CO (e.g. LV failure) &gt; blood backs up &gt; increased thoracic blood volume &gt; increased CVP
* Central venous vascular compliance
** Increased vascular tone central veins (e.g. noradrenaline) &gt; decreased compliance &gt; increased CVP
** Decreased myocardial/pericardial compliance &gt; increased CVP
** Decreased pulmonary arterial compliance &gt; increased CVP
* Tricuspid valve function
** TV regurg &gt; increased CVP (retrograde transmission of RV systolic pressure)
** TV stenosis &gt; increased CVP (increased resistance to RV inflow)
* Intrathoracic pressure
** ITP is transmitted to the central venous compartment
** Thus, increased PEEP, PPV, or a tension pneumothorax will lead to increased CVP
* Measurement technique
** Level of the transducer will clearly influence the CVP measured
** Timing of the measurement with respiratory cycle
 
 
 
<span id="examiner-comments-106"></span>
==== Examiner comments ====
 
<blockquote>18% of candidates passed this question.<br />
It was expected that answers include central venous blood volume, central venous vascular compliance, intrathoracic pressure and tricuspid valvular function. Good answers outlined how each of these factors determine CVP and whether it was increased or decreased. Many candidates incorrectly described the effect of venous return.
</blockquote>
 
 
<span id="online-resources-for-this-question-106"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2019-paper-2-saqs/question-6 Deranged Physiology]
* [https://jennysjamjar.com.au/year/19b/19b06/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-2-06.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-106"></span>
==== Similar questions ====
 
* Question 5, 2021 (1st sitting)
 
 
 
 
 
<span id="question-7-6"></span>
=== Question 7 ===
 
 
 
<span id="question-107"></span>
==== Question ====
 
Define closing capacity (10% of marks). Describe the factors that alter it (30% of marks), its clinical significance (30% of marks) and one method of measuring it (30% of marks).
 
 
 
<span id="example-answer-107"></span>
==== Example answer ====
 
 
 
Closing capacity
 
* The point in expiration when the small airways begin to collapse
* Small airway closure occurs because the elastic recoil of the lung overcomes the negative intrapleural pressure keeping the airway open.
* More likely to occur in dependant parts of the lung where airways are smaller (due to effects of gravity).
* Closing capacity = residual volume + closing volume
 
 
 
Significance of closing capacity
 
* If closing capacity exceeds the FRC then small airway collapse occurs during tidal respiration
** This leads to shunt &gt; V/Q mismatch &gt; impairs oxygenation &gt; hypoxaemia
** This also leads to gas trapping &gt; reduced compliance
* High CC will therefore also
** Decrease the effect of anaesthetic pre-oxygenation
** Increases dependant atelectasis.
*** Cyclic opening/closing of airways due to increased atelectasis &gt; lung injury
 
 
 
Factors affecting closing capacity
 
* Age
** Normally CC is less than FRC at a young age
** Increasing age &gt; increasing closing capacity
*** At age 44, supine FRC = closing capacity
*** At age 66, erect FRC = closing capacity
* Expiratory gas flow
** Increase flow &gt; increased closing capacity
* Pathology
** Parenchymal/airway disease (e.g. COPD) &gt; loss of tissue available for radial traction &gt; (closing capacity &gt; FRC)
** Decreased surfactant &gt; increased surface tension &gt; increasing collapsing pressure &gt; increased CC
** Increased pulmonary blood volume (e.g. CCF) &gt; increased weight compressing small airways &gt; increased CC
 
 
 
Measurement of CC
 
* Closing capacity = closing volume + residual volume
* Closing volume
** Measured using the single breath nitrogen washout test
** Subject exhales to residual volume
** Pure oxygen inhaled to TLC
** Subject breaths out through a nitrogen sensor (records N2 concentration vs time curve)
** Phase 4 of this curve indicates the closing volume.
* Residual volume
** Cannot be directly measured
** FRC is first calculated by body plethysmography (or other methods)
** ERV measured using spirometry
** Residual volume is the difference between FRC and ERV
 
 
 
<span id="examiner-comments-107"></span>
==== Examiner comments ====
 
<blockquote>49% of candidates passed this question.<br />
Many candidates confused the factors that affect closing capacity (CC) with factors which affect functional residual capacity (FRC). Some candidates confused airway closure with expiratory flow limitation secondary to dynamic airway compression. A good answer would have included the following:<br />
Small airway closure occurs because the elastic recoil of the lung overcomes the negative intrapleural pressure keeping the airway open. Thus, airway closure is more likely to occur in dependant parts of the lung where airways are smaller. Normally closing capacity is less than FRC in young adults but increases with age. Closing capacity becomes equal to FRC at age 44 in the supine position and equal to FRC at age 66 in the erect position. Closing capacity is increased in neonates because of their highly compliant chest wall and reduced ability to maintain negative intrathoracic pressures. In addition, neonates have lower lung compliance which favours alveolar closure. Closing capacity is also increased in subjects with peripheral airways disease due to the loss of radial traction keeping small airways open.<br />
The consequences of airway closure during tidal breathing include shunt and hypoxaemia, gas trapping and reduced lung compliance. In addition, cyclic closure and opening of peripheral airways may result in injury to both alveoli and bronchioles. Closing volume (CV) may be measured by the single breath nitrogen washout test or by analysis of a tracer gas such as xenon during a slow exhaled vital capacity breath to residual volume. Residual volume (RV) cannot be measured directly but is calculated as follows: the FRC is measured using one of three methods: helium dilution, nitrogen washout or body plethysmography. The expiratory reserve volume (ERV) may be measured using standard spirometry. Using the measured FRC and ERV we may calculate RV from the equation:<br />
RV = FRC – ERV. Then CC = RV + CV.
</blockquote>
 
 
<span id="online-resources-for-this-question-107"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2019-paper-2-saqs/question-7 Deranged Physiology]
* [https://jennysjamjar.com.au/year/19b/19b07/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-2-07.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-107"></span>
==== Similar questions ====
 
* None
 
 
 
 
 
<span id="question-8-6"></span>
=== Question 8 ===
 
 
 
<span id="question-108"></span>
==== Question ====
 
Outline the pharmacology of drugs used to treat asthma.
 
 
 
<span id="example-answer-108"></span>
==== Example answer ====
 
 
 
Oxygen
 
* Increases FiO2 &gt; increased SaO<sub>2</sub> (by increasing P<sub>A</sub>O<sub>2</sub> as per Alveolar gas equation).
* Given by numerous devices (nasal prongs, masks, NIV, ETT)
* Dose titrated to SaO<sub>2</sub>
** Hypoxemia is harmful (but optimal target SaO<sub>2</sub> unclear)
** Generally titrated to Sats 94-98% (with caveats for some subgroups of patients)
** Hyperoxia may lead to hypercapnia, worsening of V/Q mismatch (through alteration of HPVC), lung damage
 
 
 
Beta-adrenergic agonists
 
* Long acting B2 selective agonists (e.g. salmeterol) are used in prevention
* Short acting B2 selective agonists (e.g. salbutamol) are preferred first line therapy for exacerbation
* Nonselective adrenergic agonists (e.g. adrenaline) can also be used in severe exacerbations
* SABAs can be given inhaled (via spacer), nebulised or via IV infusion (if unresponsive to inhaled)
* Example: Salbutamol
** Short acting B2 agonist
** MOA: Acts on B<sub>2</sub> receptors (Gs protein coupled receptors) in bronchial smooth muscle cells &gt; activates activates adenyl cyclase-CAMP system &gt; increase cAMP &gt; decreased intracellular Ca &gt; SM relaxation / bronchodilation
** Side effects: Tachycardia, Anxiety, tremor, Hypokalaemia, lactic acidosis
 
 
 
Anticholinergics
 
* Example: ipratropium bromide
* Routes: Inhaled, nebuliser
* MOA: Competitive antagonism of muscarinic ACh receptors &gt; bronchodilation + decreased secretions
* Side effects: dry mouth, N/V, headache, blurred vision
 
 
 
Corticosteroids
 
* Examples: hydrocortisone (IV), prednisone (PO), budesonide (inhaled)
* Systemic corticosteroids should be given to all mod-severe asthma &gt; improve outcomes
* MOA: bind to cytoplasmic glucocorticoid receptors &gt; change in gene transcription &gt; down-regulates the synthesis of proinflammatory cytokines/mediators
* Effects: increased B receptor responsiveness, decreased inflammation, decreased mucus secretion
* Side effects: numerous! Depends on dose/duration. Examples:
** Short term: hyperglycaemia, hypokalaemia, immunosuppression, insomnia/confusion/psychosis,
** Long term: cushings, osteoporosis, skin thinning, weight gain, immunosuppression
 
 
 
Other potential treatment options (and MOA)
 
* Magnesium sulphate &gt; inhibits L type calcium channels &gt; bronchodilation/SM relaxation
* Ketamine &gt;inhibits L type calcium channels &gt; Bronchial smooth muscle relaxation
* Aminophylline &gt; PDEI &gt; SM relaxation / bronchodilation
* Heliox &gt; Improves laminar airflow &gt; may improve ventilation
 
 
 
<span id="examiner-comments-108"></span>
==== Examiner comments ====
 
<blockquote>29% of candidates passed this question.<br />
Answers should have included the most important aspects of the pharmacology of the most commonly used drugs e.g. class, mechanism of action, pharmacodynamics and important adverse reactions. More information on beta-agonists and corticosteroids (mainstays of management) was expected than drugs like magnesium, ketamine and other adjunctive treatments.
</blockquote>
 
 
<span id="online-resources-for-this-question-108"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2019-paper-2-saqs/question-8 Deranged Physiology]
* [https://jennysjamjar.com.au/year/19b/19b08/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-2-08.pdf CICM Wrecks]
* [https://partone.litfl.com/anti-asthma_drugs.html#id Part One, LITFL]
 
 
 
<span id="similar-questions-108"></span>
==== Similar questions ====
 
* Question 12, 2019 (1st sitting)
* Question 4, 2016 (2nd sitting)
* Question 11, 2014 (2nd sitting)
* Question 9, 2010 (1st sitting)
 
 
 
 
 
<span id="question-9-6"></span>
=== Question 9 ===
 
 
 
<span id="question-109"></span>
==== Question ====
 
Compare and contrast the pharmacology of propofol and midazolam.
 
 
 
<span id="example-answer-109"></span>
==== Example answer ====
 
{|
! Name
! Midazolam
! Propofol
! Notes/comparisons
|-
| '''Class'''
| Benzodiazepine (sedative)
| Phenolic derivative (IV anaesthetic)
| -
|-
| '''Indications'''
| Anaesthesia, sedation, treatment of seizures, anxiolysis
| Anaesthesia, sedation
| -
|-
| '''Pharmaceutics'''
| IV: clear solution, pH 3.5. High water solubility
| White, opaque, liquid emulsion. Contains soybean oil, egg lecithin, glycerol. Poor water solubility
| Midaz clear, propofol distinctive white colout
|-
| '''Routes of administration'''
| IV, IM, S/C, intranasal, buccal, PO
| IV
|
|-
| '''Dose'''
| Dose depends on many pt. factors. 1-5mg premedication. 2.5-10mg seizures. Infusions.
| RSI 1-2mg/kg. Infusion (4-12mg/kg/hr)
|
|-
| pKa
| 6.5
| 11 (almost completely unionised)
| Propofol has higher pKa
|-
| '''Pharmacodynamics'''
|
|
|
|-
| MOA
| Allosteric modulator of GABA<sub>A</sub> receptors (ionotropic ligand gated channel) in the CNS. Binds to distinct site from GABA. Leads to Cl enters &gt; hyperpolarisation.
| Propofol binds to B subunit of GABA<sub>A</sub> receptor &gt; Cl enters &gt; hyperpolarisation
| Midaz binds to site distinct from GABA
|-
| Effects
| CNS: sedation, amnesia, anticonvulsant effects, decreased cerebral O2 demand
| CNS: depression, anti-epileptic, decreased CMRO2/CBF/ICP <br />
RESP: depression, apnoea
| Both cause sedation and respiratory depression
|-
| Side effects
| CVS: bradycardia, hypotension<br />
CNS: confusion, restlessness<br />
RESP: respiratory depression/ apnoea
| RENAL: green urine <br />
CNS: depression, pain injection site <br />
CVS: decreased SVR &gt; hypotension, bradycardia<br />
MET: high lipids
| Both cause cardiovascular instability and respiratory depression
|-
| '''Pharmacokinetics'''
|
|
|
|-
| Onset
| peak effect 2-3 minutes (IV)
| Seconds
| Propofol has faster onset / offset
|-
| Absorption
| ~40% oral bioavailability<br />
Absorbed well, but sig. 1st pass metabolism
| IV Only (high first pass metabolism)
| Propofol is IV only
|-
| Distribution
| 95% protein bound, very lipid soluble<br />
Vd = 1L / kg
| 98% protein bound<br />
VOD 2-10L/kg<br />
Readily crosses BBB
| Both highly protein bound.
|-
| Metabolism
| Hepatic metabolism by hydroxylation <br />
Active (1-a hydroxymidazolam) and inactive metabolites
| Hepatic &gt; inactive metabolites (glucuronides and sulphates)
| Both metabolised by liver. Midaz has active metabolites
|-
| Elimination
| Renal excretion<br />
T 1/2 = 4 hours
| Renal excretion <br />
Bolus T1/2 - 120s.
|
|-
| '''Special points'''
| Flumazenil - antagonist (reversal agent)
| No reversal agent
|
|}
 
 
 
<span id="examiner-comments-109"></span>
==== Examiner comments ====
 
<blockquote>77% of candidates passed this question.<br />
Highlighting important similarities and differences between the drugs scored higher marks than listing the pharmacology of each drug separately. More pharmacokinetic information was required than simply stating both drugs “are metabolized in the liver and excreted by the kidney”.
</blockquote>
 
 
<span id="online-resources-for-this-question-109"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2019-paper-2-saqs/question-9 Deranged Physiology]
* [https://jennysjamjar.com.au/year/19b/19b09/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/02/2019-2-09.pdf CICM Wrecks]
* [https://partone.litfl.com/propofol.html#id Part One - Propofol] and [https://partone.litfl.com/benzodiazepines.html Part One - Benzos]
 
 
 
<span id="similar-questions-109"></span>
==== Similar questions ====
 
* Midazolam
** Question 7, 2019 (1st sitting)
** Question 9, 2019 (2nd sitting)
** Question 4, 2018 (2nd sitting)
** Question 24, 2016 (1st sitting)
** Question 2, 2008 (2nd sitting)
* Propofol
** Question 11, 2017 (2nd sitting)
** Question 14, 2015 (2nd sitting)
** Question 21, 2013 (2nd sitting)
** Question 5, 2012 (1st sitting)
** Question 20, 2008 (2nd sitting)
 
 
 
 
 
<span id="question-10-6"></span>
=== Question 10 ===
 
 
 
<span id="question-110"></span>
==== Question ====
 
Describe the principles of capnography, including calibration, sources of error and limitations.
 
 
 
<span id="example-answer-110"></span>
==== Example answer ====
 
 
 
Capnography
 
* The graphical display of expired CO<sub>2</sub> concentration over time
* This is different to ETCO<sub>2</sub> (which is the CO<sub>2</sub> concentration at end-expiration) and capnometry (which is the measurement of CO<sub>2</sub> concentration)
 
 
 
Measurement / Principles
 
<ul>
<li><p>CO<sub>2</sub> concentrations (capnometry) is measured in clinical practice using infrared spectroscopy and applying the principles of the Beer-Lambert Law</p>
<ul>
<li><p>The concentration of CO<sub>2</sub> is measured by exploiting the differences in CO2 absorption of light in the NIR spectrum. With the degree of absorption related to concentration of substance. </p></li></ul>
</li>
<li><p>Components: light emitting diode, photosensor, circuitry, microprocessor, output device</p></li>
<li><p>Can be monitored using 'side stream' (sampling line with sensor) or 'inline' (sensor directly inline with breathing system) methods</p></li>
<li><p>Calibration: capnometers are zeroed to room air</p>
<p></p></li></ul>
 
Limitations + Sources of error
 
* Cannot distinguish Nitrous Oxide (N<sub>2</sub>O shares similar absorption spectra to CO<sub>2</sub>)
* Not diagnostic
** Waveforms are helpful in assessment (e.g. of bronchospasm, oesophageal intubation) but not diagnostic
** Patients may have mixed disorders which lead to increased and decreased ETCO<sub>2</sub> which are cancelled out and appear falsely normal
* Side stream monitoring have short delay in measurement and small air leak
* In line monitoring devices increase dead space (more relevant in paeds)
* Sensor is susceptible to blockage by secretions
* Incorrect calibration
* Water condensation &gt; absorbs IR light &gt; overestimates CO2
 
 
 
<span id="examiner-comments-110"></span>
==== Examiner comments ====
 
<blockquote>31% of candidates passed this question.<br />
Answers that scored well followed the structure outlined in the question and explained the principles of each component of the question.
</blockquote>
 
 
<span id="online-resources-for-this-question-110"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2019-paper-2-saqs/question-10 Deranged Physiology]
* [https://jennysjamjar.com.au/year/19b/19b10-describe-the-principles-of-capnography-including-calibration-sources-of-error-and-limitations/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-2-10.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-110"></span>
==== Similar questions ====
 
* Question 9, 2015 (2nd sitting)
 
 
 
 
 
<span id="question-11-6"></span>
=== Question 11 ===
 
 
 
<span id="question-111"></span>
==== Question ====
 
Outline the composition of plasma (50% of marks). Describe the functions of albumin (50% of marks).
 
 
 
<span id="example-answer-111"></span>
==== Example answer ====
 
 
 
Plasma
 
* Cell free liquid component of blood
* Constitutes ~55% of circulating blood volume
* Components
** 92% water
** 7% proteins (Albumin, globulin, fibrinogen)
** ~1% other (carbohydrates, lipids, gases, hormones, electrolytes)
 
 
 
Proteins (~7% plasma)
 
* 60-80g/L in blood
* Albumin
** Majority of plasma protein (35-45g/L)
* Globulins
** Second largest component (25-35g/L)
** Subtypes
*** <math display="inline">\alpha</math>1 globulin (<math display="inline">\alpha</math>1 antitripsin, <math display="inline">\alpha</math>-lipoproteins)
*** <math display="inline">\alpha</math>2 globulin (Haptoglobin, prothrombin, <math display="inline">\alpha</math>2 macroglobulin)
*** <math display="inline">\beta</math>-globulins (CRP, transferrin)
*** <math display="inline">\gamma</math> globulins (Immunoglobulins)
* Fibrinogen
** 1-5 g/L
* Clotting factors
 
 
 
Other solutes (~1% plasma)
 
* Carbohydrates (i.e. glucose)
* Lipids (e.g. LDL, VLDL, HDL, TGs)
* Gases (e.g. oxygen, carbon dioxide)
* Hormones (e.g. thyroxine, cortisol, IGF-1)
* Electrolytes (e.g. Na, Cl, HCO3, K, Mg, Ca)
 
 
 
Albumin (functions)
 
* Osmotic pressure
** Responsible for 80% of the plasma colloid osmotic pressure
** Helps keep fluid intravascularly
* Transport function
** Transports hormones (e.g. thyroxine), fatty acids, electrolytes (e.g. calcium) and drugs
* Extracellular acid-base buffer
** Imidazole side chains can bind hydrogen ions and can buffer against change to pH
* Anticoagulant
** Has heparin like activity. Low albumin attenuates fibrinolysis
* Protein store:
** ~50-60% of plasma protein
* Anti-oxidant effect
** Abundant in thio groups which readily scavenge reactive oxygen and nitrogen species
* Inflammatory marker
** Negative phase protein (decreases in response to inflammation)
 
 
 
<span id="examiner-comments-111"></span>
==== Examiner comments ====
 
<blockquote>30% of candidates passed this question.<br />
A good answer began with a definition of plasma and then listed the components - water, albumin, globulins, fibrinogen and other proteins before mentioning the lipid content, nutrient content, wastes and electrolytes. Frequently the breakdown of the globulin component was inaccurate. A common omission was dissolved gas components. Descriptions of the calculation of oncotic pressure and GFR were not asked and hence did not attract marks.<br />
The functions of albumin may be subdivided into: Osmotic pressure, transport function, acid-base buffer, anti-oxidant, anticoagulant effect, protein store, metabolism and 'other'.
</blockquote>
 
 
<span id="online-resources-for-this-question-111"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2019-paper-2-saqs/question-11 Deranged Physiology]
* [https://jennysjamjar.com.au/year/19b/19b11-outline-the-composition-of-plasma-50-of-marks-describe-the-functions-of-albumin-50-of-marks/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/02/2019-2-11.pdf CICM Wrecks]
* [https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-017-0111-x NCBI]
 
 
 
<span id="similar-questions-111"></span>
==== Similar questions ====
 
* Question 16, 2012 (2nd sitting)
 
 
 
 
 
<span id="question-12-6"></span>
=== Question 12 ===
 
 
 
<span id="question-112"></span>
==== Question ====
 
Define pain. Outline the processes by which pain is detected in response to a peripheral noxious stimulus
 
 
 
<span id="example-answer-112"></span>
==== Example answer ====
 
 
 
Pain
 
* &quot;An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage&quot; (IASP, 2020)
* Can be broadly classified by duration (e.g. acute vs chronic) or aetiology (e.g. visceral vs neuropathic)
 
 
 
PAIN PATHWAY
 
 
 
Nociceptors
 
* Free unmyelinated nerve endings which convert noxious stimuli into action potentials (APs)
* Activation
** Activated by thermal, mechanical, and chemical stimuli
** Sensitised by inflammatory mediators (e.g bradykinin, histamine, Substance P)
* Leads do conformational change in nociceptor &gt; ion channel opening &gt; depolarisation
* Relay APs from the nociceptor receptor to the dorsal horn of the spinal cord (primary afferent)
** Neuron may travel up/down the tract of Lissauer 1-2 levels prior to synapsing in the dorsal horn
* Two types of nociceptor neurons
** Type A<math display="inline">\delta</math> fibres
*** Impulses from mechanical and thermal stimuli
*** Large, myelinated, fast (40m/s)
** Type C fibres
*** Impulses from thermal, mechanical and chemical stimuli
*** Small, unmyelinated, slow (2m/s)
 
 
 
Second order neurons (afferent)
 
* Synapse with primary afferents in Dorsal horn
* Decussates in the anterior commissure, ascends in the spinothalamic tract, synapses in the thalamus with third order neurons
 
 
 
Third order neuron (afferent)
 
* Relays information from the thalamus to the cerebral cortex for central processing of pain
 
 
 
PAIN MODULATION
 
<ul>
<li><p>Descending inhibition</p>
<ul>
<li><p>Neurons from periaqueductal grey matter project to the spinal cord</p></li>
<li><p>Noradrenaline and serotonin are main neurotransmitters</p></li>
<li><p>Have inhibitory effects on the synapse of 1st/2nd order neurons</p></li></ul>
</li>
<li><p>Segmental inhibition</p>
<ul>
<li><p>Initially thought to be due to gate control theory</p></li>
<li><p>Now other mechanisms though to be responsible</p></li></ul>
</li>
<li><p>Endogenous opioid system </p>
<ul>
<li><p>(e.g. endorphins) which can bind to opioid receptors &gt; reduced nociception</p></li></ul>
 
<p></p></li></ul>
 
<span id="examiner-comments-112"></span>
==== Examiner comments ====
 
<blockquote>33% of candidates passed this question.<br />
Starting with the WHO definition of pain, followed by a brief description of the nature of noxious stimuli (thermal, mechanical, chemical) then proceeding to mention the nature of the cutaneous receptors would have been a very good start to this question. Following this, a description of the various substances involved in pain (K, prostaglandins, bradykinin, serotonin, substance P) and outlining the types of nerve fibres involved in pain transmission and how they synapse in the spinal cord and cortex was expected. The presence and nature of the descending inhibitory pathways was mentioned by very few.
</blockquote>
 
 
<span id="online-resources-for-this-question-112"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2019-paper-2-saqs/question-12 Deranged Physiology]
* [https://jennysjamjar.com.au/year/19b/19b12/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-2-12.pdf CICM Wrecks]
* [https://ketaminenightmares.com/pex/saqs/physiology/pain/2021A05_nociceptive_pathways.htm Ketamine Nightmares]
 
 
 
<span id="similar-questions-112"></span>
==== Similar questions ====
 
* Question 1, 2014, (1st sitting)
* Question 22, 2013 (2nd sitting)
* Question 15, 2011 (2nd sitting)
 
 
 
 
 
<span id="question-13-6"></span>
=== Question 13 ===
 
 
 
<span id="question-113"></span>
==== Question ====
 
Describe the exocrine functions of the pancreas.
 
 
 
<span id="example-answer-113"></span>
==== Example answer ====
 
 
 
Exocrine function of pancreas
 
* ~1L - 1.5L of exocrine pancreatic secretions are produced per day
* Pancreatic (exocrine) secretions are
** Isotonic
** Alkaline (pH ~8) - Rich in HCO3
** Main cation is Na
* Pancreatic secretions are important for
** Reducing acidity of contents from stomach (rich in HCO3)
** Assisting in completion of digestion (contains enzymes)
 
 
 
Main components of exocrine secretions
 
* Bicarbonate
** Produced by ductal cells (up to 150mmol/L)
** Indirect process driven by Na/H exchanger in basolateral membrane
*** CO2 dissolves into ductal cell. Converted to HCO3 and H+
*** H+ is pumped back out (NA/H exchanger) to maintain gradient
*** HCO3 &gt; facilitated diffusion into lumen
* Digestive enzymes
** Produced by rough ER in acinar cells
** Stored in zymogen granules as pro-enzymes while awaiting release
** Enzymes
*** Proteases
**** Includes trypsinogen and chromotripsinogen (converted to active form by enterokinase in duodenum)
**** Hydrolyse peptide bonds between amino acids
*** Amylase
**** Secreted in active form
**** Hydrolyses glycogen, starch other carbohydrate complexes &gt; disaccharides
*** Lipases
**** Lipase and phospholipase
**** Hydrolyses TGs to glycerol and fatty acids
*** Other enzymes
**** Elastase (breaks down eleastic tissue)
**** Ribonuclease/deoxyribonuclease (break down RNA/DNA)
* Water and electrolytes
 
 
 
Control of exocrine secretions
 
* Neural and hormonal control
* Cephalic phase
** Thought, taste, sight, smell food &gt; increased PSNS (vagal activity)
** Vagal (ACh mediated) efferents innervate the acinar cells
** Leads to release of pancreatic juice (~20%)
* Gastric phase
** Mechanical stretch of stomach by food
** Leads to increased PSNS (Vagal activity) + Gastrin release (from G cells in stomach/duodenum)
** Leads to release of pancreatic juice (~10%)
* Intestinal phase
** Acidification of duodenum (from stomach acid) &gt; increased pancreatic exocrine secretion
** Mediated by secretin (released from S cells of duodenum) and CCK (enteroendocrine cells in duodenum)
** Major factor which leads to increased secretion of pancreatic juice.
* Inhibitory factors
** Glucagon
** Somatostatin
 
 
 
<span id="examiner-comments-113"></span>
==== Examiner comments ====
 
<blockquote>33% of candidates passed this question.<br />
Most candidates were able to mention some pancreatic enzymes, though often in insufficient detail to attract full marks. The amount, type, pH, etc. of pancreatic secretions was often not included. Many candidates did not describe the stimuli for pancreatic secretion. Better answers described the cephalic, gastric and intestinal phases of pancreatic secretion.
</blockquote>
 
 
<span id="online-resources-for-this-question-113"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2019-paper-2-saqs/question-13 Deranged Physiology]
* [https://jennysjamjar.com.au/year/19b/19b13-describe-the-exocrine-functions-of-the-pancreas/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-2-13.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-113"></span>
==== Similar questions ====
 
* None
 
 
 
 
 
<span id="question-14-6"></span>
=== Question 14 ===
 
 
 
<span id="question-114"></span>
==== Question ====
 
Outline the classification and effects of beta-blocking drugs with examples (50% of marks). Compare and contrast the pharmacokinetics of metoprolol with esmolol (50% of marks).
 
 
 
<span id="example-answer-114"></span>
==== Example answer ====
 
 
 
Classification of beta blockers
 
* All beta blockers are competitive antagonists
* Can be classified according to
** Receptor selectivity
*** Non selective (B1 and B2) e.g. sotalol, propranolol
*** B1 selective e.g. metoprolol, esmolol, atenolol
*** A and B effects: labetalol, carvedilol
** Membrane stabilising effects
*** Stabilising e.g. Propanolol, metoprolol, labetalol
*** Non stabilising e.g. atenolol, esmolol, bisoprolol
** Intrinsic sympathomimetic activity
*** ISA e.g. labetalol, pindolol
*** Non ISA e.g. metoprolol, sotalol, propranolol, esmolol
 
 
 
Effects of beta blockers
 
* B1 antagonism
** Heart: decreased inotropy and chronotropy (decreased BP), decreased myocardial oxygen consumption + increased supply (increased diastolic time), decreased dromotropy
** Kidneys: decreased renin release &gt; decreased RAAS activation &gt; decreased BP
* B2 antagonism
** Respiratory: bronchoconstriction
** Circulation: vasoconstriction
** Skeletal muscle: reduced glucose uptake
** Eye: decreased aqueous humour production &gt; decrease
* B3 antagonism
** Adipose tissue: reduced lipolysis
 
 
 
Compare/contrast metoprolol and esmolol pharmacokinetics
 
{|
! Name
! Metoprolol
! Esmolol
|-
| '''Pharmacokinetics'''
|
|
|-
| Onset
| Immediate when IV
| Immediate (only given IV
|-
| Absorption
| 95% absorption, 50% oral bioavailability (1st pass effect)
| 0% oral bioavailability
|-
| Distribution
| VOD 5 L/kg<br />
10% Protein bound<br />
High lipid solubility, readily crosses BBB
| VOD 3L/kg<br />
60% protein bound<br />
High lipid solubility, can cross BBB
|-
| Metabolism
| - Hepatic CYP450<br />
- Significant 1st pass metabolism. <br />
- Inactive metabolites
| - Blood<br />
- Hydrolysis by RBC esterase &gt; inactive metabolites
|-
| Elimination
| Renal excretion<br />
T 1/2 approx 4 hours
| Renal excretion <br />
T 1/2 10 mins
|}
 
 
 
<span id="examiner-comments-114"></span>
==== Examiner comments ====
 
<blockquote>47% of candidates passed this question.<br />
Beta-blocking drugs were generally well classified. Selectivity, membrane stabilising activity and ISA should have been mentioned. Many candidates omitted or poorly answered the ‘effects’ of beta blockers. Candidates who performed well answering the pharmacokinetics of metoprolol and esmolol provided a table of the two drugs. Superficial statements such as “hepatic metabolism and renal excretion” attracted minimal marks. The mechanism of action of beta blockers was not requested
</blockquote>
 
 
<span id="online-resources-for-this-question-114"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2019-paper-2-saqs/question-14 Deranged Physiology]
* [https://jennysjamjar.com.au/year/19b/19b14-outline-the-classification-and-effects-of-beta-blocking-drugs-with-examples-505-of-marks-compare-and-contrast-the-pharmacokinetics-of-metoprolol-with-esmolol-50-of-marks/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-2-14.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-114"></span>
==== Similar questions ====
 
* Question 9, 2021 (2nd sitting)
 
 
 
 
 
<span id="question-15-6"></span>
=== Question 15 ===
 
 
 
<span id="question-115"></span>
==== Question ====
 
Define clearance and hepatic extraction ratio (30% of marks). Describe the role of the liver in drug clearance with examples (70% of marks).
 
 
 
<span id="example-answer-115"></span>
==== Example answer ====
 
 
 
Clearance
 
<ul>
<li><p>The volume of plasma that is cleared of a drug per unit time (ml/min)</p></li>
<li><p><math display="inline">Clearance = \frac {elimination \ rate}{plasma \ concentration}</math></p>
<p></p></li></ul>
 
Hepatic Extraction Ratio (HER)
 
* The fraction of drug entering the liver in the blood that is irreversibly removed as it is filtered through during one pass
* Can be expressed by
 
<math display="block">ER (Hepatic) = \frac {FU \times Cl_{int} } {Q_H \; + \; FU \; \times Cl_{int}}</math>
* Whereby
** FU = fraction of unbound drug in plasma (drug bound to protein cannot be cleared)
** <math display="inline">Cl_{int}</math> = intrinsic hepatic enzymatic capacity
** <math display="inline">Q_H</math> = hepatic blood flow
 
 
 
Hepatic clearance
 
* The two major determinants of hepatic clearance are the HER and the hepatic blood flow
 
<math display="block">Clearance_{Hepatic} = Q_H \times ER_{Hepatic}</math>
* Effect of hepatic blood flow changes in relation to HER
** For drugs with low ER (e.g. diazepam, warfarin) increasing Q<sub>H</sub> leads to:
*** Minimal increase in clearance (capacity limited)
*** Decreased hepatic ER (more pronounced relatively)
** For drugs with high ER (e.g. propofol and GTN) increasing Q<sub>H</sub> leads to:
*** Marked increase in clearance (flow limited)
*** Decreased hepatic ER (less pronounced relatively)
 
* Role of liver in drug clearance
** Liver is heavily involved in drug metabolism
*** Phase 1 metabolic reactions
**** Involves oxidation (loss of electrons), reduction (gain of electrons) and hydrolysis (addition of H<sub>2</sub>O molecule)
**** Driven predominately by the Cytochrome p450 system and esterases in liver
**** E.g. metabolism of Propofol, benzodiazipines, opioids, volatiles anaesthetics
**** There can be significant variability in activity of CYP enzymes which leads to variability in drug response (e.g. CYP2C19 polymorphism &gt; variability in phenytoin and clopidogrel metabolism)
 
<ul>
<li><p>Phase 2 reactions</p>
<ul>
<li><p>Involves conjugation (increasing water solubility)</p>
<ul>
<li><p>Typically occurs in hepatic endoplasmic reticulum</p></li>
<li><p>Includes glucuronidation (e.g. morphine), sulfation (e.g. quetiapine), acetylation (e.g. hydralazine), methylation (e.g. catecholamines)</p></li></ul>
</li></ul>
 
<p></p>
<p></p></li></ul>
 
<span id="examiner-comments-115"></span>
==== Examiner comments ====
 
<blockquote>70% of candidates passed this question.<br />
Clearance was generally well answered. It is the volume of plasma cleared of a drug per unit time, not the mass of drug cleared. An equation was helpful in identifying the relevant components of hepatic clearance.<br />
ClHep=QH X ERHep<br />
ERHep= FU x ClInt / QH + FU x ClInt<br />
QH = hepatic blood flow<br />
ERHep = hepatic extraction ratio<br />
FU = fraction of drug unbound in plasma<br />
ClInt = hepatic enzymatic capacity<br />
Many candidates did not describe the effects of hepatic blood flow and intrinsic clearance on drugs with high and low hepatic extraction ratios. Some discussion of Phase I and II reactions was also expected.
</blockquote>
 
 
<span id="online-resources-for-this-question-115"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2019-paper-2-saqs/question-15 Deranged Physiology]
* [https://jennysjamjar.com.au/year/19b/19b15-define-clearance-and-her-describe-the-role-of-the-liver-in-drug-clearance-w-examples/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-2-15.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-115"></span>
==== Similar questions ====
 
<ul>
<li><p>Question 20, 2016 (1st sitting)</p>
<p></p></li></ul>
 
 
 
<span id="question-16-6"></span>
=== Question 16 ===
 
 
 
<span id="question-116"></span>
==== Question ====
 
Compare the structure, function and coronary circulation of the right and left ventricles
 
 
 
<span id="example-answer-116"></span>
==== Example answer ====
 
 
 
Structure/blood supply
 
{|
!
! Right ventricle
! left ventricle
|-
| Shape
| More triangular
| More conical
|-
| Valves
| Tricuspid (3 valve leaflets + papillary muscle)<br />
Pulmonary (3 cusps: right, left, anterior)
| Mitral (2 valve leaflet + papillary muscle)<br />
Aortic (3 cusps: Right, left, posterior)
|-
| Wall thickness
| Relatively thinner (2-5mm)
| Relatively thicker (5-10mm)
|-
| Mass
| Lighter (25g)
| Heavier (100g) - due to increased afterload on LV
|-
| Position in chest
| Right/anterior
| Left/posterior
|-
| Arterial supply
| Predominately RCA
| Predominately LAD, LCx, PDA
|-
| Venous drainage
| Small + anterior cardiac veins
| Great and middle cardiac veins
|-
| Blood flow
| Constant, maximal flow rate during systole (majority still occurs in diastole due to increase duration)
| Intermittent (no flow in early systole), maximal flow rate + total flow occurs diastole
|}
 
 
 
Function/Physiology
 
{|
!
! Right ventricle
! Left ventricle
|-
| Function
| Receive deoxygenated blood from systemic circulation &gt; pump to pulmonary circulation
| Receive oxygenated blood from pulmonary circulation and pump to the systemic circulation
|-
| Blood flow
| RA &gt; tricuspid valve &gt; RV &gt; pulmonary valve &gt; pulmonary trunk
| LA &gt; mitral valve &gt; LV &gt; aortic valve &gt; aorta
|-
| C VO2
| Lower
| Higher
|-
| EDV
| Higher
| Lower
|-
| ESV
| Higher
| Lower
|-
| Stroke volume
| Equal
| Equal
|-
| Systolic pressure
| Lower (~15-25mmhg)
| Higher (~120mmHg)
|-
| Diastolic pressure
| Lower (0-5mmhg)
| Higher (5-15mmHg)
|-
| ESPVR (contractility)
| Lower
| Higher
|-
| EDPVR (elastance)
| Lower
| Higher
|-
| Ea (afterload)
| Lower
| Higher
|-
| Work
| Lower
| Higher
|}
 
 
 
<span id="examiner-comments-116"></span>
==== Examiner comments ====
 
<blockquote>27% of candidates passed this question.<br />
The question sought information on the structure (anatomy), function (physiology) and vascular supply of the right and left ventricle. Good answers provided detail in each section e.g. values for ventricular pressure rather than simply stating “high- and low-pressure systems”.<br />
Many marks may be gained by a simple anatomical description &amp; labelled PV loop for each ventricle. Many candidates focussed solely on the coronary circulation, to which only a proportion of the marks were allocated.
</blockquote>
 
 
<span id="online-resources-for-this-question-116"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2019-paper-2-saqs/question-16 Deranged Physiology]
* [https://jennysjamjar.com.au/year/19b/19b16-compare-the-structure-function-and-coronary-circulation-of-the-right-and-left-ventricles/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-2-16.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-116"></span>
==== Similar questions ====
 
* None
 
 
 
 
 
<span id="question-17-6"></span>
=== Question 17 ===
 
 
 
<span id="question-117"></span>
==== Question ====
 
Explain respiratory compliance and outline the factors that affect it.
 
 
 
<span id="example-answer-117"></span>
==== Example answer ====
 
 
 
Respiratory compliance
 
* <math display="inline">Compliance \; = \; \frac{\Delta \;volume}{\Delta \;  pressure}</math>
* Compliance in the respiratory system (C<sub>RS</sub>) is a function of lung (C<sub>lung</sub>) and chest wall (C<sub>CW</sub>) compliance
** <math display="inline">\frac {1}{C_{RS}}\; = \; \frac {1}{C_{Lung}} \; + \; \frac {1}{C_{CW}}</math>
** Chest wall and lung compliance are roughly equal in healthy individual
* Normal compliance of the respiratory system is approximately 200mls.cmH2O
* Static compliance
** Compliance of the respiratory system at a given volume when there is no flow
* Dynamic compliance
** Compliance of the system when there is flow (respiration)
** Will always be less than static compliance due to airway resistance
** At a normal RR is approximately equal to static compliance
* Specific compliance
** The compliance of the system divided by the FRC
** Allows comparisons between patients which are independent of lung volumes
 
 
 
Factors effecting compliance
 
Chest wall
 
* Increased
** Collagen disorders such as Ehlers-Danlos syndrome
** Cachexia
** Rib resection
* Decreased
** Obesity
** Kyphosis / scoliosis / Pectus excavatum
** Circumferential burns
** Prone positioning
 
Lung compliance
 
<ul>
<li><p>Increased</p>
<ul>
<li><p>Normal ageing</p></li>
<li><p>Emphysema</p></li>
<li><p>Upright posture</p></li>
<li><p>Lung volume (highest compliance at FRC)</p></li></ul>
</li>
<li><p>Decreased</p>
<ul>
<li><p>Loss of surfactant (E.g. ARDS, hyaline membrane disease)</p></li>
<li><p>Loss of functional lung volume (e.g. pneumonia, lobectomy, pneumonectomy, atelectasis)</p></li>
<li><p>Pulmonary venous congestion (pHTN) and interstitial oedema (APO)</p></li>
<li><p>Reduced long elasticity (e.g. Pulmonary fibrosis)</p></li>
<li><p>Positioning (e.g. supine positioning)</p></li></ul>
 
<p></p></li></ul>
 
<span id="examiner-comments-117"></span>
==== Examiner comments ====
 
<blockquote>51% of candidates passed this question.<br />
Answers were generally well structured. Better answers described lung and chest wall compliance and the pressures which are used to calculate compliance. Better answers displayed an understanding of dynamic, static and specific compliance and provided a reasonably comprehensive list of the physiological factors affecting chest and lung compliance.
</blockquote>
 
 
<span id="online-resources-for-this-question-117"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2019-paper-2-saqs/question-17 Deranged Physiology]
* [https://jennysjamjar.com.au/year/19b/17b17-3/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2007-2-13-lung-compliance.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-117"></span>
==== Similar questions ====
 
* Question 14, 2017 (1st sitting)
* Question 15, 2014 (1st sitting)
* Question 7, 2011 (2nd sitting)
* Question 13, 2007 (1st sitting)
 
 
 
 
 
<span id="question-18-6"></span>
=== Question 18 ===
 
 
 
<span id="question-118"></span>
==== Question ====
 
Compare and contrast the pharmacology of metaraminol and noradrenaline
 
 
 
<span id="example-answer-118"></span>
==== Example answer ====
 
{|
! Name
! Noradrenaline
! Metaraminol
|-
| '''Class'''
| Endogenous catecholamine
| Synthetic non-catecholamine
|-
| '''Indications'''
| Vasopressor (Hypotension/shock)
| Vasopressor (hypotension/shock)
|-
| '''Pharmaceutics'''
| Clear solution. 1:1000. Brown ampule (prevent light oxidation). Diluted in dextrose.
| Clear solution. Typically 0.5mg/ml syringes, or 10mg/ml vials.
|-
| '''Routes of administration'''
| IV only (central vein)
| IV, IM
|-
| '''Dose'''
| Infusion titrated to effect (generally 0 - 0.5 mcg/kg/min)
| 0.5mg boluses, infusion
|-
| pKA
| 8.85
| 8.79
|-
| '''Pharmacodynamics'''
|
|
|-
| MOA
| Predominately Alpha 1 agonism. Some beta adrenergic receptor agonism. a1 &gt; B1 &gt; B2
| Direct and indirect alpha-1 agonism (very weak B agonism)
|-
| Effects
| CVS: peripheral vasoconstriction &gt; increased SVR &gt; inc. BP
| CVS: peripheral vasoconstriction &gt; increased SVR &gt; increased BP. Also increased PVR. Reflex bradycardia.
|-
| Side effects
| CVS: Hypertension, reflex bradycardia, increased afterload<br />
Extravasation &gt; necrosis<br />
Renal, hepatic vasoconstriction &gt; decreased blood flow
| CVS: Increased afterload &gt; worsen heart failure, bradycardia
|-
| '''Pharmacokinetics'''
|
|
|-
| Onset
| Immediate
| Immediate
|-
| Absorption
| IV only (0% oral bioavailability)
| IV (though some oral bioavailability)
|-
| Distribution
| Does not cross BBB. 25% taken up in lungs.
| VOD = 4L/kg<br />
45% protein bound
|-
| Metabolism
| Readily metabolised intro adrenaline by MAO and COMT
| Not metabolised
|-
| Elimination
| Excreted in urine as inactive metabolites (&gt;85%).<br />
Half life ~2 mins
| Minutes, renal elimination
|-
| '''Special points'''
| Tachyphylaxis (slow)<br />
Effect exaggerated in patients taking MAOI (less breakdown)
| Tachyphylaxis (fast( with infusion))
|}
 
 
 
<span id="examiner-comments-118"></span>
==== Examiner comments ====
 
<blockquote>71% of candidates passed this question.<br />
Marks were distributed across pharmaceutics, uses, dose &amp; administration, mechanism of action, Pharmacokinetcs and Pharmacodynamics. Common omissions were doses/rates of infusion, effects other than on heart/SVR (e.g. splanchnic, renal blood flow), indirect effect of metaraminol, receptor effect of noradrenaline other than alpha 1 and tachyphylaxis.
</blockquote>
 
 
<span id="online-resources-for-this-question-118"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/19b/19b18-compare-and-contrast-the-pharmacology-of-metaraminol-and-noradrenaline/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/02/2019-2-18.pdf CICM Wrecks]
* [https://partone.litfl.com/adrenergic_drugs.html#id Part One, LITFL]
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2019-paper-2-saqs/question-18#answer-anchor Deranged Physiology]
 
 
 
<span id="similar-questions-118"></span>
==== Similar questions ====
 
* Noradrenaline
** Question 12, 2009 (2nd sitting)
** Question 7, 2007 (1st sitting)
** Question 23, 2011 (1st sitting)
** Question 10, 2020 (1st sitting)
** Question 15, 2016 (2nd sitting)
* Metaraminol
** New!
 
 
 
 
 
<span id="question-19-6"></span>
=== Question 19 ===
 
 
 
<span id="question-119"></span>
==== Question ====
 
Describe the pharmacology of atropine.
 
 
 
<span id="example-answer-119"></span>
==== Example answer ====
 
{|
! Name
! Atropine
|-
| '''Class'''
| Naturally occurring tertiary amine. Muscarinic antagonist.
|-
| '''Indications'''
| Bradycardia<br />
Organophosphate poisoning<br />
Counteract muscarinic effects of anticholinesterases<br />
drying of secretions
|-
| '''Pharmaceutics'''
| Clear colourless solution. 600mcg/ml. Racemic mixture with the L-isomer being active
|-
| '''Routes of administration'''
| IV, IM, topical (eye)
|-
| '''Dose'''
| 600mcg - repeated administration can be given
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Competitive antagonism of muscarinic anticholinergic receptors
|-
| Effects
| CVS: increased HR (and CO), decreased AV conduction time<br />
RESP: bronchodilation<br />
GIT: Drying of secretions
|-
| Side effects
| CNS: Hallucinations, confusion, amnesia, delirium, central anticholinergic syndrome<br />
GIT: dry mouth, delayed GIT motility<br />
CVS: may cause initial transient bradycardia when given slowly<br />
MSK: inhibits sweating
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| Seconds. Duration 2-3hours
|-
| Absorption
| IV
|-
| Distribution
| 50% protein bound. VOD=3L/kg. Crosses blood brain barrier and placenta
|-
| Metabolism
| Extensive hepatic hydrolysis into tropine and tropic acid
|-
| Elimination
| Renal elimination of metabolites. T 1/2 approx 2 hours
|-
| '''Special points'''
|
|}
 
 
 
<span id="examiner-comments-119"></span>
==== Examiner comments ====
 
<blockquote>53% of candidates passed this question.<br />
Most candidates used a good structure to compose their answer. Better candidates understood that CNS effects occur as atropine is a tertiary amine that crosses the blood brain barrier. The mechanism of action was required. Indications for use should have included bradycardia, organophosphate poisoning, drying of secretions etc. Reasonably extensive details regarding pharmacodynamics was expected, including potential toxic effects. There was limited knowledge regarding pharmacokinetics.
</blockquote>
 
 
<span id="online-resources-for-this-question-119"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/19b/19b19-saq-19-describe-the-pharmacology-of-atropine/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/02/2019-2-19.pdf CICM Wrecks]
* [https://partone.litfl.com/atropine.html Part One, LITFL]
 
 
 
<span id="similar-questions-119"></span>
==== Similar questions ====
 
* Question 3, 2011 (1st sitting)
 
 
 
 
 
<span id="question-20-6"></span>
=== Question 20 ===
 
 
 
<span id="question-120"></span>
==== Question ====
 
Compare the pharmacology of piperacillin-tazobactam and ciprofloxacin
 
 
 
<span id="example-answer-120"></span>
==== Example answer ====
 
{|
! Name
! Piperacillin-Tazobactam
! Ciprofloxacin
|-
| '''Class'''
| Semi-synthetic penicillin (piperacillin)<br />
B-lactamase inhibitor (tazobactam)
| Fluroquinolone
|-
| '''Indications'''
| Pseudomonal infection<br />
Broad spectrum antimicrobial cover of severe infections/sepsis
| Effective for many infections (skin, joint, gastro, UTI, LRTI)
|-
| '''Pharmaceutics'''
| Powder, reconstitutes in water/NaCl/glucose
| Tablet (250-750mg) or yellowish powder for dilution.
|-
| '''Routes of administration'''
| IV/IM
| IV, PO
|-
| '''Dose'''
| 4g/0.5g 8hrly or 4g/0.5g 6hrly (pseudomonas cover)<br />
Dose reduced renal failure
| 250-750mg BD (PO), 200-400mg BD/TDS (IV)
|-
| '''Pharmacodynamics'''
|
|
|-
| MOA
| Piperacillin: bactericidal - inhibits cell wall synthesis by preventing cross linking of peptidoglycans by replacing the natural substrate (D-ala-D-ala) with their B-lactam ring<br />
Tazobactam: B lactamase inhibitor (prevents piperacillin degradation)
| Bactericidal - Inhibits DNA gyrase and topoisomerase IV &gt; inhibits DNA synthesis
|-
| Antimicrobial cover
| Broad spectrum coverage of gram positive bacteria, gram negative bacteria, anaerobes. Covers pseudomonas.<br />
Doesn't cover: MRSA, VRE, ESBL, atypical
| Broad spectrum (GN &gt; GP).<br />
Effective against pseudomonas + anthrax. Effective against some atypicals (legionella, mycoplasma).<br />
No anaerobe cover.
|-
| Side effects
| GIT: diarrhoea, nausea, vomiting<br />
Renal: AKI<br />
Allergy (up to 10%), rash most common, skin eruptions/SJS and anaphylaxis (&lt;1/10,000)
| MSK: tendon rupture, arthritis, myalgia<br />
CNS: peripheral neuropathy, headache<br />
GIT: nausea, vomiting, abdominal pain, dyspepsia<br />
CVS: Qtc prolongation, arrhythmias <br />
RENAL: AKI, nephritis
|-
| '''Pharmacokinetics'''
|
|
|-
| Absorption
| Minimal oral absorption &gt; IV<br />
Peak concentrations immediately after dose.
| 70% oral bioavailability
|-
| Distribution
| Very good tissue penetration (minimal CNS without active inflammation)<br />
Low protein binding (&lt;30%)
| Low protein binding (25%). Great tissue penetration. VOD 2.5L/kg.
|-
| Metabolism
| Piperacillin: not metabolised<br />
Tazobactam: metabolised to M1, an inactive metabolite
| Limited hepatic metabolism (15%)
|-
| Elimination
| Renal (80% unchanged)<br />
T 1/2 2 hrs
| Renal excretion of metabolites. T1/2 3-5 hours.
|-
| '''Special points'''
| Removed by haemodialysis
| Worldwide resistance to quinolones is increasing
|}
 
 
 
<span id="examiner-comments-120"></span>
==== Examiner comments ====
 
<blockquote>58% of candidates passed this question.<br />
This question was most effectively answered using a tabular format. Only a minority of candidates demonstrated a comprehensive knowledge of these level 1 drugs and very few candidates compared the two in areas which lent themselves to comparison. The spectrum of activity generally lacked detail. Few candidates mentioned that piperacillin-tazobactam had superior gram-positive cover, both have extensive gram-negative cover including Pseudomonas. Piperacillin-tazobactam is effective against anaerobes; whilst ciprofloxacin has some atypical cover against Mycoplasma.<br />
The mechanism of action was generally well described for piperacillin; many candidates incorrectly stated the mechanism of action for ciprofloxacin, confusing the drug with a macrolide. Better answers included time- dependant and concentration-dependent killing. The concept of half-life was frequently confused with the dosing interval.<br />
Minimal marks were awarded for “allergy” and “gastrointestinal side-effects”. Better candidates mentioned Liver function derangement, neutropenia, interstitial nephritis for piperacillin and tendonitis for ciprofloxacin.
</blockquote>
 
 
<span id="online-resources-for-this-question-120"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2020/02/2019-2-20.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/19b/19b20/ Jenny's Jam Jar]
 
 
 
<span id="similar-questions-120"></span>
==== Similar questions ====
 
* PipTaz: Question 16, 2021 (1st sitting)
* Cipro: Question 5, 2020 (1st sitting)
 
 
 
 
 
<span id="2019-1st-sitting"></span>
== 2019 (1st sitting) ==
 
 
 
<span id="question-1-7"></span>
=== Question 1 ===
 
 
 
<span id="question-121"></span>
==== Question ====
 
Describe the pharmacology of lignocaine.
 
 
 
<span id="example-answer-121"></span>
==== Example answer ====
 
{|
! Name
! Lidocaine (lignocaine)
|-
| '''Class'''
| Amide anaesthetic / Class 1b antiarrhythmic
|-
| '''Indications'''
| Local/regional/epidural anaesthesia, ventricular dysrhythmias
|-
| '''Pharmaceutics'''
| Clear colourless solution (1%, 2%, 4%). Can come with/without adrenaline. Also available as cream/spray
|-
| '''Routes of administration'''
| SC, IV, epidural, inhaled
|-
| '''Dose'''
| Regional Use: Toxic dose 3mg/kg (without adrenaline), 7mg/kg (with adrenaline)<br />
IV use: 1mg/kg initially, then ~1-2mg/kg/hr
|-
| pKA
| 7.9, 25% unionised at normal body fluid pH
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Class 1b anti-arrhythmic: blocks Na channels, raising threshold potential + reducing slope of Phase 0 of action potential, shortened AP<br />
Local anaesthetic: binds to, and blocks, internal surface of Na channels
|-
| Effects
| Analgesic, anaesthetic, anti-arrhythmic
|-
| Side effects
| CNS: headache, dizziness, confusion, paraesthesia, reduced LOC, seizures<br />
CVS: hypotension, bradycardia, AV Block, arrhythmia<br />
CC/CNS ratio = 7 (lower number = more cardiotoxic)
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| Rapid onset (1-5 minutes)
|-
| Absorption
| IV &gt; Epidural &gt; subcut. Oral bioavailability 35%
|-
| Distribution
| 70% protein bound, Vd 0.9L/kg. Crosses BBB
|-
| Metabolism
| Hepatic, some active metabolites
|-
| Elimination
| Metabolites excreted in urine. Half life ~90mins. Increased with adrenaline (SC). Reduced in cardiac/hepatic failure.
|-
| '''Special points'''
|
|}
 
 
 
<span id="examiner-comments-121"></span>
==== Examiner comments ====
 
<blockquote>16% of candidates passed this question.<br />
Comprehensive answers included uses (including antiarrhythmic action and a role in analgesia), physical properties and preparations, pharmacodynamics and pharmacokinetics. Its mode of action should also have been described. Many candidates focussed on toxicity and its management but provided little information on pharmacodynamics and pharmacokinetics, commonly omitting factors which affect its systemic absorption. Other common omissions were the dose required for its local anaesthetic effect and for its antiarrhythmic effect
</blockquote>
 
 
<span id="online-resources-for-this-question-121"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/main/cicm-primary-exam/required-reading/nervous-system/Chapter%20326/lignocaine Deranged Physiology]
* [https://partone.litfl.com/local_anaesthetics.html Part One, LITFL] and [https://partone.litfl.com/sodium_channel_blockers.html Part One, LITFL]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-1-01.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-121"></span>
==== Similar questions ====
 
<ul>
<li><p>Question 17, 2014 (1st sitting)</p></li>
<li><p>Question 2, 2021 (2nd sitting)</p>
<p></p></li></ul>
 
 
 
<span id="question-2-7"></span>
=== Question 2 ===
 
 
 
<span id="question-122"></span>
==== Question ====
 
Outline the components required to measure blood pressure from an intra-arterial catheter (75% of marks). What information (other than blood pressure) may be gained from an arterial line trace (25% of marks)?
 
 
 
<span id="example-answer-122"></span>
==== Example answer ====
 
 
 
Components
 
* Intra-arterial catheter
** narrow (generally 18-22G) and relatively short - minimises resonance
** Provides conduit to transmit blood pressure wave to circuit
* Fluid filled tubing
** Permits hydraulic coupling of mechanical signical
** Non compressible fluid filled (usually saline) tubing minimises damping
* Counterpressure bag with flush system
** pressure of~300mmHg - counteracts arterial pressure
** Fluid provides slow continuous infusion to maintain catheter patency (prevent clots etc)
** Can be used for diagnostic/trouble shooting purposes with 'fast flush test'
* An electrical transducer
** Usually a Wheatstone bridge peizoresistive transducer
** Movement of the diaphragm caused by arterial pressure changes leads to stretching/compression of the strain gauges and is converted into an electrical signal
** Placed at phlebostatic axis and requires calibration
* Microprocessor + amplifier
** Processor uses Fourier analysis to break down the waveform into component sine waves which are reconstructed with 8-10 harmonic sine waves
** Amplifies signal
* Cabling
** To transmit the information/electrical signals
* Monitor
** To visualise the information (including pressures and waveform)
* 3 way tap
** Allows sampling of arterial blood for diagnostic purposes
** Allows 'zeroing' to atmosphere for calibration
 
 
 
Information gained
 
* Heart rate
* Heart rhythm - regular or irregular
* Blood pressures - Systolic pressure, diastolic pressure, mean arterial pressures, pulse pressures
* Pulse pressure variation
* Issues with system - Dampened trace may indicate kinks, bubbles, clots in the circuit
* Cardiac output, stroke volume, stroke volume variation by pulse contour analysis (e.g. FloTrac)
* Waveform may indicate underlying pathology with modest accuracy (e.g. collapsing wave in AS)
 
 
 
<span id="examiner-comments-122"></span>
==== Examiner comments ====
 
<blockquote>44% of candidates passed this question.<br />
Most of the marks were allocated to the components of the measuring system (as detailed in the question), hence a level of detail was required. An explanation of how the various components work was required; e.g. hydraulic coupling and transducers. Some candidates forgot to include heart rate as a piece of information derived from the trace.
</blockquote>
 
 
<span id="online-resources-for-this-question-122"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/19a/19a02/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-1-02.pdf CICM Wrecks]
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2019-paper-1-saqs/question-2#answer-anchor Deranged Physiology]
 
 
 
<span id="similar-questions-122"></span>
==== Similar questions ====
 
* Previous questions on damping/resonance - nil on arterial line setup.
 
 
 
 
 
<span id="question-3-7"></span>
=== Question 3 ===
 
 
 
<span id="question-123"></span>
==== Question ====
 
Compare and contrast fresh frozen plasma and prothrombin complex concentrate
 
 
 
<span id="example-answer-123"></span>
==== Example answer ====
 
{|
! Name
! FFP
! Prothrombinex
|-
| Description
| Human plasma including all coagulation factors
| Human plasma derivative containing a concentrate of specific clotting factors
|-
| Preparation
| 1) Separation of whole blood or apheresis <br />
2) Frozen and stored<br />
3) Rethawed in water bath prior to use
| 1) Separation of whole blood or apheresis<br />
2) Separation of clotting factors II, IX and X via ion exchange chromatography<br />
3) Freeze dried powder
|-
| Indications
| Coagulopathy<br />
Plasma exchange<br />
ACE-I angioedema, suxamethonium apnoea
| Warfarin reversal<br />
Correction of coagulopathy from factor II, IX or X deficiency
|-
| Pharmaceutics
| 250-300ml bags, labelled with donor blood types
| Glass vial with powdered concentrate for reconstitution with water. Generally 500U per vial<br />
Contains small amount of heparin
|-
| Storage
| Stored for 12 months
| Stored for 6 months
|-
| Routes of administration
| IV
| IV
|-
| Dose
| 2-4 units (varies)
| 25-50 u/kg
|-
| Contraindications
| ABO incompatibility
| DIC, HITS (contains heparin), liver failure
|-
| Contents/factors
| All clotting factors (except fibrinogen)
| Contains factors II, IX, X (500 units each)
|-
| Adverse effects
| Blood product, with all the risks associated with this (fluid overload, infection, allergic responses)
| Allergic or anaphylactic reactions<br />
Thrombosis in predisposed individuals
|-
| Pros
| Contains all necessary clotting factors<br />
Less expensive than PTX
| Does not need group/crossmatch (therefore available for immediate use) <br />
Smaller fluid volume
|-
| Cons
| Requires ABO grouping <br />
Requires time for thawing etc<br />
More fluid, more side effects
| Factor 7 absent<br />
More expensive than FFP
|}
 
 
 
<span id="examiner-comments-123"></span>
==== Examiner comments ====
 
<blockquote>10% of candidates passed this question.<br />
Very few answers included details on prothrombin complex concentrate which meant it was difficult to score well. Useful headings included preparation and administration, dose, indications and adverse effects. Not many candidates knew the dose of FFP, and few were able to describe the preparation/production of the product. Few candidates knew the factors available from either product. Commonly missed was the need for ABO typing for FFP and that Prothrombin complex concentrate did not require this.
</blockquote>
 
 
<span id="online-resources-for-this-question-123"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/19a/19a03/ Jennys Jam Jar]
* [https://derangedphysiology.com/main/cicm-primary-exam/required-reading/haematological-system/Chapter%20333/plasma-components-and-other-blood-products Deranged Physiology]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-1-03.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-123"></span>
==== Similar questions ====
 
* ? None
 
 
 
 
 
<span id="question-4-7"></span>
=== Question 4 ===
 
 
 
<span id="question-124"></span>
==== Question ====
 
Outline the functional anatomy of the kidney (40% of marks). Outline the regulation of renal blood flow (60% of marks)
 
 
 
<span id="example-answer-124"></span>
==== Example answer ====
 
 
 
Gross anatomy of kidney
 
* Gross anatomy
** Paired retroperitoneal organ
** Sits at ~ T12-L3 (right lower than left)
* Structure
** Outer fibrous capsule &gt; Outer 'cortex' &gt; Inner 'medulla' &gt; renal pelvis
* Blood supply
** Arterial: renal arteries from abdominal aorta
** Venous: renal veins &gt; IVC
* Innervation
** SNS (T9-13)
 
 
 
Functional anatomy
 
* The nephron is the basic functional unit of kidney (~1-2 million nephrons per kidney)
** 85% of nephrons are predominately located in cortex (cortical nephrons)
** 15% are juxtamedullary and extend deep into the medulla.
* Nephron structure
** Renal corpuscle (filtration): with glomerulus + bowman's capsule
** Juxtaglomerular apparatus (adjustments to GFR): contains macula densa, JG cells, mesangial cells
** Tubular system (reabsorption/regulation): PCT &gt; LOH &gt; DCT
** Collecting duct system
* Vascular
** Afferent arteriole: blood supply to individual nephron
** Efferent arteriole: carries blood away from individual nephron
 
 
 
Renal blood flow regulation
 
* Normal RBF = ~20% of CO (~1L / min), predominately distributed to cortex &gt; medulla
* Kidneys are able to autoregulate (maintain constant blood flow) across a wide range of MAP (~70-170mmhg)
* Myogenic regulation
** Intrinsic constriction of afferent arterioles in response to increased transmural pressure of vessel wall (e.g. increased BP)
* Tubuloglomerular feedback
** Regulated by macula densa
** Increased perfusion pressure &gt; Increased Na/Cl sensed by macula densa &gt; adenosine released &gt; constriction &gt; decreased GFR. Vice versa (except NO is released with decreased Na/Cl delivery to vasodilate and increased GFR)
* Neuronal control
** SNS activation &gt; afferent and efferent arteriole constriction &gt; decreased flow
* Hormonal control
** Renin-angiotensin system: Renin released (SNS stimulation, hypotension, decreased Na at JGA) &gt; increased AG1 &gt; increased AG2 &gt; constriction of arterioles &gt; decreased RBF/GFR
 
 
 
<span id="examiner-comments-124"></span>
==== Examiner comments ====
 
<blockquote>71% of candidates passed this question.<br />
It was expected that answers include sections on the blood supply, the nephron (including the difference between the cortical and juxta-medullary nephrons) and innervation. A number of candidates failed to quantify renal blood flow and to define autoregulation. The concept that it’s the flow that’s regulated was not described by some. Tubuloglomerular feedback was generally described correctly but a reasonable number had the blood flow increasing when an increased sodium was sensed at the macula densa.
</blockquote>
 
 
<span id="online-resources-for-this-question-124"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/19a/19a04/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-1-04.pdf CICM Wrecks]
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2019-paper-1-saqs/question-4#answer-anchor Deranged] and [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-18#answer-anchor Deranged]
 
 
 
<span id="similar-questions-124"></span>
==== Similar questions ====
 
* Renal blood flow and autoregulation
** Question 18, 2007 (1st sitting)
** Question 12, 2008 (2nd sitting)
** Question 11, 2012 (1st sitting)
** Question 3, 2015 (2nd sitting)
* Functional anatomy of kidneys
** Question 21, 2011 (2nd sitting)
* Functional anatomy + autoregulation of blood flow
** Question 18, 2017 (1st sitting)
 
 
 
 
 
<span id="question-5-7"></span>
=== Question 5 ===
 
 
 
<span id="question-125"></span>
==== Question ====
 
Define volume of distribution (15% of marks). Outline the factors affecting volume of distribution (60% of marks) and explain how it may be measured (25% of marks).
 
 
 
<span id="example-answer-125"></span>
==== Example answer ====
 
 
 
Volume of distribution
 
* The '''theoretical''' volume in which an amount of drug would distribute to produce an observed plasma concentration
* Note: Does not correspond to any real volume. Can often exceed total body water
 
 
 
Measurement
 
<ul>
<li><p>Assumes that</p>
<ol style="list-style-type: decimal;">
<li><p>The drug is evenly distributed (often not the case)</p></li>
<li><p>Metabolism and elimination have not taken place (often not the case)</p></li></ol>
</li>
<li><p>Requires drug dose to be given, then plasma samples to be taken </p></li>
<li><p>Semilogarithmic plasma concentration vs time curve plotted. </p></li>
<li><p>In a single compartment model, VOD can then be calculated as VOD = dose given / plasma concentration at time 0 (which is back extrapolated on the curve from 1st time point.)</p>
[[File:C:\Users\ethan\AppData\Roaming\Typora\typora-user-images\image-20220804131048030.png|thumb|none]]
</li></ul>
 
Factors affecting volume of distribution
 
* Patient factors
** Age: decreasing water content with age = decreased Vd (water soluble drugs)
** TBW: decreases with age = decreased Vd (water soluble drugs)
** Fat %: increased body fat = increased Vd of lipophilic drugs
** Gender: women generally have lower Vd (water soluble drugs) due to lower TBW but higher Vd for fat soluble drugs
* Drug factors
** Molecular size: decreased size = increased Vd
** Lipid solubility: increased lipophilicity = increased Vd
** pKa: basic drug in low pKa = increased Vd
** Protein binding: increased protein binding = decreased Vd
** Charge: ionised molecules &gt; may be traped in central compartment &gt; decreased Vd
* Logistical factors
** Timing of measurement
** Modelling used (e.g. single compartment)
* Pathological factors
** Renal failure/hepatic failure: may lead to low protein = decreased Vd
** Oedema, ascites - reservoir for water soluble drugs
 
 
 
<span id="examiner-comments-125"></span>
==== Examiner comments ====
 
<blockquote>51% of candidates passed this question.<br />
The first two parts of the question were reasonably done. Most candidates had well-structured answers which included drug factors and patient factors. In addition to listing the factors it was expected candidates state how these factors affect volume of distribution. Explaining how volume of distribution is determined was not so well done.
</blockquote>
 
 
<span id="online-resources-for-this-question-125"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/main/cicm-primary-exam/required-reading/pharmacokinetics/Chapter%20202/volume-distribution Deranged Physiology]
* [https://jennysjamjar.com.au/year/19a/19a05-define-volume-of-distribution-15-of-marks-outline-the-factors-affecting-volume-of-distribution-60-of-marks-and-explain-how-it-may-be-measured-25-of-marks/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-1-05.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-125"></span>
==== Similar questions ====
 
* Question 12, 2015 (second sitting)
 
 
 
 
 
<span id="question-6-7"></span>
=== Question 6 ===
 
 
 
<span id="question-126"></span>
==== Question ====
 
Outline the physiology of the adrenal gland (70% of marks). Describe the actions of aldosterone (30% of marks).
 
 
 
<span id="example-answer-126"></span>
==== Example answer ====
 
 
 
Adrenal gland
 
* Paired organs, immediately superior to kidneys
* Broken up into an outer adrenal cortex (80%) and an inner adrenal medulla (20%)
 
 
 
Adrenal cortex
 
* Three zones of cells
* Zona glomerulosa
** Outermost zone of cortex
** Synthesises mineralocorticoids (e.g. aldosterone)
** Important for regulation of electrolytes (Na, K) and water balance
** Regulated by ACTH from anterior pituitary, angiotensin II and plasma potassium levels
* Zone fasiculata
** Secretes glucocorticoids (e.g. cortisol ~95% of activity)
** Widely important, particularly for metabolism and cardiovascular function (HR, BP etc)
** Regulated by ACTH from the anterior pituitary gland
* Zona reticularis
** Innermost zone of cortex
** Secretes androgen precursors (e.g. DHEA) which get converted into testosterone and oestrogen
** Regulated by ACTH and androgen stimulating hormones
 
 
 
Adrenal medulla
 
* Innermost portion of the adrenal gland
* Responsible for producing catecholamines (adrenaline, noradrenaline)
* Chromaffin cells (modified neuroendocrine cells) are responsible for storing/synthesising the catecholamines
* Regulated by SNS activity from T5-T11 (thus stress, hypoglycaemia, etc can activate)
 
 
 
Aldosterone
 
<ul>
<li><p>Primary mineralocorticoid hormone from adrenal gland (90% of activity)</p></li>
<li><p>Actions of aldosterone</p>
<ul>
<li><p>Increases reabsorption of Na in the DCT and CD (principle cells)</p></li>
<li><p>Increases secretion of potassium in the DCT and CD (principle cells)</p></li>
<li><p>Increased Na reabsorption in sweat glands, salivary glands and GIT</p></li>
<li><p>Increases ECF volume (by increased H2O reabsorption by osmosis with the Na)</p></li>
<li><p>Increased H+ excretion in DCT (leads to Cl reabsorption and metabolic alkalosis)</p></li></ul>
 
<p></p></li></ul>
 
 
 
<span id="examiner-comments-126"></span>
==== Examiner comments ====
 
<blockquote>43% of candidates passed this question.<br />
Lack of breadth and detail were in many of the answers. Physiology of the adrenal gland includes an outline of the adrenal medulla, the types of chromaffin cells, hormones secreted and how secretion is stimulated. The three zones of the adrenal cortex should have been outlined including substances secreted, their function and again how their secretion is stimulated. The actions of aldosterone should have been described; a comment on sodium and water excretion was insufficient to attain many marks for this section. The extra-renal actions of aldosterone were missing from most answers.
</blockquote>
 
 
<span id="online-resources-for-this-question-126"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-1-06.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/19a/19a06-outline-the-physiology-of-the-adrenal-gland-70-of-marks-describe-the-actions-of-aldosterone-30-of-marks/ Jennys Jam Jar]
* [https://courses.lumenlearning.com/boundless-ap/chapter/the-adrenal-suprarenal-glands/ Random Website]
 
 
 
<span id="similar-questions-126"></span>
==== Similar questions ====
 
* None ?
 
 
 
 
 
<span id="question-7-7"></span>
=== Question 7 ===
 
 
 
<span id="question-127"></span>
==== Question ====
 
Compare and contrast the pharmacokinetics and pharmacodynamics of midazolam and dexmedetomidine.
 
 
 
<span id="example-answer-127"></span>
==== Example answer ====
 
{|
! Name
! Midazolam
! Dexmedetomidine
! Notes
|-
| '''Class'''
| Benzodiazepine (sedative)
| Central alpha agonist (sedative)
| Diff. classes
|-
| '''Indications'''
| Anaesthesia, sedation, treatment of seizures, anxiolysis
| Short term sedation and anxiolysis
| Dexmed = short term and no anticonvulsant / amnesic properties
|-
| '''Pharmaceutics'''
| IV: clear solution, pH 3.5. Diluted in water.
| Clear colourless isotonic solution. Or white powder for dilution
|
|-
| '''Routes of administration'''
| IV, IM, S/C, intranasal, buccal, PO
| IV only in AUS
| Midaz has more routes available
|-
| '''Dose'''
| Dose depends on many pt. factors. 1-5mg premedication. 2.5-10mg seizures. Infusions.
| Infusion (though loading boluses can be given)
|
|-
| pKa
| 6.5
| 7.1
|
|-
| '''Pharmacodynamics'''
|
|
|
|-
| MOA
| Midazolam (BZD) binds to GABA<sub>A</sub> receptors (ionotropic ligand gated channel) in the CNS. Cl enters &gt; hyperpolarisation.
| Selective central a2 agonism (predom. at the locus coeruleus and spinal cord)
| Different receptors
|-
| Effects
| CNS: sedation, amnesia, anticonvulsant effects, decreased cerebral O2 demand
| CNS: Sedation, anxiolysis
| No amnesia with dexmed
|-
| Side effects
| CVS: bradycardia, hypotension<br />
CNS: confusion, restlessness<br />
RESP: respiratory depression/ apnoea
| CVS: hypotension, bradycardia<br />
Other: hyperthermia, confusion, dry mouth
| Bradycardia worse with dexmed. No Resp depression with dexmed.
|-
| '''Pharmacokinetics'''
|
|
|
|-
| Onset
| peak effect 2-3 minutes (IV)
| ~30 mins (without bolus)
| Midaz = quicker onset
|-
| Absorption
| ~40% oral bioavailability<br />
Absorbed well, but sig. 1st pass metabolism
| IV only in Aus. Low PO bioavailability
| Midaz has greater PO bioavailability
|-
| Distribution
| 95% protein bound, very lipid soluble<br />
Vd = 1L / kg
| 95% protein bound, very lipid soluble <br />
Vd = 1.3L/kg
| Similar
|-
| Metabolism
| Hepatic metabolism by hydroxylation <br />
Active (1-a hydroxymidazolam) and inactive metabolites
| Biotransformation (direct glucuronidation and CYP450 metabolism) &gt; inactive metabolites
| Midas has active metabolites
|-
| Elimination
| Renal excretion<br />
T 1/2 = 4 hours
| Renal excretion (5% stool)<br />
t 1/2 = 2 hours
| Similar
|-
| '''Special points'''
| Flumazenil - antagonist (reversal agent)
| Atipamezole = antagonist (reversal agent)
|
|}
 
 
 
<span id="examiner-comments-127"></span>
==== Examiner comments ====
 
<blockquote>27% of candidates passed this question.<br />
Most candidates used the effective tabular format presenting pharmacokinetics and pharmacodynamics of each drug side by side. Many answers demonstrated a lack of correct detail with respect to the pharmacokinetics and pharmacodynamics of these two level 1 drugs. Many included pharmaceutics which attracted no marks as it was not asked.
</blockquote>
 
 
<span id="online-resources-for-this-question-127"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/required-reading/nervous-system/Chapter%20233/dexmedetomidine Deranged: Dexmed] and [https://derangedphysiology.com/cicm-primary-exam/required-reading/nervous-system/Chapter%20232/midazolam Deranged: MIdaz]
* [https://jennysjamjar.com.au/year/19a/19a07/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-1-07.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-127"></span>
==== Similar questions ====
 
* Midazolam
** Question 9, 2019 (2nd sitting)
** Question 4, 2018 (2nd sitting)
** Question 24, 2016 (1st sitting)
** Question 2, 2008 (2nd sitting)
* Dexmed
** Question 22, 2015 (1st sitting)
** Question 5, 2012 (1st sitting)
** Question 2, 2008 (2nd sitting)
 
 
 
 
 
<span id="question-8-7"></span>
=== Question 8 ===
 
 
 
<span id="question-128"></span>
==== Question ====
 
Compare and contrast the measurement (40% of marks) and interpretation (60% of marks) of both central venous and mixed venous oxygen saturations.
 
 
 
<span id="example-answer-128"></span>
==== Example answer ====
 
 
 
Central venous oxygen saturations (ScvO2)
 
* The oxygen saturation of haemoglobin at the cavo-atrial junction
* Normally measured using a CVC
* ScvO2 is normally ~70% (slightly lower than SmvO2 in well patients due to higher oxygen extraction from upper body)
* ScvO2 is used as a surrogate for SmvO2 as it is more accessible for most ICU patients as need a CVC not PAC
 
 
 
Mixed venous oxygen saturation (SmvO2)
 
* The oxygen saturation of haemoglobin when measured in the pulmonary artery (after venous mixing in the right ventricle)
* Measured using a pulmonary artery catheter
* SmvO2 is normally ~75%
* SmvO2 provides better idea of whole body venous O2 sats (blood from SVC, IVC and coronary sinus)
* Can be used to estimate the cardiac output via the modified fick equation
** CO = oxygen consumption / (Oxygen content arterial blood - oxygen content mixed venous blood)
 
 
 
Measurement
 
* Both can be measured using the same methods
** Intermittent sampling
*** ABG: derivation of the SvO2 value from the PO2, pH and pCO2, using the oxygen-haemoglobin dissociation curve.
*** Co-oximetry: measures absorption of near-IR light by haemoglobin species, and the use of the Beer-Lambert law to calculate the concentrations of oxyhaemoglobin and deoxyhaemoglobin
** Continuous monitoring
*** Using a CVC or PAC with with fibre optic reflectance spectrophotometer
*** Near IR light reflectance strength used to determine ratio of Oxy and deoxy Hb
 
 
 
Interpretation of ScvO2 / SmvO2
 
* Increased saturation
** Anaesthesia
** Septic shock
** Cyanide toxicity
** High output cardiac failure
** Hypothermia
** Severe liver disease
* Decreased saturation
** Cardiogenic shock
** Septic shock
** Hyperthermia
* Importantly, not sensitive to regional hypoxia/dysoxia
 
 
 
Evidence
 
* No evidence to support targeting ScvO2 or SmvO2 saturations at present
 
 
 
<span id="examiner-comments-128"></span>
==== Examiner comments ====
 
<blockquote>8% of candidates passed this question.<br />
Many candidates did not appreciate that ScvO2 refers to SVC / RA junction venous oximetry and not femoral or peripheral venous oximetry. Methods of measurement such as co-oximetry and reflectance spectrophotometry needed to be explained. Marks were awarded for the normal values. Discussion of the relationship between ScvO2 and SmvO2 and changes during shock attracted marks. Better answers quoted the modified Fick equation and related this to cardiac output and factors affecting oxygen consumption versus delivery.
</blockquote>
 
 
<span id="online-resources-for-this-question-128"></span>
==== Online resources for this question ====
 
* Ohs intensive care (monitoring oxygen chapter)
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-1-08.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/19a/19a08-compare-and-contrast-the-measurement-40-of-marks-and-interpretation-60-of-marks-of-both-central-venous-and-mixed-venous-oxygen-saturations/ Jennys Jam Jar]
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2019-paper-1-saqs/question-8#answer-anchor Deranged Physiology]
 
 
 
<span id="similar-questions-128"></span>
==== Similar questions ====
 
* ? None
 
 
 
 
 
<span id="question-9-7"></span>
=== Question 9 ===
 
 
 
<span id="question-129"></span>
==== Question ====
 
Classify antibiotics with respect to their mechanism of action (50% of marks). Outline the mechanisms of antimicrobial resistance (50% of marks). Give specific examples of each.
 
 
 
<span id="example-answer-129"></span>
==== Example answer ====
 
 
 
Classification of antibiotics
 
* Inhibitors of cell wall synthesis
** Beta-lactams: e.g. flucloxacillin
** Cephalosporins: e.g. ceftriaxone
** Carbapenems: e.g. meropenem
** Monobactams: eg. aztreonam
** Glycopeptides e.g. vancomycin
* Inhibitors of cytoplasmic membrane function
** Polymyxins: e.g. colistin
** Lipopetides e.g daptomycin
* Inhibitors of nucleic acid synthesis
** Quinolones e.g ciprofloxacin
** Rifamycins e.g. rifampicin
** Nitroimidazoles e.g. metronidazole
* Folate metabolism inhibitors
** e.g. trimethoprim
* Inhibitor of protein synthesis
** Aminoglycosides: e.g. gentamycin
** Tetracyclines: doxycycline
** Lincosamides: e.g clindamycin
** Macrolides: e.g. erythromycin
 
 
 
Antimicrobial resistance
 
* Occurs when the maximal level of drug tolerated in insufficient to inhibit growth
* Broadly occurs via genetic alteration or changes to protein expression
 
 
 
Mechanisms of resistance
 
# Prevent access to drug target
#* Decrease permeability
#** E.g. pseudomonas aeruginosa resistance to carbapenems due to reduction in porins
#* Active efflux of drug
#** Efflux pumps &gt; extrude antibiotics (eg. fluoroquinolone resistance with E.coli)
# Alter antibiotic target site
#* Alteration to Peptidoglycan binding site protein, reducing affinity of drug.
#* E.g. Vancomycin and VRE (e.g. E. faecium)
# Modification / inactivation of drug
#* E.g. ESBL and penicillin's/cephalosporins whereby b-lactamases hydrolyse B-lactam rings
# Modification of metabolic pathways
#* Metabolic pathways bypass site of antibiotic action
#* E.g. Bactrim resistance (synthesise their own folic acid)
 
 
 
<span id="examiner-comments-129"></span>
==== Examiner comments ====
 
<blockquote>70% of candidates passed this question.<br />
This question was well answered. Marks were awarded for correct pairing of mechanism of action and resistance with examples of drug class. Few mentioned the mechanisms by which resistance is present; acquired or generated.
</blockquote>
 
 
<span id="online-resources-for-this-question-129"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/19a/19a09/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-1-09.pdf CICM Wrecks]
* [https://derangedphysiology.com/required-reading/infectious-diseases-antibiotics-and-sepsis/Chapter%202.2.1/antibiotic-agents-classified-mechanism-action Deranged Physiology]
 
 
 
<span id="similar-questions-129"></span>
==== Similar questions ====
 
* Question 5, 2020 (1st sitting)
 
 
 
 
 
<span id="question-10-7"></span>
=== Question 10 ===
 
 
 
<span id="question-130"></span>
==== Question ====
 
Outline the sequence of haemostatic events after injury to a blood vessel wall (50% of marks). Discuss the role of naturally occurring anticoagulants in preventing clot formation in-vivo (50% of marks).
 
 
 
<span id="example-answer-130"></span>
==== Example answer ====
 
 
 
# Vascular constriction
#* Occurs instantly, lasts a few minutes
#* Due to
#** Local myogenic spasm
#** Nervous reflexes
#** Release of local vasoconstrictors (e.g. Thromboxane A2)
#* Limits the amount of haemorrhage and creates environment suitable for clot formation
 
 
 
<ol style="list-style-type: decimal;">
<li><p>Primary haemostasis (platelet plug formation)</p>
<ul>
<li><p>Platelet adhesion</p>
<ul>
<li><p>Exposed vWF in endothelium binds to glycoprotein receptor complex on platelets</p></li>
<li><p>Platelet GP1a binds to subendothelial collagen fibres by vWF bridge</p></li></ul>
</li>
<li><p>Platelet activation</p>
<ul>
<li><p>Activated following exposure to tissue factor, vWF and collagen</p></li>
<li><p>Results in them </p>
<ul>
<li><p>Changing shape (large, more irregular, pseudopod formation) &gt; assists with clot formation</p></li>
<li><p>Release molecules (Thromboxane A2, ADP, serotonin) &gt; vasoconstricts + activates platelets</p></li></ul>
</li></ul>
</li>
<li><p>Platelet aggregation</p>
<ul>
<li><p>Activated platelets bind fibringoen, vWF and fibronectin forming a soft platelet plug</p></li></ul>
 
<p></p></li></ul>
</li>
<li><p>Secondary haemostasis (clot formation)</p>
<ul>
<li><p>Two main models: classical (in vitro) model and modern cell based (in vivo) model</p></li>
<li><p>Cell based model</p>
<ul>
<li><p>Initiation</p>
<ul>
<li><p>Vessel damage exposes plasma to tissue factor</p></li>
<li><p>tissue factor binds to and activates factor VII</p></li>
<li><p>TF-Factor VIIa complex activates factor X</p></li>
<li><p>Factor X activates prothrombin &gt; thrombin (small amounts)</p></li></ul>
</li>
<li><p>amplification</p>
<ul>
<li><p>This causes local activation of platelets (via vWF), Factor V, Factor VIII and factor XI</p></li>
<li><p>This greatly accelerates the production of thrombin around the surface of the platelets</p></li></ul>
</li>
<li><p>Propagation</p>
<ul>
<li><p>Begins with formation of tenase complexes on platelet surfaces (IXa-VIIIa) which greatly increases the rate of Factor X activation</p></li>
<li><p>The large amounts of Xa interacts with factor Va forming prothrombinase complex (Va-Xa) which catalyses the conversion of prothrombin to thrombin </p></li>
<li><p>Positive feedback loop</p></li></ul>
</li></ul>
</li></ul>
</li></ol>
 
 
 
Natural anticoagulants --&gt; prevent unnecessary coagulation
 
* Antithrombin 3
** Inactivates IIa and Xa
* Protein C
** Inactivates Va and VIIa
* Protein S
** Cofactor for upregulating protein C
* Thrombomodulin
** Bound to the endothelial membrane
** Binds thrombin and activates protein C
* Heparan
** Activates AT-3, which in turn inactivates thrombin
 
 
 
<span id="examiner-comments-130"></span>
==== Examiner comments ====
 
<blockquote>40% of candidates passed this question.<br />
This question was best answered in a chronological manner. Many candidates omitted initial vasoconstriction and its mechanism. The platelet plug and formation of the clot should have then been described followed by the fate of the clot, including in-growth of fibroblasts. Strictly, fibrinolysis is a system for repairing / limiting clot propagation after the fact. Anticoagulants refer to antithrombin III, heparin, thrombomodulin and protein C and S. An explanation of the interaction of these naturally occurring anticoagulants was expected. The clotting factors that are specifically inhibited was expected as part of the discussion. The glycocalyx and vessel wall also plays a role in preventing coagulation.
</blockquote>
 
 
<span id="online-resources-for-this-question-130"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-1-10.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/19a/19a10-outline-the-sequence-of-haemostatic-events-after-injury-to-a-blood-vessel-wall-50-of-marks-discuss-the-role-of-naturally-occurring-anticoagulants-in-preventing-clot-formation-in-vivo-50-of/ Jennys Jam Jar]
 
 
 
<span id="similar-questions-130"></span>
==== Similar questions ====
 
* Question 4 (part 2), 2009 (1st sitting)
* Question 17, 2011 (1st sitting)
 
 
 
 
 
<span id="question-11-7"></span>
=== Question 11 ===
 
 
 
<span id="question-131"></span>
==== Question ====
 
Describe the physiology of cerebrospinal fluid (CSF) (60% of marks). Describe the anatomy relevant to performing a lumbar puncture (40% of marks).
 
 
 
<span id="example-answer-131"></span>
==== Example answer ====
 
 
 
CSF
 
* ECF located in the ventricles and subarachnoid space
* volume: ~2ml/kg
* Divided evenly between the cranium and spinal column
 
 
 
Formation
 
* Constantly produced (~24mls/hr)
* Produced by choroid plexus (70%) and capillary endothelial cells (30%)
* Produced by a combination of ultrafiltration (via fenestrated choroidal capillaries) and active secretion
 
 
 
Composition relative to plasma
 
* Similar: Na, osmolality, HCO3
* Increased: Cl, Mg, CO2
* Decreased: pretty much everything else
 
 
 
Circulation
 
* CSF flows from lateral ventricles &gt; foramen of Monro &gt; 3rd ventricle &gt; Sylvian aqueduct &gt; 4th ventricle &gt; cisterna magna (via foramen megendie and luschka) &gt; spreads between spinal/cranial subarachnoid spaces
 
 
 
Reabsorption
 
<ul>
<li><p>Reabsorption by the arachnoid villi located predominately in the dural walls of the sagittal + sigmoid sinuses (one way valves)</p></li>
<li><p>Reabsorbed at ~24mls/hr</p>
<p></p></li></ul>
 
Functions
 
* Mechanical protection: low specific gravity of CSF &gt; decreased effective weight of brain &gt; no contact with skull base + less inertia forces
* Buffering of ICP - CSF can be displaced / reabsorbed to offset increase in ICP
* Stable extracellular environment for neuronal activit
* Control of respiration: pH regulates respiration via central chemoreceptors
* Nutrition: supply of oxygen, sugars, amino acids to supply the brain
 
 
 
Anatomy of LP
 
* Positioning:
** lateral decubitus or sitting position
* Level:
** L2-5 possible (below conus medullaris)
** L3/4 or L4/5 are recommended (safety).
* Surface landmarks:
** Line between iliac crests (Tuffiers line) = L4/5
** Line between PSISs = L3/4
** Central positioning by spinous processes'
* Angle of needle
** Toward umbilicus (~15 degrees)
* Order of tissues/structures passed through by needle
** Skin
** Subcut tissue
** Supraspinous ligament
** Interspinous ligament
** Ligamentum flavum
** Epidural space
** Dura mater
** Arachnoid mater
** Subarachnoid space = CSF
 
 
 
<span id="examiner-comments-131"></span>
==== Examiner comments ====
 
<blockquote>86% of candidates passed this question.<br />
Better answers had a structure with headings such as function, formation, circulation, absorption and composition with dot point facts under each heading. The second part of the question lent itself to a diagram with labelling which scored well. Precise surface anatomy and mentioning all layers from the skin to the sub-arachnoid space scored well
</blockquote>
 
 
<span id="online-resources-for-this-question-131"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-1-11.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/19a/19a11/ Jennys Jam Jar]
 
 
 
<span id="similar-questions-131"></span>
==== Similar questions ====
 
<ul>
<li><p>Question 16, 2020 (1st sitting)</p></li>
<li><p>Question 15, 2018 (2nd sitting)</p></li>
<li><p>Question 9, 2017 (2nd sitting)</p></li>
<li><p>Question 24, 2017 (1st sitting)</p></li>
<li><p>Question 16, 2015 (1st sitting)</p></li>
<li><p>Question 2, 2013 (1st sitting)</p></li>
<li><p>Question 22, 2007 (1st sitting)</p></li>
<li><p>Question 6, 2008 (2nd sitting)</p>
<p></p></li></ul>
 
 
 
<span id="question-12-7"></span>
=== Question 12 ===
 
 
 
<span id="question-132"></span>
==== Question ====
 
Compare and contrast the pharmacology of salbutamol and ipratropium bromide.
 
 
 
<span id="example-answer-132"></span>
==== Example answer ====
 
{|
! Name
! Salbutamol
! Ipratropium bromide
! Notes
|-
| '''Class'''
| Short acting B2 agonist (synthetic sympathomimetic amine)
| Anticholinergic (quaternary ammonium derivative of atropine)
|
|-
| '''Indications'''
| Bronchoconstriction, hyperkalaemia, tocolytic
| Bronchoconstriction
|
|-
| '''Pharmaceutics'''
| Clear solution for neb, solution for IV (post dilution), powder / aerosol for inhalation, PO tablets
| Aerosol for inhalation, clear colourless solution for neb
|
|-
| '''Routes of administration'''
| Neb, IV, INH, PO
| Neb, INH
| Salbutamol can be given IV
|-
| '''Dose'''
| 2.5mg-5mg PRN (Neb)<br />
200-400mcg PRN (INH)<br />
0.5mch/kg.min (infusion)
| Neb: 100-500mcg QID<br />
INH: 100-500mcg BD
| Salbutamol given more regularly
|-
| '''Pharmacodynamics'''
|
|
|
|-
| MOA
| B2 agonism &gt; increased cAMP &gt; decreased Ca &gt; bronchial smooth muscle relaxation
| Competitive antagonism of muscarinic ACh receptors &gt; bronchodilation + decreased secretions
| Can be used synergistically (different MOA)
|-
| Side effects
| CNS: anxiety, tremor<br />
RESP: reverses HPVC<br />
CVS: tachycardia<br />
MET: hypoK (stimulates Na/K ATPAse), lactic acidosis
| RESP: dry mouth, N, V<br />
CNS: headache, blurred vision
|
|-
| '''Pharmacokinetics'''
|
|
|
|-
| Onset/duration
| Immediate, fast offset (mins)
| Peak effect 1-2 hours, lasts 6 hours
| Ipratropium has slow onset, longer duration of effect
|-
| Absorption
| 50% bioavailability
| 5% inhaled absorbed systemically
| Salbutamol can be given PO
|-
| Distribution
| VOD: ~150L/kg<br />
10% protein bound<br />
Can cross placenta
| VOD: 4-5L/kg<br />
Very weak protein binding
| Salbutamol crosses placenta
|-
| Metabolism
| Metabolised in liver &gt; inactive + active metabolites
| Metabolised in liver by CYP450 &gt; inactive
| Salbutamol has active metabolites
|-
| Elimination
| Metabolites via urine + faeces<br />
T 1/2: 4 hours
| Metabolites via urine + faeces<br />
Elimination half life 3 hours
| Similar
|-
| '''Special points'''
|
|
|
|}
 
 
 
<span id="examiner-comments-132"></span>
==== Examiner comments ====
 
<blockquote>46% of candidates passed this question.<br />
Overall candidates had a superficial knowledge of these level 1 drugs. To pass candidates needed to identify points of difference and overlap in various areas such as structure, pharmaceutics, pharmacokinetics, pharmacodynamics, mechanism of action, adverse effects and contraindications.
</blockquote>
 
 
<span id="online-resources-for-this-question-132"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/main/cicm-primary-exam/required-reading/respiratory-system/Chapter%20314/pharmacology-drugs-used-treat-asthma Deranged physiology]
* [https://jennysjamjar.com.au/year/19a/19a12/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-1-12.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-132"></span>
==== Similar questions ====
 
* None directly
* Bronchodilators more broadly have been asked for in
** Question 4, 2016 (2nd sitting)
** Question 11, 2014 (2nd sitting)
** Question 9, 2010 (1st sitting)
 
 
 
 
 
<span id="question-13-7"></span>
=== Question 13 ===
 
 
 
<span id="question-133"></span>
==== Question ====
 
Classify circulatory shock and provide examples (40% of marks). Outline the cardiovascular responses (60% of marks).
 
 
 
<span id="example-answer-133"></span>
==== Example answer ====
 
 
 
Shock
 
* Life threatening, generalised maldistribution of blood flow resulting in failure to deliver and/or utilise oxygen, leading to tissue dysoxia.
 
 
 
Classifications
 
* Hypovolaemic
** Caused by intravascular volume depletion
** Includes haemorrhage, fluid loss (e.g. dehydration) and fluid shifts (e.g. pancreatitis)
* Cardiogenic
** Caused by cardiac pump failure or dysfunction
** Includes: cardiomyopathy, ACS, arrhythmia, valve failure
* Distributive
** Caused by significant peripheral vascular dilation leading to fall in PVR
** Includes: sepsis, inflammation (e.g. post cardiopulmonary bypass), anaphylaxis, neurogenic (e.g. high spinal cord injury)
* Obstructive
** Caused by circulatory obstruction/impedance
** Includes: tamponade, tension pneumothorax, pulmonary embolism
 
 
 
Cardiovascular response to circulatory shock
 
{|
! Stimulus
! Sensor
! Integrator
! Effector
|-
| Hypotension
| Baroreceptors
| Nucleus of the solitary tract (NTS)
| - CNX inhibition (increased HR) - SNS activation (vasoconstriction, redistribution of BV, increased CO) - RAAS activation
|-
| Decreased VO2
| Aortic arch chemoreceptors
| NTS
| As above
|-
| Decreased circulatory volume
| Atrial myocytes
| -
| Decreased release ANP
|-
| Decreased circulatory volume
| Baroreceptors
| Hypothalamus
| Increased release of vasopressin
|-
| Decreased circulatory volume
| Renal JG cells
| -
| Increased release of renin, RAAS activation
|-
| Inadequate tissue perfusion
| vascular SM and endothelium
| -
| Autoregulatory vasodilation
|}
 
 
 
<span id="examiner-comments-133"></span>
==== Examiner comments ====
 
<blockquote>83% of candidates passed this question.<br />
Answers should have included the various types of shock and provided clear examples. Cardiovascular responses including sensor, integrator, effector mechanisms were necessary to pass.
</blockquote>
 
 
<span id="online-resources-for-this-question-133"></span>
==== Online resources for this question ====
 
<ul>
<li><p>[https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2019-paper-1-saqs/question-13#answer-anchor Deranged Physiology]</p></li>
<li><p>[https://cicmwrecks.files.wordpress.com/2020/03/2019-1-13.pdf CICM Wrecks]</p></li>
<li><p>[https://jennysjamjar.com.au/year/19a/19a13-classify-circulatory-shock-and-provide-examples-40-marks-outline-the-cardiovascular-responses-60/ Jennys Jam Jar]</p>
<p></p></li></ul>
 
<span id="similar-questions-133"></span>
==== Similar questions ====
 
* ? None
 
 
 
 
 
<span id="question-14-7"></span>
=== Question 14 ===
 
 
 
<span id="question-134"></span>
==== Question ====
 
Compare and contrast the mechanism of action, pharmacokinetics and adverse effects of digoxin and sotalol.
 
 
 
<span id="example-answer-134"></span>
==== Example answer ====
 
{|
! Name
! Digoxin
! Sotalol
! Notes
|-
| '''Class'''
| Cardiac glycoside (antiarrhythmic)
| B-blocker
| Different class
|-
| '''Indications'''
| tachyarrhythmias (e.g. AF, SVT), heart failure
| tachyarrhythmias (e.g. AF, SVT) and ventricular arrhythmias
| Sotalol can be used for ventricular arrhythmias
|-
| '''Pharmaceutics'''
| 62.5mcg/250mcg (PO tablets), 25/250 mcg/ml (IV)
| 80+160mg PO tablets. IV in racemix mixture of enantiomers (through SAS).
| Digoxin available IV
|-
| '''Routes of administration'''
| IV and PO
| PO, IV (via SAS)
|
|-
| '''Dose'''
| Generally load with 250-500mcg, then 62.5-125mcg daily thereafter
| 40-160mg PO BD
| No loading for sotalol
|-
| pKA
| 7.2
| 9.8
|
|-
| '''Pharmacodynamics'''
|
|
|
|-
| MOA
| Direct cardiac: inhibits Na/K ATPase &gt; increased Ca &gt; positive inotropic effect + increased refractory period<br />
Indirect cardiac: increased PSNS release of ACh at M receptors &gt; slowed conduction at AV node/bundle<br />
| 1) Non selective B-blocker (class II) &gt; decreased chronotropy and inotropy<br />
2) Class III activity (K channel blocker) &gt; prolonged refractory period + repolarisation &gt; slow AV conduction and lengthens QT
| Dig = increased inotropy and short QT <br />
Sotalol = decreased inotropy + prolonged QT
|-
| Side effects
| CVS: May worsen arrhythmia (lead to VF), AV block, shortened QT interval, scooped ST, TWI, bradycardia<br />
GIT: nausea, anorexia, vomiting<br />
CNS: dizziness, drowsiness
| CVS: precipitation of tDP, bradycardia, prolonged QT int, bradycardia, hypotension <br />
Resp: bronchospasm<br />
CNS: dizziness, drowsiness
| Dig shortens Qt, sotalol prolongs it.
|-
| '''Pharmacokinetics'''
|
|
|
|-
| Onset/duration
| 2-3 hours (PO), 10-30mins (IV), duration of action 3-4 days
| 2-3 hours (PO)
| Similar onset
|-
| Absorption
| 80% oral bioavailability
| 95% oral bioavailability
| Both have good OBA
|-
| Distribution
| Protein binding 25%<br />
VOD 6-7L/kg
| No protein binding <br />
VOD 1-2L/kg
| Dig = larger VOD and protein binding
|-
| Metabolism
| minimal hepatic metabolism (15%)
| Nil
|
|-
| Elimination
| T 1/2 48 hours<br />
urine excretion (70% unchanged)
| T 1/2 12 hours<br />
Urine excretion (unchanged)
| Dig lasts longer in system
|-
| '''Special points'''
| Reduce dose in renal failure, monitor with dig level. not removed by dialysis
| Reduce dose in renal failure<br />
Requires SAS for IV
| Both require renal adjustment
|}
 
 
 
<span id="examiner-comments-134"></span>
==== Examiner comments ====
 
<blockquote>19% of candidates passed this question.<br />
Good answers listed class and the multiple mechanisms of action for both these antiarrhythmics, briefly outlining relevant downstream physiological effects and contrasting effects on inotropy. Knowledge of specific pharmacokinetic parameters of these agents was generally lacking. Clinically relevant adverse effects were frequently omitted (e.g. prolonged QT/Torsades for sotalol, hypokalaemia potentiating toxicity of digoxin).
</blockquote>
 
 
<span id="online-resources-for-this-question-134"></span>
==== Online resources for this question ====
 
* [https://jennysjamjar.com.au/year/19a/19a14-compare-and-contrast-the-mechanism-of-action-pharmacokinetics-and-adverse-effects-of-digoxin-and-sotalol/ Jennys Jam Jar]
* [https://derangedphysiology.com/main/cicm-primary-exam/required-reading/cardiovascular-system/Chapter%20965/classification-antiarrhythmic-agents Deranged Physiology]and [https://derangedphysiology.com/main/cicm-primary-exam/required-reading/cardiovascular-system/Chapter%20968/digoxin Deranged Physiology]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-1-14.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-134"></span>
==== Similar questions ====
 
* Digoxin
** Question 2, 2018 (2nd sitting)
** Question 10, 2013, (2nd sitting)
** Question 22, 2010 (2nd sitting)
 
 
 
 
 
<span id="question-15-7"></span>
=== Question 15 ===
 
 
 
<span id="question-135"></span>
==== Question ====
 
Describe the physiology of the NMDA (N-Methyl D-aspartate) receptor (40% of marks). Outline the pharmacology of ketamine (60% of marks).
 
 
 
<span id="example-answer-135"></span>
==== Example answer ====
 
 
 
NMDA receptor
 
* Structure
** Tetrameric, ligand gated, transmembrane receptor
* Location
** Abundant in the CNS (brain, spinal cord)
* Ion permeability
** Ca, Na, K
* Activated by
** Glutamate (excitatory neurotransmitter) and glycine
** Activation leads to removal of central Mg plus (Na/Ca in, K out) &gt; EPSP
* Blocked by
** Ketamine, Mg, memantidine
 
 
 
{|
! Name
! Ketamine
|-
| '''Class'''
| Anaesthetic (phencyclidine derivative)
|-
| '''Indications'''
| induction GA, conscious sedation, analgesia,
|-
| '''Pharmaceutics'''
| 100mg/ml. Clear colourless solution. Racemic mixture of S and R enantiomers, or S+ enantiomer alone. Water soluble.
|-
| '''Routes of administration'''
| IV/IM/PO/SC/PR
|-
| '''Dose'''
| 0-0.25mg/kg/hr (analgesia), 1-2mg/kg (GA), 0.5mg/kg (sedation)
|-
| pKa
| 7.5
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| NMDA antagonism, weak opioid receptor agonism, weak Ca ch inhibition
|-
| Effects
| CNS: dissociative anaesthesia and analgesia. <br />
CVS: increased HR/BP, decreased pulmonary and systemic vascular resistance,<br />
Resp: bronchodilation
|-
| Side effects
| CNS: emergence reactions including hallucinations, unpleasant dreams. may increase ICP in non ventilated patients<br />
CVS: may increase HR/BP, increased myocardial O2 req.<br />
GIT: Nausea, vomiting, increased salivation<br />
RESP: apnoea
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| 30s IV, duration of effect 10-20mins
|-
| Absorption
| Lipid soluble &gt; readily absorbed. But poor OBA (16%) due to 1st pass metabolism
|-
| Distribution
| Large (5L/kg) VOD. small protein binding (25%). Crosses placenta.
|-
| Metabolism
| Metabolised by CYP450 &gt; majority inactive metabolites (norketamine active)
|-
| Elimination
| Elimination T1/2 = 2 hours. Kidneys (95%), faeces (5%)
|-
| '''Special points'''
|
|}
 
 
 
<span id="examiner-comments-135"></span>
==== Examiner comments ====
 
<blockquote>49% of candidates passed this question.<br />
The NMDA receptor is a ligand gated voltage dependent ion channel located on post synaptic membranes throughout the CNS, with glutamate, an excitatory neurotransmitter, its natural ligand. A brief description of its structure, roles of glycine and magnesium, ions conducted, result of activation, role in memory and learning and agonists/antagonists was expected. Detail on structure and functions of the receptor were a common omission.<br />
Ketamine, a phencyclidine derivative, is a non-competitive antagonist at the NMDA receptor. It is presented as a racemic mixture or as the single S(+) enantiomer (2-3 X potency). Administration routes and doses scored marks. Pharmacodynamics were generally well covered including CVS (direct and indirect effects), CNS (anaesthesia, analgesia, amnesia, delirium, effects on CBF and ICP) respiratory (bronchodilator with preservation of airway reflexes) GIT effects (salivation, N and V). Knowledge of specific pharmacokinetic parameters was less well covered, including low oral bioavailability and protein binding and active metabolite (norketamine).
</blockquote>
 
 
<span id="online-resources-for-this-question-135"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/main/cicm-primary-exam/required-reading/nervous-system/Chapter%20221/ketamine Deranged Physiology]
* [https://jennysjamjar.com.au/year/19a/19a15/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-1-15.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-135"></span>
==== Similar questions ====
 
<ul>
<li><p>Ketamine</p>
<ul>
<li><p>Question 4, 2018 (2nd sitting)</p></li>
<li><p>Question 22, 2015 (1st sitting)</p></li>
<li><p>Question 16, 2011 (2nd sitting)</p></li>
<li><p>Question 7, 2010 (2nd sitting)</p></li></ul>
 
<p></p></li></ul>
 
 
 
<span id="question-16-7"></span>
=== Question 16 ===
 
 
 
<span id="question-136"></span>
==== Question ====
 
Describe the role of carbon dioxide in the control of alveolar ventilation
 
 
 
<span id="example-answer-136"></span>
==== Example answer ====
 
 
 
SENSORS
 
Peripheral chemoreceptors
 
* Located in the carotid body
** Sense a rise in PaCO2 (as well as a fall in PaO2 or pH)
** Afferent nerve = CN IX
* Located in the aortic body
** Sense a rise in PaCO2 (or fall in PaO2)
** Afferent nerve CN X
 
 
 
Central chemoreceptors
 
* Located in the ventral medulla near the respiratory centre
* Stimulated by a fall in pH of the CSF
* The most important mediator of the change in pH is PaCO2 which freely diffuses across the blood-brain-barrier and dissociates into H+
* The reduced buffering capacity (HCO3 cannot pass the BBB) make these receptors very sensitive to change in CSF pH
 
 
 
CENTRAL PROCESSOR
 
* Respiratory centre in the medulla and pons
** Nucleus retroambigualis --&gt; Expiratory muscle control via UMN
** Nucleus parambigualis --&gt; Inspiratory muscle control via UMN
** Nucleus ambigualis --&gt; Pharyngeal/laryngeal muscles via CN 9/10
** pre-Botzinger complex --&gt; respiratory pacemaker
 
 
 
EFFECTORS
 
* Muscles of respiration (diaphragm, intercostals, accessory muscles etc)
 
 
 
Ventilatory response to CO2 change
 
* Linear response (increase in PaCO2 = increase in minute ventilation)
** Left shift: metabolic acidosis, hypoxia
** Right shift: sleep, anaesthesia, opiates
 
[[File:https://derangedphysiology.com/main/sites/default/files/sites/default/files/CICM Primary/F Respiratory system/ventilatory response to CO2 under different conditions.jpg|thumb|none]]
 
 
 
<span id="examiner-comments-136"></span>
==== Examiner comments ====
 
<blockquote>57% of candidates passed this question.<br />
Better answers considered the role of CO2 in the control of alveolar ventilation in terms of sensors, central processing and effectors - with an emphasis on sensors. Features of central and peripheral chemoreceptors should have been described in detail. The PCO2/ventilation response curve is best described using a graph, with key features of the curve identified (including gradient and axes). Various factors affecting the gradient of this curve and how CO2 affects the response to hypoxic drive should be described.
</blockquote>
 
 
<span id="online-resources-for-this-question-136"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-1-16.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/19a/19a16/ Jennys Jam Jar]
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2019-paper-1-saqs/question-16#answer-anchor Deranged Physiology]
 
 
 
<span id="similar-questions-136"></span>
==== Similar questions ====
 
<ul>
<li><p>None the same, but broadly related to</p>
<ul>
<li><p>Question 21, 2013 (1st sitting)</p></li>
<li><p>Question 1, 2015 (1st sitting)</p></li>
<li><p>Question 13, 2015 (2nd sitting)</p></li></ul>
 
<p></p></li></ul>
 
 
 
<span id="question-17-7"></span>
=== Question 17 ===
 
 
 
<span id="question-137"></span>
==== Question ====
 
Explain the physiology of neuromuscular transmission
 
 
 
<span id="example-answer-137"></span>
==== Example answer ====
 
 
 
Neuromuscular junction (NMJ)
 
* Synapse between a motor neuron and a muscle cell
* Components
** Terminal bouton of nerve axon
** Synaptic cleft
** Junctional folds
** Motor end plate
* The neurotransmitter of the NMJ is acetylcholine (Ach) which is synthesised in the nerve axoplasm
 
[[File:C:\Users\ethan\AppData\Roaming\Typora\typora-user-images\image-20220304095424224.png|thumb|none]]
 
 
 
Neuromuscular transmission
 
* Action potential depolarised nerve terminal
* Voltage gated calcium channels open &amp; calcium enters
* Calcium influx, triggers synaptic vesicles to release Ach into the synaptic cleft via exocytosis
* ACh diffuses across the synaptic cleft and binds to post-synaptic nicotinic receptors
** Nicotinic ACh receptors (nAChR) are transmembrane ligand gated, ion channel linked receptors
* Activation of nAChR leads to Na influx, which depolarises the cell (excitatory post synaptic potential)
* Muscle contraction occurs via muscle excitation-contraction coupling
* ACh is subsequently metabolised by acetylcholinesterase (into Acetyl CoA and choline) and the NMJ returns to its resting state
 
[[File:https://cdn.kastatic.org/ka-perseus-images/c2792e65f78b25734f78a5f34cd296104a2e5d86.png|thumb|none]]
 
 
 
<span id="examiner-comments-137"></span>
==== Examiner comments ====
 
<blockquote>60% of candidates passed this question.<br />
Description of sequential events from axon conduction to detail at the neuromuscular junction was required. Well-constructed answers defined neuromuscular transmission, elucidated the structure of the neuromuscular junction (best done with a detailed diagram), described the central importance of acetylcholine, including synthesis, storage, receptors, and degradation. An ideal answer also described both pre-synaptic (e.g. voltage-gated calcium channels, exocytosis of vesicles) and post-synaptic events (acetylcholine receptors, end plate potentials, and the events that lead to excitation-contraction coupling in skeletal muscle).
</blockquote>
 
 
<span id="online-resources-for-this-question-137"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-1-17.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/19a/19a17-explain-the-physiology-of-neuromuscular-transmission/ Jennys Jam Jar]
 
 
 
<span id="similar-questions-137"></span>
==== Similar questions ====
 
* ? None
 
 
 
 
 
<span id="question-18-7"></span>
=== Question 18 ===
 
 
 
<span id="question-138"></span>
==== Question ====
 
Describe the pharmacology of frusemide
 
 
 
<span id="example-answer-138"></span>
==== Example answer ====
 
{|
! Name
! Furosemide
|-
| '''Class'''
| Loop diuretic
|-
| '''Indications'''
| Oedema/fluid overload, renal insufficiency, hypertension
|-
| '''Pharmaceutics'''
| Tablet, clear colourless solution (light sensitive),
|-
| '''Routes of administration'''
| IV, PO,
|-
| '''Dose'''
| Varies (~40mg daily commonly used for well patients, can be sig. increased)
|-
| pKA
| 3.6 (highly ionised; poorly lipid soluble)
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Binds to NK2Cl transporter in the thick ascending limb LOH, leads to decreased Na,K, Cl reabsorption &gt; decreased medullary tonicity + Inc Na/Cl delivery to distal tubules &gt; decreased water reabsorption &gt; diuresis
|-
| Effects
| Renal: diuresis<br />
CVS: hypovolaemia, arteriolar vasodilation + decreased preload (=mechanism for improvement of dyspnoea before diuretic effect)<br />
Renal: increase in RBF
|-
| Side effects
| CVS: hypovolaemia, hypotension<br />
Renal/metabolic: Metabolic alkalosis, LOW Na, K, Mg, Cl, Ca, increased Cr<br />
Ototoxicity, tinnitus, deafness
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| 5 mins (IV), 30-60 mins (PO), Effect lasts 6 hours.
|-
| Absorption
| Bioavailability varies person-person (40-80%)
|-
| Distribution
| Vd = 0.1L/Kg, 95% protein bound (albumin)
|-
| Metabolism
| &lt; 50% metabolised renally into active metabolite
|-
| Elimination
| Renally cleared (predominately unchanged). T1/2 ~90 mins.
|-
| '''Special points'''
| Deafness can occur with rapid administration in large doses
|}
 
 
 
<span id="examiner-comments-138"></span>
==== Examiner comments ====
 
<blockquote>13% of candidates passed this question.<br />
The majority of answers were well structured, some using tables and others using key headings. In general, for a commonly used drug that is listed in the syllabus as Level 1 of understanding, detailed information was lacking. In particular, mechanism of action, dose threshold and ceiling effect and pharmacokinetics lacked detail and/or accuracy.
</blockquote>
 
 
<ul>
<li><p>Online resources for this question</p>
<ul>
<li><p>[https://derangedphysiology.com/cicm-primary-exam/required-reading/renal-system/Chapter%20022/furosemide Deranged Physiology]</p></li>
<li><p>[https://partone.litfl.com/diuretics.html#id Part One, LITFL]</p></li>
<li><p>[https://jennysjamjar.com.au/year/20a/20a14/ Jenny's Jam Jar]</p></li>
<li><p>[https://cicmwrecks.files.wordpress.com/2020/07/2020-1-14.pdf CICM Wrecks]</p></li></ul>
 
<p></p>
<span id="similar-questions-138"></span>
==== Similar questions ====
 
<ul>
<li><p>Question 20, 2013 (1st sitting)</p></li>
<li><p>Question 16, 2018 (1st sitting)</p></li>
<li><p>Question 14, 2020 (1st sitting)</p></li></ul>
</li></ul>
 
 
 
 
 
<span id="question-19-7"></span>
=== Question 19 ===
 
 
 
<span id="question-139"></span>
==== Question ====
 
Describe the effects of ageing on the respiratory system.
 
 
 
<span id="example-answer-139"></span>
==== Example answer ====
 
 
 
{|
! Age relate changes
! Effects of change
|-
| Airway<br />
- Increased airway reactivity<br />
- Decreased ciliary number/activity<br />
- Diminished airway reflexes
| - Increased risk of bronchospasm<br />
- Reduced clearance of secretions<br />
-Increased propensity towards pharyngeal collapse
|-
| Chest wall <br />
- Calcification of costal ligaments<br />
-Reduced vertebral body height<br />
-Kyphosis
| - Decreased chest wall compliance<br />
- Reduced vital capacity<br />
- Increased RV and FRC
|-
| Respiratory muscles<br />
- Decreased muscle mass/strength<br />
-Decreased proportion fast-twitch fibres
| - Decreased FEV1<br />
- Fatigue develops faster
|-
| Lungs<br />
- Senile emphysema (hyperinflation)<br />
- Degradation of elastic fibres and supporting tissues
| - Increased lung compliance<br />
- Increased dead space<br />
- Decreased elastic recoil<br />
-Increased closing volume
|-
| Gas exchange<br />
-Increased alveolar-capillary membrane thickness<br />
-Senile emphysema
| - Decline in DLCO<br />
- Decreased surface area for gas exchange<br />
- Increased shunt / V/W mismatch
|-
| Control of ventilation<br />
- Decrease in efferent neural output to respiratory muscles<br />
- Minute volume remains similar
| - Reduction in response to hypoxia and hypercarbia<br />
-Decrease in Vt --&gt; increase in RR to maintain MV
|-
| Work of breathing
| Overall increased due to the net effect of the above changes
|}
 
 
 
<span id="examiner-comments-139"></span>
==== Examiner comments ====
 
<blockquote>5% of candidates passed this question.<br />
Answers should have included the effects of ageing on the efficiency of gas exchange, how the expected PaO2 changes with age, and its causation. Anatomical changes should have been included as should changes in lung volumes, particularly the significance of an increased closing volume. Marks were not awarded for the effects of disease states.
</blockquote>
 
 
<span id="online-resources-for-this-question-138"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-1-19.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/19a/19a19/ Jennys Jam Jar]
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2019-paper-1-saqs/question-19#answer-anchor Deranged Physiology]
 
 
 
<span id="similar-questions-139"></span>
==== Similar questions ====
 
* None :(
 
 
 
 
 
<span id="question-20-7"></span>
=== Question 20 ===
 
 
 
<span id="question-140"></span>
==== Question ====
 
Describe the cardiovascular effects of positive pressure ventilation on a patient who has received a long acting muscle relaxant.
 
 
 
<span id="example-answer-140"></span>
==== Example answer ====
 
 
 
Overview
 
* Normal spontaneous ventilation generates negative intrapleural pressure
* PPV has numerous cardiovascular implications
 
 
 
Effects of PPV
 
* Left ventricle
** Decreased preload
** Decreased afterload
* Right ventricle
** Decreased preload
** Increased afterload
 
 
 
Mechanism of PPV effects
 
* Right heart
** Increased intrathoracic pressure (ITP) is transmitted to central veins + right atrium (RA)
*** Leads to increased RA pressure &gt; impairs venous return &gt; decreased RV preload
*** Leads to increased pulmonary vascular resistance &gt; increased RV afterload
** Increased RV afterload + reduced RV preload &gt; decreased RV stroke volume
** Increased RV afterload leads to increased RV end diastolic pressure
*** If RVEDP is greater than LVEDP &gt; bulging of IV septum into LV &gt; ventricular interdependence
* Left heart
** Decreased preload
*** Due to reduced RV stroke volume and ventricular interdependence (explained above)
** Decreased afterload
*** PPV &gt; reduction in LV end systolic transmural pressure &gt; decreased afterload (Law of LaPlace)
 
 
 
Net effect on cardiac output
 
* If the patient has normal LV
** Net decrease in CO
** Decreased preload has overall greater impact compared to decreased afterload
* If the patient has impaired LV
** Net increase in CO
** Decrease in afterload has overall greater impact, compared to decreased preload
 
 
 
<span id="examiner-comments-140"></span>
==== Examiner comments ====
 
<blockquote>33% of candidates passed this question.<br />
Structured answers separating effects of positive pressure on right and left ventricle, on preload and on afterload were expected. Overall there was a lack of depth and many candidates referred to pathological states such as the failing heart. Simply stating that positive pressure ventilation reduced right ventricular venous return and/or left ventricular afterload, without some additional explanation was not sufficient to achieve a pass level.
</blockquote>
 
 
<span id="online-resources-for-this-question-139"></span>
==== Online resources for this question ====
 
* [https://cicmwrecks.files.wordpress.com/2020/03/2019-1-20.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/19a/19a20/ Jennys Jam Jar]
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2019-paper-1-saqs/question-20#answer-anchor Deranged Physiology]
 
 
 
<span id="similar-questions-140"></span>
==== Similar questions ====
 
* None the same
* Broadly related to physiological changes of PEEP/PPV
** Question 17, 2009 (1st sitting)
** Question 3, 2014 (2nd sitting)
** Question 2, 2016, (1st sitting)
 
 
 
 
 
<span id="2018-2nd-sitting"></span>
== 2018 (2nd sitting) ==
 
 
 
<span id="question-1-8"></span>
=== Question 1 ===
 
 
 
<span id="question-141"></span>
==== Question ====
 
Describe the surface anatomy of the anterior neck (30% of marks) and the underlying structures relevant to performing a tracheostomy (70% of marks).
 
 
 
<span id="example-answer-141"></span>
==== Example answer ====
 
 
 
Structure
 
* Fibromuscular tube ~10cm long
* Supported by 16-20 incomplete cartilaginous rings which joined by fibroelastic tissue and are connected posteriorly by smooth muscle (the trachealis)
* Divided into cervical and thoracic parts
 
 
 
Course
 
* Trachea begins approximately C6 where it is continuous with the larynx
* Trachea travels inferoposteriorly
* Enters thoracic cavity through the superior thoracic aperture, at the level of the jugular notch
* Ends approximately at level of sternal angle (T4/5) where it divides into left and main bronchi
 
 
 
Relations
 
* Posterior: oesophagus
* Anterior: thyroid gland (isthmus), cervical fascia, manubrium, thymus remnants,
* Right lateral: thyoid gland (lobe), carotid sheath ( common carotid, vagus, IJV), RLN
* Left lateral: thyroid gland (lobe), carotid sheath ( common carotid, vagus, IJV), RLN
 
 
 
Neurovascular supply
 
* SNS: sympathetic trunks
* PSNS: recurrent laryngeal and vagus nerves
* Arterial supply: Branches from inferior thyroid arteries
* Venous drainage: Inferior thyroid veins
 
 
 
Surface anatomy of anterior neck (superior --&gt; inferior)
 
* Hyoid bone (C3)
* Thyroid cartilage
* Cricothyroid membrane
* Cricoid cartilage (C6)
* Thyroid gland
* Sternohyoid muscle just lateral to the midline structures, overlies sternothyroid and thyrohyoid
 
 
 
Layers of dissection in tracheostomy (from anterior --&gt; posterior)
 
* Skin
* Subcutaneous tissue
* Fat
* Pretracheal fascia
* Fibroelastic tissue between tracheal cartilage rings
* Trachea
 
 
 
<span id="examiner-comments-141"></span>
==== Examiner comments ====
 
<blockquote>79% of candidates passed this question.<br />
Answers required a description of the surface anatomy outlining the midline structures including<br />
the hyoid bone and cartilages. The tissue layers should have been mentioned as should the<br />
relevant tracheal anatomy. The anterior, posterior and lateral relations of the trachea should<br />
also have been included along with the relevant nerves and blood vessels. Diagrams were not<br />
essential but could have been included.<br />
Candidates should note that marks were not awarded for a description of how to perform a<br />
tracheostomy.
</blockquote>
 
 
<span id="online-resources-for-this-question-140"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-2-saqs/question-1 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18b/18b01/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2012-1-10.pdf CICM Wrecks]
* [https://litfl.com/anatomy-for-tracheostomy/ LITFL]
 
 
 
<span id="similar-questions-141"></span>
==== Similar questions ====
 
* Question 11, 2017 (1st sitting)
 
 
 
 
 
<span id="question-2-8"></span>
=== Question 2 ===
 
 
 
<span id="question-142"></span>
==== Question ====
 
Compare and contrast amiodarone and digoxin.
 
 
 
<span id="example-answer-142"></span>
==== Example answer ====
 
{|
! Name
! Digoxin
! Amiodarone
|-
| '''Class'''
| Cardiac glycoside (antiarrhythmic)
| Antiarrhythmic (Class III), though other class (I, II, IV) activity
|-
| '''Indications'''
| tachyarrhythmias (e.g. AF, SVT), heart failure
| Tachyarrhythmias (e.g. SVT, VT, WPW)
|-
| '''Pharmaceutics'''
| 62.5mcg/250mcg (PO tablets)<br />
25/250 mcg/ml (IV)
| 100-200mg tablets<br />
Clear solution in ampoules (150mg) for dilution in dextrose
|-
| '''Routes of administration'''
| IV and PO
| IV and PO
|-
| '''Dose'''
| Generally load with 250-500mcg, then 62.5-125mcg daily thereafter. Digoxin level (0.7 - 1.0) for most conditions.
| IV: 5mg/kg, then 15mg/kg infusion / 24hrs. <br />
Oral: 200mg TDS (1/52) &gt; BD (1/52) &gt; daily
|-
| pKA
| 7.2
| 6.6 (highly lipid soluble)
|-
| '''Pharmacodynamics'''
|
|
|-
| MOA
| Direct cardiac: inhibits Na/K ATPase &gt; increased Ca &gt; positive inotropic effect + increased refractory period<br />
Indirect cardiac: increased PSNS release of ACh at M receptors &gt; slowed conduction at AV node/bundle<br />
| - Blocks K channels (Class III effects) prolonging repolarisation and therefore refractory period.<br />
- Decreases velocity of Phase 0 by Blocking Na channels (Class I effects)<br />
- Non-competitive inhibition of Ca channels prolonging depolarisation + AV nodal conduction time (Class IV effects)<br />
- Slows AV/SA nodal conduction via anti-adrenergic activity (Class II effects)
|-
| Side effects
| CVS: May worsen arrhythmia (lead to VF), AV block, shortened QT interval, scooped ST, TWI, bradycardia<br />
GIT: nausea, anorexia, vomiting<br />
CNS: dizziness, drowsiness
| Side effects worsen w. time!<br />
RESP: pneumonitis, fibrosis<br />
CVS: bradycardia, QT prolongation<br />
CNS: peripheral neuropathy<br />
Thyroid: hypo/hyperthyroidism<br />
LIVER: cirrhosis, hepatitis<br />
DERM: photosensitivity, skin discolouration
|-
| '''Pharmacokinetics'''
|
|
|-
| Onset
| 2-3 hours (PO), 10-30mins (IV), duration of action 3-4 days
| Immediate (IV), 4 hours (PO)
|-
| Absorption
| 80% oral bioavailability
| PO bioavailability 40-60%
|-
| Distribution
| Protein binding 25%<br />
VOD 6-7L/kg
| Highly protein bound (&gt;95%)<br />
VOD: ~70L /kg
|-
| Metabolism
| Minimal hepatic metabolism (15%)
| Hepatic (CYP3A4) with active metabolites (desmethylamiodarone)
|-
| Elimination
| T 1/2 48 hours<br />
urine excretion (70% unchanged)
| T 1/2 = 1 month<br />
Faces, urine, skin
|-
| '''Special points'''
| Reduce dose in renal failure, monitor with dig level. not removed by dialysis
| Amiodarone increases digoxin level (by preventing renal excretion and lowering protein binding)
|}
 
 
 
<span id="examiner-comments-142"></span>
==== Examiner comments ====
 
<blockquote>82% of candidates passed this question.<br />
Most candidates had a good structure for answering this question; a table was commonly used.<br />
Marks were awarded for indications and an explanation of the mechanism of action of both<br />
drugs, which was generally well explained. The pharmacodynamic effects were often listed in a<br />
general manner and more detail would have achieved a higher mark, including a list of the ECG<br />
effects. Some detail on the pharmacokinetics and adverse effects of the drugs was expected<br />
and this section was generally well answered. Better answers noted digoxin levels and potential<br />
drug interactions.
</blockquote>
 
 
<span id="online-resources-for-this-question-141"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-2-saqs/question-2 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18b/18b02-compare-and-contrast-amiodarone-and-digoxin/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2010-2-22-digoxin-vs-amiodarone.pdf CICM Wrecks]
* [https://partone.litfl.com/amiodarone.html Part One, LITFL]
 
 
 
<span id="similar-questions-142"></span>
==== Similar questions ====
 
* Amiodarone
** Question 5, 2008 (2nd sitting)
** Question 22, 2010 (2nd sitting)
** Question 14, 2014 (2nd sitting)
** Question 11, 2016 (1st sitting)
** Question 11, 2021 (2nd sitting)
* Digoxin
** Question 14, 2019 (1st sitting)
** Question 10, 2013, (2nd sitting)
** Question 22, 2010 (2nd sitting)
 
 
 
 
 
<span id="question-3-8"></span>
=== Question 3 ===
 
 
 
<span id="question-143"></span>
==== Question ====
 
Explain the causes of the differences between measured end tidal and arterial partial pressures of carbon dioxide (CO2).
 
 
 
<span id="example-answer-143"></span>
==== Example answer ====
 
 
 
ETCO2 - PaCO2 gradient
 
* There is normally a gradient between PaCO2 and ETCO2 of 0-5mmHg (where ETCO2 is lower)
* The difference between the values is due to alveolar dead space
** Alveolar dead space is due to alveoli which are ventilated but not perfused (e.g. west zone 1 lungs)
** These alveoli do not participate in gas exchange (there is no perfusion), thus contain very little CO2 and a lot of O2 (the same amount as in inspired air)
** This relatively CO2 deplete gas mixes with the rest of the expired gas, diluting the ETCO2 reading, thus leading to an observed discrepancy
** Note: It is not due to anatomical dead space as this gas has already been washed out in the early stages of exhalation and thus does not contributed to ETCO2
* Healthy/awake patients have near zero alveolar dead space, so near zero gradient
 
 
 
Factors affecting ETCO2 - PaCO2 gradient
 
<ul>
<li><p>Changes in pulmonary perfusion</p>
<ul>
<li><p>Global reduction in pulmonary perfusion</p>
<ul>
<li><p>e.g. pHTN, heart failure, Cardiac arrest, Severe shock</p></li></ul>
</li>
<li><p>Regional decreases in pulmonary perfusion</p>
<ul>
<li><p>e.g. pulmonary embolism, fat embolism</p></li></ul>
</li></ul>
</li>
<li><p>Changes in ventilation</p>
<ul>
<li><p>Excessively high PEEP --&gt; increased West Zone 1</p></li></ul>
</li>
<li><p>Measurement error</p>
<ul>
<li><p>Inline HME filters</p></li>
<li><p>Timing of measurement (measuring before end-expiration)</p></li>
<li><p>Poor / loss of ETCO2 calibration</p></li>
<li><p>Interference from other gases (e.g. N2O and collision broadening)</p></li></ul>
</li>
<li><p>Physiological factors</p>
<ul>
<li><p>Increasing age &gt; increased gradient</p></li></ul>
 
<p></p></li></ul>
 
<span id="examiner-comments-143"></span>
==== Examiner comments ====
 
<blockquote>29% of candidates passed this question.<br />
The answer required an explanation of the causes of the difference between the PaCO2 and ETCO2. This required recognising how the end point of phase 3 of the capnograph trace corresponds with end tidal CO2. The difference is caused by the alveolar dead space. The difference is normally very small in healthy adults with the ETCO2 being lower than the PaCO2. It is increased with increasing alveolar dead space. Many incorrectly attributed anatomical dead space as a contributor to the PaCO2-ETCO2 gradient. Discussion of the various types of dead space did not score marks. Marks were awarded for the processes that cause an increased gradient e.g. low cardiac output and pulmonary embolism. Recognising physiological factors such as increasing gradient with increasing age scored marks. Marks were not awarded for descriptions on how dead space is measured.
</blockquote>
 
 
<span id="online-resources-for-this-question-142"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-2-saqs/question-3 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18b/18b03-explain-the-causes-of-the-differences-between-measured-end-tidal-and-arterial-partial-pressures-of-carbon-dioxide-co2/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2007-2-24-etco2-vs-arterial-differece.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-143"></span>
==== Similar questions ====
 
* Question 21, 2017 (1st sitting)
* Question 9, 2009 (1st sitting)
* Question 24, 2007 (1st sitting)
 
 
 
 
 
<span id="question-4-8"></span>
=== Question 4 ===
 
 
 
<span id="question-144"></span>
==== Question ====
 
Compare and contrast ketamine and midazolam.
 
 
 
<span id="example-answer-144"></span>
==== Example answer ====
 
{|
! Name
! Midazolam
! Ketamine
! Notes
|-
| '''Class'''
| Benzodiazepine (sedative)
| Anaesthetic (phencyclidine derivative)
|
|-
| '''Indications'''
| Anaesthesia, sedation, treatment of seizures, anxiolysis
| induction GA, conscious sedation, analgesia,
|
|-
| '''Pharmaceutics'''
| IV: clear solution, pH 3.5. Diluted in water.
| 100mg/ml. Clear colourless solution. Racemic mixture of S and R enantiomers, or S+ enantiomer alone. Water soluble.
|
|-
| '''Routes of administration'''
| IV, IM, S/C, intranasal, buccal, PO
| IV/IM/PO/SC/PR
|
|-
| '''Dose'''
| Dose depends on many pt. factors. 1-5mg premedication. 2.5-10mg seizures. Infusions.
| 0-0.25mg/kg/hr (analgesia), 1-2mg/kg (GA), 0.5mg/kg (sedation)
|
|-
| pKa
| 6.5
| 7.5
|
|-
| '''Pharmacodynamics'''
|
|
|
|-
| MOA
| Midazolam (BZD) binds to GABA<sub>A</sub> receptors (ionotropic ligand gated channel) in the CNS. Cl enters &gt; hyperpolarisation.
| NMDA antagonism, weak opioid receptor agonism, weak Ca ch inhibition
| - Ketamine has weak GABA effects
|-
| Effects
| CNS: sedation, amnesia, anticonvulsant effects, decreased cerebral O2 demand
| CNS: dissociative anaesthesia and analgesia. <br />
CVS: increased HR/BP, decreased pulmonary and systemic vascular resistance<br />
RESP: bronchodilation
| - Ketamine has analgesic and bronchodilator properties<br />
- Midaz has anticonvulsant properties
|-
| Side effects
| CVS: bradycardia, hypotension<br />
CNS: confusion, restlessness<br />
RESP: respiratory depression/ apnoea
| CNS: emergence reactions including hallucinations, unpleasant dreams. May increase ICP in non vent. pts.<br />
CVS: may increase HR/BP, increased myocardial O2 req. <br />
GIT: Nausea, vomiting, increased salivation
| - Ketamine does not cause respiratory depression and preserves airway reflexes
|-
| '''Pharmacokinetics'''
|
|
|
|-
| Onset
| peak effect 2-3 minutes (IV)
| 30s IV, duration of effect 10-20mins
|
|-
| Absorption
| ~40% oral bioavailability<br />
Absorbed well, but sig. 1st pass metabolism
| Lipid soluble &gt; readily absorbed. But poor OBA (16%) due to 1st pass metabolism
| Both have poor PO bioavailability
|-
| Distribution
| 95% protein bound, very lipid soluble<br />
Vd = 1L / kg
| Large (5L/kg) VOD.<br />
Small protein binding (25%). Crosses placenta.
| - Midaz will rapidly accumulate with infusions, ketamine will not
|-
| Metabolism
| Hepatic metabolism by hydroxylation <br />
Active (1-a hydroxymidazolam) and inactive metabolites
| Metabolised by CYP450 &gt; majority inactive metabolites (norketamine active 33% potency)
| Similar
|-
| Elimination
| Renal excretion<br />
T 1/2 = 4 hours
| Elimination T1/2 = 2 hours. Kidneys (95%), faeces (5%)
| Both predominately renal excretion
|-
| '''Special points'''
| Flumazenil - antagonist (reversal agent)
| Nil reversal agent
| No reversal agent for ketamine<br />
- Midaz exhibits tolerance, withdrawal, dependence, ketamine does not.
|}
 
 
 
<span id="examiner-comments-144"></span>
==== Examiner comments ====
 
<blockquote>62% of candidates passed this question.<br />
In addition to the key PK and PD properties of each drug, a clear comparison was required to score well (why choose one drug over the other?). When a table was used the addition of a comparison column was helpful. A good answer covered the following: ketamine has analgesic properties whilst midazolam does not; ketamine preserves airway reflexes and does not cause respiratory depression unlike midazolam; whilst ketamine increases cerebral blood flow and CMRO2, midazolam decreases t; ketamine has a direct myocardial depressant effect which is often offset by an increase in sympathetic tone, whilst midazolam has no direct cardiac depressant effects but may reduce BP due to reduced SVR; midazolam has anticonvulsant properties, ketamine does not; ketamine is a bronchodilator; both drug effects are offset by redistribution; midazolam is lipophillic at body pH and will accumulate with prolonged infusions, ketamine will not; both are metabolised in the liver; midazolam can be reliably reversed by flumazenil, whereas there is no reliable complete reversal of ketamine; midazolam exhibits tolerance, dependence and withdrawal, whereas patients will only experience tolerance to the analgesic properties of ketamine. “Drugs in Anaesthesia and Intensive care” chapters on midazolam and ketamine outline the key facts to include in this answer; interpretation and comparison of these facts will help achieve a good mark.
</blockquote>
 
 
<span id="online-resources-for-this-question-143"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-2-saqs/question-4 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18b/18b04/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-2-04.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-144"></span>
==== Similar questions ====
 
* Midazolam
** Question 7, 2019 (1st sitting)
** Question 9, 2019 (2nd sitting)
** Question 24, 2016 (1st sitting)
** Question 2, 2008 (2nd sitting)
* Ketamine
** Question 15, 2019 (1st sitting)
** Question 22, 2015 (1st sitting)
** Question 16, 2011 (2nd sitting)
** Question 7, 2010 (2nd sitting)
 
 
 
 
 
<span id="question-5-8"></span>
=== Question 5 ===
 
 
 
<span id="question-145"></span>
==== Question ====
 
Describe the carriage of carbon dioxide (CO2) in the blood.
 
 
 
<span id="example-answer-145"></span>
==== Example answer ====
 
 
 
Overview
 
<ul>
<li><p>CO<sub>2</sub> is constantly produced as a by-product of metabolism and needs to be cleared</p></li>
<li><p>CO<sub>2</sub> content of blood</p>
<ul>
<li><p>Mixed venous: 52mls/100mls blood, at PaCO<sub>2</sub> of ~45mmHg</p></li>
<li><p>Arterial: 48mls/100mls blood, at PaCO<sub>2</sub> of ~40mmHg</p></li></ul>
 
<p></p></li></ul>
 
CO<sub>2</sub> is transported in three main forms in the blood:
 
 
 
Dissolved CO<sub>2</sub>
 
* Accounts for
** ~5% of the total carbon dioxide in the blood
** ~10% of the CO<sub>2</sub> evolved by the lung
* The amount dissolved is proportional to the partial pressure (Henry's Law)
* 20x more soluble than O<sub>2</sub>, so dissolved CO<sub>2</sub> plays a more significant role in transport
 
 
 
Bicarbonate
 
<ul>
<li><p>Accounts for </p>
<ul>
<li><p>~90% of the carbon dioxide in the blood</p></li>
<li><p>~60% of the CO<sub>2</sub> evolved by the lung</p></li></ul>
</li>
<li><p>Bicarbonate is formed by the following sequence </p>
<math display="block">CO_2 + H_{2}O \leftrightarrow H_{2}CO_{3} \leftrightarrow H^+  + HCO_3^-</math></li>
<li><p>Process</p>
<ul>
<li><p>CO2 dissolves into RBC and leads to H+ and HCO3 (per above equation)</p></li>
<li><p>HCO3 moves into plasma, H+ binds to reduced (deoxy) Hb</p></li>
<li><p>Cl moves into the cell to maintain electroneutrality (chloride shift)</p></li>
<li><p>When Hb is oxygenated in the lungs, H+ dissociates and coverted back to CO2 by the above equation and is exhaled</p></li>
<li><p>Haldane effect accounts for the increased capacity of Hb to carry CO2 when poorly oxygenated</p></li></ul>
</li></ul>
 
 
 
Carbamino compounds
 
* Accounts for
** ~5% of the CO<sub>2</sub> in the blood
** ~30% of the CO<sub>2</sub> evolved by the lung
* Formed by the combination of CO<sub>2</sub> with terminal amine groups in blood proteins
* Haemoglobin is the most abundant protein and has most imadazole side chains (greatest carrier capacity)
** The reaction occurs faster with deoxHb than oxy-Hb (Haldane effect)
 
 
 
<span id="examiner-comments-145"></span>
==== Examiner comments ====
 
<blockquote>65% of candidates passed this question.<br />
A definition of arterial and venous CO2 content (mls and partial pressure) and an outline of the 3 forms of CO2 in the blood and their contribution to the AV difference, followed by a detailed explanation of each form of carriage was required for this question. A good answer included a table of the contribution of each form of carriage to arterial and venous content and the AV difference; explained the concepts of chloride shift when describing carriage as HCO3 -; detailed the Haldane effect and its contribution to carbamino carriage and referenced Henry’s law when describing dissolved CO2. West’s Chapter 6 on gas transport details the key information to score well on this question
</blockquote>
 
 
<span id="online-resources-for-this-question-144"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2020-paper-1-saqs/question-1#answer-anchor Deranged Physiology]
* [https://cicmwrecks.files.wordpress.com/2020/07/2020-1-01.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/20a/20a01-describe-the-carriage-of-carbon-dioxide-in-blood/ Jenny's Jam Jar]
* [https://partone.litfl.com/carbon_dioxide_transport.html Part One, LITL]
* [https://propofoldreams.files.wordpress.com/2015/04/resp-co2-carriage.pdf Propofol dreams]
* [https://ketaminenightmares.com/pex/saqs/physiology/respiratory/2019A04_co2_carriage_in_blood.htm Ketamine Nightmares]
 
 
 
<span id="similar-questions-145"></span>
==== Similar questions ====
 
* Question 6, 2012 (1st sitting)
* Question 1, 2012 (2nd sitting)
* Question 13, 2015 (1st sitting)
* Question 5, 2018 (2nd sitting)
* Question 1, 2020 (1st sitting)
 
 
 
 
 
<span id="question-6-8"></span>
=== Question 6 ===
 
 
 
<span id="question-146"></span>
==== Question ====
 
Outline the determinants of venous return to the heart
 
 
 
<span id="example-answer-146"></span>
==== Example answer ====
 
 
 
Venous return
 
* Rate of blood flow back to the right atrium
* In healthy state: venous return = cardiac output (else pathological pooling of blood occurs)
* Can be defined by following eqns:
** VR = CO
** VR = MSFP - RAP / resistance to venous return
* Therefore factors effecting venous return are those that affect
** MSFP
** RAP
** Resistance to venous return
** Cardiac output
 
 
 
Cardiac output
 
* Normally ~5L/min
* Increased CO = increased venous reutn
* CO is effected by
** Afterload (reduced afterload = increased cardiac output = increased VR)
** Contractility (increased contractility = increased CO = increased VR)
 
 
 
MSFP
 
* Normally ~7mmHg
* Increased MSFP = increased VR
* Affected by venomotor tone and blood volume
* Increased VR (= increased blood volume and increased venomotor tone)
 
 
 
RAP
 
* Normally 2-6mmHg
* Increased RAP = reduced driving pressure = reduced venous return
* Factors which increase RAP
** Positive intrathoracic pressure (e.g. PPV)
** Reduced pericardial compliance (e.g. effusion)
** Reduced RA compliance/contractility (e.g. AF)
** TVR
 
 
 
Resistance to venous return
 
* Increased RVR = reduced VR (due to ohms law)
* Factors effecting RVR
** Autonomic tone
** Intrabdominal pressure
** IVC Obstruction (e.g. pregnancy) reduces VR
** Posture (decreased VR with erect posture)
** Vasoactive drugs
** skeletal muscle pump
 
 
 
<span id="examiner-comments-146"></span>
==== Examiner comments ====
 
<blockquote>31% of candidates passed this question.<br />
Answers should have included a description of the need for a pressure gradient for flow and a discussion on right atrial pressure, mean systemic filling pressure and resistance to blood flow. The discussion of each of these factors included definitions, normal values, factors affecting them and the direction of change on venous return. Diagrams were not essential, but their use assisted some candidates in explaining the effects of RAP on venous return.
</blockquote>
 
 
<span id="online-resources-for-this-question-145"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-2-saqs/question-6 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18b/18b06/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-2-06.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-146"></span>
==== Similar questions ====
 
* Question 19, 2020 (1st sitting)
 
 
 
 
 
<span id="question-7-8"></span>
=== Question 7 ===
 
 
 
<span id="question-147"></span>
==== Question ====
 
Describe protein binding and its significance in pharmacology.
 
 
 
<span id="example-answer-147"></span>
==== Example answer ====
 
 
 
Protein binding
 
<ul>
<li><p>Drugs in blood can exist in two forms (protein bound, protein unbound)</p></li>
<li><p>Protein binding of drugs involves the formation of reversible drug-protein complexes</p>
<ul>
<li><p>Protein + drug &lt;-&gt; protein-drug complex</p></li></ul>
</li>
<li><p>Drugs vary greatly in degree of plasma protein binding</p>
<ul>
<li><p>e.g. warfarin and phenytoin which are &gt;95% protein bound</p></li>
<li><p>e.g. rocuronium which is approx. 10% protein bound</p></li></ul>
</li>
<li><p>Types of proteins</p>
<ul>
<li><p>Drugs can bind to proteins in the plasma (e.g. albumin, globulins) or tissue</p></li>
<li><p>Albumin is the most sig. drug binder and binds neutral/acidic drugs (e.g. barbiturates)</p></li>
<li><p>a-1 glycoproteins and globulins bind basic drugs (e.g. morphine)</p></li>
<li><p>Haemoglobin can bind some drugs e.g. phenytoin</p></li></ul>
</li>
<li><p>Effect of protein binding</p>
<ul>
<li><p>Only unbound fraction exerts can interact with receptors and exert its pharmacologic effect</p></li>
<li><p>Only unbound drug in plasma can freely cross cell membranes</p></li>
<li><p>Only unbound drugs can undergo filtration or metabolism</p></li>
<li><p>For drugs which are highly protein bound (&gt;90%), small changes in degree of protein binding can have sig. clinical effects. I.e. protein binding from 99% to 98% doubles to unbound (active) drug concentration (from 1% to 2%)</p></li>
<li><p>Highly tissue bound drugs have long duration of action, high volume of distribution and readily build up in the body</p></li></ul>
</li>
<li><p>Protein binding is affected by</p>
<ul>
<li><p>Protein factors</p>
<ul>
<li><p>Concentration of protein (decreased protein &gt; increased unbound drug)</p></li>
<li><p>Number of available protein binding sites</p></li></ul>
</li>
<li><p>Drug factors</p>
<ul>
<li><p>Protein affinity</p></li>
<li><p>Concentration of drug - higher drug concentration &gt; saturation of protein &gt; higher unbound (free) drug</p></li></ul>
</li>
<li><p>Patient factors</p>
<ul>
<li><p>temperature and pH</p></li>
<li><p>Inflammation, infection, surgery &gt; increased acute phase reactants &gt; increased protein binding</p></li>
<li><p>Age</p></li></ul>
</li></ul>
 
<p></p></li></ul>
 
<span id="examiner-comments-147"></span>
==== Examiner comments ====
 
<blockquote>19% of candidates passed this question.<br />
Descriptions of protein binding were generally too brief (e.g. a statement saying that drugs and hormones bind to proteins in the plasma rather than a description of usually reversible binding with a drug-protein equilibrium). It was expected that the factors which determine protein binding would be described. Marks were attributed if proteins, along with characteristics of the drugs they bind, were named. Candidates achieved better marks if they named the pharmacological parameters affected by protein binding and explained how and why change occurs along with the significance of those changes. Few candidates differentiated between tissue and plasma protein binding and the different effects on the volume of distribution.
</blockquote>
 
 
<span id="online-resources-for-this-question-146"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-2-saqs/question-7 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18b/18b07-describe-protein-binding-and-its-significance-in-pharmacology/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/03/2018-2-7.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-147"></span>
==== Similar questions ====
 
* Nil
 
 
 
 
 
<span id="question-8-8"></span>
=== Question 8 ===
 
 
 
<span id="question-148"></span>
==== Question ====
 
Describe gastric emptying (40% of marks) and outline its regulation (60% of marks).
 
 
 
<span id="example-answer-148"></span>
==== Example answer ====
 
 
 
Gastric emptying
 
* The coordinated emptying of chyme from the stomach to the duodenum
* Regulated by food, local mechanical, neural, hormonal and drug factors
* Mechanism
** During fasting
*** Migrating motor complexes (Slow peristaltic waves that originate in fundus) sweep through stomach at regular intervals
*** Role is to keep the stomach empty of secretions and food debris
*** Interrupted by food consumption
** During fed state
*** Receptive relaxation of stomach following swollowing
*** Tonic contraction / peristalsis &gt; propelling food towards pylorus &gt; mixing
*** Small food particles &lt;2mm are pushed through pyloric sphincter at a stable rate
**** Half time of solids is ~2 hours
*** Liquids empty more rapidly and the rate of emptying is dependant on the antral-duodenal pressure gradient.
**** Half time of liquids &lt;30 minutes
 
 
 
Regulation
 
* Food factors
** Fluids have half time of 30 mins, solids have half time of 2 hours
** Carbohydrates (fastest) &gt; proteins &gt; fatty acids (slowest)
** Tonicity: increased tonicity = decreases emptying rate
* Local factors
** Increased gastric volume &gt; increased gastric emptying
** Duodenal stretch / wall irritation / acidity &gt;reflex inhibition &gt; decreased gastric emptying
* Neural factors
** Increased SNS stimulation &gt; decreased contractility + gastric emptying
** Increased PSNS (vagal) activity &gt; increased contractility + gastric emptying
* Hormonal factors
** secretin (stimulated by low duodenal pH) &gt; decreased emptying
** Cholecystokinin (stimulated by fatty acids) &gt; decreased emptying
** Somatostatin &gt; decreased emptying
** Gastrin (stimulated by stretch, amino acid content) &gt; increased emptying)
** Motilin: stimulates migrating motor complex &gt; increased emptying
* Drugs factors
** e.g. opioids &gt; decreased empyting
** eg. metoclopramide &gt; increased emptying
 
 
 
<span id="examiner-comments-148"></span>
==== Examiner comments ====
 
<blockquote>24% of candidates passed this question.<br />
Candidates were required to provide a description of gastric emptying (40% marks). Although<br />
the question showed the allocation of marks, many candidates did not provide sufficient detail<br />
for this section. This required some description of what gastric emptying is (the co-ordinated<br />
emptying of chyme from the stomach into the duodenum).<br />
Better answers provided detail regarding the process of gastric emptying in the fed and fasted<br />
state and differentiated between liquids, solids, carbohydrate, protein and fats. Factors<br />
regulating emptying included an outline of peristaltic waves, the basal electrical rhythm and its<br />
modulation, the migratory motor complex (MMC) and its modulation, neural input, stretch and<br />
hormonal control.<br />
Many candidates erred by answering the question &quot;the regulation of gastric secretions&quot; rather<br />
than the question (the regulation of gastric emptying). Although they scored well for hormonal<br />
control, they missed out on marks for the other factors relevant to the regulation of gastric<br />
emptying.
</blockquote>
 
 
<span id="online-resources-for-this-question-147"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-2-saqs/question-8 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18b/18b08/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-2-08.pdf CICM Wrecks]
* [https://partone.litfl.com/control_of_gastric_emptying.html Part One, LITFL]
 
 
 
<span id="similar-questions-148"></span>
==== Similar questions ====
 
* Question 21, 2010 (2nd sitting)
* Question 8, 2012 (2nd sitting)
* Question 24, 2014 (2nd sitting)
 
 
 
 
 
<span id="question-9-8"></span>
=== Question 9 ===
 
 
 
<span id="question-149"></span>
==== Question ====
 
Describe the renal handling of water including the modulation of water excretion
 
 
 
<span id="example-answer-149"></span>
==== Example answer ====
 
 
 
Renal handling of water
 
* Glomerulus
** Water is freely filtered at the glomerulus (~180L / day)
** The amount filtered will depend on the GFR and starlings forces
* Proximal convoluted tubule (PCT)
** Approximately 60-70% of the filtered water is reabsorbed
** Secondary active transport of Na in the PCT creates an osmotic gradient which allows passive absorption of water via osmosis
* Loop of Henle (LOH)
** Approximately 10-15% of the filtered water is reabsorbed in the descending LOH
*** Iso-osmotic absorption due to the increased medullary concentration gradient
** The ascending LOH is relatively water impermeable
* Distal convoluted tubule (DCT)
** Approximately 0-5% water reabsorbed in DCT
** Relatively impermeable
* Collecting duct (CD)
** Reabsorbs 5-20% of the remaining water (depending on the level of ADH)
** ADH inserts luminal aquaporins in collecting duct cells which allows increased reabsorption of water down the osmotic concentration gradient
 
 
 
Regulation
 
<ul>
<li><p>There is an obligatory water loss of ~500mls a day needed for waste clearance</p></li>
<li><p>The body also needs to maintain fluid and osmolality homeostasis</p></li>
<li><p>The main site of water regulation in the nephron is in the collecting ducts via the action of ADH</p></li>
<li><p>Mechanism</p>
<ul>
<li><p>Primary:</p>
<ul>
<li><p>Osmoreceptors in hypothalamus detect increased osmolality &gt; increased production of ADH &gt; increased release of ADH from posterior pituitary &gt; increased luminal aquaporins in CD &gt; increased water reabsorption</p></li></ul>
</li>
<li><p>Secondary</p>
<ul>
<li><p>Baroreceptors detect reduced blood pressure &gt; increased ADH secretion</p></li>
<li><p>ANP/BNP secretion is reduced with decreased BP (stretch) &gt; decreased GFR + activation of RAAS</p></li></ul>
</li></ul>
 
<p></p></li></ul>
 
<span id="examiner-comments-149"></span>
==== Examiner comments ====
 
<blockquote>37% of candidates passed this question.<br />
This question required a brief introduction of the role the kidney plays in water balance; a more<br />
detailed description of how water is handled as it passes through the various segments of the nephron (glomerulus, PCT, Loop of Henle, DCT and Collecting Duct); the modulation of water excretion by the kidney due to ADH (vasopressin) and how this operates; and the stimuli (osmotic and non-osmotic) for ADH secretion. Although worth mentioning in the context of the effect they have on water movement through the kidney, detailed explanations of Starling's forces in the glomerulus, and of the operation and maintenance of the counter-current mechanism, were not required. More important was describing the control of water reabsorption in the collecting ducts (and thus modulation of water excretion by the kidney) under the influence of ADH
</blockquote>
 
 
<span id="online-resources-for-this-question-148"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-2-saqs/question-9 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18b/18b09/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-2-09.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-149"></span>
==== Similar questions ====
 
* Question 8, 2008 (1st sitting)
* Question 4, 2015 (1st sitting)
 
 
 
 
 
<span id="question-10-8"></span>
=== Question 10 ===
 
 
 
<span id="question-150"></span>
==== Question ====
 
Compare and contrast the pharmacology of vancomycin and flucloxacillin.
 
 
 
<span id="example-answer-150"></span>
==== Example answer ====
 
{|
! Name
! Vancomycin
! Flucloxacillin
|-
| '''Class'''
| Glycopeptides (antibiotic)
| Penicillins (antibiotic)
|-
| '''Indications'''
| Severe gram positive infections,MRSA, C.diff
| Gram positive infections (particularly staph)
|-
| '''Pharmaceutics'''
| White powder for reconstitution
| Capsule, tablet or white power for reconstitution
|-
| '''Routes of administration'''
| PO, IV, PR, intrathecal
| PO, IV,
|-
| '''Dose'''
| Dose/interval adjusted according to desired peak/trough levels
| 250-1g, every 6 hrs
|-
| '''Pharmacodynamics'''
|
|
|-
| MOA
| Inhibits cell wall synthesis by binding to D-ala-D-Ala portion of growing cell wall
| Beta-lactam ring binds to penicillin binding protein &gt; prevents crosslinking &gt; impaired cell wall synthesis
|-
| Microbial coverage
| Gram positives, including MRSA. C diff coverage
| Narrow spectrum<br />
Gram positive bacteria<br />
Does
|-
| Side effects
| CNS: ototoxicity<br />
RENAL: nephrotoxicity<br />
HAEM: thrombocytopaenia, leukopenia<br />
IMMUNO: red man syndrome
| GIT: diarrhoea, nausea, cholestatic hepatitis<br />
IMMUNO: penicillin allergy<br />
CNS: neurotoxicity<br />
Haem: blood dyscrasias
|-
| '''Pharmacokinetics'''
|
|
|-
| Absorption
| PO bioavailability &lt;1%. Only given orally for C. diff infections.
| PO bioavailability 70%
|-
| Distribution
| Poor CSF penetration (requires higher dosing)<br />
VOD = 0.5L / kg<br />
50% protein bound
| 95% protein bound<br />
VOD = 0.3 L /kg<br />
CNS penetration with meningitis only
|-
| Metabolism
| No metabolism
| Hepatic metabolism
|-
| Elimination
| Unchanged in the urine<br />
T 1/2 = 6 hrs
| Renal elimination (predominately unchanged)<br />
T 1/2 = 1 hour
|-
| '''Monitoring'''
| Renal function
| Monitor LFTs, renal function
|-
| Resistance
| Cannot treat VRE (VanA/B resistance genes)
| Can treat b-lactamase producing bacteria, but not MRSA (mecA gene)
|}
 
 
 
<span id="examiner-comments-150"></span>
==== Examiner comments ====
 
<blockquote>49% of candidates passed this question.<br />
Most candidates structured their answers well. Expected information included: the class of antibiotic of each agent, their respective pharmaceutics, pharmacodynamics, pharmacokinetics, indications and adverse effects. Better answers provided pharmacodynamic and pharmacokinetic information relevant to each drug rather than generic statements. Good answers also included the common resistance mechanisms for both agents.
</blockquote>
 
 
<span id="online-resources-for-this-question-149"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-2-saqs/question-10 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18b/18b10/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-2-10.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-150"></span>
==== Similar questions ====
 
* Question 22, 2016 (1st sitting)
 
 
 
 
 
<span id="question-11-8"></span>
=== Question 11 ===
 
 
 
<span id="question-151"></span>
==== Question ====
 
Describe the anatomy relevant to the insertion of an intercostal catheter.
 
 
 
<span id="example-answer-151"></span>
==== Example answer ====
 
 
 
Surface anatomy
 
* Lateral approach
** ICC is inserted in the 'triangle of safety' based off surface landmarks
*** Anterior border: lateral border of the pectoralis major
*** Posterior Border: lateral border of latissimus dorsi
*** Inferior border: 5th intercostal space
*** Superior: base of axilla
* Anterior approach
** Second intercostal space, midclavicular line
 
 
 
Layers of dissection / path of needle
 
* Skin
* Subcutaneous tissue
* Pectoralis muscle (in anterior approach only)
* External intercostal muscle
* Internal and innermost intercostal muscles
* Parietal pleura
* Pleural space
 
 
 
Important anatomical considerations
 
* Intercostal neurovascular bundle
** Sits in the inferior aspect of the rib, between innermost and internal IC muscles
** Vein &gt; artery &gt; nerve (from superior to inferior)
** Care to avoid this by aiming for the rib below, and guiding over the top of the inferior rib
* Anterior approach
** Variable degrees of breast/subcutaneous tissue
** Will also contain the pectoralis major muscle (variable thickness) between subcutaneous tissue and intercostal muscles
* 5th intercostal space
** The reason it is important to place above the 5th intercostal space as this reduces of inadvertently placing the ICC into intrabdominal structures (e.g. liver, spleen) or penetration of the diaphragm (as the diaphragm can go as high as 5th intercostal space during expiration / pregnancy)
* Deeper structures
** Beneath pleural space is the visceral pleura and lung parenchyma, which should be avoided..obviously
* Internal mammary artery / lymphatic ducts
** Too far medial on anterior approach risks damage to these structures
 
 
 
<span id="examiner-comments-151"></span>
==== Examiner comments ====
 
<blockquote>56% of candidates passed this question.<br />
An anatomy question expects the use of anatomical nomenclature to describe relationships. Good answers defined the “safe triangle” for the lateral approach, soft-tissue layers passed through from skin to pleura and relationship of the neurovascular bundle to the ribs and intercostal muscles. Additional marks were gained for describing the anterior approach and related structures. Common omissions included description of deeper structures (relations) including intrathoracic and intra-abdominal organs and level of the diaphragm with regard to rib space. No marks were awarded for a description of intercostal catheter insertion.
</blockquote>
 
 
<span id="online-resources-for-this-question-150"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-2-saqs/question-11 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18b/18b11/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-2-11.pdf CICM Wrecks]
* [https://partone.litfl.com/intercostal_catheter.html Part One, LITFL]
 
 
 
<span id="similar-questions-151"></span>
==== Similar questions ====
 
* ? Nil
 
 
 
 
 
<span id="question-12-8"></span>
=== Question 12 ===
 
 
 
<span id="question-152"></span>
==== Question ====
 
Outline the control of blood glucose.
 
 
 
<span id="example-answer-152"></span>
==== Example answer ====
 
 
 
Overview
 
* Normal blood glucose levels (BGLs) are ~4-6mmol/L
* BGL will rise following carbohydrate consumption
* Regulation of BGL is via short and long term mechanisms
* Insulin and glucagon are the main regulatory hormones
 
 
 
High BGL
 
* Increased BGL (&gt;6.0mmols) is sensed directly by the pancreas
* The increased glucose is taken up by GLUT receptors &gt; undergoes glycolysis &gt; increased ATP/ADP ratio &gt; depolarisation &gt; exocytosis of insulin from pancreatic B-islet cells
* There is an initial rapid release, followed by a prolonged slow release
* The increased insulin results in
** Increased glucose uptake into cells and Glycogenesis (liver)
** Decreased gluconeogenesis, glycogenolysis and lipolysis
* The net effect is reduced BGL
 
 
 
Low BGL
 
* Decreased BGL (or during times of fasting) is sensed by pancreas
* Leads to
** Increased glucagon secretion from a-islet cells in pancreas (&lt;3.0 mmols)
** Decreased insulin secretion from the B-islet cells in pancreas (&lt;4.0 mmols)
* Glucagon acts via GPCR (Gs) to
** Increased glycogenolysis and gluconeogenesis in the liver
** Increased lipolysis and ketoacid formation
* Hypoglycaemia also directly stimulates the hypothalamus (with prolonged hypoglycaemia, starvation)
** Stimulates GHRH release &gt; decreased glucose uptake + increased fat utilisation
** Stimulates ACTH release &gt; increased cortisol &gt; decreased glucose uptake + increased fat utilisation
** Stimulates TRH release &gt; increased TSH &gt; increased GIT absorption of glucose
** Stimulates &quot;hunger&quot; centre in the lateral hypothalamus &gt; seek food
** Direct SNS stimulation of adrenal medulla &gt; increased adrenaline &gt; increased catabolism
* The net effect is increased BGL
 
 
 
Other factors
 
* BGL control is interconnected to liver function
** Involved in glycogenolysis/glycogenesis functions regulated by insulin/glucagon
** Hence liver dysfunction can impair its glucostat function and BSL control
* BGL control is interconnected to renal function
** Can help modulate BGL control through control of absorption of glucose
* Other
** Insulin and glucagon also affected by: cholecystokinin, somatostatin, food intake
 
 
 
<span id="examiner-comments-152"></span>
==== Examiner comments ====
 
<blockquote>53% of candidates passed this question.<br />
A definition of normal glucose levels was expected, mentioning how it is regulated despite variable intake. Most answers incorporated the roles of insulin/glucagon and the glucostat function of the liver. Sufficient detail regarding the mechanism of insulin release was often lacking. Extra marks were awarded for description of the role of the satiety centre in the hypothalamus, glucokinase and processes in fasting and starvation that maintain blood glucose levels. Marks were not awarded for describing effects of insulin and glucagon unrelated to glucose control.
</blockquote>
 
 
<span id="online-resources-for-this-question-151"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-2-saqs/question-12 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18b/18b12-outline-the-control-of-blood-glucose/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-2-12.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-152"></span>
==== Similar questions ====
 
* ? None
 
 
 
 
 
<span id="question-13-8"></span>
=== Question 13 ===
 
 
 
<span id="question-153"></span>
==== Question ====
 
Compare and contrast rocuronium and cisatracurium
 
 
 
<span id="example-answer-153"></span>
==== Example answer ====
 
{|
! Name
! Rocuronium
! Cisatracurium
|-
| '''Class'''
| Aminosteroid NMB
| Benzylisoquinolinium derivative (NMB)
|-
| '''Indications'''
| NMB (e.g. RSI)
| NMB (i.e. RSI)
|-
| '''Pharmaceutics'''
| Clear colourless solution (50mg/5ml vials) Shelf life increased in fridge.
| Clear colourless solution (10mg/5ml vials) stored at 4 degrees
|-
| '''Routes of administration'''
| IV (can also be given IM)
| IV (can also be given IM))
|-
| '''Dose'''
| 0.6 - 1.2mg/kg (RSI dose)
| 0.15-0.2mg/kg (RSI) Used more commonly as an infusion (titrated to desired TOF)
|-
| '''Pharmacodynamics'''
|
|
|-
| MOA
| Non depolarising NMB Inhibits the action of ACh at the NMJ by competitively binding to alpha subunit of nAChR on pre and post junctional membrane
| Non-depolarising NMB Inhibits the action of ACh at the NMJ by competitively binding to alpha subunit of nAChR on pre and post junctional membrane
|-
| Effects
| NMB &gt; paralysis
| NMB &gt; muscle paralysis
|-
| Side effects
| Histamine release: none ANS: vagolytic (inc HR) OTHER: anaphylaxis (&lt;0.1%), pain on injection
| Histamine release: none ANS: no vagolysis OTHER: anaphylaxis (very rare)
|-
| '''Pharmacokinetics'''
|
|
|-
| Onset
| Onset: 45-90s Duration: ~30 mins
| Onset: 1-3 minutes Duration: 30-45 minutes
|-
| Absorption
| IV only
| IV only
|-
| Distribution
| VOD = 0.2 L /kg Protein binding = 10% Doesn't cross BBB
| VOD = 0.15 L/kg Protein binding = 15%
|-
| Metabolism
| Minimal hepatic metabolism (&lt;5%)
| Organ independent Hoffman elimination (70-90%) &gt; laudanosine and acrylate
|-
| Elimination
| Bile 70%, Renal 30% elimination Unchanged drug T 1/2 = 90 mins
| Renal and biliary elimination (10-30%) Inactive metabolites T 1/2 - 30 mins
|-
| '''Special points'''
| Reversible with sugammadex
| '''Not''' reversible with sugammadex
|}
 
<span id="examiner-comments-153"></span>
==== Examiner comments ====
 
<blockquote>32% of candidates passed this question.<br />
This question was best answered using a tabular format outlining class of drug, pharmaceutics, pharmacokinetics, reversibility and side effects. Better answers commented on the significance of the differences between the two agents and its relevance to ICU practice. Many candidates confused these muscle relaxants with each other and with depolarising muscle relaxants.
</blockquote>
 
 
<span id="online-resources-for-this-question-152"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-2-saqs/question-13 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18b/18b13-compare-and-contrast-rocuronium-and-cisatracurium/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/06/2018-2-13.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-153"></span>
==== Similar questions ====
 
* None
 
 
 
 
 
 
 
<span id="question-14-8"></span>
=== Question 14 ===
 
 
 
<span id="question-154"></span>
==== Question ====
 
Explain the detection and response to hypoxaemia
 
 
 
<span id="example-answer-154"></span>
==== Example answer ====
 
 
 
Hypoxaemia
 
* Abnormally low concentration of oxygen in arterial blood
* Usually defined clinically as a PaO2 &lt; 60mmhg or SaO2 &lt; 0.9
 
 
 
Hypoxia
 
* Oxygen deficiency at the tissues which is typically, but not always, due to hypoxaemia
* Prolonged hypoxaemia may often result in hypoxia
 
 
 
Detection of hypoxaemia
 
* Stimulus
** Decreased PaO2
* Sensors
** Peripheral chemoreceptors located in the carotid body and aortic arch
* Afferents
** CN IX (carotid body receptors)
** CN X (aortic arch receptors)
* Integrator/controller
** Medullary and pontine respiratory control centres
** Includes nucleus retroambiualis, parambigualis, ambigualis, PreBotzinger and Botziner complexes
* Efferents and effectors
** Phrenic nerve (diaphragm) - predominant
** UMN nerves to the other muscles of respiration
* Effector muscles
** Diaphragm and intercostal muscles
** Accessory muscles of respiration (SCM, pectoral, scalene, pharyngeal, abdominal muscles )
 
 
 
Response to hypoxaemia
 
* Ventilatory response
** Increased minute ventilation (hyperbolic relationship with rapidly increasing MV when PaO2 &lt;50-60)
* Cardiovascular response
** Hypoxic vasoconstriction of pulmonary circulation
** Hypoxic vasodilation of systemic circulation
* Autonomic response
** Relative increase in sympathetic tone
*** Leads to tachycardia, increased CO, increased SVR
*** BP stable / slight increase
* Metabolic changes
** If concurrent hypoxia there will be a switch from aerobic to anaerobic metabolism
* Hypoxia inducible factors (HIF)
** With tissue hypoxia, hypoxia inducible transcription factors are no longer broken down.
** HIFs &gt; increased erythropoiesis (increased EPO), cell differentiation and angiogenesis
 
 
 
<span id="examiner-comments-154"></span>
==== Examiner comments ====
 
<blockquote>34% of candidates passed this question.<br />
A logical approach to answering this question included a definition of hypoxaemia and then a<br />
discussion of the sensors, integrators and effectors involved. It was expected that candidates<br />
would cover the peripheral chemoreceptor response (including the respiratory, cardiovascular<br />
and autonomic effects), time course of the ventilatory response, hypoxia-inducible factors,<br />
vascular effects (hypoxic vasoconstriction in the pulmonary circulation and vasodilatation in the<br />
systemic circulation) and metabolic changes (switch to anaerobic metabolism). No marks were<br />
awarded for discussing the causes of hypoxaemia. Many candidates incorrectly stated that<br />
hypoxaemia is detected by the central chemoreceptors.
</blockquote>
 
 
<span id="online-resources-for-this-question-153"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-2-saqs/question-14 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18b/18b14-explain-the-detection-and-response-to-hypoxaemia-%e2%80%8b/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-2-14.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-154"></span>
==== Similar questions ====
 
* ? None
 
 
 
 
 
<span id="question-15-8"></span>
=== Question 15 ===
 
 
 
<span id="question-155"></span>
==== Question ====
 
Outline the production / absorption (30% of marks), composition (30% of marks) and function of cerebrospinal fluid (CSF) (40% of marks).
 
 
 
<span id="example-answer-155"></span>
==== Example answer ====
 
 
 
CSF
 
* ECF located in the ventricles and subarachnoid space
* ~2ml/kg of CSF
* Divided evenly between the cranium and spinal column
 
 
 
Production
 
* Constantly produced
* ~550ml produced per day (~24mls/hr)
* Produced by
** Choroid plexus (70%) - located in ventricles of brain
** Capillary endothelial cells (30%)
* Produced by a combination of ultrafiltration (via fenestrated choroidal capillaries) and active secretion
** Na actively transported out. Gradient drives co-transport of HCO3 + Cl
** Glucose via facilitated diffusion, water by osmosis
 
 
 
Composition relative to plasma
 
* Similar: Na, osmolality, HCO3
* Increased: Cl, Mg, CO2
* Decreased: pretty much everything else (protein, potassium, calcium, glucose, pH)
 
 
 
Circulation
 
<ul>
<li><p>Circulation is driven by</p>
<ul>
<li><p>Ciliary movement of ependymal cells</p></li>
<li><p>Respiratory oscillations and arterial pulsations</p></li>
<li><p>Constant production and absorption</p></li></ul>
</li>
<li><p>CSF flows from </p>
<ul>
<li><p>Lateral ventricles &gt; foramen of Monro &gt; 3rd ventricle &gt; Sylvian aqueduct &gt; 4th ventricle &gt; cisterna magna (via foramen megendie and luschka) &gt; spreads between spinal/cranial subarachnoid spaces</p></li></ul>
 
<p></p></li></ul>
 
Reabsorption
 
<ul>
<li><p>Rate of ~24mls/hr</p></li>
<li><p>By the arachnoid villi</p>
<ul>
<li><p>Located predominately in the dural walls of the sagittal + sigmoid sinuses</p></li>
<li><p>Function as one way valves, with driving pressure leading to absorption.</p>
<p></p></li></ul>
</li></ul>
 
Functions
 
* Mechanical protection
** The low specific gravity of CSF &gt; decreased effective weight of the brain (1500g &gt; 50g)
** With the reduced weight
*** Less inertia = less acceleration/deceleration forces
*** Suspended &gt; no contact with the rigid skull base
* Buffering of ICP
** CSF can be displaced / reabsorbed to offset any increase in ICP
* Stable extracellular environment
** Provides a constant, tightly controlled, ionic environment for normal neuronal activity
* Control of respiration
** The pH of CSF is important in the control of respiration (CO2 freely diffuses into CSF and can activate central chemoreceptors)
* Nutrition
** Provides a supply of oxygen, sugars, amino acids to supply the brain
 
 
 
<span id="examiner-comments-155"></span>
==== Examiner comments ====
 
<blockquote>71% of candidates passed this question.<br />
This question was generally well answered. Better answers noted production including an<br />
amount, site and mechanism. Similarly, absorption included the site, the rate and factors which<br />
affect the rate. The electrolyte and pH and how they compare to extracellular fluid should have<br />
been included in the section on composition.
</blockquote>
 
 
<span id="online-resources-for-this-question-154"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-2-saqs/question-15 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18b/18b15/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2015-1-16-csf-physiology.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-155"></span>
==== Similar questions ====
 
<ul>
<li><p>Question 16, 2020 (1st sitting)</p></li>
<li><p>Question 11, 2019 (1st sitting)</p></li>
<li><p>Question 9, 2017 (2nd sitting)</p></li>
<li><p>Question 24, 2017 (1st sitting)</p></li>
<li><p>Question 16, 2015 (1st sitting)</p></li>
<li><p>Question 2, 2013 (1st sitting)</p></li>
<li><p>Question 22, 2007 (1st sitting)</p></li>
<li><p>Question 6, 2008 (2nd sitting)</p>
<p></p></li></ul>
 
 
 
<span id="question-16-8"></span>
=== Question 16 ===
 
 
 
<span id="question-156"></span>
==== Question ====
 
Describe the forces that result in fluid exchange across capillary membranes
 
 
 
<span id="example-answer-156"></span>
==== Example answer ====
 
 
 
Fluid exchange across membranes
 
<ul>
<li><p>Bulk flow of fluid across a semi-permeable membrane is a balance of Starling forces</p></li>
<li><p>Can be expressed using the following formula</p>
<ul>
<li><p><math display="inline">Bulk  \: flow \: = \: \kappa[(P_c \; - \; P_{if}) \; - \; \delta(\pi_p \; - \pi_{if})]</math></p></li></ul>
</li>
<li><p>Where:</p>
<ul>
<li><p>Kappa = membrane filtration constant</p>
<ul>
<li><p>Accounts for membrane permeability and surface area </p></li></ul>
</li>
<li><p>Delta = reflection constant</p>
<ul>
<li><p>Takes into consideration protein leakage</p></li>
<li><p>Values range from 0-1</p></li></ul>
</li>
<li><p>Capillary hydrostatic pressure (P<sub>c</sub>)</p>
<ul>
<li><p>Main factor determining bulk flow under physiological conditions</p></li>
<li><p>Normally ~35mmhg at arterial end, 15mmHg at venous end of capillary.</p></li>
<li><p>Determined by </p>
<ul>
<li><p>The ratio of resistances between pre/post capillary arterioles</p></li>
<li><p>Arterial and venous blood pressure and gravity</p></li></ul>
</li></ul>
</li>
<li><p>Interstitial hydrostatic pressure(P<sub>if</sub>)</p>
<ul>
<li><p>Normally ~0mmhg (there is minimal interstitial fluid which is draining away)</p></li>
<li><p>Affected by anything that modifies lymphatic drainage (e.g. immobility, tourniquet)</p></li></ul>
</li>
<li><p>Plasma oncotic pressure (Ï€<sub>p</sub>) </p>
<ul>
<li><p>The osmotic pressure attributed to by large insoluble proteins (e.g. albumin) within plasma</p></li>
<li><p>Normally ~28mmHg. Does not rapidly change</p></li>
<li><p>Affected by plasma protein concentrations and intravascular fluid status</p></li></ul>
</li>
<li><p>Interstitial oncotic pressure (Ï€<sub>if</sub>)</p>
<ul>
<li><p>Osmotic pressure attributed to by small amounts of insoluble proteins which have leaked into interstitial space</p></li>
<li><p>Normally ~3mmHg. Does not rapidly change</p></li>
<li><p>Affected by membrane integrity</p></li></ul>
</li></ul>
</li>
<li><p>Using the above values at venous/arterial ends, it is demonstrated that bulk flow occurs</p>
<ul>
<li><p>OUT of the vessel at arterial end</p></li>
<li><p>IN to the vessel at venous end </p></li></ul>
</li>
<li><p>Main factor as described is the Capillary hydrostatic pressure gradient (Pc - Pif)</p>
<p></p></li></ul>
 
 
 
<span id="examiner-comments-156"></span>
==== Examiner comments ====
 
<blockquote>57% of candidates passed this question.<br />
The expected answer included a clear explanation of Starling’s forces, including an understanding of the importance of the relative difference along the length of the capillary, with approximate values and examples of factors that influence them. Some explanation of what contributed to the hydrostatic or osmotic pressure gained more marks than merely stating there was a pressure. Several candidates digressed to Fick’s law of diffusion or intracellular flow of ions which was not directly relevant to capillary flow.
</blockquote>
 
 
<span id="online-resources-for-this-question-155"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-2-saqs/question-16 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18b/18b16/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-2-16.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-156"></span>
==== Similar questions ====
 
* Question 19, 2016 (2nd sitting)
* Question 18, 2011 (1st sitting)
 
 
 
 
 
<span id="question-17-8"></span>
=== Question 17 ===
 
 
 
<span id="question-157"></span>
==== Question ====
 
Describe ketone bodies including their synthesis and metabolism
 
 
 
<span id="example-answer-157"></span>
==== Example answer ====
 
 
 
Ketone Bodies
 
* Water soluble molecules, derived from fatty acids, that contain ketone groups
* Three main compounds: acetoacetate, 3-β-Hydroxybutyrate, and acetone
* Normal plasma level is &lt;0.6mmol/L
 
 
 
Ketogenesis
 
* Ketone bodies can only be produced in the liver
* β-oxidation of fatty acids in the liver produces acetyl-CoA
* Acetyl-CoA usually enters the citric acid cycle to produce ATP
* When large amounts of acetyl CoA are produced they condense to form acetoacetate
* Acetoacetate is then reduced in the mitochondria to 3-β-hydroxybutyrate (majority) or acetone (minority).
 
 
 
Regulation
 
* The body constantly produces small amounts of ketone bodies (even during fed states)
* When carbohydrate stores are available the main pathway for energy utilisation is glycogenolysis
* Ketogenesis is accelerated by decreased insulin levels and increased glucagon levels (e.g. in times of starvation or carbohydrate restriction). This leads to increased activity of hormone sensitive lipase and acetyl Coa Carboxlyase which drive ketogensis
* As the lack of insulin is the main driver of ketogenesis, it explains why Type 1 diabetics develop diabetic ketoacidosis
 
 
 
Metabolism/utilisation
 
* Ketone bodies can be used as an energy substrate by
** Kidney, skeletal muscle and cardiac muscle cells (under physiological conditions)
** Nervous tissue (during times of starvation)
* Process
** Ketone bodies enter mitochondria
** Ketone body reconstituted to Aceto-acetyl CoA (by SCOT)
** Cleavage of acetyl group by MAT to form Acetyl CoA
** Acetyl CoA enters the Citric acid cycle
 
 
 
<span id="examiner-comments-157"></span>
==== Examiner comments ====
 
<blockquote>35% of candidates passed this question.<br />
Whilst most candidates understood that ketones provided an alternative source of substrate for energy production, many lacked a basic understanding of their synthesis and metabolism Important facts included what ketone bodies are, where they were synthesised, where they were taken up and used as fuel, under what circumstances they are used and the integral role of insulin. Many candidates accurately reproduced the glycolytic and/or the TCA cycle, but this was not being examined, and did not score additional marks. Many candidates incorrectly stated that ketone production was the result of anaerobic metabolism.
</blockquote>
 
 
<span id="online-resources-for-this-question-156"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-2-saqs/question-17 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18b/18b17/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-2-17.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-157"></span>
==== Similar questions ====
 
* ? None
 
 
 
 
 
 
 
<span id="question-18-8"></span>
=== Question 18 ===
 
 
 
<span id="question-158"></span>
==== Question ====
 
Describe the factors affecting left ventricular function
 
 
 
<span id="example-answer-158"></span>
==== Example answer ====
 
<blockquote>Not 100% if this answer is exactly what they want tbh.
</blockquote>
 
 
Factors affecting LV systolic function
 
* Preload
** Frank starling mechanism
*** Increased preload &gt; increased sarcomere length &gt; increased force of LV contraction &gt; increased SV
* Afterload
** LV is afterload independent (due to compensatory mechanisms)
* Contractility
** Anrep effect
*** Means of autoregulating contractility with changes in preload
*** Increase in afterload &gt; increased ESV &gt; increased sarcomere stretch &gt; increased force of subsequent contraction &gt; increased SV
** Bowditch effect
*** A means of compensating for decreased diastolic filling time with fast heart rates
*** Increased HR &gt; decreased time to expel intracellular calcium &gt; accumulation &gt; increased inotropy
** Integrity of myofilaments
*** Damaged myocardial tissue &gt; impaired LV contraction (e.g. in ischaemia/infarction)
** Coordinated depolarisation
*** Suboptimal myocardial depolarisation in the LV &gt; impaired coordination of LV contraction
*** e.g. in heart block, sinus node dysfunction
** Substrate supply
*** Adequate supply of ATP (derived from glucose,fat, protein) to ensure ability of LV to function as needed
** Hormones
*** e.g. catecholamines --&gt; increased inotropy/chronotropy/lusitropy
** Autonomic tone
*** Increased SNS activity / decreased PSNS activity &gt; increased chronotropy and inotropy
** Drugs
*** E.g. B agonists --&gt; increased chronotropy and inotropy
** Electrolytes
*** E.g. Calcium: too little = impaired systolic function, too much = impaired diastolic function
 
 
 
Factors affecting LV diastolic function
 
* LV diastolic function is determined by it compliance
** LV systolic function
*** Poor LV systolic function &gt; high end systolic volume &gt; impedes diastolic filling
** Heart rate
*** Increased HR &gt; shorter time in diastole &gt; reduced compliance; filling is time dependant
** Lusitropic properties of the ventricle
*** Increased by SNS tone and catecholamines
** Wall thickness
*** Increased thickness = reduced compliance
 
 
 
<span id="examiner-comments-158"></span>
==== Examiner comments ====
 
<blockquote>12% of candidates passed this question.<br />
Candidates often misinterpreted the question and described determinants of cardiac output. The answer should have focussed on factors affecting/contributing to normal LV function - not pathological states. Some answers showed a lack of appreciation that normal left ventricular function is afterload independent, due to compensatory reflexes. Answers needed to consider intrinsic and extrinsic factors affecting LV function - the latter (e.g. SNS, PSNS, hormones, drugs) was often left out. Answers needed to consider both systolic and diastolic function. An excellent answer included physiological phenomena such as the Treppe effect, Anrep effect and baroreceptor and chemoreceptor reflexes. Mention of normal conduction and pacing as well as blood supply limited by diastole scored additional marks.
</blockquote>
 
 
<span id="online-resources-for-this-question-157"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-2-saqs/question-18 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18b/18b18/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-2-18.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-158"></span>
==== Similar questions ====
 
* ? None directly
 
 
 
 
 
 
 
<span id="question-19-8"></span>
=== Question 19 ===
 
 
 
<span id="question-159"></span>
==== Question ====
 
Describe toxicity of local anaesthetic agents
 
 
 
<span id="example-answer-159"></span>
==== Example answer ====
 
 
 
Local anaesthetic toxicity
 
* Typically occurs ~3mg/kg (without adrenaline) ~6-7mg/kg (with adrenaline) when used regionally
* CNS and CVS side effects are most evident
* CNS effects occurring at lower plasma drug concentrations
* CNS side effects
** Lower doses: Visual disturbances, perioral numbness, tremors
** Higher doses: Slurred speech, confusion, decreased level of consciousness
** Highest doses: Seizures, coma, apnoea
* CVS side effects
** Lower doses: Hypertension, tachycardia
** Higher doses: Hypotension, bradycardia,
** Highest doses: Cardiovascular collapse, arrhythmias
* Other effects
** Methemoglobinemia
** Allergy
 
 
 
Factors affecting toxicity
 
* Patient factors
** Acidosis: decreases protein binding &gt; increased unbound fraction
** Increased age: decreased clearance
** Pregnancy: decreased protein levels &gt; increased unbound fraction
** Hyperkalaemia: decreased dose required for toxicity
** Hepatic dysfunction: reduced metabolism &gt; increased risk of toxicity
** Renal dysfunction: reduced clearance &gt; increased risk of toxicity
* Drug factors
** Increasing dose = increased risk of toxicity
** Type of local anaesthetic
*** e.g. bupivacaine has lower CC/CNS ratio than lidocaine (more likely to be cardiotoxic than CNS toxic)
** Site of administration: more vascular areas &gt; higher risk
** Coadministration with vasoconstrictors (e.g. adrenaline) &gt; slower absorption &gt; reduced risk toxicity
** Drug interactions: displacement from protein binding sites by highly protein bound drugs e.g. phenytoin &gt; increased unbound fraction &gt; increased risk of toxicity
 
 
 
Management of local anaesthetic toxicity
 
* Alkalinise
** Decreases the unbound (active) fraction of the drug
* Give intralipid
** Increases the lipid bound fraction (decreases active unbound fraction)
 
 
 
<span id="examiner-comments-159"></span>
==== Examiner comments ====
 
<blockquote>28% of candidates passed this question.<br />
Most questions lacked a systematic approach to the question and specific detail. The relationship between systemic toxicity (CNS and CVS) and plasma levels should be described. Many candidates did not clearly state that CNS toxicity occurs at lower plasma levels that CVS toxicity. Factors that affect toxicity (e.g. drug factors, patient factors, interactions) needed to be elaborated with some detail. Patient factors such as age, pregnancy, acidosis, hyperkalaemia, hepatic failure were often omitted. Finally, marks were also awarded for noting methaemoglobinaemia as possible toxicity and the existence of specific therapy (intralipid).
</blockquote>
 
 
<span id="online-resources-for-this-question-158"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-2-saqs/question-19 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18b/18b19/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-2-19.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-159"></span>
==== Similar questions ====
 
* Question 22, 2012 (2nd sitting)
* Question 3, 2009 (1st sitting)
 
 
 
 
 
 
 
<span id="question-20-8"></span>
=== Question 20 ===
 
 
 
<span id="question-160"></span>
==== Question ====
 
Describe the pharmacology of heparin highlighting important differences between unfractionated and fractionated (low molecular weight) heparin
 
 
 
<span id="example-answer-160"></span>
==== Example answer ====
 
{|
! Name
! HMWH (heparin)
! LMWH (enoxaparin)
|-
| '''Class'''
| Anticoagulant
| Anticoagulant
|-
| '''Indications'''
| Prophylactic and therapeutic anticoagulation (e.g. AF, DVT, PE, ACS etc)
| Prophylactic and therapeutic anticoagulation (e.g. AF, DVT, PE, ACS etc)
|-
| '''Pharmaceutics'''
| MW = 5,000-25,000 Da <br />
Clear solution for injection
| MW = 5,000 Daltons <br />
Clear solution for injection
|-
| '''Routes of administration'''
| IV, SC
| SC (main), can also be given IV
|-
| '''Dose'''
| Prophylactic: 5,000 IU BD-TDS Therapeutic: infusion (APTT target)
| Therapeutic: 1mg/kg BD or 1.5mg/kg OD <br />
Prophylactic: 20-40mg OD
|-
| pKA
|
|
|-
| '''Pharmacodynamics'''
|
|
|-
| MOA
| Heparin binds to antithrombin 3 &gt; conformational change &gt; increases affinity for inactivating thrombin (factor IIa) and Factor Xa
| Enoxaparin binds to AT-3 &gt; conformational change &gt; increases affinity for inactivating factor Xa (and weakly factor IIa - 4x less activity)
|-
| Effects
| Anticoagulation
| Anticoagulation
|-
| Side effects
| HAEM: increased risk of haemorrhage, bruising, HITTS (higher than LMWH)
| HAEM: increased risk of haemorrhage, bruising, HITTS (lower than HMWH)
|-
| '''Pharmacokinetics'''
|
|
|-
| Onset
| Immediate (IV), 30 mins (SC)
| Peak effect 3-4 hrs post SC injection
|-
| Absorption
| PO bioavailability - 0% <br />
Variable SC absorption
| PO bioavailability - 0% <br />
&gt;90% bioavailability post SC injection
|-
| Distribution
| VOD = 0.1L/kg <br />
Lipid solubility: low <br />
Protein binding: high <br />
Does not cross BBB / placenta
| VOD = 4.3L <br />
Protein binding: does not bind to heparin binding proteins
|-
| Metabolism
| Reticuloendothelial system
| Minimal hepatic metabolism
|-
| Elimination
| Renal elimination (very minimal) - hence preferred in renal failure <br />
T 1/2 = 1 hrs
| Renal elimination of active and inactive metabolites <br />
T 1/2 = 6-12 hours
|-
| '''Special points'''
| Reversal: protamine (1mg = 100IU) - 100% <br />
Monitoring: APTT level
| Reversal: protamine (&lt;75% efficacy) Monitoring: Anti-Xa level
|}
 
 
 
<span id="examiner-comments-160"></span>
==== Examiner comments ====
 
<blockquote>71% of candidates passed this question.<br />
Better answers were tabulated and included sections on pharmaceutics, indications and an explanation on how the difference in molecular weight influenced pharmacodynamics and pharmacokinetics. Knowledge of adverse effects was limited to bleeding and HITTS, often without consideration of relative risk from LMWH. Many candidates did not know the t1/2 of UFH or LMWH.
</blockquote>
 
 
<span id="online-resources-for-this-question-159"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-2-saqs/question-20 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18b/18b20/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-2-20.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-160"></span>
==== Similar questions ====
 
* Question 5, 2017 (2nd sitting)
* Question 8, 2009 (2nd sitting)
* Question 2, 2008 (2nd sitting)
 
 
 
<span id="2018-1st-sitting"></span>
== 2018 (1st sitting) ==
 
 
 
<span id="question-1-9"></span>
=== Question 1 ===
 
 
 
<span id="question-161"></span>
==== Question ====
 
Describe the carriage of oxygen in the blood, including total oxygen delivery per minute
 
 
 
<span id="example-answer-161"></span>
==== Example answer ====
 
Oxygen is transported in the blood in two main forms:
 
* Dissolved oxygen
* Combined with haemoglobin (oxyhaemoglobin)
 
 
 
Dissolved oxygen
 
* Amount of oxygen dissolved in blood is proportional to Henrys Law
* There is 0.03ml oxygen per 1L blood for each mmHg of PO2 at 37 degrees
* Thus for PO2 of 100 there is 3 ml dissolved oxygen per 1L blood
 
 
 
Oxyhaemoglobin
 
<ul>
<li><p>98% of oxygen in the blood is carried by haemoglobin</p></li>
<li><p>Haemoglobin reversibly binds O2 and transports it around the body</p></li>
<li><p>One haem group binds 1 oxygen molecule. Each Hb molecule binds four O2 molecules</p></li>
<li><p>Oxygen capacity of Hb (1g of Hb carries 1.34ml Oxygen)</p></li>
<li><p>Binding of O2 to Hb</p>
<ul>
<li><p>Hb exists in tense (unbound) and relaxed (bound states)</p></li>
<li><p>As Hb binds oxygen, it exhibits positive cooperativity (additional binding is easier), as the R state Hb has increased oxygen affinity. Explains sigmoidal shape of oxy-dissociation curve</p></li></ul>
</li>
<li><p>Oxygen bound to Hb does not contribute to PO2 of blood - maintaining diffusion gradient</p>
<p></p></li></ul>
 
Oxygen content of blood (CaO2)
 
* <math display="inline">CaO_2 = (1.34 \; \times \; [Hb] \; \times \; SaO_2) \; + \; (0.03 \times PO_2)</math>
* Where [Hb] is the Hb concentration, 1.34 is the oxygen carrying capacity of Hb (Huffners constant), SaO2 is the percentage of Hb saturated with oxyge, 0.03 is the dissolved oxygen content of blood, and PO2 is the partial pressure of oxygen in blood
 
 
 
Oxygen delivery (DO2)
 
* Oxygen delivery (DO2) is a function of the cardiac output and oxygen content of blood (CaO2)
** <math display="inline">DO2 \; = \; CO \; \times CaO_2</math>
** <math display="inline"> DO2    \; = \; CO \; \times (1.34 \; \times \; Hb \; \times \; SaO_2) \; + \; (0.03 \times PO_2)</math>
* Assuming CO of 5L/min, 100% sats, 150g/L Hb, PO2 of 100mmHg = 1L/min
 
 
 
<span id="examiner-comments-161"></span>
==== Examiner comments ====
 
<blockquote>32% of candidates passed this question.<br />
Better answers divided oxygen carriage into that bound to haemoglobin and that carried in the dissolved form. A reasonable amount of detail on the haemoglobin structure and its binding of oxygen was expected, including an explanation of co-operative binding and the oxygen carrying capacity of haemoglobin. Better answers mentioned Henry’s law in the description of dissolved oxygen, along with an estimation of the amount of oxygen that is normally in the dissolved form.<br />
It was expected that answers include the equation for oxygen delivery, a brief description of the components of that equation and the normal value, which a large number of candidates omitted.
</blockquote>
 
 
<span id="online-resources-for-this-question-160"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-1-saqs/question-1 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18a/18a01/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-1-01.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-161"></span>
==== Similar questions ====
 
<ul>
<li><p>Question 1, 2012 (2nd sitting)</p>
<p></p></li></ul>
 
 
 
<span id="question-2-9"></span>
=== Question 2 ===
 
 
 
<span id="question-162"></span>
==== Question ====
 
Compare and contrast the pharmacology of adrenaline and milrinone
 
 
 
<span id="example-answer-162"></span>
==== Example answer ====
 
{|
! Name
! Adrenaline
! Milrinone
! Comments
|-
| '''Class'''
| Naturally occurring catecholamine
| Phosphodiesterase inhibitor
| Different classes
|-
| '''Indications'''
| Haemodynamic support, anaphylaxis, bronchoconstriction/airway obstruction
| Haemodynamic support for acute heart failure
| Adrenaline has more/other uses
|-
| '''Pharmaceutics'''
| Clear solution, light sensitive (brown glass), 1:1000 or 1:10,000
| Yellow solution, 10mg/ml ampoules,
|
|-
| '''Routes of administration'''
| IV, IM, INH, ETT, Topical, subcut
| IV only in AUS
| Milrinone only IV in Aus.
|-
| '''Pharmacodynamics'''
|
|
|
|-
| MOA
| Non-selective adrenergic receptor agonist. <br />
At low doses B effects dominate, at high doses alpha dominate.<br />
Adrenaline &gt; a-1 receptor &gt; increased IP3 (2nd messenger) &gt; increased Ca <br />
Adrenaline &gt; B1,B2,B3 receptors &gt; increased cAMP (second messenger)
| PDE III inhibition &gt; decreased cAMP breakdown &gt; increased Ca
| Different MOA - can be used synergistically
|-
| Effects
| CVS: vasoconstriction (high doses), vasodilation (low doses), increased inotropy + chronotropy<br />
RESP: bronchodilation, increased minute ventilation<br />
METABOLIC: hyperglycaemia (glycogenolysis, lipolysis, gluconeogenesis)<br />
CNS: increased MAC<br />
GIT: decreased intestinal tone/secretions
| CVS: increased inotropy, lusitropy, minimal chronotropy, vasodilation
| Milrinone is cardiovascularly selective.
|-
| Side effects
| Extravasation &gt; tissue necrosis, pHTN due to increased PVR, hyperglycaemia, tachyarrhythmias,
| May precipitate an arrhythmia, hypotension (vasodilator)
| Milrinone is a vasodilator and may need adjunct vasopressor
|-
| '''Pharmacokinetics'''
|
|
|
|-
| Onset/Offset
| Immediate / immediate
| 5-10 minutes / 3 hours
| Adrenaline has faster onset/offset
|-
| Absorption
| Zero oral bioavailability due to GIT inactivation. variable/erratic ETT absorption.
| Readily absorbed orally (tablets not available in AUS)
| Milrinone readily PO absorbaable
|-
| Distribution
| Poor lipid solubility, doesn't cross BBB, crosses placenta
| Small VOD = 0.4L/kg, protein binding 80%
|
|-
| Metabolism
| Metabolised by MAO (mitochondria) and COMT (liver, blood, kidney) to VMA and metadrenaline
| Minimal hepatic metabolism (10%)
|
|-
| Elimination
| T 1/2: ~2 mins (due to rapid metabolism)<br />
Metabolites (above) are excreted in the urine
| Renal excretion (unchanged 80%). T1/2 = 3 hours
| Milrinone requires dose adjustment in renal impairment + has longer half life
|-
| '''Special points'''
|
| Dose adjust in renal failure
|
|}
 
 
 
<span id="examiner-comments-162"></span>
==== Examiner comments ====
 
<blockquote>45% of candidates passed this question.<br />
This question was best answered using a table. Better answers included: the mechanisms of action, the pharmacokinetics and pharmacodynamics, indications for use and adverse effects. To complete the answer, the two drugs should have been compared and contrasted. There are many areas which could be contrasted e.g. different indications, different mechanisms of action, different half-lives and duration of action, different metabolism and different pharmacodynamic effects, in particular the effects on the cardiovascular system and the pulmonary circulation. Similarities should also have been highlighted.
</blockquote>
 
 
<span id="online-resources-for-this-question-161"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-1-saqs/question-2#answer-anchor Deranged Physiology]
* [https://jennysjamjar.com.au/syllabus/g/g8/g8i-18a02-compare-and-contrast-the-pharmacology-of-adrenaline-and-milrinone/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-1-02.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-162"></span>
==== Similar questions ====
 
* Milrinone
** Question 14, 2011 (2nd sitting)
* Adrenaline
** Question 1, 2021 (1st sitting)
** Question 8, 2012 (1st sitting)
 
 
 
 
 
<span id="question-3-9"></span>
=== Question 3 ===
 
 
 
<span id="question-163"></span>
==== Question ====
 
Define dead space and its components (30% of marks). Explain how these may be measured (35% of marks) and describe the physiological impact of increased dead space (35% of marks).
 
 
 
<span id="example-answer-163"></span>
==== Example answer ====
 
Dead space
 
* The fraction of the tidal volume that does not participate in gas exchange
* Made up of
** Apparatus dead space
*** Related to artificial breathing circuits/equipment (e.g. NIV)
** Physiological dead space (sum of alveolar and anatomical dead space)
*** Alveolar dead space
**** Volume of gas in poorly perfused lung units (West Zone 1)
*** Anatomical deadspace
**** Volume of gas in conducting airways
**** Approx 2ml/kg
 
 
 
Measurement of dead space
 
* Physiological deadspace
** Calculated using the modified version (Enghoff) of the Bohr Equation
*** <math display="inline">\frac {V_D}{V_T} = \frac {P_aCO_2 - P_ECO_2}{P_aCO_2}</math>
* Anatomical deadspace
** Can be calculated using Fowlers method
*** Subject exhales to residual volume. Pure oxygen is inhaled to total lung capacity. Subject breathes out through a nitrogen sensor. A nitrogen concentration vs volume can be generated
*** The midpoint of phase 2 = anatomical dead space
* Alveolar dead space
** Equals the difference between physiological and anatomical dead space
 
 
 
Impact of increased dead space
 
* Increasing dead space has the same effects on gas exchange as decreased tidal volumes
** Reduced CO<sub>2</sub> clearance
** Decreased oxygenation (due to increased CO2)
* This results in decreased efficiency of ventilation
** For any given minute volume, CO2 clearance is reduced
** Leads to increased minute ventilation &gt; increased work of breathing
 
 
 
<span id="examiner-comments-163"></span>
==== Examiner comments ====
 
<blockquote>59% of candidates passed this question.<br />
Some candidates failed to provide a correct definition of dead space. An outline of anatomical, alveolar and physiological dead space was expected. The Bohr equation was commonly incorrect, and many did not comment on how to measure the components of the Bohr equation. Fowler’s method was generally well described though some plotted the axes incorrectly.<br />
The impact of increased dead space was not often well explained. Very few people stated the major impact of increased dead space is reduced minute ventilation and how this would affect CO2.
</blockquote>
 
 
<span id="online-resources-for-this-question-162"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-1-saqs/question-3 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18a/18a03/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-1-03.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-163"></span>
==== Similar questions ====
 
* Question 19, 2010 (1st sitting)
 
 
 
 
 
 
 
<span id="question-4-9"></span>
=== Question 4 ===
 
 
 
<span id="question-164"></span>
==== Question ====
 
Describe the renal handling of sodium
 
 
 
<span id="example-answer-164"></span>
==== Example answer ====
 
 
 
Renal handling of sodium
 
* Sodium is freely filtered in the glomerulus
* PCT:
** ~60-70% reabsorbed
** Driven predominately by Na/K ATPase pump on the basolateral membrane which creates an electrochemical gradient for Na to flow down into.
* dLOH
** Nil reabsorbed (impermeable)
* aLOH
** ~25% reabsorbed
** Driven by the Na-K-2Cl co-transporter
* DCT
** ~5% Na reabsorbed
** Driven by the Na-Cl co-transporter
* Collecting duct
** &lt;5% Na reabsorbed
** Driven by ENaC channels
 
 
 
Regulation
 
* Tubuloglomerular feedback (release of renin in response to reduced Na/flow sensed at the JGA)
* Aldosterone
** Increases ENaC and Na/K ATPase activity in the DCT and collecting ducts
* Angiotensin II
** Increases Na/K ATPase activity on basolateral membrane - creates electrochemical gradient
** Increases Na-H reabsorption on luminal membrane in PCT
* ANP
** Inhibits ENaC (in collecting ducts)
* Pharmacological agents
 
 
 
<span id="examiner-comments-164"></span>
==== Examiner comments ====
 
<blockquote>46% of candidates passed this question.<br />
A description of filtration and reabsorption, including amounts was required. Better answers described sodium handling in a logical sequence as it progressed through the nephron including the percentages reabsorbed in each segment. In addition to the amounts reabsorbed, the mechanisms of transport across the tubular luminal and basolateral membranes into interstitial space should have been described.
</blockquote>
 
 
<span id="online-resources-for-this-question-163"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-1-saqs/question-4 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18a/18a04/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-1-04.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-164"></span>
==== Similar questions ====
 
* Question 22, 2009 (2nd sitting)
* Question 23, 2014 (2nd sitting)
 
 
 
 
 
<span id="question-5-9"></span>
=== Question 5 ===
 
 
 
<span id="question-165"></span>
==== Question ====
 
Compare and contrast the pharmacokinetics and pharmacodynamics of IV fentanyl and IV remifentanil (60% of marks). Discuss the concept of context sensitive half-time using these drugs as examples (40% of marks).
 
 
 
<span id="example-answer-165"></span>
==== Example answer ====
 
{|
! Name
! Fentanyl
! Remifentanyl
|-
| '''Class'''
| Opioid<br />
Synthetic phenylpiperidine derivative
| Opioid <br />
Synthetic phenylpiperidine derivative
|-
| '''Indications'''
| Analgesia
| Analgesia
|-
| '''Pharmaceutics'''
| Colourless solution (50ug/ml)
| Crystalline white powder for reconstitution
|-
| '''pKa'''
| 8.4
| 7.3
|-
| '''Routes of administration'''
| SC, IM, IV, epidural, intrathecal, transdermal
| IV, intranasal
|-
| '''Pharmacodynamics'''
|
|
|-
| MOA
| Mu-opioid receptor agonist &gt; hyperpolarisation
| Mu-opioid receptor agonist &gt; hyperpolarisation
|-
| Effects
| Analgesia
| Analgesia
|-
| Side effects
| CVS: bradycardia<br />
Resp: respiratory depression, blunted cough reflex<br />
GIT: decreased GI motility, nausea/vomiting<br />
CNS: Dysphoria, confusion,
| CVS: bradycardia + hypotension<br />
Resp: respiratory depression<br />
GIT: Decreased GI motility<br />
MSK muscle rigidity at high doses
|-
| '''Pharmacokinetics'''
|
|
|-
| Onset/Offset
| Rapid onset (2-5 mins)<br />
Rapid offset (30mins)
| Rapid onset (1 mins)<br />
Rapid offset (5-10mins)
|-
| Absorption
| PO bioavailability (33%). Mucosal absorption is poor
| PO Bioavailability (0%). Mucosal absorption is rapid
|-
| Distribution
| VOD high = 6L / kg<br />
Highly protein bound (90%)<br />
Good lipid solubility
| VOD low = 0.1L/kg<br />
Highly protein bound (70%)<br />
Very lipid solubility
|-
| Metabolism
| Hepatic metabolism &gt; demethylation &gt; inactive metabolites
| Ester hydrolysis by plasma and tissue esterases &gt; inactive metabolites
|-
| Elimination
| T 1/2 = 4 hours, prolonged with infusions. <br />
Excreted in urine
| T 1/2 5 mins. No CSHT<br />
Excreted in urine
|}
 
 
 
Context sensitive half time (CSHT)
 
* CSHT is the time required for 50% decrease in central compartment drug concentration after an infusion of the drug is ceased (context refers to the duration of infusion)
* Drugs with high VOD and minimal metabolism (e.g. fentanyl) will have different CSHT depending on the duration of infusion
** Short infusion = short CSHT. Long infusion = long CSHT
* Drugs with small VOD and extensive metabolism (e.g. remifentanil) has a CSHT which is independent of duration of infusion
 
 
 
<span id="examiner-comments-165"></span>
==== Examiner comments ====
 
<blockquote>66% of candidates passed this question.<br />
Well-constructed answers were presented in a table to compare pharmacokinetics and pharmacodynamics with a separate paragraph to discuss the concept of context sensitive half-time. Important pharmacokinetic points included: the differences in lipid solubility, ionised fractions and onset, and differences in metabolism. Marks were awarded for a definition of context-sensitive half-time. A discussion of these two drugs’ context-sensitive half-times should have included the differences in re-distribution into other compartments and rates of elimination.
</blockquote>
 
 
<span id="online-resources-for-this-question-164"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-1-saqs/question-5 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18a/18a05-compare-and-contrast-the-pharmacokinetic-and-pharmacodynamics-of-iv-fentanyl-and-iv-remifentanil-60-marks-discuss-the-concept-of-context-sensitive-half-time-using-these-drugs-as-examples-40/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-1-05-1.pdf CICM Wrecks]
* [https://ketaminenightmares.com/pex/saqs/pharmacology/analgesics/2011A06_remifentanil.htm Ketamine Nightmares]
 
 
 
<span id="similar-questions-165"></span>
==== Similar questions ====
 
* Fentanyl and remifentanyl
** Question 16, 2011 (1st sitting)
* Fentanyl
** Question 12, 2016 (2nd sitting)
** Question 13, 2017 (2nd sitting)
 
 
 
 
 
<span id="question-6-9"></span>
=== Question 6 ===
 
 
 
<span id="question-166"></span>
==== Question ====
 
Define a buffer (25% of marks). Describe how acid and base shifts in the blood are buffered (75% of marks).
 
 
 
<span id="example-answer-166"></span>
==== Example answer ====
 
 
 
Buffers
 
* A solution consisting of a weak acid and its conjugate base
* Main function is to resist change to pH, with the addition of stronger acids/bases, through reversible binding of H+ ions
* Effectiveness depends on the buffer pKa, the pH of the solution, the amount of buffer present, whether the system is open or closed
* All buffers participate in equilibrium with each other in defence of pH (Isohydric principle)
 
 
 
MAIN BUFFER SYSTEMS
 
 
 
Bicarbonate-carbonic acid system
 
* pKa of 6.1
* Consists of weak acid (H<sub>2</sub>CO<sub>3</sub>) and base (HCO<sub>3</sub> salt)
* Via reaction: <math display="inline"> CO_2 \; + H_2O \; \leftrightarrow \; H_2CO_3 \; \leftrightarrow \; HCO_3^- \; + H^+</math>
* Increased acid &gt; increased CO<sub>2</sub> (excreted via lungs)
* Increased base &gt; increased HCO<sub>3</sub> (excreted via kidneys)
* OPEN system - hence most important - responsible for 80% of the ECF buffering
 
 
 
Protein buffering system (including Hb)
 
* Includes haemoglobin (150g/L) and plasma proteins (70g/L)
* Proteins buffer by binding H+ to imidazole side chains of their histidine residues
* Hb is quantitatively 6 times more important than plasma proteins, as the concentration is double and there are three times as many histidine residues in Hb compared to plasma proteins
* Hb has pKa of 6.8. Weak acid (HHb) and weak base (KHb)
* Mechanism: H+ binds to the histidine residues on imidazole side chains, the HCO<sub>3</sub> diffuses down concentration gradient into ECF
 
 
 
Phosphate buffering system
 
* Overall pKa 6.8
* Tribasic (HPO<sub>4</sub>, H<sub>2</sub>PO<sub>4</sub>, H<sub>3</sub>PO<sub>4</sub>) though only the H<sub>2</sub>PO<sub>4</sub> has a physiological pKa to be useful
* Overall contribution is minimal to the blood due to the low concentration of phosphate. However more important in the urine where the concentration is higher
* closed system
 
 
 
<span id="examiner-comments-166"></span>
==== Examiner comments ====
 
<blockquote>45% of candidates passed this question.<br />
Few candidates defined a buffer making it difficult to award 25% of the marks for this question. The three main buffers in blood should have been described: bicarbonate system, haemoglobin and proteins. The pKa, the buffering mechanism and the capacity of the system should have been described. The Henderson Hasselbach equation was sometimes incorrect. Marks were only awarded for buffers in blood and unfortunately some candidates described non-blood buffers.
</blockquote>
 
 
<span id="online-resources-for-this-question-165"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-1-saqs/question-6 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18a/18a06/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-1-06.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-166"></span>
==== Similar questions ====
 
* Question 11, 2021 (1st sitting)
* Question 22, 2014 (1st sitting)
* Question 19, 2011 (1st sitting)
* Question 3, 2008 (2nd sitting)
 
 
 
 
 
<span id="question-7-9"></span>
=== Question 7 ===
 
 
 
<span id="question-167"></span>
==== Question ====
 
Outline the blood supply to the gastrointestinal system (arteries and veins).
 
 
 
<span id="example-answer-167"></span>
==== Example answer ====
 
 
 
Arterial supply
 
* The aorta (and its branches) supplies the entire arterial supply to the GIT
* The oesophagus is supplied by various arterial branches
** Cervical portion- inferior thyroid artery
** thoracic portion - bronchial arteries
** Abdominal portion - left gastric, inferior phrenic arteries
* The abdominal aorta then has three main branches which supply the remainder of the GIT
** Celiac trunk
*** Arises from abdominal aorta immediately below aortic hiatus at T12/L1
*** Divides into left gastric artery, splenic artery, common hepatic artery
**** Left gastric a. (supplies stomach)
**** Splenic a. (supplies spleen, pancreas)
**** Common hepatic, divides into
***** Hepatic a. proper (supplies liver)
***** Gastroduodenal (supplies pancreas, duodenum, stomach)
***** Right gastric (supplies stomach)
** Superior mesenteric artery (SMA)
*** Arises from abdominal aorta immediately interior to coeliac trunk (L1)
*** Multiple branches (15-20) which joint in an arcade
*** supplies the midgut structures (from duodenum to 2/3 transverse colon)
** Inferior mesenteric artery (IMA)
*** Arises from abdominal aorta ~L3
*** Multiple branches (including Left colic, sigmoid, superior rectal arteries), join in arcade
*** Supplies the hindgut (distal 1/3 transverse colon - rectum)
 
 
Venous drainage
 
<ul>
<li><p>For the most part, the venous drainage of the GIT is via veins which accompany the arterial system</p></li>
<li><p>They return via the portal vein</p>
<ul>
<li><p>Portal vein</p>
<ul>
<li><p>Combination SMV and splenic vein</p></li>
<li><p>Receives drainage from forgut structures</p></li></ul>
</li>
<li><p>Splenic vein</p>
<ul>
<li><p>Travels along with the splenic artery + drains corresponding regions (foregut)</p></li>
<li><p>Combines with SMV to form portal vein</p></li></ul>
</li>
<li><p>Superior mesenteric vein (SMV)</p>
<ul>
<li><p>Travels along with the SMA + drains corresponding regions (midgut)</p></li>
<li><p>Combines with splenic vein to form portal vein</p></li></ul>
</li>
<li><p>Inferior mesenteric vein (IMV)</p>
<ul>
<li><p>Travels along with the IMA + drains corresponding regions (hindgut)</p></li>
<li><p>Drains into the splenic vein</p></li></ul>
 
<p></p></li></ul>
</li></ul>
 
<span id="examiner-comments-167"></span>
==== Examiner comments ====
 
<blockquote>7% of candidates passed this question.<br />
An outline of the blood supply from the oesophagus down to the anus was expected. Very few candidates knew the branches of the main 3 arteries and which portion of the gastrointestinal system they supplied. Concepts related to control of blood flow and autoregulation of blood flow were not asked and therefore marks were not awarded for this information.
</blockquote>
 
 
<span id="online-resources-for-this-question-166"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-1-saqs/question-7 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18a/18a07-outline-the-blood-supply-to-the-gastrointestinal-system-arteries-and-veins/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-1-07.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-167"></span>
==== Similar questions ====
 
* Question 7, 2021 (1st sitting)
 
 
 
 
 
<span id="question-8-9"></span>
=== Question 8 ===
 
 
 
<span id="question-168"></span>
==== Question ====
 
Outline the principle of co-oximetry (40% of marks), describe what a co-oximeter is able to measure (30% of marks), and compare its limitations to those of a pulse oximeter (30% of marks).
 
 
 
<span id="example-answer-168"></span>
==== Example answer ====
 
CO-oximetry
 
* A laboratory device that uses spectrophotometry to measure relative blood concentrations of Hb species
* Principle
** Blood sample is heparinised, heated to 37 degrees, haemolysed by vibations
** Multiple wavelengths of light are then passed through the sample and the absorption spectra is assessed, using principles of Beer-Lambert law
** There is no need for pulsatile flow
* There is becoming available pulse co-oximetry which is similar to pulse-oximeters though can detect some of the other Hb species (e.g. COHb)
 
 
 
Measured indices
 
* SaO2 %
* Total [Hb]
* Met Hb %
* Sulpha Hb %
* CO Hb %
* Most co-oximetry machines can also obtain all the regular blood gas tensions/values
 
 
 
Interpretation
 
{|
!
! High pulse oximetry
! Low pulse oximetry
|-
| '''High Co-oximetry'''
| Reflects normal SpO2
| Reflects normal SpO2 <br />
Differences possibly due to:<br />
1) Poor tissue perfusion + shock <br />
2) Dyes (e.g. methylene blue) <br />
3) Tricuspid regurgitation <br />
4) Poor probe contact <br />
5) Contamination (ambient light)
|-
| '''Low Co-oximetry'''
| Reflects low SpO2<br />
Differences possibly due to: <br />
1) Carboxyhaemaglobinaemia <br />
2) Methaemaglobinaemia <br />
3) Radiofrequency interference
| Reflects low SpO2
|}
 
 
 
Co-oximeter vs Pulse-oximeter
 
* Advantages of co-oximetry
** More accurate sats (i.e. low reading = low sats) as accounts for other Hb species
** Not confused by ambient light, poor tissue perfusion, dyes etc
** Does not require pulsatile flow
* Disadvantages of co-oximetry
** More invasive (requires blood sample) - though pulse co-oximetry becoming available
** Heavy machinery, requiring calibration, less accessible
** Not continuous measurements
 
 
 
<span id="examiner-comments-168"></span>
==== Examiner comments ====
 
<blockquote>32% of candidates passed this question.<br />
Most candidates confused co-oximetry with other methods of measuring oxygenation of blood. Whilst there were a number of excellent descriptions of pulse oximetry, these attracted no marks for the first two sections. Structuring the answer based on the three parts asked, would have improved answers ensuring all aspects of the question were addressed.
</blockquote>
 
 
<span id="online-resources-for-this-question-167"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-1-saqs/question-8 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18a/18a08-outline-the-principle-of-co-oximetry-40-marks-describe-what-a-co-oximeter-is-able-to-measure-30-marks-compare-its-limitations-to-those-of-a-pulse-oximeter-30-marks/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-1-08.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-168"></span>
==== Similar questions ====
 
* None
 
 
 
 
 
<span id="question-9-9"></span>
=== Question 9 ===
 
 
 
<span id="question-169"></span>
==== Question ====
 
Describe the functions of the placenta (80% of marks). Outline the determinants of placental blood flow (20% of marks).
 
 
 
<span id="example-answer-169"></span>
==== Example answer ====
 
 
 
FUNCTIONS OF PLACENTA
 
 
 
Nutrient/gas exchange
 
<ul>
<li><p>The foetus relies on maternal transfer of gasses, nutrients and wastes</p></li>
<li><p>Nutrients/wastes</p>
<ul>
<li><p>Active transport e.g Amino acids, calcium, some vitamins/minerals</p></li>
<li><p>Facilitated diffusion e.g. glucose (GLUT1 and GLUT3)</p></li>
<li><p>Passive diffusion e.g. Na, Cl, urea, creatinine</p></li></ul>
</li>
<li><p>Gasses</p>
<ul>
<li><p>Oxygen</p>
<ul>
<li><p>Passive diffusion</p></li>
<li><p>Facilitated by higher oxygen carrying capacity and affinity of foetal Hb as well as the Bohr/Double bohr effects</p></li></ul>
</li>
<li><p>Carbon dioxide</p>
<ul>
<li><p>Passive diffusion</p></li>
<li><p>Facilitated by the Haldane and double Haldane effects</p></li></ul>
</li></ul>
 
<p></p></li></ul>
 
Immunological function
 
* Foetus is genetically distinct with a non functioning immune system
* Trophoblast cells
** Lose MHC molecules and become coated in mucoprotein &gt; less immunogenic
* Chorionic cells
** Prevent maternal T cells and most immunoglobulins (except IgG) from entering &gt; less immunogenic
** Barrier to some bacteria/viruses and allows IgG across &gt; some immune protection
* Yolk sac
** a-fetoprotein and progesterone are immunosuppressive &gt; less immunogenic
 
 
 
Endocrine function
 
* Syncytiotrophoblast of placenta produces
** B-HCG - prolongs corpus luteum (prevents early miscarriage)
** Oestrogen - increases uteroplacental blood flow, stimulates uterine growth
** Progesterone - uterine relaxation, development of lactation glands
** hPL - maternal lipolysis, breath growth/development
 
 
 
PLACENTAL BLOOD FLOW
 
 
 
Flow
 
* Blood flow to the uterus in a non pregnant woman is normally around 200mls/min (~4% of CO)
* In a pregnant woman at term this increases to up to 750mls/min (~15% of CO)
* Majority of this &gt; placenta, with some supplying the hypertrophied uterus.
 
 
 
Determinants of flow
 
<ul>
<li><p>No autoregulation of uteroplacental blood flow </p></li>
<li><p>Most important factor governing flow is therefore perfusion pressure</p>
<ul>
<li><p>Increased uteroplacental perfusion pressure &gt; increase flow</p></li></ul>
</li>
<li><p>Uterine perfusion pressure is therefore effected by</p>
<ul>
<li><p>Maternal MAP</p>
<ul>
<li><p>Effected by positioning (e.g. aortocaval compression), cardiac output, systemic vascular resistance</p></li></ul>
</li>
<li><p>Intrauterine pressure </p>
<ul>
<li><p>Effected by contractions &gt; increased intrauterine pressure &gt; decreased flow</p></li></ul>
</li>
<li><p>Uterine vascular ressistance</p>
<ul>
<li><p>Modestly effected by exogenous vasopressors, catecholamines</p></li></ul>
</li></ul>
</li>
<li><p>Compensates for the lack of autoregulation by increasing oxygen extraction</p>
<p></p></li></ul>
 
<span id="examiner-comments-169"></span>
==== Examiner comments ====
 
<blockquote>32% of candidates passed this question.<br />
Many candidates provided a broad overview of functions of the placenta but lacked detail. Placental blood flow has maternal and foetal components, though most only considered the maternal circulation to the placenta and didn't mention the foetal vessels. Many were not specific as to what blood vessels were described.<br />
Many stated that uterine blood flow is not autoregulated, however went on to describe myogenic and neuro-humoral mechanisms of autoregulation.
</blockquote>
 
 
<span id="online-resources-for-this-question-168"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-1-saqs/question-9 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18a/18a09/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-1-09.pdf CICM Wrecks]
* [https://partone.litfl.com/the_placenta.html Part One, LITFL]
 
 
 
<span id="similar-questions-169"></span>
==== Similar questions ====
 
* Question 6, 2021 (2nd sitting)
 
 
 
 
 
<span id="question-10-9"></span>
=== Question 10 ===
 
 
 
<span id="question-170"></span>
==== Question ====
 
Outline the advantages (15% of marks) and disadvantages (85% of marks) of the clinical use of suxamethonium.
 
 
 
<span id="example-answer-170"></span>
==== Example answer ====
 
 
 
Suxamethonium
 
<ul>
<li><p>Depolarising muscle relaxant</p></li>
<li><p>Used to facilitate endotracheal intubation during anaesthesia (i.e. RSI)</p></li>
<li><p>MOA: Binds to the nACh receptor on motor end plate &gt; depolarisation. Cannot be hydrolysed by Acetylcholinesterase in NMJ &gt; sustained depolarisation &gt; muscle relaxation</p>
<p></p></li></ul>
 
Advantages
 
<ul>
<li><p>Cheaper than other NMB agents</p></li>
<li><p>Pre-mixed</p></li>
<li><p>Can be IV or IM</p></li>
<li><p>Rapid onset (&lt;1 min)</p></li>
<li><p>Rapid offset (&lt; 10 mins)</p></li>
<li><p>Safe in pregnancy/neonates</p></li>
<li><p>Not end-organ dependant for metabolism (plasma cholinesterase)</p>
<p></p></li></ul>
 
Disadvantages
 
* Needs to be stored at 4 degrees
* Numerous side effects
** Major: anaphylaxis, suxamethonium apnoea, malignant hyperthermia<br />
Minor: hyperkalaemia, myalgia, fasiculations, bradycardia/arrhythmia<br />
Pressure related: increased IOP, ICP, intragastric pressure.
* Numerous contraindications
** Hyperkalaemic patients and those at risk (renal failure, sepsis, burns)
** Burns patients
** Personal/family history of malignant hyperthermia or plasma cholinesterase deficiency
** Muscular dystrophies, myasthenia gravis
** Penetration eye injury
* Issues with repeat dosing
** Repetitive dosing may lead to phase 2 (depolarising) block &gt; requiring reversal
 
 
 
<span id="examiner-comments-170"></span>
==== Examiner comments ====
 
<blockquote>46% of candidates passed this question.<br />
This commonly used drug should be very well-known. The question asked for an outline, hence long explanations of various aspects of pharmacology (e.g. pseudocholinesterase deficiency) were unnecessary.<br />
Headings should have included: advantages (e.g. rapid onset, rapid offset, short acting, IV or IM administration, not end organ dependent for metabolism, premixed, safe in pregnancy and neonates). The disadvantages section should have included the following headings: pharmaceutical, adverse drug reactions (including several potentially fatal ones), numerous contraindications, unpleasant side-effects and potential problems with repeat dosing.
</blockquote>
 
 
<span id="online-resources-for-this-question-169"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-1-saqs/question-10 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18a/18a10-outline-the-advantages-15-of-marks-and-disadvantages-85-of-marks-of-the-clinical-use-of-suxamethonium/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-1-10.pdf CICM Wrecks]
* [https://partone.litfl.com/depolarising_nmbs.html#id Part One, LITFL]
 
 
 
<span id="similar-questions-170"></span>
==== Similar questions ====
 
* Question 6, 2011 (1st sitting)
* Question 2, 2012 (2nd sitting)
* Question 1, 2013 (2nd sitting)
* Question 10, 2020 (2nd sitting)
 
 
 
 
 
<span id="question-11-9"></span>
=== Question 11 ===
 
 
 
<span id="question-171"></span>
==== Question ====
 
Describe the regulation of the coronary circulation
 
 
 
<span id="example-answer-171"></span>
==== Example answer ====
 
 
 
Coronary blood flow
 
* Normal resting coronary artery blood flow (CBF) is ~250mls/min (5% CO)
* RCA: blood flow is constant, pulsatile and higher flow rate during systole
* LCA: blood flow is intermittent, pulsatile, and higher flow rate during diastole
* Oxygen extraction is high (70%) and near maximal - increased CBF is needed for increased O2 demand.
 
 
 
Regulation of flow
 
* Autoregulation
** CBF is autoregulated over a wide range of BPs (perfusion pressure 50-120mmhg)
** Metabolic autoregulation
*** Anaerobic metabolism &gt; increased vasoactive substances (lactate, adenosine, CO2, NO) &gt; vasodilation &gt; increased flow
*** Predominant means of autoregulation
** Myogenic autoregulation
*** Increased transmural pressure &gt; vasoconstriction &gt; flow reduction
*** Modest means of autoregulation
* Direct autonomic control
** Weak effect
** a1 activation &gt; vasodilation; B/muscarinic activation &gt; vasoconstriction
* Indirect autonomic control
** Increase / decrease HR to alter time in diastole/systole which will lead to increased/decreased flow
** i.e. Increased PSNS activity &gt; decreased HR &gt; increased diastolic time &gt; increased CBF
* External (e.g drugs)
** Nitrates (dilate)
** BBlockers (reduce HR &gt; reduced O2 use and increased diastole time)
** CCB (coronary vasodilation)
 
 
 
<span id="examiner-comments-171"></span>
==== Examiner comments ====
 
<blockquote>46% of candidates passed this question.<br />
Some answers suffered from listing things rather than describing things as the question required.<br />
Better answers included a description of metabolic, physical and neuro-humoral factors and the relative importance of each.<br />
Many described detailed anatomy which was not necessary.
</blockquote>
 
 
<span id="online-resources-for-this-question-170"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-1-saqs/question-11 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18a/18a11/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2014-2-10-coronary-circ.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-171"></span>
==== Similar questions ====
 
* Question 11, 2008 (2nd sitting)
* Question 10, 2014 (2nd sitting)
* Question 19, 2021 (1st sitting)
 
 
 
 
 
<span id="question-12-9"></span>
=== Question 12 ===
 
 
 
<span id="question-172"></span>
==== Question ====
 
Briefly describe the cardiac events that occur during ventricular diastole.
 
 
 
<span id="example-answer-172"></span>
==== Example answer ====
 
 
 
Cardiac cycle
 
* Can be broken into two phases: systole and diastole
* Diastole is the phase corresponding to ventricular relaxation
* Diastole can be broken into 4 stages (below; using LV as example)
 
 
 
Isovolumetric relaxation
 
* Aortic valve closes (producing 2nd heart sound) ending systole, beginning diastole
* LV begin to relax without any change in volume &gt; decreasing LV pressure
* There is ongoing LA filling leading to increased LA pressure and the V wave.
* Corresponds with the peak of the T wave
 
 
 
Early diastolic (rapid ventricular) filling
 
* When LV pressure &lt; LA pressure the mitral valve opens
* This leads to increased LV volume and reduced LA pressure (the y descent on CVP waveform)
* With continued ventricular relaxation there is ongoing decrease in LV pressure
* This corresponds to the 3rd heart sound and isoelectric baseline on ECG
* There remains no further aortic flow
* Coronary blood flow is highest
 
 
 
Late diastolic (reduced ventricular or diastasis) filling
 
* Ongoing slow ventricular filling leading to gradual rise in atrial, ventricular and venous pressures as well as ventricular volume
* Corresponds to isoelectric baseline on ECG just prior to P wave
 
 
 
Atrial systole
 
* Begins just after the start of the P wave on ECG and finish before Q wave
* Leads to atrial contraction which increases atrial pressure, and leads to further ejection of blood into the ventricles (increasing LV volume and pressure).
* Atrial contraction produces the a wave on the CVP trace
* Fourth heart sound heard here: caused by oscillation of blood into ventricles following atrial systole
 
 
 
<span id="examiner-comments-172"></span>
==== Examiner comments ====
 
<blockquote>29% of candidates passed this question.<br />
Many answers lacked structure and contained insufficient information. Better answers defined diastole and described the mechanical events in the 4 phases of diastole. A common error was the ECG events in diastole. The electrical events and coronary blood flow should have been mentioned.
</blockquote>
 
 
<span id="online-resources-for-this-question-171"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-1-saqs/question-12 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18a/18a12/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2011-1-21-diastole.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-172"></span>
==== Similar questions ====
 
* Question 21, 2011 (1st sitting)
 
 
 
 
 
<span id="question-13-9"></span>
=== Question 13 ===
 
 
 
<span id="question-173"></span>
==== Question ====
 
Explain the difference between viscosity and density (10% of marks). Describe the effects of changes in viscosity and density on the flow of gases and liquids (90% of marks).
 
 
 
<span id="example-answer-173"></span>
==== Example answer ====
 
 
 
Viscosity (n)
 
* Liquids/gas internal resistance to flow
 
 
 
Density (p)
 
* Mass of a substance per unit volume
 
 
 
Flow (Q)
 
* The volume of liquid/gas moved per unit time
* Can be laminar, turbulent or transitional - determined by Reynolds number
 
 
 
Reynolds number
 
* <math display="inline">Re \; = \; \frac {2 \; r \; v \; p} {n}</math>
* Where r = radius, v=velocity, p=density, n=viscosity
* If Reynolds number is
** Re &lt;2000 = laminar flow
** Re 2000-4000 = transitional flow
** Re &gt;4000 flow is predominately turbulent
* Increased density (p) = increased Reynolds number = more likely to be turbulent flow
* Increased viscosity (n) = decreased Re = more likely to be laminar flow
* Density is a more important determinant of Re
 
 
 
Laminar flow
 
* Smooth flow of gas in layers that do not mix
* Flow is proportional to driving pressure, linear relationship
* Flow (Q) rate can be calculated using the Hagen-Poiseuille equation
* <math display="inline">Q = \frac {\pi r^4 \Delta P}{8nl}</math>
* <math display="inline">Resistance (R) = \frac {8nl} {\pi r^4}</math>
* Therefore viscosity (n), not density, affects the laminar pressure-flow relationship
** Increased viscosity = increased resistance = decreased flow
 
 
 
Turbulent flow
 
<ul>
<li><p>Eddies and swirls of gas that mix layers of gas</p></li>
<li><p>Flow is proportional to the square root of driving pressure, non linear relationship</p></li>
<li><p>Resistance increases in proportion to flow rate, but cannot be described using the Hagen-Poiseuille equation but instead by the Fanning Equation</p></li>
<li><p>Density (p), not viscosity, affects the turbulent pressure-flow relationship</p>
<p></p></li></ul>
 
Examiner comments
 
<blockquote>46% of candidates passed this question.<br />
Whilst most candidates defined density correctly, there was a lot of uncertainty regarding viscosity. Most candidates recognised that flow may be laminar, turbulent or transitional. Most accurately recounted Reynolds number and applied this correctly. Additionally, the Poiseuille equation was correctly stated by most candidates and correctly related to laminar flow. Few candidates recalled the equation describing turbulent flow.
</blockquote>
 
 
<span id="online-resources-for-this-question-172"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-1-saqs/question-13 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18a/18a13/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-1-13.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-173"></span>
==== Similar questions ====
 
* ? None
 
 
 
 
 
<span id="question-14-9"></span>
=== Question 14 ===
 
 
 
<span id="question-174"></span>
==== Question ====
 
Classify anticholinesterase drugs according to chemical interaction with an example of each (30% of marks). Outline the pharmacodynamic effects of anticholinesterase drugs and their clinical indications (70% of marks).
 
 
 
<span id="example-answer-174"></span>
==== Example answer ====
 
Anticholinesterase drugs
 
* Bind to and inhibit the action of Acetylcholinesterase (AChE)
* AChE is an enzyme found in synaptic clefts which hydrolyses acetylcholine (ACh) into choline and acetate, terminating synaptic transmission
 
 
 
Anticholinesterase drugs classification (according to method of inhibition)
 
* Reversible antagonists (via electrostatic binding)
** E.g. edrophonium
* Reversible antagonist (via covalent bonding, susceptible to hydrolysis)
** e.g. neostigmine, physostigmine
* Irreversible antagonist (via covalent bonding, resistant to hydrolysis)
** e.g. organophosphates, insecticides, nerve gases
 
 
 
Pharmacodynamic effects
 
* Anticholinesterase drugs inhibit AChE at both muscarinic and nicotinic ACh receptors
* Nicotinic effects (nAChR) - &quot;target&quot;
** Reversal of non-depolarising NMBs
* Muscarinic effects (mAChR) - &quot;off target&quot;
** CVS: bradycardia, hypotension
** RESP: bronchoconstriction/spasm
** CNS: miosis, cholinergic syndrome (confusion, agitation, nausea)
** GIT: hypersalivation, increased GIT motility, N/V
** GUT: urination/incontinence
** OTHER: diaphoresis, lacrimation
 
 
 
Clinical indications
 
* Reversal of non-depolarising neuromuscular blockers
** Increased synaptic ACh competes with non-depolarising NMBs for nAChR &gt; reversal of NMB (e.g. neostigmine, plus atropine/glycopyrrolate to offset AEs)
* Diagnosis + treatment of myasthenia gravis
** Increased synaptic ACh &gt; competes with myasthenia autoantibodies for nACHR &gt; increased muscle strength (e.g. pyridostigmine)
* Treatment of neurodegenerative disorders
** Increased synaptic ACh &gt; increased cholinergic transmission (e.g. donepezil)
* Treatment of glaucoma
** Increased ACh &gt; mAChR &gt; miosis &gt; decreased IOP (e.g. physostigmine)
* Treatment of anticholinergic syndrome
** features: delirium, tachycardia, dilated pupils, agitation, seizures
** Drugs: antiparkinsons, atropine, anti histamines, antispasmodics
** Management: physostigmine &gt; increase ACh
 
 
 
<span id="examiner-comments-173"></span>
==== Examiner comments ====
 
<blockquote>32% of candidates passed this question.<br />
Many candidates who scored poorly confused anticholinesterase drugs with anticholinergic drugs. Some described pharmacokinetics when it was not asked. Similarly, treatment of organophosphate poisoning and/or cholinergic crisis was not asked for in the question.
</blockquote>
 
 
<span id="online-resources-for-this-question-173"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-1-saqs/question-14 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18a/18a14-classify-anticholinesterase-drugs-according-to-chemical-interaction-with-an-example-of-each-30-of-marks-outline-the-pharmacodynamic-effects-of-anticholinesterase-drugs-and-their-clinical-ind/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-1-14.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-174"></span>
==== Similar questions ====
 
* Question 21, 2015 (1st sitting)
 
 
 
 
 
<span id="question-15-9"></span>
=== Question 15 ===
 
 
 
<span id="question-175"></span>
==== Question ====
 
Describe the physiological regulation of intracranial pressure
 
 
 
<span id="example-answer-175"></span>
==== Example answer ====
 
 
 
Intracranial pressure (ICP)
 
* ICP = The pressure within the intracranial space, relative to atmospheric pressure
* Normal ICP is &lt; 15 mmHg
* Governed by the Monro-Kellie doctrine
* There is rhythmic variation in ICP due to variations in respiration and blood pressure
 
 
 
Monro-Kellie doctrine
 
* The skull is a rigid container of fixed volume
* The skull contents include: brain (~1400ml), CSF (~150ml), blood (~150ml)
* Therefore any increase in volume of one substance must be met by a decrease in volume of another, or else there will be rise in the ICP
 
 
 
Physiological regulation of ICP
 
* Brain tissue
** No capacity to alter volume under physiologically normal circumstances
* CSF
** CSF can be displaced from the cranium into the spinal subarachnoid space (as the spinal meninges have better compliance)
** With increased ICP there is also increased driving pressure for CSF reabsorption
* Blood
** Compression of the dural venous sinuses can displace venous blood from the cranium
 
 
 
Pressure volume relationship
 
<ul>
<li><p>Hyperbolic relationship - indicating that there is limited capacity to buffer increased volume, before large increases in ICP</p>
<p></p></li></ul>
 
[[File:C:\Users\ethan\AppData\Roaming\Typora\typora-user-images\image-20211012142839178.png|thumb|none|alt=image-20211012142839178|image-20211012142839178]]
 
 
 
<span id="examiner-comments-174"></span>
==== Examiner comments  ====
 
<blockquote>45% of candidates passed this question.<br />
A definition and a normal value were expected. A description of the Monro-Kellie doctrine was expected. Better answers divided into the various components of the cranium with the answer focussing on cerebral blood volume and CSF volume as the brain tissue as no capacity to change its volume.
</blockquote>
 
 
<span id="online-resources-for-this-question-174"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-1-saqs/question-15 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18a/18a15/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-1-15.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-175"></span>
==== Similar questions ====
 
* Question 18, 2016 (2nd sitting)
* Question 14, 2016 (1st sitting)
* Question 18, 2010 (1st sitting)
 
 
 
 
 
<span id="question-16-9"></span>
=== Question 16 ===
 
 
 
<span id="question-176"></span>
==== Question ====
 
Compare and contrast the pharmacology of furosemide (frusemide) and acetazolamide
 
 
 
<span id="example-answer-176"></span>
==== Example answer ====
 
{|
! Name
! Frusemide
! Acetazolamide
! Notes
|-
| '''Class'''
| Loop diuretic
| Carbonic anhydrase inhibitor
| Different class
|-
| '''Indications'''
| Oedema/fluid overload, renal insufficiency, hypertension
| Metabolic alkalosis, glaucoma, altitude sickness
| Different indications
|-
| '''Pharmaceutics'''
| Tablet, clear colourless solution (light sensitive),
| White scored tablets (250mg), colourless solution
| -
|-
| '''Routes of administration'''
| IV, PO,
| PO, IV
| Both available IV and PO
|-
| '''Dose'''
| Varies (~40mg daily commonly used for well patients, can be sig. increased)
| 125mg-1g, up to 4 hourly
| -
|-
| pKA
| 3.6 (highly ionised; poorly lipid soluble)
| pKa 7.2
| Acetazolamide more lipid solu
|-
| '''Pharmacodynamics'''
|
|
|
|-
| MOA
| Binds to NK2Cl transporter in the thick ascending limb LOH, leads to decreased Na,K, Cl reabsorption &gt; decreased medullary tonicity + Inc Na/Cl delivery to distal tubules &gt; decreased water reabsorption &gt; diuresis
| Inhibits carbonic anhydrase in PCT &gt; decreased reabsorption of filtered HCO3
| Different MOA
|-
| Effects
| Renal: diuresis<br />
CVS: hypovolaemia, arteriolar vasodilation + decreased preload (=mechanism for improvement of dyspnoea before diuretic effect in APO)<br />
Renal: increase in RBF
| CNS: decreased IOP by decrease aqueous humour<br />
RENAL: diuresis, decreased HCO3 reabsorption (metabolic acidosis),
| Both lead to diuresis/hypovolaemia. Acetazolamide has extra-renal effects (e.g. IOP effects)
|-
| Side effects
| CVS: hypovolaemia, hypotension<br />
Renal/metabolic: Metabolic alkalosis, LOW Na, K, Mg, Cl, Ca, increased Cr<br />
Ototoxicity, tinnitus, deafness
| CNS: paraesthesia, fatigue, drowsiness<br />
RENAL: hypoNa, HypoK, HyperCl<br />
GIT: Nz/Vz/Dz
| Both lead to electrolyte disturbances (hypoNa and HypoK). Frusemide &gt; metabolic alkalosis, Acetazolamide &gt; metabolic acidosis
|-
| '''Pharmacokinetics'''
|
|
|
|-
| Onset
| 5 mins (IV), 30-60 mins (PO), Effect lasts 6 hours.
| Onset 1-2hrs
| Frusemide has faster onset
|-
| Absorption
| Bioavailability varies person-person (40-80%)
| PO bioavailability 60%
| Similar
|-
| Distribution
| Vd = 0.1L/Kg, 95% protein bound (albumin)
| 95% protein bound, VOD 0.3L/kg
| Both have small VOD and are highly protein bound
|-
| Metabolism
| &lt; 50% metabolised renally into active metabolite
| Nil metabolism
| Acetazolamide not metabolised
|-
| Elimination
| Renally cleared (predominately unchanged). T1/2 ~90 mins.
| Renal clearance, T 1/2 = 6hrs
| Acetazolamide has longer T1/2
|-
| '''Special points'''
| Deafness can occur with rapid administration in large doses
|
|
|}
 
 
 
<span id="examiner-comments-175"></span>
==== Examiner comments ====
 
<blockquote>30% of candidates passed this question.<br />
The use of a table assisted with both clarity and the ability to compare the two drugs. Writing separate essays about each makes it difficult to score well. It was expected that candidates would follow a standard pharmacology format and discuss pharmaceutics, pharmacokinetics, pharmacodynamics and adverse drug reactions. Both of these drugs are ‘Level A’ in the syllabus and a suitable level of detail was expected.<br />
It was expected candidates would discuss in detail the mechanism of action, electrolyte and acid-base effects. Pharmacokinetic values were poorly answered. Qualitative terms such as ‘moderate, good and some’ are vague and should be avoided. Only correct numerical values (or ranges) attracted full marks.
</blockquote>
 
 
<span id="online-resources-for-this-question-175"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-1-saqs/question-16#answer-anchor Deranged Physiology]
* [https://cicmwrecks.files.wordpress.com/2017/04/2013-1-20-frusemide-vs-acetazolamide.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/18a/18a16/ Jennys Jam Jar]
 
 
 
<span id="similar-questions-176"></span>
==== Similar questions ====
 
* Frusemide + acetazolamide
** Question 20 , 2013 (1st sitting)
* Frusemide
** Question 18, 2019 (1st sitting)
** Question 14, 2020 (1st sitting)
 
 
 
 
 
<span id="question-17-9"></span>
=== Question 17 ===
 
 
 
<span id="question-177"></span>
==== Question ====
 
Define the osmolality and tonicity of an intravenous fluid (20% of marks). Compare and contrast the pharmacology of intravenous Normal Saline 0.9% and 5% Dextrose (80% of marks).
 
 
 
<span id="example-answer-177"></span>
==== Example answer ====
 
 
 
Osmolality
 
* The measure of solute concentration per unit mass of solvent.
* Measured in osmoles / kg solvent
 
 
 
Tonicity
 
* The measure of the osmotic pressure gradient between two solutions separated by a semi permeable membrane
* Only influenced by the solutes which cannot cross the semi-permeable membrane
* Can be hypotonic, isotonic, hypertonic
 
 
 
Normal saline vs 5% dextrose
 
{|
! Name
! 0.9% normal saline (IV)
! 5% dextrose (IV)
|-
| '''Class'''
| Crystalloid fluid
| Crystalloid fluid
|-
| '''Pharmaceutics'''
| Clear solution, various volume bags (e.g. 100ml, 500mls, 1L)<br />
| Clear solution, various volume bags (e.g. 1L, 500mls)
|-
| Osmolality
| 308 mOsm / Kg (calculated)<br />
286 mOsm/kg (measured)
| 278 mOsm/kg
|-
| Tonicity
| Isotonic
| Hypotonic (dextrose rapidly metabolised)
|-
| Contents
| 9g NaCl / 1L solution
| 50g dextrose / 1L solution
|-
| '''Pharmacodynamics'''
|
|
|-
| MOA
| Expands the ECF volume and changes biochemistry of body fluids
| Expands ECF volume and changes body fluid biochemistry
|-
| Effects
| Increased ECF volume
| Increased ECF volume<br />
Glucose replacement
|-
| Side effects
| Fluid overload, hyperchloraemic metabolic acidosis, electrolyte imbalances
| Fluid overload, cerebral oedema, hyperglycaemia, vein irritation, electrolyte imbalances (e.g. HypoNa)
|-
| '''Pharmacokinetics'''
|
|
|-
| Onset
| Immediate (IV)
| Immediate (IV)
|-
| Absorption
| IV bioavailability = 100%
| IV bioavailability = 100%
|-
| Distribution
| VOD = 0.2 L/Kg <br />
&gt; 25% intravascular<br />
&gt; 75% interstitial
| VOD = 0.6L/Kg <br />
&gt; 5% intravascular <br />
&gt; 25% interstitial<br />
&gt; 70% intracellular
|-
| Metabolism
| Not metabolised
| Metabolised by all body tissues (esp liver) into water and CO2
|-
| Elimination
| Renal
| Water eliminated renally, CO2 eliminated by lungs
|}
 
 
 
<span id="examiner-comments-176"></span>
==== Examiner comments ====
 
<blockquote>29% of candidates passed this question.<br />
Most candidates gave an adequate definition of osmolality and tonicity. A single concise sentence for each attracted full marks. Some candidates drew diagrams &amp; equations, which added few marks. Some candidates confused osmolarity (mOsm/L) and osmolality (mOsm/kg).<br />
Tonicity was best defined as the number of ‘effective’ osmols (those that cannot cross the cell membrane) in a solution relative to plasma. The use of a table greatly facilitated the comparison of 0.9% saline and 5% dextrose solutions. Values for composition, osmolarity and osmolality were poorly done. Some manufacturers state calculated values and some approximate values on the bags – both were accepted.<br />
No candidate correctly pointed out the fluids respectively have 9g NaCl and 50g dextrose per litre.
</blockquote>
 
 
<span id="online-resources-for-this-question-176"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-1-saqs/question-17 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18a/18a17-define-the-osmolality-and-tonicity-of-an-intravenous-fluid-20-of-marks-compare-and-contrast-the-pharmacology-of-intravenous-normal-saline-0-9-and-5-dextrose-80-of-marks/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-1-17.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-177"></span>
==== Similar questions ====
 
* None
 
 
 
 
 
<span id="question-18-9"></span>
=== Question 18 ===
 
 
 
<span id="question-178"></span>
==== Question ====
 
Compare and contrast non-invasive oscillometric and invasive arterial blood pressure monitoring.
 
 
 
<span id="example-answer-178"></span>
==== Example answer ====
 
 
 
Non-invasive oscillometric vs invasive arterial BP monitoring
 
{|
!
! Invasive arterial BP
! Oscillometric (non invasive) BP
|-
| Equipment
| - Arterial catheter<br />
- Incompressible tubing<br />
- Pressure transducer<br />
- Counterpressure fluid<br />
- Microprocessor
| - Inflatable cuff<br />
- Cuff manometer<br />
- Release valve<br />
- Microprocessor
|-
| Method/ principles
| 1) Pressure wave of the arterial blood is transmitted via a fluid column to a transducer<br />
2) Pressure changes converted to resistance changes in Wheatstone bridge transducer <br />
3) Converted to electrical signal &gt; transmitted to microprocessor<br />
4) Microprocessor uses Fourier analysis to breakdown waves
| 1) counterpressure (cuff) applied to limb over artery (e.g. brachial)<br />
2) cuff inflated above SBP<br />
3) cuff deflated slowly, measuring amplitude of the pulse pressure which is transmitter to cuff<br />
4) Maximal amplitude of PP = MAP<br />
5) SBP and DBP are then derived
|-
| Advantages
| - Gold standard BP measurement (all variables directly derived)<br />
- Can measure continuously<br />
- Can derive other variables (e.g. CO)<br />
- Can be used to generate waveform which can be used clinically
| - Non invasive<br />
- Relatively cheap<br />
- Convenient and fast to obtain<br />
- Reusable
|-
| Disadvantages
| - More expensive<br />
- More invasive <br />
- Takes time / less portable <br />
- All the risks associated with arterial puncture (infection, thrombosis etc)<br />
-Not re-usable
| - Less accurate<br />
- Not continuous
|-
| Sources of error
| - Incorrect position of transducer<br />
- Incorrect calibration <br />
- Counterpressure bag not adequately inflated <br />
- Damping and resonance
| - Wrong cuff size <br />
- Movement <br />
- Arrhythmias<br />
- Faint pulse (e.g hypotension and peripheral vascular disease)
|}
 
 
 
<span id="examiner-comments-177"></span>
==== Examiner comments ====
 
<blockquote>52% of candidates passed this question.<br />
There were some good answers, though invasive BP measurement was better answered than oscillometry. Many candidates provided extensive detail in one area i.e. the workings of a Wheatstone bridge, to the detriment of a balanced answer.<br />
Few seemed to have a structure consisting of &quot;equipment, method, sources of error, advantages, disadvantages&quot; or similar and missed providing important information as a result. Several described auscultatory non-invasive blood pressure measurement, rather than oscillometry, which although related in principle is a different process.
</blockquote>
 
 
<span id="online-resources-for-this-question-177"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-1-saqs/question-18 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18a/18a18/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-1-18.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-178"></span>
==== Similar questions ====
 
* None
 
 
 
 
 
<span id="question-19-9"></span>
=== Question 19 ===
 
 
 
<span id="question-179"></span>
==== Question ====
 
Explain the mechanisms by which normal body temperature is maintained and regulated
 
 
 
<span id="example-answer-179"></span>
==== Example answer ====
 
 
 
Overview
 
<ul>
<li><p>Temperature: the average kinetic energy of the atoms/molecules that make up a substance</p></li>
<li><p>Human 'core temperature' is the 'deep body' temperature of the internal organs and viscera</p></li>
<li><p>Humans maintain a core temperature of 37°C <math display="inline">\pm</math> 0.4°C, despite changes in ambient temperature</p>
<ul>
<li><p>Rectal, bladder, oesophageal, central vascular temperatures are often used as approximations. </p></li></ul>
</li>
<li><p>Peripheral temperatures are variable and generally less than the core temperature</p></li>
<li><p>Significant hypothermia (e.g. &lt;35°C) or hyperthermia (e.g. &gt;41°C) can lead to multi-organ dysfunction</p></li>
<li><p>Humans have multiple thermoregulatory mechanisms to resist change in core body temperature</p></li>
<li><p>In general, heat is lost by 4 mechanism: conduction, convection, evaporation, radiation</p></li>
<li><p>In general, heat is gained by 5 mechanisms: conduction, convection, evaporation, radiation, metabolism</p>
<p></p></li></ul>
 
Thermoregulatory system &amp; regulation
 
* Sensor
** Peripheral: Skin thermoreceptors (cold= bulbs of Krause; warm=bulbs of Ruffini)
*** Travels via spinothalamic tract to hypothalamus
** Central: Hypothalamic thermoreceptors
* Integrator/controller
** Hypothalamus
*** Functions as the thermostat
*** Stimulation of anterior hypothalmus leads to heat loss
*** Stimulation of the posterior hypothalamus leads to heat conservation/generation
* Effector/Response
** Response to cold
*** Shivering -&gt; involuntary muscle contractions that generate heat (ATP hydrolysis)
*** Peripheral vasoconstriction (ANS) --&gt; decreased cutaneous blood flow --&gt; decreased heat transfer from ambient air
*** Increase metabolic rate, thyroid hormone secretion, Non shivering thermogenesis (paeds) -&gt; increased heat generation
*** Behavioural changes (seek warmth)
*** Piloerection (unimportant in humans)
** Response to heat
*** Peripheral vasodilation (ANS) --&gt; increased cutaneous blood flow &gt; increased heat loss
*** Sweating --&gt; evaporative heat loss
*** Behavioural changes (seek cool)
 
 
 
<span id="examiner-comments-178"></span>
==== Examiner comments ====
 
<blockquote>52% of candidates passed this question.<br />
The best answers were systematic, using a sensor, integrator, effector approach, while also mentioning physiological variations i.e. diurnal, with ovulatory cycle etc.<br />
Few candidates raised the concept of central and peripheral compartments. The differentiation of the concepts of set point, interthreshold range and thermoneutral zone was often confused.
</blockquote>
 
 
<span id="online-resources-for-this-question-178"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-1-saqs/question-19 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18a/18a19/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-1-19.pdf CICM Wrecks]
* [https://icuprimaryprep.files.wordpress.com/2012/05/thermoregulation.pdf ICU Primary Prep]
* [https://partone.litfl.com/regulation_of_body_temperature.html#id Part one LITFL]
* Kerry brandis, page 285
 
 
 
<span id="similar-questions-179"></span>
==== Similar questions ====
 
* Question 6, 2007 (1st sitting)
* Question 4, 2009 (1st sitting)
* Question 9, 2021 (1st sitting)
 
 
 
 
 
<span id="question-20-9"></span>
=== Question 20 ===
 
<span id="question-180"></span>
==== Question ====
 
Outline the structure (20% of marks) and function (80% of marks) of the hypothalamus.
 
 
 
<span id="example-answer-180"></span>
==== Example answer ====
 
 
 
Overview
 
* Small (4g) almond shaped structure
* Posterior: mammillary bodies. Anterior: anterior commissure. Superior: thalamus. Inferior: pituitary
* Can be broken up into four functional regions, with discrete nuclei with various functions
 
 
 
Structure and function
 
{|
! Region
! Nuclei
! Function
|-
| Anterior hypothalamus
| - Supraoptic nuclei (ADH, oxytocin)<br />
- Paraventricular nuclei (TRH, CRH)
| - PSNS activity (increased)<br />
- Thermoregulation (leads to heat loss)<br />
- Water balance (ADH production / release)<br />
- Sleep/wake cycle (promotes sleep)
|-
| Medial hypothalamus
| - Ventromedial nuclei<br />
- Dorsomedial nuclei
| - Sexual function (release of GnRH) <br />
- Energy balance (BGL)<br />
- Satiety centre (inhibits appetite)
|-
| Lateral hypothalamus
| - Tuberal nuclei<br />
- Forebrain bundle
| - Behaviour/emotions (inc. punishment/reward)<br />
- Regulation of body water (thirst centre)<br />
- Regulation of hunger (increased)
|-
| Posterior hypothalamus
| - Mammillary nuclei
| - SNS activity (increased HR, BP, constriction)<br />
- Vasomotor control <br />
- Thermoregulation (heat gain)<br />
- Sleep wake cycle (wakefulness)
|}
 
 
 
Regulation of pituitary function
 
* Hypothalamus exerts control of pitutiary gland via two mechanisms
** Anterior lobe of pituitary
*** Controlled by secretion of hypothalamic hormones along the portal vein
**** TRH &gt; TSH release
**** CRH &gt; ACTH release
**** GHRH &gt; GH release
**** GnRH &gt; TSH/FSH release
**** PRH &gt; prolactin
** Posterior lobe pituitary
*** Controlled by direct neural connections from the anterior hypothalamus &gt; pituitary
*** Pituitary hormones (ADH, oxytocin)
 
 
 
<span id="examiner-comments-179"></span>
==== Examiner comments ====
 
<blockquote>21% of candidates passed this question.<br />
Most candidates understood the endocrine functions of the hypothalamus, and to some degree its interactions with the pituitary. Fewer candidates mentioned the importance of the hypothalamus as an integrator for the autonomic nervous system, or its roles in arousal/emotions.<br />
Many candidates had only a vague idea of the structure of the hypothalamus, while the best candidates were able to relate function to structure quite accurately.
</blockquote>
 
 
<span id="online-resources-for-this-question-179"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2018-paper-1-saqs/question-20 Deranged Physiology]
* [https://jennysjamjar.com.au/year/18a/18a20-outline-the-structure-20-of-marks-and-function-80-of-marks-of-the-hypothalamus/ Jennys Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2018-1-20.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-180"></span>
==== Similar questions ====
 
* ? None
 
 
 
 
 
 
 
<span id="2017-2nd-sitting"></span>
== 2017 (2nd sitting) ==
 
 
 
<span id="question-1-10"></span>
=== Question 1 ===
 
 
 
<span id="question-181"></span>
==== Question ====
 
Compare and contrast the pharmacology of ibuprofen and paracetamol.
 
 
 
<span id="example-answer-181"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-180"></span>
==== Examiner comments ====
 
<blockquote>65% of candidates passed this question.
 
This was a standard compare and contrast question of common analgesic pharmacology and it<br />
was generally well answered. The use of a table ensured all areas were covered including<br />
class, indications, pharmaceutics, mode of action, pharmacodynamics, pharmacokinetics and<br />
adverse effects. The uncertain nature (and possibilities) of the mechanism of action of<br />
paracetamol was alluded to in better responses.
 
Details of the comparative pharmacokinetics were often lacking. Answers should have included<br />
a comment on first-pass effect, the significance of the difference in protein binding and the<br />
details of metabolism, particularly paracetamol. Metabolism limited to &quot;hepatic metabolism and<br />
renal excretion” gained no marks as better responses were more detailed and clearer about the<br />
differences between the two drugs. Knowledge of metabolism at therapeutic doses and the<br />
effect of overdose were expected. Better answers included potential interactions with other<br />
drugs (e.g. warfarin) and contraindications to the use of these drugs.
</blockquote>
 
 
<span id="online-resources-for-this-question-180"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-1 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b01/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-2-01.pdf CICM Wrecks]
* [https://partone.litfl.com/paracetamol.html Part One - Paracetamol] and [https://partone.litfl.com/cox_inhibitors.html Part One - Ibuprofen]
 
 
 
<span id="similar-questions-181"></span>
==== Similar questions ====
 
* ? None
 
 
 
 
 
<span id="question-2-10"></span>
=== Question 2 ===
 
 
 
<span id="question-182"></span>
==== Question ====
 
Outline the daily nutritional requirements, including electrolytes, for a normal 70 kg adult.
 
 
 
<span id="example-answer-182"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-181"></span>
==== Examiner comments ====
 
<blockquote>21% of candidates passed this question
 
The provision of nutrition is a core skill in ICU. An understanding of its key elements enables prescription and modification. However, most answers lacked detailed information which is available in the standard texts. Better responses outlined the caloric requirements including each major element (water, carbohydrate, fat and protein) along with the caloric values and potential sources. Essential amino acids, fatty acids, fat and water-soluble vitamins were expected. A list of the requirements for major electrolytes and some of the trace elements were expected. Some candidates seemed to confuse calories, kilocalories and kilojoules.
 
Some answers did not provide the nutritional requirements, as asked, but instead discussed the<br />
fate of the nutrients; hence did not score marks. Candidates are reminded to read the question<br />
carefully.
</blockquote>
 
 
<span id="online-resources-for-this-question-181"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-2 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b02/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-2-02.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-182"></span>
==== Similar questions ====
 
* Question 9, 2020 (2nd sitting)
 
 
 
 
 
 
 
<span id="question-3-10"></span>
=== Question 3 ===
 
 
 
<span id="question-183"></span>
==== Question ====
 
Describe the factors that determine the filtered load of a substance at the renal glomerulus.
 
 
 
<span id="example-answer-183"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-182"></span>
==== Examiner comments ====
 
<blockquote>67% of candidates passed this question
 
A good place to start was with the correct equation for a filtered load and a description of the<br />
components. Better answers described the components and how they differ and change over<br />
the glomerulus. Many candidates usefully based answers around the Starling forces.
 
A summary of factors including the role of plasma concentration, protein binding, molecular size<br />
and charge was required to pass. Many answers gave examples for the effects of size and<br />
charge and relate endocrine responses to specific alterations in arteriolar tone and how this<br />
affected filtration. A detailed discussion of cardiovascular and endocrine responses to<br />
hypovolaemia was not required.
 
Some candidates confused clearance with filtered load. Candidates are reminded to write<br />
legibly - especially where subscripts and Greek letters are used. Directional arrows (if used)<br />
should correlate with text.
</blockquote>
 
 
<span id="online-resources-for-this-question-182"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-3 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b03/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-2-03.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-183"></span>
==== Similar questions ====
 
* Question 13, 2009 (1st sitting)
* Question 4, 2016 (1st sitting)
 
 
 
 
 
<span id="question-4-10"></span>
=== Question 4 ===
 
 
 
<span id="question-184"></span>
==== Question ====
 
Describe how interstitial fluid recirculates to the vascular system.
 
 
 
<span id="example-answer-184"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-183"></span>
==== Examiner comments ====
 
<blockquote>10% of candidates passed this question
 
Candidates had a limited understanding of this area of the syllabus. It was expected that answers would describe important concepts including the anatomy of venous structures, valves and lymphatics, permeability and factors which influence permeability. A description of hydrostatic forces, other pressures involved, and the role of osmotic and electric forces were required.
</blockquote>
 
 
<span id="online-resources-for-this-question-183"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-4 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b04-describe-how-interstitial-fluid-recirculates-to-the-vascular-system/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-2-04.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-184"></span>
==== Similar questions ====
 
* ? None
 
 
 
 
 
 
 
<span id="question-5-10"></span>
=== Question 5 ===
 
 
 
<span id="question-185"></span>
==== Question ====
 
Compare and contrast unfractionated heparin with low molecular weight heparin.
 
 
 
<span id="example-answer-185"></span>
==== Example answer ====
 
{|
! Name
! HMWH (heparin)
! LMWH (enoxaparin)
|-
| '''Class'''
| Anticoagulant
| Anticoagulant
|-
| '''Indications'''
| Prophylactic and therapeutic anticoagulation (e.g. AF, DVT, PE, ACS etc)
| Prophylactic and therapeutic anticoagulation (e.g. AF, DVT, PE, ACS etc)
|-
| '''Pharmaceutics'''
| MW = 5,000-25,000 Da Clear solution for injection
| MW = 5,000 Daltons Clear solution for injection
|-
| '''Routes of administration'''
| IV, SC
| SC (main), can also be given IV
|-
| '''Dose'''
| Prophylactic: 5,000 IU BD-TDS Therapeutic: infusion (APTT target)
| Therapeutic: 1mg/kg BD or 1.5mg/kg OD Prophylactic: 20-40mg OD
|-
| pKA
|
|
|-
| '''Pharmacodynamics'''
|
|
|-
| MOA
| Heparin binds to antithrombin 3 &gt; conformational change &gt; increases affinity for inactivating thrombin (factor IIa) and Factor Xa
| Enoxaparin binds to AT-3 &gt; conformational change &gt; increases affinity for inactivating factor Xa (and weakly factor IIa - 4x less activity)
|-
| Effects
| Anticoagulation
| Anticoagulation
|-
| Side effects
| HAEM: increased risk of haemorrhage, bruising, HITTS (higher than LMWH)
| HAEM: increased risk of haemorrhage, bruising, HITTS (lower than HMWH)
|-
| '''Pharmacokinetics'''
|
|
|-
| Onset
| Immediate (IV), 30 mins (SC)
| Peak effect 3-4 hrs post SC injection
|-
| Absorption
| PO bioavailability - 0% <br />
Variable SC absorption - less predictable response
| PO bioavailability - 0% <br />
&gt;90% bioavailability post SC injection
|-
| Distribution
| VOD = 0.1L/kg Lipid solubility: low Protein binding: high Does not cross BBB / placenta
| VOD = 4.3L <br />
Protein binding: does not bind to heparin binding proteins
|-
| Metabolism
| Reticuloendothelial system
| Minimal hepatic metabolism
|-
| Elimination
| Renal elimination (very minimal) - hence preferred in renal failure<br />
T 1/2 = 1 hrs
| Renal elimination of active and inactive metabolites <br />
T 1/2 = 6-12 hours
|-
| '''Special points'''
| Reversal: protamine (1mg = 100IU) - 100% Monitoring: APTT level
| Reversal: protamine (&lt;75% efficacy) Monitoring: Anti-Xa level
|}
 
 
 
<span id="examiner-comments-184"></span>
==== Examiner comments ====
 
<blockquote>68% of candidates passed this question.
 
This question was generally well answered and lent itself well to a tabular format. Expected information included an approximation of the molecular weights / significance of the differences in size and therefore its mechanism of action. Other pertinent areas to mention included pharmacokinetic differences and its use in renal failure, side effect profiles, monitoring, predictability of response and reversibility for the two agents.
</blockquote>
 
 
<span id="online-resources-for-this-question-184"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-5 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b05/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-2-05.pdf CICM Wrecks]
* [https://partone.litfl.com/anticoagulants.html#id Part One, LITFL]
 
 
 
<span id="similar-questions-185"></span>
==== Similar questions ====
 
* Question 20, 2018 (2nd sitting)
* Question 2, 2008 (1st sitting)
* Question 20, 2009 (2nd sitting)
 
 
 
 
 
<span id="question-6-10"></span>
=== Question 6 ===
 
 
 
<span id="question-186"></span>
==== Question ====
 
Describe the effects of Ventilation/Perfusion (V/Q) inequality on the partial pressure of oxygen (PaO2) in arterial blood.
 
 
 
<span id="example-answer-186"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-185"></span>
==== Examiner comments ====
 
<blockquote>48% of candidates passed this question
 
Overall answers lacked sufficient detail on a core area of respiratory physiology. Answers expected included a description of V/Q ratios throughout the lungs and an explanation of how V/Q inequality lowers PaO2.
</blockquote>
 
 
<span id="online-resources-for-this-question-185"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-6 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b06/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2014-2-5-vq-po2-pco2-changes.pdf CICM Wrecks]
* [https://partone.litfl.com/shunt.html Part One, LITFL]
 
 
 
<span id="similar-questions-186"></span>
==== Similar questions ====
 
* Question 6, 2008 (1st sitting)
* Question 5, 2014 (2nd sitting)
 
 
 
 
 
<span id="question-7-10"></span>
=== Question 7 ===
 
 
 
<span id="question-187"></span>
==== Question ====
 
Compare and contrast the sympathetic and parasympathetic nervous systems.
 
 
 
<span id="example-answer-187"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-186"></span>
==== Examiner comments ====
 
<blockquote>75% of candidates passed this question
 
This question was generally well answered A table or diagram lent structure to the answer. More complete answers included details on the function, anatomy, a description of the pre- and post-ganglionic fibres, ganglia, receptors and neurotransmitters involved.
 
Whilst most commented on ‘fight or flight’ for the SNS and ‘rest and digest’ for the PNS, no candidate observed that the SNS is a diffuse physiological accelerator and that the PNS acts as a local brake. No candidate included the fact that the SNS supplies viscera and skin whilst the PNS only supplies the viscera. Many candidates failed to make reference to the fact that the postganglionic SNS receptor is G protein coupled and the PNS postganglionic receptor is Gcoupled on muscarinic receptors but operates an ion channel when nicotinic.
 
Candidates may have scored higher if they had provided a little more detail in their answers.
</blockquote>
 
 
<span id="online-resources-for-this-question-186"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-7 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b07/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-2-07.pdf CICM Wrecks]
* [https://partone.litfl.com/autonomic_nervous_system.html Part One, LITFL]
 
 
 
<span id="similar-questions-187"></span>
==== Similar questions ====
 
* ? None
 
 
 
 
 
<span id="question-8-10"></span>
=== Question 8 ===
 
 
 
<span id="question-188"></span>
==== Question ====
 
Classify calcium channel antagonists and give one example of each class (30% of marks). Describe the pharmacology of Nimodipine including important drug interactions (70% of marks).
 
 
 
<span id="example-answer-188"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-187"></span>
==== Examiner comments ====
 
<blockquote>19% of candidates passed this question
 
The classification was done well. Most candidates demonstrated that they had a structure for a “drug” question, but were often challenged to fill in the detail of that structure and failed to deliver enough content to secure a pass. Many candidates wrote a generic answer for calcium channel blockers instead of the specifics of nimodipine.
 
Frequently the pharmacokinetic data recounted was incorrect. Candidates failed to distinguish between absorption and bioavailability. The difference between oral and intravenous dosing was often omitted. Few answered the section on important drug interactions.
</blockquote>
 
 
<span id="online-resources-for-this-question-187"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-8 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b08-classify-calcium-channel-antagonists-and-give-one-example-of-each-class-30-of-marks-describe-the-pharmacology-of-nimodipine-including-important-drug-interactions-70-of-marks/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2011-2-17-ca-channel.pdf CICM Wrecks]
* [https://partone.litfl.com/calcium_channel_blockers.html Part One, LITFL]
 
 
 
<span id="similar-questions-188"></span>
==== Similar questions ====
 
* Question 17, 2011 (2nd sitting)
* Question 2, 2014 (1st sitting)
 
 
 
 
 
 
 
<span id="question-9-10"></span>
=== Question 9 ===
 
 
 
<span id="question-189"></span>
==== Question ====
 
Briefly outline the formation, absorption, distribution, role and composition of cerebrospinal fluid
 
 
 
<span id="example-answer-189"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-188"></span>
==== Examiner comments ====
 
<blockquote>44% of candidates passed this question
 
The question spelt out very specific areas of CSF physiology to outline and the marks were evenly distributed among these areas. The candidates who did not pass this question usually did not provide enough detailed information. Details of the production and absorption of CSF were commonly lacking. The majority of candidates correctly described the composition of CSF; indicating whether a particular variable was higher or lower than in plasma, scored less marks than more specific information.
</blockquote>
 
 
<span id="online-resources-for-this-question-188"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-9 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b09/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2015-1-16-csf-physiology.pdf CICM Wrecks]
* [https://partone.litfl.com/csf.html Part One, LITFL]
 
 
 
<span id="similar-questions-189"></span>
==== Similar questions ====
 
* Question 22, 2007 (1st sitting)
* Question 6, 2008 (2nd sitting)
* Question 2, 2013 (1st sitting)
* Question 16, 2015 (1st sitting)
* Question 24, 2017 (1st sitting)
* Question 15, 2018 (2nd sitting)
* Question 11, 2019 (1st sitting)
* Question 166, 2020 (1st sitting)
 
 
 
 
 
<span id="question-10-10"></span>
=== Question 10 ===
 
 
 
<span id="question-190"></span>
==== Question ====
 
Compare and contrast two methods of measuring cardiac output.
 
 
 
<span id="example-answer-190"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-189"></span>
==== Examiner comments ====
 
<blockquote>35% of candidates passed this question
 
Good answers began with a definition of cardiac output. For each method, it was expected that<br />
candidates discuss the theoretical basis, equipment, advantages and disadvantages / sources<br />
of error and limitations. Additional marks were awarded when an attempt was made to compare<br />
and contrast the two methods (often helped by the use of a table).
</blockquote>
 
 
<span id="online-resources-for-this-question-189"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-10 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b10/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-2-10.pdf CICM Wrecks]
* [https://partone.litfl.com/cardiac-output.html Part One, LITFL]
 
 
 
<span id="similar-questions-190"></span>
==== Similar questions ====
 
* ? None
 
 
 
 
 
 
 
<span id="question-11-10"></span>
=== Question 11 ===
 
 
 
<span id="question-191"></span>
==== Question ====
 
Describe the pharmacology of propofol
 
 
 
<span id="example-answer-191"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-190"></span>
==== Examiner comments ====
 
<blockquote>76% of candidates passed this question.
 
A structured approach proved a good basis to answer this question. It was expected candidates<br />
would outline the uses such as anaesthesia, more prolonged sedation or possible additional roles in patients with seizures or head injuries. Discussion of the presentation and pharmaceutics, including a comment on antibacterial preservatives or lack thereof was expected. The mechanism of action should have been described. It was expected candidates could provide an indication of the usual dose (and how it differs in the more unwell / elderly patient population). A maximal rate and possible toxicity was expected.
 
A discussion on the pharmacodynamics by major organ systems was expected and credit was given for additional comments about hyperlipidaemia, urine colour changes or metabolic alterations. It was expected that candidates would mention propofol infusion syndrome at some point in their answer with some mention of clinical features or pathophysiology.
 
The important aspects of its pharmacokinetics should have been mentioned (high protein binding, large volume of distribution, termination of effect by redistribution, hepatic metabolism, context sensitive half life). A mention of adverse effects would complete the answer.
</blockquote>
 
 
<span id="online-resources-for-this-question-190"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-11 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b11/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2015-2-14-propofol-pharmacology.pdf CICM Wrecks]
* [https://partone.litfl.com/propofol.html#id Part One, LITFL]
 
 
 
<span id="similar-questions-191"></span>
==== Similar questions ====
 
* Question 14, 2015 (2nd sitting)
* Question 21, 2013 (2nd sitting)
* Question 5, 2012 (2nd sitting)
* Question 10, 2008 (2nd sitting)
 
 
 
 
 
<span id="question-12-10"></span>
=== Question 12 ===
 
 
 
<span id="question-192"></span>
==== Question ====
 
Compare and contrast aspirin and clopidogrel
 
 
 
<span id="example-answer-192"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-191"></span>
==== Examiner comments ====
 
<blockquote>68% of candidates passed this question
 
Both of these commonly used agents are level A in the syllabus and thus a high level of detail was expected. Marks were awarded in the following areas - pharmaceutics, mechanism of action, pharmacokinetics (PK) and side effects. For the PK parameters a general description rather than exact values was sufficient (i.e. ‘high protein binding’ rather than ‘98% protein bound’). It was expected that candidates would mention the fact that clopidogrel is a pro-drug and the factors which influence its conversion to the active form. Additional marks were awarded for well-structured answers which attempted a comparison between the two drugs (helped by the use of a table).
</blockquote>
 
 
<span id="online-resources-for-this-question-191"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-12 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b12-compare-and-contrast-aspirin-and-clopidogrel/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-2-12.pdf CICM Wrecks]
* [https://partone.litfl.com/antiplatelets.html Part One - Clopidogrel] and [https://partone.litfl.com/cox_inhibitors.html Part One - Aspirin]
 
 
 
<span id="similar-questions-192"></span>
==== Similar questions ====
 
* Question 3, 2013 (2nd sitting)
* Question 20, 2015 (2nd sitting)
 
 
 
 
 
<span id="question-13-10"></span>
=== Question 13 ===
 
 
 
<span id="question-193"></span>
==== Question ====
 
Compare and contrast the pharmacology of intravenous fentanyl and morphine
 
 
 
<span id="example-answer-193"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-192"></span>
==== Examiner comments ====
 
<blockquote>68% of candidates passed this question
 
Good candidates produced a well-structured answer and highlighted the differences between the two drugs. It was important to include the dose, potency, time course of effect of both agents, and differences in pharmacokinetic and pharmacodynamic effects. Candidates should have specific knowledge of these important drugs. Many candidates failed to focus the question on intravenous fentanyl and intravenous morphine as asked. No marks were given for information about other routes of administration.
</blockquote>
 
 
<span id="online-resources-for-this-question-192"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-13 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b13-compare-and-contrast-the-pharmacology-of-intravenous-fentanyl-and-morphine/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-2-13.pdf CICM Wrecks]
* [https://partone.litfl.com/opioids.html#id Part One, LITFL]
 
 
 
<span id="similar-questions-193"></span>
==== Similar questions ====
 
* Question 12, 2016 (2nd sitting)
* Question 16, 2011 (1st sitting)
 
 
 
 
 
<span id="question-14-10"></span>
=== Question 14 ===
 
 
 
<span id="question-194"></span>
==== Question ====
 
Explain the mechanisms responsible for the cell resting membrane potential (60% of marks) and describe the Gibbs Donnan effect (40% of marks)
 
 
 
<span id="example-answer-194"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-193"></span>
==== Examiner comments ====
 
<blockquote>35% of candidates passed this question.
 
A good answer included a definition of the resting membrane potential and a clear description of<br />
the factors that determine it. Explanation of these factors should have included a detailed description of the selective permeability of the membrane, electrochemical gradients and active transport mechanisms. Answers should demonstrate awareness of the Nernst equation and the Goldman-Hodgkin-Katz equation. These were often confused, sometimes with the GibbsDonnan effect. Descriptions of the Gibbs-Donnan effect generally lacked detail and understanding. The better answers included a definition and discussed in detail the influence of non-diffusible ions (intracellular proteins) on the distribution of diffusible ions
</blockquote>
 
 
<span id="online-resources-for-this-question-193"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-14 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b14-explain-the-mechanisms-responsible-for-the-cell-resting-membrane-potential-60-of-marks-and-describe-the-gibbs-donnan-effect-40-of-marks/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-2-14.pdf CICM Wrecks]
* [https://partone.litfl.com/transport_across_cell_membranes.html Part One, LITFL]
 
 
 
<span id="similar-questions-194"></span>
==== Similar questions ====
 
* ? none
 
 
 
 
 
<span id="question-15-10"></span>
=== Question 15 ===
 
 
 
<span id="question-195"></span>
==== Question ====
 
List the properties of an ideal inotrope (50% of marks). How does adrenaline compare to these ideal properties (50% of marks)?
 
 
 
<span id="example-answer-195"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-194"></span>
==== Examiner comments ====
 
<blockquote>98% of candidates passed this question
 
Many candidates scored very highly on this core topic. It was expected information be included<br />
on pharmaceutics, cost, availability and compatibilities. Relevant pharmacokinetics (onset/offset, titratability) and pharmacodynamics (including relevant receptors, nuances of haemodynamic effects e.g. effect on diastolic pressure and regional perfusion) should have been detailed. Adverse effects and safety profile (e.g. use in pregnancy, therapeutic index) should also have been included. Good answers were structured and highlighted differences with specific facts and data
</blockquote>
 
 
<span id="online-resources-for-this-question-194"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-15 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b15-list-the-properties-of-an-ideal-inotrope-50-of-marks-how-does-adrenaline-compare-to-these-ideal-properties-50-of-marks/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-2-15.pdf CICM Wrecks]
* [https://partone.litfl.com/adrenergic_drugs.html Part One, LITFL]
 
 
 
<span id="similar-questions-195"></span>
==== Similar questions ====
 
* Question 18, 2012 (2nd sitting)
 
 
 
 
 
<span id="question-16-10"></span>
=== Question 16 ===
 
 
 
<span id="question-196"></span>
==== Question ====
 
Classify and describe adverse drug reactions with examples of each.
 
 
 
<span id="example-answer-196"></span>
==== Example answer ====
 
'''Adverse drug reaction'''
 
* Noxious or unintended effect associated with drug administration at a normal dose
** This is different from an adverse drug event which is the occurrence of any untoward event following administration of a drug (thus all ADRs are ADEs)
* Risk factors: extremes of age, polypharmacy, genetic variability (e.g. CYP enzymes), concurrent illness (renal, liver, cardiac impairment), pregnancy
 
 
 
'''Classification of adverse drug reactions'''
 
{|
! Reaction type
! Mechanism
! Features
! Example/s
! Management
|-
| Type A<br />
'Augmented'
| Related to the pharmacological action of the drug (dose related)
| - Common<br />
- Predictable<br />
- Low mortality
| - Bleeding related to administration of anticoagulants (e.g. heparin)
| Reduce or withhold
|-
| Type B<br />
'Bizarre'
| Non-dose related (any exposure &gt; reaction)
| - Rare<br />
- Unpredictable<br />
- Not related to action of drug<br />
- High mortality
| Anaphylaxis to penicillin's
| Withhold and avoid future use
|-
| Type C<br />
'Chronic'
| Due to the cumulative dose received (dose and time related)
| - Uncommon
| Adrenal suppression with prolonged course of corticosteroids.
| Reduce or withhold (may need to happen over time)
|-
| Type D<br />
'Delayed'
| Does not appear for a prolonged period after exposure (time related)
| - Uncommon <br />
- Usually also dose related
| Tardive dyskinesia from long term use of typical antipsychotics
| Can be intractable
|-
| Type E<br />
'End of treatment'
| Withdrawal reactions from drug cessation
| - Uncommon<br />
- Fast onset
| Seizures from abrupt withdrawal of benzodiazepines or alcohol
| Reintroduce + withdraw slowly
|-
| Type F<br />
'Failure'
| Unexpected failure or decrease in efficacy
| - Common<br />
- Dose related
| Ineffectiveness of clopidogrel (non metabolisers)
| Increase dosage / alternative therapy
|}
 
 
 
<span id="examiner-comments-195"></span>
==== Examiner comments ====
 
<blockquote>44% of candidates passed this question.<br />
Candidates should have provided a definition of adverse drug reactions and then a classification. There are at least two widely accepted systems for classification, either was acceptable; though candidates often switched between both which led to a less structured answer. The WHO classification is comprehensive and logical, though both Rang and Dale and Goodman and Gilman also have sections on this topic. Common errors were the citing of examples with the incorrect mechanism, describing only drug interactions rather than all adverse reactions and focussing the answer on the 4 hypersensitivity reactions which could only score a low mark. Some candidates confused drug errors with adverse reactions
</blockquote>
 
 
<span id="online-resources-for-this-question-195"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-16 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b16-classify-and-describe-adverse-drug-reactions-with-examples-of-each/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2012-1-14-advers-drug-reaction.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-196"></span>
==== Similar questions ====
 
* Question 14, 2012 (2nd sitting)
 
 
 
 
 
<span id="question-17-10"></span>
=== Question 17 ===
 
 
 
<span id="question-197"></span>
==== Question ====
 
Define and explain damping, resonance, critical damping and optimum damping.
 
 
 
<span id="example-answer-197"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-196"></span>
==== Examiner comments ====
 
<blockquote>25% of candidates passed this question
 
Concise definitions were required with a clear explanation of the underlying physical principles.<br />
The response time of the system, degree of overshoot, effect on amplitude, noise and ability to<br />
faithfully reproduce frequencies relative to the natural resonant frequency were important considerations.<br />
Many candidates interpreted the question as relating to arterial lines and a detailed discussion<br />
of the components and characteristics of an intra-arterial catheter and transducer system did not<br />
attract marks.
</blockquote>
 
 
<span id="online-resources-for-this-question-196"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-17 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b17/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2015-1-12-resonance-and-damping.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-197"></span>
==== Similar questions ====
 
* Question 12, 2020 (1st sitting)
* Question 24, 2012 (2st sitting)
* Question 12, 2015 (1st sitting)
 
 
 
 
 
<span id="question-18-10"></span>
=== Question 18 ===
 
 
 
<span id="question-198"></span>
==== Question ====
 
Draw and numerically label, on a spirogram, the lung volumes and capacities of a 30 kg child.
 
 
 
<span id="example-answer-198"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-197"></span>
==== Examiner comments ====
 
<blockquote>87% of candidates passed this question.
 
This core respiratory physiology topic was well answered by most candidates. Candidates generally were able to draw a spirogram. A common omission was inspiratory capacity.
</blockquote>
 
 
<span id="online-resources-for-this-question-197"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-18 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b18/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-2-18.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-198"></span>
==== Similar questions ====
 
* ? none
 
 
 
 
 
<span id="question-19-10"></span>
=== Question 19 ===
 
 
 
<span id="question-199"></span>
==== Question ====
 
Describe the physiology of a vasovagal syncope
 
 
 
<span id="example-answer-199"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-198"></span>
==== Examiner comments ====
 
<blockquote>41% of candidates passed this question
 
Generally, there was a lack of knowledge about this topic with many candidates confusing vasovagal syncope with a Valsalva or orthostatic hypotension. A “vasovagal” is from excessive autonomic reflex activity in contrast to orthostatic hypotension which is a failure of the autonomic reflex response.<br />
A good place to start was with a description of vasovagal syncope, also known as neurocardiogenic syncope. It is benign, self-limiting and caused by an abnormal or exaggerated autonomic response to various stimuli (which should have been listed). The mechanism should have been described including the various receptors involved
</blockquote>
 
 
<span id="online-resources-for-this-question-198"></span>
==== Online resources for this question ====
 
<ul>
<li><p>[https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-19 Deranged Physiology]</p></li>
<li><p>[https://jennysjamjar.com.au/year/17b/17b19-describe-the-physiology-of-a-vasovagal-syncope/ Jenny's Jam Jar]</p></li>
<li><p>[https://cicmwrecks.files.wordpress.com/2019/04/2017-2-19.pdf CICM Wrecks]</p>
<p></p></li></ul>
 
<span id="similar-questions-199"></span>
==== Similar questions ====
 
* ? None
 
 
 
 
 
<span id="question-20-10"></span>
=== Question 20 ===
 
 
 
<span id="question-200"></span>
==== Question ====
 
Outline the functions of the liver
 
 
 
<span id="example-answer-200"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-199"></span>
==== Examiner comments ====
 
<blockquote>86% of candidates passed this question
 
This is a very straightforward question testing breadth of knowledge rather than depth. It was<br />
well answered by the majority of candidates.
</blockquote>
 
 
<span id="online-resources-for-this-question-199"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-20 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b20/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-2-20.pdf CICM Wrecks]
* [https://partone.litfl.com/functions_of_the_liver.html#id Part One, LITFL]
 
 
 
<span id="similar-questions-200"></span>
==== Similar questions ====
 
<ul>
<li><p>Question 22, 2017 (1st sitting)</p></li>
<li><p>Question 4, 2013 (2nd sitting)</p></li>
<li><p>Question 12, 2011 (2nd sitting)</p>
<p></p></li></ul>
 
 
 
<span id="question-21"></span>
=== Question 21 ===
 
 
 
<span id="question-201"></span>
==== Question ====
 
Describe and compare the action potentials from cardiac ventricular muscle and the sinoatrial node.
 
 
 
<span id="example-answer-201"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-200"></span>
==== Examiner comments ====
 
<blockquote>95% of candidates passed this question
 
This topic was well understood and answered by most candidates. Some candidates had a good knowledge base but missed out on potential marks by failing to compare and contrast. A diagram outlining the various phases was a useful way to approach the question.
</blockquote>
 
 
<span id="online-resources-for-this-question-200"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-21 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b21/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2013-1-19-ap-generation-and-conduction-prevention-of-arrhythmia.pdf CICM Wrecks]
* [https://partone.litfl.com/exams/2020A/2020A10.html Part One, LITFL]
 
 
 
<span id="similar-questions-201"></span>
==== Similar questions ====
 
* Question 1, 2020 (2nd sitting)
* Question 23, 2010 (2nd sitting)
* Question 19, 2013 (1st sitting)
* Question 11, 2016 (2nd sitting)
 
 
 
 
 
<span id="question-22"></span>
=== Question 22 ===
 
 
 
<span id="question-202"></span>
==== Question ====
 
Define bioavailability. Outline the factors which affect it.
 
 
 
<span id="example-answer-202"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-201"></span>
==== Examiner comments ====
 
<blockquote>33% of candidates passed this question
 
Many candidates did not specify that bioavailability describes the proportion/fraction of drug<br />
reaching the systemic circulation (to differentiate from the portal circulation). Some candidates considered only factors impacting absorption from the GI tract or stated that bioavailability related only to orally administered drugs. Candidates failed to provide an equation, or got equations or graphs wrong. Nearly all candidates failed to provide a comprehensive list of factors affecting bioavailability.
</blockquote>
 
 
<span id="online-resources-for-this-question-201"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-22 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b22-define-bioavailability-outline-the-factors-which-affect-it/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2020/08/2017-2-22.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-202"></span>
==== Similar questions ====
 
* Question 15, 2020 (1st sitting)
 
 
 
 
 
<span id="question-23"></span>
=== Question 23 ===
 
 
 
<span id="question-203"></span>
==== Question ====
 
Outline the anatomy of the internal jugular vein relevant to central venous line cannulation (80% of marks). Include important anatomical variations (20% of marks).
 
 
 
<span id="example-answer-203"></span>
==== Example answer ====
 
 
 
Internal jugular vein
 
* Originates at the jugular bulb (confluence of the inferior petrosal and sigmoid sinus')
* Exits skull via the jugular foramen with CN IX, X, XI
* Descends inferolaterally in the carotid sheath (initially posterior &gt; lateral to carotid artery with descent)
* Terminates behind the sternal end of the clavicle where it joins with the subclavian vein to form the brachiocephalic vein
* Tributaries: facial, thyroid, pharyngeal, lingual veins
* Usually larger on the right
 
 
 
Relations
 
* Anterior to IJV: SCM, lymph nodes, CN XI
* Posterior to IJV: scalene muscles, lung pleura, lateral mass C1, vagus (poster-medial)
* Inferior/at termination: pleura (which extends ~2cm above clavicle)
* Medial: vagus, carotid artery
 
 
 
Variations
 
* Stenosis, complete occlusion, aneurysms, absence
* Variation in relation to carotid (e.g. anterior) in up to 1/4 cases
 
 
 
Ultrasound anatomy
 
* Often lateral to carotid (not always) and often larger than carotid
* Unlike carotid: Non pulsatile, thin walled, compressible
* Doppler flows can also be helpful.
 
 
 
Surface anatomy
 
* Identify triangle between the clavicle and two heads of SCM
* Palpate carotid
* Puncture lateral to carotid artery at 30 degree angle
* Aim caudally towards ipsilateral nipple
 
 
 
<span id="examiner-comments-202"></span>
==== Examiner comments ====
 
<blockquote>14% of candidates passed this question.
 
Good answers were structured including origin, termination, tributaries, relationships, surface<br />
anatomy and common variations.<br />
Factual inaccuracies were common and there was confusion about the relations of the internal<br />
jugular vein. Many candidates did not mention the changing relationship between the internal<br />
jugular and the carotid artery as they travel through the neck or the changes that result from<br />
repositioning for insertion. Many candidates also forgot to mention surface anatomy and a<br />
number talked about ultrasound and views used for insertion of central lines. Common<br />
omissions included the origin, tributaries, relationship with the correct cranial nerves and the fact<br />
that it is usually larger on the right. Almost nobody mentioned the relationship to the pleura.
</blockquote>
 
 
<span id="online-resources-for-this-question-202"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-23 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b23/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-2-23.pdf CICM Wrecks]
* [https://partone.litfl.com/internal_jugular_vein.html Part One, LITFL]
 
 
 
<span id="similar-questions-203"></span>
==== Similar questions ====
 
* Question 8, 2021 (2nd sitting)
* Question 18, 2014 (1st sitting)
 
 
 
 
 
<span id="question-24"></span>
=== Question 24 ===
 
 
 
<span id="question-204"></span>
==== Question ====
 
What is functional residual capacity (30% of marks)? Describe two methods of measuring functional residual capacity (70% of marks).
 
 
 
<span id="example-answer-204"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-203"></span>
==== Examiner comments ====
 
<blockquote>59% of candidates passed this question
 
Most candidates could state 2 methods of measuring FRC. Some candidates (especially for<br />
nitrogen wash out) failed to provide enough information e.g. statements such as &quot;if the amount<br />
of nitrogen is measured then FRC can be derived&quot; were insufficient to score many marks.
</blockquote>
 
 
<span id="online-resources-for-this-question-203"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-2-saqs/question-24 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17b/17b24/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2015-2-4-functional-residual-capacity.pdf CICM Wrecks]
* [https://partone.litfl.com/volumes_and_capacities.html Part One, LITFL]
 
 
 
<span id="similar-questions-204"></span>
==== Similar questions ====
 
* Question 2, 2020 (2nd sitting)
* Question 15, 2010 (2nd sitting)
* Question 4, 2015 (2nd sitting)
* Question 8, 2017 (1st sitting)
* Question 24, 2017 (2nd sitting)
 
 
 
 
 
<span id="2017-1st-sitting"></span>
== 2017 (1st sitting) ==
 
 
 
<span id="question-1-11"></span>
=== Question 1 ===
 
 
 
<span id="question-205"></span>
==== Question ====
 
Outline the anatomy and physiology of the parasympathetic nervous system.
 
 
 
<span id="example-answer-205"></span>
==== Example answer ====
 
 
 
PSNS
 
* Division of the autonomic nervous system
* Important for physiological regulation of our organ systems
* Broadly speaking, there are pre + post ganglionic neurons
** Preganglionic neurons
*** CN 3,7,9,10, as well as S2-4 (craniosacral outflow)
*** Long and synapse close to the effector organ
*** Neurotransmitter is ACh &gt; nicotinic receptor
** Postganglionic neurons
*** Short
*** Neurotransmitter is ACh &gt; muscarinic receptor
 
 
 
Anatomy + effects (based on &quot;target&quot; organ system)
 
{|
! Target Organ
! Pre- Ganglionic fibre origin
! Pre- Ganglionic nerve
! Ganglion
! Post- Ganglionic Receptor
! Effect
|-
| Heart
| Vagal nucleus in Medulla
| CN X
| Cardiac plexus ganglia
| M2
| Decreased inotropy and chronotropy
|-
| Lung
| Vagal nucleus in Medulla
| CN X
| Pulmonary plexus ganglia
| M3
| Bronchoconstriction
|-
| Pupils
| Oculomotor nucleus
| CN III
| Ciliary ganglion
| M3
| Constriction
|-
| Salivary glands
| Superior and inferior salivary nuclei
| CN VII (mandibular, maxillary)<br />
CN IX (parotid)
| -Submaxillary ganglion<br />
- Otic ganglion
| M3
| Salivation
|-
| GIT
| Vagal nucleus<br />
Spinal cord
| CN X<br />
S2,3,4 nerves
| Gastric and hypogastric plexus
| M3
| Increased peristalsis
|-
| Bladder, Penis
| Spinal cord
| S2,3,4 nerves
| Hypogastric plexus
| M3
| Contraction of bladder, erection
|-
| Adrenal gland
| -
| -
| -
| -
| No effect
|-
| Arterioles
| -
| -
| -
| -
| No effect
|-
| Sweat gland
| -
| -
| -
| -
| No effect
|}
 
 
 
<span id="examiner-comments-204"></span>
==== Examiner comments ====
 
<blockquote>32% of candidates passed this question
 
An efficient way to answer this question was to describe the anatomy and physiology of both cranial and sacral sections together. High scoring answers included an outline of the relevant nerves, the various ganglia, neurotransmitters and physiological effects. Some candidates described the cellular basis of Nicotinic, Muscarinic and M1-M5 receptors which didn't attract marks.
</blockquote>
 
 
<span id="online-resources-for-this-question-204"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-1 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a01/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-1-01.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-205"></span>
==== Similar questions ====
 
* Question 4, 2014 (2nd sitting)
* Question 7, 2017 (2nd sitting)
 
 
 
 
 
<span id="question-2-11"></span>
=== Question 2 ===
 
 
 
<span id="question-206"></span>
==== Question ====
 
Outline the components of dietary fat (20% of marks). Describe their possible metabolic fates (80% of marks).
 
 
 
<span id="example-answer-206"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-205"></span>
==== Examiner comments ====
 
<blockquote>21% of candidates passed this question
 
Almost all candidates interpreted &quot;metabolic fate&quot; to mean absorption, digestion and transport of <br />
fat. Hence a lot of time was spent on this and little on the fate of fat once it enters the blood stream. The processes of neither beta oxidation, nor lipogenesis were not well understood. Ketone body production was better understood.
</blockquote>
 
 
<span id="online-resources-for-this-question-205"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-2 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a02/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-1-02.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-206"></span>
==== Similar questions ====
 
* Question 9, 2014 (2nd sitting)
 
 
 
 
 
<span id="question-3-11"></span>
=== Question 3 ===
 
 
 
<span id="question-207"></span>
==== Question ====
 
Classify and describe the mechanisms of drug interactions with examples
 
 
 
<span id="example-answer-207"></span>
==== Example answer ====
 
 
 
{|
! Classification of drug-drug interactions
! Example
|-
| '''BEHAVIOURAL'''
|
|-
| - One drug alters behaviour of patient for another
| - A depressed patient taking an antidepressant may be more compliant with other medications for unrelated conditions
|-
| '''PHARMACEUTIC'''
|
|-
| - Formulation of one drug is altered by another before administration
| - Precipitation of thiopentone (basic) and vecuronium (acidic) in a giving set
|-
| '''PHARMACOKINETIC'''
|
|-
| Absorption
| Bioavailability of bisphosphonates is reduced when co-administered with calcium as the drugs interact to form insoluble complexes
|-
| Distribution
| Valproate and phenytoin compete for the same transport protein binding sites &gt; decreased protein binding phenytoin &gt; increased effect
|-
| Metabolism
| Macrolides reduce metabolism of warfarin by outcompeting it for similar metabolic pathways (CYP450 enzymes) &gt; increased duration of effect
|-
| Elimination
| Probenecid decreases the active secretion of B-lactams and cephalosporins in renal tubular cells by competing for transport mechanisms &gt; decreased elimination of B-lactams / cephalosporins
|-
| '''PHARMACODYNAMIC'''
|
|-
| Homodynamic effects
| Drugs bind to the same receptor site (e.g. naloxone reverses the effects of opioids by outcompeting for the opioid receptor sites)
|-
| Allosteric modulation
| Drugs bind to the same receptor (GABA) but at different sites (e.g. barbiturates and benzodiazepines) &gt; increased effect
|-
| Heterodynamic modulation
| drugs bind to different receptors but affect the same second messenger system (e.g. glucagon reverses the effects of B-blockers by activating cAMP)
|-
| Drugs with opposing physiological actions (but different biological mechanisms)
| e.g. GTN vasodilates via guanyl cyclase-cGMP mediated vasodilation, while noradrenaline vasoconstricts via <math display="inline">\alpha</math> agonism
|}
 
 
 
<span id="examiner-comments-206"></span>
==== Examiner comments ====
 
<blockquote>44% of candidates passed this question
 
Candidates with a well organised answer scored highly. A list of drug interactions was not sufficient to pass, as the question asked to 'describe' the mechanism of drug interactions. Some candidates described the interaction but did not give examples. Common mistakes included using incorrect examples for a particular mechanism and describing the mechanism of action of drugs instead of drug interactions
</blockquote>
 
 
<span id="online-resources-for-this-question-206"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-3 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a03-classify-and-describe-the-mechanisms-of-drug-interactions-with-examples/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2015-1-9-mechanisms-of-drug-interactions.pdf CICM Wrecks]
* [https://www.nps.org.au/australian-prescriber/articles/drug-interactions-principles-and-practice NPS]
 
 
 
<span id="similar-questions-207"></span>
==== Similar questions ====
 
* Question 15, 2021 (2nd sitting)
* Question 9, 2015 (1st sitting)
 
 
 
 
 
<span id="question-4-11"></span>
=== Question 4 ===
 
 
 
<span id="question-208"></span>
==== Question ====
 
Describe the endocrine functions of the kidney.
 
 
 
<span id="example-answer-208"></span>
==== Example answer ====
 
 
 
The kidneys are involved in hormone production, modification and clearance
 
 
 
Production
 
* Erythropoietin (EPO)
** Production:
*** 90% produced in kidneys (~10% in liver) from fibroblast like interstitial cells
** Function:
*** Stimulates the development of proerythroblasts from haematopoietic stem cells in the bone marrow and increases the speed of their maturation
** Regulation:
*** Released in response to hypoxia, low HCT and hypotension.
*** Decreased in renal failure, increased HCT, inflammation
* Renin
** Production:
*** Produced, stored, secreted from JG cells in kidney
** Function:
*** Activation of the renin-angiotensin-aldosterone system leading to increased sodium and water reabsorption, increased vasoconstriction and blood pressure
** Regulation:
*** Stimulated by reduced GFR, direct B1 SNS activation, decreased Na/Cl delivery to JGA
*** Inhibited by negative feedback
* Thrombopoietin
** Production
*** Predominately liver, small amount in kidneys (PCT)
** Function
*** Stimulate megakaryocytes to produce platelets
** Regulation
*** Stimulated by thrombocytopaenia and inflammatory cytokines
*** Inhibited by negative feedback loop
* Urodilatin
** A natriuretic peptide secreted by DCT in response to increased Na delivery
 
 
 
Modification
 
* Vitamin D
** 25-hydroxy vitamin D3 converted into calcitriol in the PCT
** Leads to increased Ca absorption from GIT, increased liberation of Ca from bone, increased reabsorption of Ca from DCT in kidney
** Stimulated by hypocalcaemia, low vitamin D, high parathyroid hormone levels
** Inhibited by low PTH, hypercalcaemia, high calcitriol
 
 
 
Clearance
 
* Gastrin
** 90% cleared in the kidney in the PCT
* Insulin
** 30% cleared by the kidney in the PCT
 
 
 
<span id="examiner-comments-207"></span>
==== Examiner comments ====
 
<blockquote>39% of candidates passed this question
 
It was expected that candidates would discuss the major hormones produced (or activated) by the kidney. These included erythropoeitin, renin and calcitriol. Good answers included the following: the area where the hormone is produced or modified; stimuli for release; factors which inhibit release; and the subsequent actions / effects. Marks were not awarded for hormones that act on the kidney
</blockquote>
 
 
<span id="online-resources-for-this-question-207"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-4 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a04/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-1-04.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-208"></span>
==== Similar questions ====
 
* ? None
 
 
 
 
 
<span id="question-5-11"></span>
=== Question 5 ===
 
 
 
<span id="question-209"></span>
==== Question ====
 
Describe the regulation of plasma calcium concentration.
 
 
 
<span id="example-answer-209"></span>
==== Example answer ====
 
 
 
Calcium distribution
 
* Total body calcium ~400mmol/kg
* Over 99% is locked up in bone/teeth (hydroxyapatite, phosphates etc) and not readily redistributable
* Less than 1% of body calcium is located in the ECF (~2.4mmol/L)
** Approximately 45% is unbound (ionised calcium ~1.1mmol/L) and therefore in active form
* There is almost no calcium in the intracellular fluid
 
 
 
Calcium homeostatis
 
* Maintained as a balance between
** Intake:
*** Dietary intake
*** GIT absorption (passive during normocalcaemia, active during hypocalcaemia)
** Exchange:
*** With bone (balance between osteoclast and osteoblast activity)
** Loss:
*** Faecal (80% of daily losses), renal (20%)
* Principally regulated by three hormones
 
 
 
Calcium regulation
 
{|
!
! Parathyroid hormone
! Calcitriol (active VitD)
! Calcitonin
|-
| '''Production'''
| - Secreted by parathyroid gland
| - Metabolic product of vitamin D
| - Secreted from parafollicular cells (thyroid)
|-
| '''Stimulating factors'''
| - Hypocalcaemia<br />
- Hypophosphatemia
| - Hypocalcaemia<br />
- Hypophosphatemia<br />
- PTH
| - Hypercalcaemia<br />
- Gastrin
|-
| '''Inhibitory factors'''
| - Calcitriol<br />
- Hypermagnesemia<br />
- Hypercalca
| - Hypercalcaemia<br />
- Dec. sun exposure<br />
- Dec. renal function
| - Hypocalcaemia<br />
- Somatostatin
|-
| '''Effect on Calcium'''
| Increases calcium
| Increases calcium
| Decreases calcium
|-
| '''Mechanism of effect on Ca'''
| - Increased renal reabsorption (DCT)<br />
- Increased osteoclast activity<br />
- Increased production of calcitriol
| - Increased GIT absorption (ileum)<br />
- Increased renal reabsorption (DCT)<br />
- Increased osteoclast activity
| - Decreased renal reabsorption (DCT)<br />
- Inhibition of osteoclast activity
|}
 
 
 
<span id="examiner-comments-208"></span>
==== Examiner comments ====
 
<blockquote>51% of candidates passed this question
 
High scoring answers discussed the three major hormones involved in calcium regulation - parathyroid hormone, vitamin D and calcitonin. For each of these it was expected that candidates include: site of production, stimulus for release, inhibitory factors and actions. In the case of renin it was expected that candidates also include the actions of angiotensin and aldosterone. Very few answers discussed inhibitory factors or negative feedback loops.
</blockquote>
 
 
<span id="online-resources-for-this-question-208"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-5 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a05-describe-the-regulation-of-plasma-calcium-concentration/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2008-1-7-calcium-and-bisphosphonates.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-209"></span>
==== Similar questions ====
 
* Question 1, 2016 (2nd sitting)
* Question 7, 2008 (1st sitting)
 
 
 
 
 
<span id="question-6-11"></span>
=== Question 6 ===
 
 
 
<span id="question-210"></span>
==== Question ====
 
Explain the meaning of the components of a Forest plot.
 
 
 
<span id="example-answer-210"></span>
==== Example answer ====
 
Removed from primary syllabus
 
 
 
<span id="examiner-comments-209"></span>
==== Examiner comments ====
 
<blockquote>65% of candidates passed this question
 
To score full marks candidates needed to describe each feature of the forest plot provided. This included: odds ratio on the x axis; line of no effect; individual studies on the y axis; point estimate for each study (box position); weighting of the study (box size); pooled effect estimate (diamond position); size of the diamond; and the 95% confidence intervals and their interpretation.
</blockquote>
 
 
<span id="online-resources-for-this-question-209"></span>
==== Online resources for this question ====
 
* Removed from primary syllabus
 
 
 
<span id="similar-questions-210"></span>
==== Similar questions ====
 
* Removed from primary syllabus
 
 
 
 
 
 
 
<span id="question-7-11"></span>
=== Question 7 ===
 
 
 
<span id="question-211"></span>
==== Question ====
 
Compare and contrast the systemic circulation with the pulmonary circulation
 
 
 
<span id="example-answer-211"></span>
==== Example answer ====
 
{|
! Category
! Pulmonary circulation
! Systemic circulation
|-
| Anatomical features
| Thin vessel, minimal smooth muscle, elastic
| Thick vessel, abundant smooth muscle
|-
| Blood volume
| ~500mls (70kg adult) or 10% total volume
| ~4.5L (70kg adult) or 90% volume
|-
| Blood flow
| = cardiac output (~5L/min)
| = cardiac output (~5L/min)
|-
| Blood pressure
| PAP normally ~25/8mmhg (mPAP ~10-15mmHg)
| BP normally ~120/80mmHg (MAP ~90mmHg)
|-
| Circulatory resistance
| PVR ~ 100 dynes.sec.cm-5 ~10% of SVR
| SVR approx 1000 dynes.sec.cm-5
|-
| Circulatory regulation
| Minimal capacity to self regulate (except hypoxic pulmonary vasoconstriction)
| Regional blood flow readily regulated at the level of arterioles
|-
| Regional distribution of blood flow
| Flow affected by gravity, alveolar recruitment, hypoxic vasoconstriction
| Significant organ dependant variation in flow (often demand dependant) with minimal affect from gravity. Organs have capacity to autoregulate flow.
|-
| Response to hypoxia
| Vasoconstriction
| Vasodilation
|-
| Response to hypercapnia
| Vasoconstriction
| Vasodilation
|-
| Gas exchange function
| Absorbs O2, releases CO2
| Absorbs CO2, releases O2
|-
| Metabolic function
| Metabolism of PGs and substrates for ACE
| Delivers metabolic substrates, removes metabolic waste
|-
| Synthetic function
| Source of thromboplastin and heparin
| Source of nitric oxide and anticoagulants/procoagulants
|-
| Filter function
| Filters emboli &gt;8um
| Filters arterial blood in renal and hepatic vascular beds
|}
 
 
 
<span id="examiner-comments-210"></span>
==== Examiner comments ====
 
<blockquote>26% of candidates passed this question
 
This question encompasses a wide area of cardiovascular physiology. As a compare and contrast question this question was well answered by candidates who used a table with relevant headings. Comprehensive answers included: anatomy, blood volume, blood flow, blood pressure, circulatory resistance, circulatory regulation, regional distribution of blood flow, response to hypoxia, gas exchange function, metabolic and synthetic functions, role in acid base homeostasis and filter and reservoir functions. A frequent cause for missing marks was writing about each circulation separately but comparing. For example: many candidates stated 'hypoxic pulmonary vasoconstriction', but did not contrast this to 'hypoxic vasodilation' for the systemic circulation. Frequently functions of the circulations were limited to gas transport / exchange.
</blockquote>
 
 
<span id="online-resources-for-this-question-210"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-7 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a07/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-1-07.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-211"></span>
==== Similar questions ====
 
* ? None comparing
 
 
 
 
 
<span id="question-8-11"></span>
=== Question 8 ===
 
 
 
<span id="question-212"></span>
==== Question ====
 
Describe the physiological consequences of decreasing the functional residual capacity (FRC) in an adult by 1 litre.
 
 
 
<span id="example-answer-212"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-211"></span>
==== Examiner comments ====
 
<blockquote>70% of candidates passed this question
 
High scoring answers began with a definition and normal values, followed by a detailed list of the consequences of decreasing the FRC. Some candidates included descriptions of the normal function of FRC, conditions that decrease FRC and ways of improving reduced FRC. These were not required and did not attract marks. Diagrams require correctly labelled axes, values &amp; units.
</blockquote>
 
 
<span id="online-resources-for-this-question-211"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-8 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a08/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2010-2-15.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-212"></span>
==== Similar questions ====
 
* Question 15, 2010 (2nd sitting)
 
 
 
 
 
<span id="question-9-11"></span>
=== Question 9 ===
 
 
 
<span id="question-213"></span>
==== Question ====
 
Outline how the following tests assess coagulation:
 
a. Prothombin Time (PT)
 
b. Activated Partial hromboplastin Time (APTT)
 
c. Activated Clotting Time (ACT)
 
d. Thromboelastography (TEG or ROTEM)
 
 
 
<span id="example-answer-213"></span>
==== Example answer ====
 
{|
! test
! PT
! APTT
! ACT
! TEG/ROTEM
|-
| Pathway
| Extrinsic + common
| Intrinsic + common
| Intrinsic + common
| Clot formation to lysis
|-
| Use
| Warfarin monitoring<br />
Screening for coagulopathy
| Heparin monitoring<br />
Screening for coagulopathy
| Dosing/reversal of heparin in extracorporeal circuits
| Guide to product replacement
|-
| POC/LAB
| Lab
| Lab
| POC
| POC
|-
| Sample
| Plasma (post centrifuge)
| Plasma (post centrifuge)
| Whole blood
| Whole blood
|-
| Principle
| Tissue factor added to plasma &gt; activates extrinsic pathway &gt; wait until clot formation
| Phospholipid added to plasma (+ activation agent) &gt; stimulates intrinsic pathway &gt; wait until clot formation
| Blood added to kaolin clotting activator &gt; stimulates intrinsic pathway &gt; wait until clot formed
| Blood distributed into cuvettes. Pin immersed in blood and either cuvette (TEG) or pin (ROTEM) spins. As blood clots &gt; resists movement. TEG: toque exerted on the pin. ROTEM: impedance to rotation detected by optical system.
|-
| Normal
| 11-13 seconds <br />
(INR 0.8-1.2)
| 30-40 seconds
| 100-130
| INTEM: similar to APTT<br />
EXTEM: similar to PT<br />
CT = time until 2mm amplitude<br />
A10 = amplitude at 10 mins<br />
MCF = time until maximal clot firmness <br />
ML: maximal lysis
|-
| Prolonged
| Warfarin / vitamin K deficiency / factor II, VII, IX, X deficiency<br />
Liver disease<br />
Consumptive coagulopathy
| Heparin<br />
Factor deficiency (II, IX, X, XI, XII) Liver disease<br />
Consumptive coagulopathy
| Any coagulopathy (non specific) including systemic heparinisation
| Hyperfibrinolysis<br />
Factor deficiency / inhibition<br />
Platelet deficiency / dysfunction<br />
Fibrinogen deficiency
|-
| Errors
| Different thromboplastins in lab give different PT times &gt; INR standardises
| Inadequate mixing of blood<br />
Inadequate blood:citrate ratio
| Underfilling shortens ACT<br />
Overfilling, prolongs ACT
| Calibration of machine
|}
 
 
 
<span id="examiner-comments-212"></span>
==== Examiner comments ====
 
<blockquote>61% of candidates passed this question.
 
Many candidates incorrectly stated that the PT assessed the intrinsic system and that the APTT assessed the extrinsic system. This led to subsequent errors in relating a coagulation test to the appropriate coagulation factors that it assessed. Some candidates produced elaborate diagrams of the coagulation cascade in isolation without relating it to the question.
</blockquote>
 
 
<span id="online-resources-for-this-question-212"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-9 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a09-outline-how-the-following-tests-assess-coagulation/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-1-09.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-213"></span>
==== Similar questions ====
 
* Question 8, 2014 (2nd sitting)
 
 
 
 
 
 
 
<span id="question-10-11"></span>
=== Question 10 ===
 
 
 
<span id="question-214"></span>
==== Question ====
 
Describe the pharmacology of hydrocortisone.
 
 
 
<span id="example-answer-214"></span>
==== Example answer ====
 
{|
! Name
! Hydrocortisone
|-
| '''Class'''
| Glucocorticoid (endogenous)
|-
| '''Indications'''
| Glucocorticoid insufficiency, allergy/anaphylaxis/asthma, severe septic shock, immunosuppression (e.g. transplant, autoimmune dz)
|-
| '''Pharmaceutics'''
| Tablet, white powder diluted in water
|-
| '''Routes of administration'''
| IV, PO
|-
| '''Dose'''
| 50-200mg QID (commonly in ICU population)
|-
| '''Bio-equivalence'''
| 100mg hydrocort = 25mg pred = 20mg methypred = 4mg dex
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Lipid soluble &gt; crosses cell membrane &gt; binds to intracellular steroid receptors &gt; alters gene transcription &gt; metabolic, anti-inflammatory &amp; immunosuppressive effects in tissue-specific manner
|-
| Effects/side effects
| CNS: sleep disturbance, psychosis, mood changes <br />
CVS: Increased BP (mineralocorticoid effect + increased vascular smooth muscle receptor expression to catecholamines) <br />
RESP: decreased airway oedema, increased SM response to catecholamines<br />
RENAL: Na + water retention (mineralocorticoid effect) <br />
Metabolic: Hyperglycaemia, gluconeogenesis, protein catabolism, fat lipolysis and redistribution, adrenal suppression <br />
MSK: Osteoporosis, skin thinning <br />
Immune: immunosuppression + anti-inflammatory effects (decreased phospholipase, interleukins, WBC migration and function) <br />
GIT: Increased risk of peptic ulcers
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| Peak effect 1-2 hours, duration of action 8-12 hours
|-
| Absorption
| 50% oral bioavailability, 100% IV
|-
| Distribution
| 90% protein bound <br />
Small Vd (0.5L/kg)
|-
| Metabolism
| Hepatic &gt; inactive metabolites
|-
| Elimination
| Metabolites excreted renally. <br />
Elimination T/12 = ~1 hour
|-
| '''Special points'''
| Risk of reactivation of latent TB / other infections
|}
 
 
 
<span id="examiner-comments-213"></span>
==== Examiner comments ====
 
<blockquote>54% of candidates passed this question
 
Hydrocortisone is listed as a Class A drug in the syllabus and as such knowledge of its <br />
pharmacokinetics is expected. No marks were awarded for generic pharmacokinetic statements such as: &quot;average bioavailability&quot;, &quot;moderate protein binding&quot;, &quot;bioavailability 100% for IV preparation&quot; etc
</blockquote>
 
 
<span id="online-resources-for-this-question-213"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-10 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a10-describe-the-pharmacology-of-hydrocortisone/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-1-10.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-214"></span>
==== Similar questions ====
 
* Question 3, 2020 (2nd sitting)
 
 
 
 
 
<span id="question-11-11"></span>
=== Question 11 ===
 
 
 
<span id="question-215"></span>
==== Question ====
 
Outline the anatomical relations of the trachea relevant to performing a percutaneous tracheostomy.
 
 
 
<span id="example-answer-215"></span>
==== Example answer ====
 
Structure
 
* Fibromuscular tube ~10cm long, approx 2.5cm wide, ~2cm deep
* Supported by 16-20 incomplete cartilaginous rings which joined by fibroelastic tissue and are connected posteriorly by smooth muscle (the trachealis)
* Divided into cervical and thoracic parts
 
 
 
Course
 
* Trachea begins approximately C6 where it is continuous with the larynx
* Trachea travels inferoposteriorly
* Enters thoracic cavity through the superior thoracic aperture, at the level of the jugular notch
* Ends approximately at level of sternal angle (T4/5) where it divides into left and main bronchi
 
 
 
Relations
 
* Posterior: oesophagus
* Anterior: thyroid gland (isthmus), cervical fascia, manubrium, thymus remnants,
* Right lateral: thyroid gland (lobe), carotid sheath ( common carotid, vagus, IJV)
* Left lateral: thyroid gland (lobe), carotid sheath ( common carotid, vagus, IJV)
 
 
 
Neurovascular supply
 
* SNS: sympathetic trunks
* PSNS: recurrent laryngeal and vagus nerves
* Arterial supply: Branches from inferior thyroid arteries
* Venous drainage: Inferior thyroid veins
 
 
 
Surface anatomy of anterior neck (superior --&gt; inferior)
 
* Hyoid bone (C3)
* Thyroid cartilage
* Cricothyroid membrane
* Cricoid cartilage (C6)
* Thyroid gland
* Sternohyoid muscle just lateral to the midline structures, overlies sternothyroid and thyrohyoid
 
 
 
Layers of dissection in tracheostomy (from anterior --&gt; posterior)
 
* Skin
* Subcutaneous tissue
* Fat
* Pretracheal fascia
* Fibroelastic tissue between tracheal cartilage rings
* Trachea
 
 
 
<span id="examiner-comments-214"></span>
==== Examiner comments ====
 
<blockquote>44% of candidates passed this question
 
Many candidates described how to perform a tracheostomy or the structure of the trachea rather than the relevant anatomical relations. It was expected that answers include anterior, posterior and lateral relations at the correct tracheal level including relevant vascular structures.
</blockquote>
 
 
<span id="online-resources-for-this-question-214"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-11 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a11/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2012-1-10.pdf CICM Wrecks]
* [https://partone.litfl.com/tracheostomy.html Part One, LITFL]
 
 
 
<span id="similar-questions-215"></span>
==== Similar questions ====
 
* Question 1, 2018 (2nd sitting)
 
 
 
 
 
 
 
<span id="question-12-11"></span>
=== Question 12 ===
 
 
 
<span id="question-216"></span>
==== Question ====
 
Describe the pharmacology of oxycodone
 
 
 
<span id="example-answer-216"></span>
==== Example answer ====
 
{|
! Name
! Oxycodone
|-
| '''Class'''
| Semi synthetic opioid
|-
| '''Indications'''
| Analgesia
|-
| '''Pharmaceutics'''
| White tablet (IR, MR), colourless solution (10mg/ml)
|-
| '''Routes of administration'''
| PO/IV
|-
| '''Dose'''
| PO 5-10mg PRN 4hrly, IV 1mg 5 minutes PRN
|-
| '''Morphine equivalence'''
| 1.5 x morphine (10mg oxycodone = 15mg morphine )
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Mu receptor activity, weak Kappa/Delta activity
|-
| Effects
| CNS: Analgesia, sedation, euphoria <br />
CVS: bradycardia/hypotension <br />
RESP: respiratory depression <br />
GIT: decreased peristalsis. N/V. constipation <br />
MSK: pruritis
|-
| Side effects
| Everything listed above that is is not analgesia
|-
| '''Pharmacokinetics'''
|
|-
| Onset / duration
| 15 mins (PO), 4-6 hours (PO)
|-
| Absorption
| 70% oral bioavailability, pKa 8.5
|-
| Distribution
| ~50% protein bound, <br />
VD = 3L/Kg, <br />
crosses placenta and BBB
|-
| Metabolism
| Hepatic metabolism (CYP) to noroxycodone, oxymorphone
|-
| Elimination
| Half-life 2-4hrs, excreted in urine
|-
| '''Reversal'''
| Naloxone (100mcg IV boluses, PRN 3 minutely)
|}
 
 
 
<span id="examiner-comments-215"></span>
==== Examiner comments ====
 
<blockquote>53% of candidates passed this question
 
Few candidates covered the pharmacokinetic aspect of the question sufficiently. <br />
No marks were awarded for generic comments such as hepatic metabolism and renal excretion
</blockquote>
 
 
<span id="online-resources-for-this-question-215"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-12 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a12/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-1-12.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-216"></span>
==== Similar questions ====
 
* Question 12, 2021 (1st sitting)
 
 
 
 
 
 
 
<span id="question-13-11"></span>
=== Question 13 ===
 
 
 
<span id="question-217"></span>
==== Question ====
 
Outline the anatomy relevant to the insertion of a Dorsalis Pedis arterial cannula (50% of marks). Explain the differences between blood pressure measurement at this site compared to measurement at the aortic arch (50% of marks)
 
 
 
<span id="example-answer-217"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-216"></span>
==== Examiner comments ====
 
<blockquote>30% of candidates passed this question
 
The anatomy component of answers frequently lacked required detail. Many candidates listed <br />
the observed differences in the waveforms however an explanation for these differences was <br />
required.
</blockquote>
 
 
<span id="online-resources-for-this-question-216"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-13 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a13/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-1-13.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-217"></span>
==== Similar questions ====
 
* ? None
 
 
 
 
 
<span id="question-14-11"></span>
=== Question 14 ===
 
 
 
<span id="question-218"></span>
==== Question ====
 
Define respiratory compliance (20% of marks). Describe the factors that affect it (80% of marks).
 
 
 
<span id="example-answer-218"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-217"></span>
==== Examiner comments ====
 
<blockquote>54% of candidates passed this question.<br />
This question was generally well answered with good structure.
</blockquote>
 
 
<span id="online-resources-for-this-question-217"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-14 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a14/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2007-2-13-lung-compliance.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-218"></span>
==== Similar questions ====
 
* Question 17, 2019 (2nd sitting)
* Question 15, 2014 (1st sitting)
* Question 7, 2011 (2nd sitting)
* Question 13, 2007 (1st sitting)
 
 
 
 
 
<span id="question-15-11"></span>
=== Question 15 ===
 
 
 
<span id="question-219"></span>
==== Question ====
 
Outline the cardiovascular changes associated with morbid obesity.
 
 
 
<span id="example-answer-219"></span>
==== Example answer ====
 
 
 
Obesity
 
* Multisystem disorder defined by an increased BMI
** Overweight: BMI 25-30
** Obese: BMI &gt;30
** Morbidly obese: BMI &gt;35
 
 
 
Effects of obesity on CVS
 
* Oxygen demand / utilisation
** Increased due to the increased body mass (both adipose and lean body mass)
** Must be met by increased DO2 (in form of increased CO) to prevent ischaemia
* Cardiac output (including HR, SV)
** Increased to meet oxygen demand (~1L for every 12.5 BMI points)
** Predominately due increased stroke volume as HR remains stable/slight increase
* Stroke volume
** Increased
** Due to the increased preload and the frank-starling mechanism (see below)
* Heart rate
** Mostly stable / slight increase
** The required increase in CO predominately comes from the increased stroke volume
* Blood volume
** Increased
** Due to neurohormonal changes associated with obesity
** Adipocytes secrete leptin &gt; increased activation of renin-angiotensin-aldosterone system (RAAS) &gt; increased Na and water reabsorption
* Blood pressure
** Often increased (&gt;60%)
** Due to neurohormonal changes (leptin activation of RAAS) and LV remodelling (see below)
* Preload
** Generally increased
** Due to the increased blood volume which increases mean systemic filling pressure and thus venous return
* Afterload
** May be decreased or increased
* Cardiac remodelling
** LV hypertrophy (from hypertension and increased afterload and leptin)
** Chamber dilation (from chronic volume overload) &gt; increased
** Fatty infiltration &gt; increases risk of arrhythmias
** Fibrosis &gt; leads to diastolic dysfunction
* Pulmonary artery pressures
** Increased
** Due to hypoxic pulmonary vasoconstriction (obesity hypoventilation syndrome) and LV diastolic dysfunction from cardiac remodelling
 
 
 
<span id="examiner-comments-218"></span>
==== Examiner comments ====
 
<blockquote>42% of candidates passed this question
 
Many candidates did not include enough detail in their answers. Higher scoring answers included more depth such as the following: blood volume, left ventricular changes, arterial blood pressure, pulmonary artery pressures, risks of ischaemia, arrhythmias etc.
</blockquote>
 
 
<span id="online-resources-for-this-question-218"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-15 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a15/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-1-15.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-219"></span>
==== Similar questions ====
 
* Question 17, 2008 (2nd sitting)
* Question 8, 2015 (2nd sitting)
 
 
 
 
 
<span id="question-16-11"></span>
=== Question 16 ===
 
 
 
<span id="question-220"></span>
==== Question ====
 
List the potential problems resulting from blood transfusion and methods used to minimise them
 
 
 
<span id="example-answer-220"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-219"></span>
==== Examiner comments ====
 
<blockquote>53% of candidates passed this question
 
This question required a broad answer. It was generally well answered. Those candidates who scored well had a good structure to their answers e.g. grouping potential electrolyte disturbances together, and infectious risks together etc. and including methods used to minimise these risks in appropriate detail.
</blockquote>
 
 
<span id="online-resources-for-this-question-219"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-16 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a16/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-1-16.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-220"></span>
==== Similar questions ====
 
* Question 3, 2020 (1st sitting)
* Question 13, 2013 (2nd sitting)
 
 
 
 
 
<span id="question-17-11"></span>
=== Question 17 ===
 
 
 
<span id="question-221"></span>
==== Question ====
 
Compare and contrast the pharmacology of phenytoin and levetiracetam
 
 
 
<span id="example-answer-221"></span>
==== Example answer ====
 
{|
! Name
! Phenytoin
! Levetiracetam
|-
| '''Class'''
| Anticonvulsant
| Anticonvulsant
|-
| '''Indications'''
| - Seizure prophylaxis<br />
- Epilepsy (simple-complex and focal-generalised)<br />
- Status epilepticus
| - Seizure prophylaxis <br />
- Focal partial seizures (monotherapy) <br />
- Partial/generalised seizures (adjunct) <br />
- Status epilepticus
|-
| '''Pharmaceutics'''
| Capsules, syrup, clear IV solution for injection
| Oral tablet or liquid. Clear solution for injection
|-
| '''Routes of administration'''
| PO, IV, IM
| PO, IV
|-
| '''Dose'''
| 15-20mg/kg load<br />
Target plasma level of 10-20mcg/ml
| Load = 60mg/kg (Status epilepticus) <br />
500-2000mg BD (maintenance)
|-
| '''Pharmacodynamics'''
|
|
|-
| MOA
| Stabilises Na channels in their inactive state, thereby inhibiting the generation of further action potentials. <br />
Also decreases Ca entry &gt; increased GABA activity.
| Exact MOA unclear. May modulate neurotransmission by binding to synaptic vesicle protein 2A
|-
| Effects
| Prevents propagation of seizure activity
| Prevent hypersynchronization of epileptiform burst firing and propagation of seizure activity
|-
| Side effects
| CVS: hypotension, heart block <br />
GIT: Nausea, vomiting <br />
CNS: ataxia, confusion, nystagmus, visual disturbance <br />
Other: acne, hirsutism, blood dyscrasias, gingival hypertophy <br />
Pregnancy = teratogenic <br />
Many drug-drug interactions
| CNS: irritability, agitation, anxiety, drowsiness, dizziness, headache, ataxia <br />
MSK: weakness/fatigue <br />
Other: allergy, angioedema, SJS
|-
| '''Pharmacokinetics'''
|
|
|-
| Onset
| Slow oral absorption (1-3 hours onset)
| &lt; 1 hour (PO)
|-
| Absorption
| PO bioavailability = 90%
| Nearly 100% PO bioavailability
|-
| Distribution
| VOD= 1L/kg <br />
Protein binding &gt;90%
| VOD = 0.5 L / Kg <br />
Protein binding = &lt; 5%
|-
| Metabolism
| - Hepatic hydroxylation by CYP450 system (saturable) <br />
- Wide patient variation (10% population are slow hydroxylators)
| Enzymatic hydrolysis ~30% of dose to inactive metabolites
|-
| Elimination
| Renal elimination of metabolites <br />
T 1/2 = 12 hours
| Renal excretion <br />
- unchanged drug (70%) and metabolites (30%) T 1/2 = 6 hours
|-
| '''Monitoring'''
| Phenytoin level 10-20ug/ml
| Nil
|}
 
 
 
<span id="examiner-comments-220"></span>
==== Examiner comments ====
 
<blockquote>35% of candidates passed this question
 
A table was useful to answer this question. Comparing and contrasting the pharmacology was required to score well rather than listing various aspects of pharmacology. The key properties of the drugs which demonstrate their importance to ICU was required.
</blockquote>
 
 
<span id="online-resources-for-this-question-220"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-17 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17b17-2/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2014-2-2-phenytoin-vs-keppra.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-221"></span>
==== Similar questions ====
 
* Phenytoin alone
** Question 3, 2012 (1st sitting)
** Question 2, 2010 (1st sitting)
* Phenytoin vs Keppra
** Question 2, 2014 (2nd sitting)
** Question 17, 2017 (1st sitting)
* Keppra alone
** Nil
 
 
 
 
 
<span id="question-18-11"></span>
=== Question 18 ===
 
 
 
<span id="question-222"></span>
==== Question ====
 
Outline the functional anatomy of the kidneys (40% of marks). Outline the regulation of renal blood flow (60% of marks).
 
 
 
<span id="example-answer-222"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-221"></span>
==== Examiner comments ====
 
<blockquote>67% of candidates passed this question
 
Candidates who scored well weighted their answers according to the marks allocation outlined in the question and adopted a good structure. A number of candidates confused the roles of tubuloglomerular feedback and the renin angiotensin aldosterone pathway.
</blockquote>
 
 
<span id="online-resources-for-this-question-221"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-18 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a18/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-1-18.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-222"></span>
==== Similar questions ====
 
<ul>
<li><p>Question 4, 2019 (1st sitting)</p></li>
<li><p>Question 21, 2011 (2nd sitting)</p>
<p></p></li></ul>
 
 
 
<span id="question-19-11"></span>
=== Question 19 ===
 
 
 
<span id="question-223"></span>
==== Question ====
 
Define mixed venous PO2 (20% of marks). Outline the factors that affect this value (80% of marks).
 
 
 
<span id="example-answer-223"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-222"></span>
==== Examiner comments ====
 
<blockquote>37% of candidates passed this question
 
This question was in two parts – the first part was worth 20% and candidates were expected to <br />
provide a definition of mixed venous blood as well as the partial pressure of oxygen in mixed <br />
venous blood (including normal range). Good answers also provided the varying PO2 from <br />
different tissue beds that make up mixed venous blood, where the ‘mixing’ occurs (the right <br />
ventricle) and where it is sampled (pulmonary artery).<br />
For the second part of the question, worth 80% of the marks, good answers included the <br />
relationship between mixed venous PO2 and mixed venous O2 content (including the shape and <br />
position of the HbO2 dissociation curve); the variables encompassed in the modified Fick <br />
equation; arterial oxygen content and its determinants; oxygen consumption (VO2); and cardiac <br />
output (CO). Including an outline of how each affects the value of mixed venous PO2.<br />
A number of candidates wrote about mixed venous oxygen saturation. Other common errors <br />
were: missing a number of key factors that affect PO2; and using an incorrect form and/or <br />
content of the modified Fick equation.
</blockquote>
 
 
<span id="online-resources-for-this-question-222"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-19 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a19-define-mixed-venous-po2-20-of-marks-outline-the-factors-that-affect-this-value-80-of-marks/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2008-1-10-briefly-describe-the-factors-that-influence-the-partial-pressure-of-oxygen-in-mixed-venous-blood.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-223"></span>
==== Similar questions ====
 
* Question 10, 2008 (1st sitting)
* Question 8, 2019 (1st sitting)
 
 
 
 
 
<span id="question-20-11"></span>
=== Question 20 ===
 
 
 
<span id="question-224"></span>
==== Question ====
 
Describe the pharmacology of vasopressin (70% of marks) and its analogues (30% of marks).
 
 
 
<span id="example-answer-224"></span>
==== Example answer ====
 
{|
! Name
! Vasopressin (argipressin)
|-
| '''Class'''
| Endogenous nonapeptide
|-
| '''Indications'''
| Hypotension/shock (catecholamine sparing)
|-
| '''Pharmaceutics'''
| Clear colourless solution (20units/ml)
|-
| '''Routes of administration'''
| IV infusion (central vein)
|-
| '''Dose'''
| 2.4 units/hr (for vasopressor support)<br />
- At lower doses has predominant V1 activity, V2 activity at higher doses
|-
| pKA
| 10.3
|-
| '''Pharmacodynamics'''
|
|-
| MOA / effects
| Physiologically secreted by PVN of hypothalamus &gt; stored in posterior pituitary &gt; secreted in response to hypovolaemia + increased osmolality<br />
→ V1 receptor (blood vessels) agonism &gt; Vasoconstriction &gt; increased SVR &gt; increased BP <br />
→ V2 receptor (collecting ducts of nephrons) agonism &gt; increased water reabsorption &gt; increased BP<br />
→ V2 receptor (endothelial cells) agonism &gt; increased vWF release and Factor VIII activity
|-
| Side effects
| CVS: reflex bradycardia, splanchnic vasoconstriction (possible ischaemia) <br />
HAEM: Excessive platelet aggregation / thrombosis <br />
RENAL: Hyponatraemia (increased water reabsorption &gt; Na reabsorption)<br />
GIT: abdominal pain / GIT ischaemia
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| Fast (not as fast as noradrenaline)
|-
| Absorption
| IV only (0% oral bioavailability as inactivated by trypsin)
|-
| Distribution
| No (or very minimal) protein binding <br />
Vd 0.2L/Kg
|-
| Metabolism
| Extensive hepatic and renal metabolism by serine proteases and oxido-reductase enzymes &gt; inactive metabolites
|-
| Elimination
| Renal elimination of changed and unchanged drug <br />
T <sub>1/2</sub> 15 minutes
|}
 
 
 
'''Vasopressin analogues'''
 
* Desmopressin (DDAVP)
** Indications: central diabetes insipidus, vWD, slowing correction of hyponatraemia
** Route: IV, IN, SC, PO, IM
** MOA: predominately V<sub>2</sub> mediated effects (limited V<sub>1</sub> effects) &gt; increased H<sub>2</sub>O reabsorption + increased vWF and Factor VIII activity. Minimal effects on vasoconstriction activity
** Similar PK to argipressin except it is not metabolised, has a longer T <sub>1/2</sub>
* Terlipressin
** Indication: variceal bleeding, hepatorenal syndrome
** Route: IV
** MOA: predominately V<sub>1</sub> mediated effects &gt; splanchnic vasoconstriction &gt; decreased portal venous pressure. Minimal effects of platelet aggregation or fluid absorption
** Similar PK to argipressin except it is not metabolised, has a longer T<sub>1/2</sub>
 
 
 
<span id="examiner-comments-223"></span>
==== Examiner comments ====
 
<blockquote>28% of candidates passed this question
 
A pharmacology answer template outlining pharmacokinetics and dynamics was required. Candidates failed to score marks for describing the physiology of vasopressin secretion. A number of answers demonstrated limited knowledge about its indications for use and its potential adverse effects.
</blockquote>
 
 
<span id="online-resources-for-this-question-223"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-20 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a20-describe-the-pharmacology-of-vasopressin-70-of-marks-and-its-analoyues-30-of-marks/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-1-20.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-224"></span>
==== Similar questions ====
 
* Vasopressin alone
** Question 22, 2013 (1st sitting)
* Norad vs vasopressin
** Question 7, 2007 (1st sitting)
** Question 23, 2011 (1st sitting)
** Question 10, 2020 (1st sitting)
 
 
 
 
 
<span id="question-21-2"></span>
=== Question 21 ===
 
 
 
<span id="question-225"></span>
==== Question ====
 
Explain the potential causes of a difference between the measured end tidal CO2 and the arterial partial pressure of CO2.
 
 
 
<span id="example-answer-225"></span>
==== Example answer ====
 
 
 
ETCO2 - PaCO2 gradient
 
* There is normally a gradient between PaCO2 and ETCO2 of 0-5mmHg (where ETCO2 is lower)
* The difference between the values is due to alveolar dead space
** Alveolar dead space is due to alveoli which are ventilated but not perfused (e.g. west zone 1 lungs)
** These alveoli do not participate in gas exchange (there is no perfusion), thus contain very little CO2 and a lot of O2 (the same amount as in inspired air)
** This relatively CO2 deplete gas mixes with the rest of the expired gas, diluting the ETCO2 reading, thus leading to an observed discrepancy
** Note: It is not due to anatomical dead space as this gas has already been washed out in the early stages of exhalation and thus does not contributed to ETCO2
* Healthy/awake patients have near zero alveolar dead space, so near zero gradient
 
 
 
Factors affecting ETCO2 - PaCO2 gradient
 
* Changes in pulmonary perfusion
** Global reduction in pulmonary perfusion
*** e.g. pHTN, heart failure, Cardiac arrest, Severe shock
** Regional decreases in pulmonary perfusion
*** e.g. pulmonary embolism, fat embolism
* Changes in ventilation
** Excessively high PEEP --&gt; increased West Zone 1
* Measurement error
** Inline HME filters
** Timing of measurement (measuring before end-expiration)
** Poor / loss of ETCO2 calibration
** Interference from other gases (e.g. N2O and collision broadening)
* Physiological factors
** Increasing age &gt; increased gradient
 
 
 
<span id="examiner-comments-224"></span>
==== Examiner comments ====
 
<blockquote>30% of candidates passed this question.
 
Many candidates didn’t distinguish between the different types of dead space. In general this topic was not well understood.
</blockquote>
 
 
<span id="online-resources-for-this-question-224"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-21 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a21-explain-the-potential-causes-of-a-difference-between-the-measured-end-tidal-co2-and-the-arterial-partial-pressure-of-co2/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2007-2-24-etco2-vs-arterial-differece.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-225"></span>
==== Similar questions ====
 
* Question 3, 2018 (2nd sitting)
* Question 24, 2007 (1st sitting)
* Question 9, 2009 (1st sitting)
 
 
 
 
 
<span id="question-22-2"></span>
=== Question 22 ===
 
 
 
<span id="question-226"></span>
==== Question ====
 
Outline the functions of the liver
 
 
 
<span id="example-answer-226"></span>
==== Example answer ====
 
 
 
 
 
 
 
 
 
<span id="examiner-comments-225"></span>
==== Examiner comments ====
 
<blockquote>56% of candidates passed this question
 
Most candidates attempted a structure however did not expand the answers within the categories: e.g. a passing mention of glucose homeostasis is insufficient to score full marks for the carbohydrate metabolism category.
</blockquote>
 
 
<span id="online-resources-for-this-question-225"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-22 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a22/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2017-1-22.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-226"></span>
==== Similar questions ====
 
<ul>
<li><p>Question 20, 2017 (2nd sitting)</p></li>
<li><p>Question 23, 2009 (2nd sitting)</p></li>
<li><p>Question 12, 2011 (2nd sitting)</p></li>
<li><p>Question 4, 2013 (2nd sitting)</p>
<p></p></li></ul>
 
 
 
<span id="question-23-2"></span>
=== Question 23 ===
 
 
 
<span id="question-227"></span>
==== Question ====
 
Draw and label a left ventricular pressure volume loop in a normal adult (40% of marks). List the information that can be obtained from this loop (60% of marks).
 
 
 
<span id="example-answer-227"></span>
==== Example answer ====
 
 
 
[[File:C:\Users\ethan\AppData\Roaming\Typora\typora-user-images\image-20210320173717612.png|thumb|none]]
 
Information obtained
 
* Volumes
** End diastolic volume
** End systolic volume
** Stroke volume
** Ejection fraction
* Pressures
** Systolic BP
** Diastolic BP
** Pulse pressure
** End systolic pressure
* Pressure-volume relationships
** End diastolic pressure-volume relationship (EDPVR)
*** Describes elastance, Non linear
** End systolic pressure-volume relationship (ESPVR)
*** Describes contractility, Linear
** Arterial elastance
*** Approximation of afterload
*** Line between EDV and ESP
* Areas
** Total mechanical work (combination of stroke and potential work)
*** Stroke work (inside PV loop)
*** Stored potential work (outside loop, under ESPVR line)
 
 
 
<span id="examiner-comments-226"></span>
==== Examiner comments ====
 
<blockquote>65% of candidates passed this question.
 
Many candidates lost marks for poor quality diagrams with inaccurate labelling. An accurate diagram was required. Many answers lacked sufficient detail regarding contractility and afterload.
</blockquote>
 
 
<span id="online-resources-for-this-question-226"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-23 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a23/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2008-1-24-p-v-loop.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-227"></span>
==== Similar questions ====
 
* Question 24, 2008 (1st sitting)
 
 
 
 
 
<span id="question-24-2"></span>
=== Question 24 ===
 
 
 
<span id="question-228"></span>
==== Question ====
 
Outline the physiology of cerebral spinal fluid (CSF).
 
 
 
<span id="example-answer-228"></span>
==== Example answer ====
 
 
 
CSF
 
* ECF located in the ventricles and subarachnoid space
* ~2ml/kg of CSF
* Divided evenly between the cranium and spinal column
 
 
 
Production
 
<ul>
<li><p>Constantly produced</p></li>
<li><p>~550ml produced per day (~24mls/hr) </p></li>
<li><p>Produced by</p>
<ul>
<li><p>Choroid plexus (70%) - located in ventricles of brain</p></li>
<li><p>Capillary endothelial cells (30%)</p></li></ul>
</li>
<li><p>Produced by a combination of ultrafiltration (via fenestrated choroidal capillaries) and active secretion</p>
<p></p></li></ul>
 
Composition relative to plasma
 
* Similar: Na, osmolality, HCO3
* Increased: Cl, Mg, CO2
* Decreased: pretty much everything else (protein, potassium, calcium, glucose, pH)
 
 
 
Circulation
 
<ul>
<li><p>Circulation is driven by</p>
<ul>
<li><p>Ciliary movement of ependymal cells</p></li>
<li><p>Respiratory oscillations and arterial pulsations</p></li>
<li><p>Constant production and absorption</p></li></ul>
</li>
<li><p>CSF flows from </p>
<ul>
<li><p>Lateral ventricles &gt; foramen of Monro &gt; 3rd ventricle &gt; Sylvian aqueduct &gt; 4th ventricle &gt; cisterna magna (via foramen megendie and luschka) &gt; spreads between spinal/cranial subarachnoid spaces</p></li></ul>
 
<p></p></li></ul>
 
Reabsorption
 
<ul>
<li><p>Rate of ~24mls/hr</p></li>
<li><p>By the arachnoid villi</p>
<ul>
<li><p>Located predominately in the dural walls of the sagittal + sigmoid sinuses</p></li>
<li><p>Function as one way valves, with driving pressure leading to absorption.</p>
<p></p></li></ul>
</li></ul>
 
Functions
 
* Mechanical protection
** The low specific gravity of CSF &gt; decreased effective weight of the brain (1500g &gt; 50g)
** With the reduced weight
*** Less inertia = less acceleration/deceleration forces
*** Suspended &gt; no contact with the rigid skull base
* Buffering of ICP
** CSF can be displaced / reabsorbed to offset any increase in ICP
* Stable extracellular environment
** Provides a constant, tightly controlled, ionic environment for normal neuronal activity
* Control of respiration
** The pH of CSF is important in the control of respiration (CO2 freely diffuses into CSF and can activate central chemoreceptors)
* Nutrition
** Provides a supply of oxygen, sugars, amino acids to supply the brain
 
 
 
<span id="examiner-comments-227"></span>
==== Examiner comments ====
 
<blockquote>67% of candidates passed this question
 
Better answers included details on CSF production (amount, site), reabsorption and factors which influences CSF and its circulation.
</blockquote>
 
 
<span id="online-resources-for-this-question-227"></span>
==== Online resources for this question ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2017-paper-1-saqs/question-24 Deranged Physiology]
* [https://jennysjamjar.com.au/year/17a/17a24/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2015-1-16-csf-physiology.pdf CICM Wrecks]
 
 
 
<span id="similar-questions-228"></span>
==== Similar questions ====
 
* Question 22, 2007 (1st sitting)
* Question 6, 2008 (2nd sitting)
* Question 2, 2013 (1st sitting)
* Question 16, 2015 (1st sitting)
* Question 24, 2017 (1st sitting)
* Question 15, 2018 (2nd sitting)
* Question 11, 2019 (1st sitting)
* Question 16, 2020 (1st sitting)
 
 
 
 
 
 
 
<span id="2016-1st-sitting"></span>
== 2016 (1st sitting) ==
 
 
 
<span id="question-8-12"></span>
=== Question 8 ===
 
 
 
<span id="question-229"></span>
==== Question ====
 
Describe the characteristics of a drug that influence its excretion by the kidneys
 
 
 
<span id="example-answer-229"></span>
==== Example answer ====
 
 
 
Renal excretion of drugs is related to factors which affect
 
* Filtration at the glomerulus
* Secretion into the tubules
* Reabsorption in the tubules
 
 
Factors affecting glomerular filtration
 
* GFR
** Increased GFR (e.g. increased CO) will lead to increased filtration and clearance of hydrophilic drugs
* Drug size
** Increasing drug size = decreased renal clearance
** Only drugs &lt;7kDa (weight) or &lt;30 Angstrom units (width) are able to pass the capillary BM
* Protein binding
** Only unbound drugs can pass the glomerular BM (hence highly protein bound drugs are poorly filtered)
* Charge
** Negatively charged molecules cannot readily pass BM (as it is also negatively charged)
 
 
Factors affecting drug secretion
 
* Active process
* Protein binding, renal blood flow (GFR) as per above
* Concentration: Increased concentration = increased secretion (until transporters are saturated)
* Concomitant drugs - competition for receptors
 
 
Factors affecting drug reabsorption
 
* Can be active or passive (most are passive)
* Also depends on charge (ionised drugs cannot pass through BM) and become trapped in the urine
** Ionisation depends on pH urine, pKa drug (acidic drugs are ionised in alkaline urine)
* Concentration (as passive diffusion depends on concentration gradient)
* Urine flow rate
** Increased urine flow rate &gt; reduces concentration of drug in urine &gt; increased concentration gradient + elimination
 
 
 
<span id="examiner-comments-228"></span>
==== Examiner comments ====
 
<blockquote>29% of candidates passed this question.<br />
Drug characteristics that might influence the renal excretion processes include charge, size, solubility, and binding to specific structures or protein. Whether the drug is unchanged versus metabolised can influence these factors. This question tests core knowledge of pharmacology principles and should be answered with equations, graphs or simple clear descriptions of physical and chemical principles. Extended examples and hedged statements about “influencing” without the direction, magnitude and necessary conditions for the influence did not score marks.
</blockquote>
 
 
 
 
<span id="question-13-12"></span>
=== Question 13 ===
 
 
 
<span id="question-230"></span>
==== Question ====
 
Describe the cardiovascular effects of a sudden increase in afterload.
 
 
 
<span id="example-answer-230"></span>
==== Example answer ====
 
 
 
Afterload
 
* Force that must be overcome prior to the sarcomere being able to shorten during contraction (i.e. the forces opposing ventricular ejection)
 
 
 
CVS effects
 
* HR
** If the increase in afterload is associated with increase in carotid pressure &gt; baroreceptor reflex activation &gt; compensatory decrease in HR
* SV
** The increased afterload &gt; earlier closure of the AV valve (increased diastolic pressure) and decrease in velocity of myocyte shortening &gt; increased end-systolic volume (and pressure) &gt; decreased stroke volume &gt; decreased CO
* Preload
** Increase in afterload &gt; decrease in SV &gt; increase in LV end systolic volume (and pressure) &gt; Increase in EDV (preload)
* Contractility
** Increases due to the Anrep effect
*** Increase in afterload &gt; increased LV EDP &gt; frank starling effect &gt; Calcium accumulation &gt; increased contractility &gt; increased SV
* Cardiac output
** Decreases in short term
** Ideally recovers quickly if the compensatory mechanisms work
** If the LV is impaired, or the body is unable to compensate &gt; LV heart failure
* Myocardial oxygen consumption
** Increases due to increased contractility and increased work to overcome afterload
* Coronary blood flow
** Remains stable due to autoregulation
 
 
 
 
 
 
 
[[File:C:\Users\ethan\AppData\Roaming\Typora\typora-user-images\image-20220713192800402.png|thumb|none]]
 
 
 
 
 
<span id="examiner-comments-229"></span>
==== Examiner comments ====
 
<blockquote>21% of candidates passed this question.<br />
It was expected the answer would start with a definition of afterload and then proceeded to indicate what effects this increase in afterload would have on ventricular end-systolic pressure, ventricular end-diastolic pressure, left atrial pressure, cardiac output, myocardial oxygen demand and myocardial work, coronary blood flow and systemic blood pressure.<br />
Most candidates who failed to pass this question submitted answers that were just too brief, only including a small subset of the material required. Very few candidates included any mention of myocardial oxygen demand or myocardial work or the impact upon the cardiac output. A number of candidates included a detailed description of the Sympathetic Nervous System and the Renin-Angiotensin system, material which was not asked for. There were quite a number of incorrect perceptions about what effect a sudden increase in afterload would have on the systemic blood pressure. Candidates who mentioned the baroreceptor response and the stretch receptor response where rewarded with additional credit.
</blockquote>
 
 
<span id="online-resources-1"></span>
==== Online resources ====
 
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2016-paper-1-saqs/question-13#answer-anchor Deranged physiology]
 
 
 
 
 
<span id="question-20-12"></span>
=== Question 20 ===
 
 
 
<span id="question-231"></span>
==== Question ====
 
Outline the role of the liver in drug pharmacokinetics
 
 
 
<span id="example-answer-231"></span>
==== Example answer ====
 
Absorption
 
<ul>
<li><p>The liver will affect the bioavailability of drugs which are subject to first pass metabolism</p></li>
<li><p>Hence, oral absorption, high PR, &gt; subject to hepatic extraction and metabolism</p></li>
<li><p>Drugs which are not subject to first pass metabolism e.g. inhalation, intravenous, IM ,&gt; higher bioavailability if hepatically metabolism/cleared</p></li>
<li><p>Liver dysfunction &gt; alter first pass metabolism</p>
<p></p></li></ul>
 
Distribution
 
* The liver is responsible for producing majority of the proteins that drugs bind
* Hence, for highly protein bound drugs (e.g. warfarin), small changes in protein levels, can lead to large changes in the proportion of unbound (active drug)
* Liver dysfunction &gt; alter protein binding
 
 
Metabolism
 
* The liver is a primary organ of drug metabolism and biotransformation
* Phase 1 reactions
** Hydrolysis, Reduction, Oxidation
** Small increase in hydrophilicity
* Phase 2 reactions
** Glucuronidation, sulfation, conjugation, methylation
** Significantly increased hydrophilicity
* Liver dysfunction can alter biotransformation
** E.g. liver damage &gt; unable to process paracetamol &gt; increased toxicity
 
 
Elimination
 
* The hepatic system is important for drug elimination
* Drugs with a high hepatic extraction ratio, will also be dependant on the hepatic blood flow. Drugs with a low hepatic extraction ratio will depend on the function of the liver
* For hydrophilic drugs, that are highly protein bound, decreased proteins related to hepatic dysfunction will increase elimination
* Biliary section
* Drugs which rely on biliary exertion will be retained in liver dysfunction
* Portal hypertension &gt; shunting of blood &gt; decreased first pass metabolism
 
 
 
<span id="examiner-comments-230"></span>
==== Examiner comments ====
 
<blockquote>62% of candidates passed this question.<br />
Most candidates structured their answer to this question well – they were aware of first pass metabolism and the effect of protein synthesis upon volume of distribution of drugs. Knowledge concerning Phase I and Phase II reactions was frequently inadequate. Many candidates were aware that these processes as well as inactivating or activating drugs resulted in increased water solubility to aid excretion via bile or urine. Few candidates discussed the significance of the large blood flow to the liver or the implications of high and low extraction ratios especially in relation to liver blood flow
</blockquote>
 
 
 
 
<span id="question-24-3"></span>
=== Question 24 ===
 
 
 
<span id="question-232"></span>
==== Question ====
 
Describe the ideal sedative agent for an Intensive Care patient (50%). How does midazolam compare to this (50%)?
 
 
 
<span id="example-answer-232"></span>
==== Example Answer ====
 
{|
! Name
! Midazolam
! Ideal sedative agent
|-
| '''Class'''
| Benzodiazepine (sedative)
| -
|-
| '''Pharmaceutics'''
| Clear colourless solution<br />
pH 3.5. <br />
Diluted in water.
| - Water soluble<br />
- Chemically stable with long shelf life (various temperatures)<br />
- Does not need reconstitution.<br />
- Compatible w. all drugs / IVF<br />
- Enantiopure preparation <br />
- No additives
|-
| '''Routes of administration'''
| IV, IM, S/C, intranasal, buccal, PO
| Multiple routes of administration available
|-
| pKa
| 6.5
| -
|-
| Dose
| Variable
| Predictable response for a given weight based dosing regime
|-
| '''Pharmacodynamics'''
|
|
|-
| MOA
| Midazolam (BZD) binds to GABA<sub>A</sub> receptors (ionotropic ligand gated channel) in the CNS. Cl enters &gt; hyperpolarisation.
| Known MOA with specific and targeted receptors
|-
| Effects
| CNS: sedation, amnesia, anxiolysis, hypnosis, anticonvulsant effects, decreased cerebral O2 demand, MSK: muscle relaxant
| CNS: sedation, amnesia, anxiolysis, decreased cerebral O2 demand
|-
| Side effects
| CVS: bradycardia, hypotension <br />
CNS: confusion, restlessness <br />
RESP: respiratory depression/ apnoea
| No side effects, including no cardiorespiratory depression or emergence delirium
|-
| '''Pharmacokinetics'''
|
|
|-
| Onset
| peak effect 2-3 minutes (IV), offset variable
| Rapid onset / offset
|-
| Absorption
| ~40% oral bioavailability <br />
- Absorbed well, but sig. 1st pass metabolism
| Absorbed well from all routes, including oral and inhaled with minimal first pass metabolism
|-
| Distribution
| Vd = 1L / kg<br />
95% protein bound
| Vd = &lt;0.3L/Kg <br />
Minimal protein binding (decreases availability)
|-
| Metabolism
| Hepatic metabolism by hydroxylation <br />
Active (1-a hydroxymidazolam) and inactive metabolites
| Either no metabolism or organ independent metabolism with inactive metabolites (prevents accumulation)
|-
| Elimination
| Renal excretion <br />
T 1/2 = 4 hours
| Rapidly cleared with a short and predictable half life and small CSHT
|-
| '''Reversal'''
| Flumazenil - antagonist (reversal agent)
| Readily reversible with no rebound/side effects
|}
 
 
 
<span id="examiner-comments-231"></span>
==== Examiner comments ====
 
<blockquote>60% of candidates passed this question.<br />
Candidates who had a structured approach (i.e. pharmaceutical, pharmacokinetic, pharmacodynamic) provided more content and scored higher. Candidates who also approached pharmacodynamic effects in an organ system based approach scored higher. Relating a pharmacokinetic property of midazolam (e.g. volume of distribution or half-life) to a un/desirable attribute e.g. offset of action and accumulation displayed a greater understanding of the question. For many candidates, the description of an ideal drug contained more detail and candidates were not able to adequately state how midazolam compares.
</blockquote>
 
 
<span id="online-resources-2"></span>
==== Online resources ====
 
* [https://cicmwrecks.files.wordpress.com/2019/04/2016-1-24.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/syllabus/k/k2/k2i-16a24/ Jenny's Jam Jar]
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2016-paper-1-saqs/question-24 Deranged Physiology]
 
 
 
 
 
 
 
 
 
<span id="2016-2nd-sitting"></span>
== 2016 (2nd sitting) ==
 
 
 
<span id="question-4-12"></span>
=== Question 4 ===
 
 
 
<span id="question-233"></span>
==== Question ====
 
Categorise the drugs used in the treatment of asthma, give examples and outline their mechanism of action
 
 
 
<span id="example-answer-233"></span>
==== Example Answer ====
 
 
 
Oxygen
 
* Increases FiO2 &gt; increased SaO<sub>2</sub> (by increasing P<sub>A</sub>O<sub>2</sub> as per Alveolar gas equation).
* Given by numerous devices (nasal prongs, masks, NIV, ETT)
* Dose titrated to SaO<sub>2</sub>
** Hypoxemia is harmful (but optimal target SaO<sub>2</sub> unclear)
** Generally titrated to Sats 94-98% (with caveats for some subgroups of patients)
** Hyperoxia may lead to hypercapnia, worsening of V/Q mismatch (through alteration of HPVC), lung damage
 
 
 
Beta-adrenergic agonists
 
* Long acting B2 selective agonists (e.g. salmeterol) are used in prevention
* Short acting B2 selective agonists (e.g. salbutamol) are preferred first line therapy for exacerbation
* Nonselective adrenergic agonists (e.g. adrenaline) can also be used in severe exacerbations
* SABAs can be given inhaled (via spacer), nebulised or via IV infusion (if unresponsive to inhaled)
* Example: Salbutamol
** Short acting B2 agonist
** MOA: Acts on B<sub>2</sub> receptors (Gs protein coupled receptors) in bronchial smooth muscle cells &gt; activates activates adenyl cyclase-CAMP system &gt; increase cAMP &gt; decreased intracellular Ca &gt; SM relaxation / bronchodilation
** Side effects: Tachycardia, Anxiety, tremor, Hypokalaemia, lactic acidosis
 
 
 
Anticholinergics
 
* Example: ipratropium bromide
* Routes: Inhaled, nebuliser
* MOA: Competitive antagonism of muscarinic ACh receptors &gt; bronchodilation + decreased secretions
* Side effects: dry mouth, N/V, headache, blurred vision
 
 
 
Corticosteroids
 
* Examples: hydrocortisone (IV), prednisone (PO), budesonide (inhaled)
* Systemic corticosteroids should be given to all mod-severe asthma &gt; improve outcomes
* MOA: bind to cytoplasmic glucocorticoid receptors &gt; change in gene transcription &gt; down-regulates the synthesis of proinflammatory cytokines/mediators
* Effects: increased B receptor responsiveness, decreased inflammation, decreased mucus secretion
* Side effects: numerous! Depends on dose/duration. Examples:
** Short term: hyperglycaemia, hypokalaemia, immunosuppression, insomnia/confusion/psychosis,
** Long term: cushings, osteoporosis, skin thinning, weight gain, immunosuppression
 
 
 
Other potential treatment options (and MOA)
 
* Magnesium sulphate &gt; inhibits L type calcium channels &gt; bronchodilation/SM relaxation
* Ketamine &gt;inhibits L type calcium channels &gt; Bronchial smooth muscle relaxation
* Aminophylline &gt; PDEI &gt; SM relaxation / bronchodilation
* Heliox &gt; Improves laminar airflow &gt; may improve ventilation
* Inhaled anaesthetics (e.g. sevoflurane)
* Montelukast (leukotriene receptor antagonist used in children)
 
 
 
<span id="examiner-comments-232"></span>
==== Examiner comments ====
 
<blockquote>71% of candidates passed this question.<br />
Asthma drugs are typically categorised according to mechanism of action. A reasonable alternative is to categorise by clinical use, e.g. short acting, long acting, preventer, rescue etc.<br />
A lot of emphasis in marking was placed on an understanding of the beta-adrenergic pathway, its secondary messenger system and how this medicates smooth muscle relaxation. Candidates whose answers had structure as well those who described the wide range of drugs used to treat asthma scored well.
</blockquote>
 
 
 
 
 
 
<span id="question-9-12"></span>
=== Question 9 ===
 
 
 
<span id="question-234"></span>
==== Question ====
 
Describe the immunology and drug treatment of anaphylaxis.
 
 
 
<span id="answer-1"></span>
==== Answer ====
 
 
 
Anaphylaxis
 
* Life threatening systemic hypersensitivity reaction
* May be immune mediated (IgE or non IgE) or non immune mediated
 
 
 
IgE immune mediated anaphylaxis (a Type-1 hypersensitivity reaction)
 
* Initial contact between a B-cell and an antigen (allergen) leads to the formation of a IgE against it
* The specific IgE then binds to Fc receptors on mast cells (in tissues) and basophilis (in circulation)
* Further exposure of the antigen leads to formation of cross links between IgE-Fc complex and the antigen which leads to activation and release of pre-synthesised mediators
** Mediators
*** Histamine -&gt; vasodilation, increased vascular permeability, increased chronotropy
*** Leukotrienes -&gt; bronchoconstriction, increased vascular permeability
*** Serotonin -&gt; SM contraction
*** Tryptase -&gt; activates complement, coagulation and Kallikrein-kinin pathways
*** Platelet activating factor --&gt; platelet activation
* This manifests as
** CVS: Hypotension/cardiovascular collapse, flushing
** RESP: Bronchospasm, airway oedema, angioedema, dyspnoea, stridor, hypoxaemia
** DERM: pruritis, urticaria, angioedema,
** GIT: abdominal pain, nausea, vomiting, diarrhoea
 
 
 
DRUG TREATMENT
 
 
 
Oxygen
 
* Increase FiO2 &gt; improved oxygenation whilst there is bronchoconstriction/airway oedema
 
 
 
Fluids
 
* Increase in MSFP &gt; increase VR &gt; increased CO &gt; increased BP
 
 
 
Adrenaline
 
<ul>
<li><p>Mainstay of treatment for anaphylaxis </p>
<ul>
<li><p>Treats cardiovascular collapse, bronchospasm and prevents further degranulation of mast cells</p></li></ul>
</li>
<li><p>Dose is 0.3-0.5mg IM (adults), 0.01mg/kg IM (children), every 5-15 mins (or infusion as needed)</p></li>
<li><p>Effects</p>
<ul>
<li><p>Alpha 1 mediated vasconstriction &gt; increases SVR &gt; increases BP</p></li>
<li><p>B1 mediated increase in inotropy &gt; increase in CO &gt; increase in BP</p></li>
<li><p>B2 mediated bronchodilation and mast cell/basophil stabilisation </p>
<p></p></li></ul>
</li></ul>
 
Supplemental drug treatment
 
 
 
Bronchodilators
 
* E.g. salbutamol, adrenaline
* Supportive management for severe bronchospasm
** B2 agonism &gt; bronchodilation &gt; decrease airways resistance &gt; improve WOB and oxygenation
* Does not alter the course of the illness
 
 
 
Glucocorticoids
 
<ul>
<li><p>e.g. methylpred, pred, hydrocort</p></li>
<li><p>binds to intracellular steroid receptors &gt; alters gene transcription &gt; anti-inflammatory &amp; immunosuppressive effects </p></li>
<li><p>Do not alter acute course of illness</p></li>
<li><p>May prevent biphasic responses / prolonged course of illness</p>
<p></p></li></ul>
 
Antihistamines
 
* e.g. loratadine, premethazine
* Symptomatic treatment strategy in mild disease
** May provide some relief from pruritis/rash (via blocking H1 receptor)
** Minimal effects on systemic mast cell and basophil degranulation
** No effects on outcomes
* Not recommended for severe disease
 
 
 
Glucagon
 
* For patients who have taken b-blockers (and thus have reduced responsiveness to adrenaline)
 
 
 
 
 
<span id="examiner-comments-233"></span>
==== Examiner comments ====
 
<blockquote>32% of candidates passed this question.<br />
It was expected candidates would detail the process of IgE mediated type I hypersensitivity reaction with some discussion of the mediators (Histamine / tryptase and others) and their consequences. Some detail describing time frame of response and the pre-exposure to Antigen (or a similar Antigen) was expected. Drug treatments would include oxygen and fluids as well as more specific agents such as adrenaline and steroids. Adrenaline is the mainstay of therapy and some comment on its haemodynamic role and prevention of ongoing mast cell degranulation was required.<br />
Better answers noted steroids take time to work and some also discussed the role of histamine blocking agents
</blockquote>
 
 
<span id="online-resources-3"></span>
==== Online resources ====
 
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2016-paper-2-saqs/question-9 Deranged physiology]
* [https://jennysjamjar.com.au/year/16b/16b09-describe-the-immunology-and-drug-treatment-of-anaphylaxis/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2016-2-09.pdf CICM Wrecks]
 
 
 
 
 
 
 
 
 
 
 
<span id="question-16-12"></span>
=== Question 16 ===
 
 
 
<span id="question-235"></span>
==== Question ====
 
Outline the influence of pregnancy on pharmacokinetics
 
 
 
<span id="example-answer-234"></span>
==== Example answer ====
 
Absorption
 
* Oral
** Nausea and vomiting in early preg &gt; reduced PO absorption
** Increased intestinal blood flow (due to increased CO) &gt; increased PO absorption
** Decreased gastric acid production &gt; increased pH &gt; unionised drugs absorbed more
** Delayed gastric emptying peri-labour may increase/decrease absorption depending on drug
* IM / SC / Transdermal
** Increased absorption due to increased CO + increased skin/muscle blood flow
* IV
** Faster IV onset due to increased CO
* Neuraxial
** Decreased peridural space (venous engorgement) &gt; decreased dose required
 
 
Distribution
 
* Volume of distribution
** Increased total body water &gt; increased Vd for hydrophilic drugs
** Increased body fat &gt; increased Vd for lipophilic drugs
* Plasma proteins
** Decreased protein binding (increased free fraction) due to reduced concentrations albumin and a-1 glycoprotein
 
 
Metabolism
 
* Hepatic
** Some metabolic enzymes reduced / some increased (due to progesterone/oestrogen ratio)
** Leads to variable drug responses
** E.g. increased metabolism of midazolam, phenytoin, but decreased caffeine.
* Placenta metabolises some drugs (COMT and MOA enzymes &gt; metabolises catecholamines)
* Decreased plasma cholinesterase (though no change in Succinylcholine effect)
 
 
Elimination
 
* Renal
** Increased clearance due to increased GFR (e.g. gentamycin)
* Hepatobiliary
** Decreased clearance due to cholestatic effects of oestrogen (e.g. rifampicin)
* Resp
** Increased volatile washout due to increased minute ventilation
 
 
 
<span id="examiner-comments-234"></span>
==== Examiner comments ====
 
<blockquote>47 % of candidates passed this question.<br />
Most candidates divided the answer into effects on absorption, distribution, metabolism and elimination, which is a good way of presenting the answer. However, the good candidates also mentioned effects on the foetus due to ion trapping caused by the more acidic foetal blood.<br />
Many candidates forgot to include effect on epidural administration of drugs in pregnancy caused by engorged epidural veins during labour.<br />
Candidates lost marks for omitting the effect of increased cardiac output on the rate of distribution of IV drugs to effector sites, the effect of increased hepatic blood flow on drugs with high intrinsic clearance, the increased clearance of drugs with renal clearance due to increased GFR &amp; renal plasma flow
</blockquote>
 
 
 
 
<span id="question-23-3"></span>
=== Question 23 ===
 
 
 
<span id="question-236"></span>
==== Question ====
 
Compare and contrast the mechanism of action, spectrum of activity and adverse effects of benzyl penicillin and fluconazole.
 
 
 
<span id="answer-2"></span>
==== Answer ====
 
{|
!
! Benzylpenicillin
! Fluconazole
|-
| Mechanism of action
| Penicillin antibiotic<br />
Both disrupt cell wall synthesis (but different mechanisms): Binds to penicillin binding proteins &gt; inhibits peptidoglycan cross linking &gt; bactericidal
| Azole antifungal<br />
Inhibits the fungal CYP450 enzyme responsible for ergosterol production (needed for fungal cell membrane synthesis) &gt; cell death
|-
| Spectrum of activity
| Narrow spectrum penicillin<br />
'''Covers:''' Most GPC (staph, strep, enterococci), some GPB (e.g. listeria), very few GNC (e.g. Neisseria sp). <br />
'''Does not cover:''' MRSA, CRE, VRE, manty other GN bacteria + anaerobes, all fungi/yeasts, all parasites/ protozoans
| Narrow spectrum azole<br />
'''Covers''': Candida and cryptococcal species <br />
'''Does not cover:''' some candida sp (e.g. krusei), aspergillus and most other fungi/yeast, all bacteria (GP and GN), all parasites/protozoa
|-
| Adverse effects
| CNS: confusion, coma, seizure<br />
CVS: Nil major<br />
RESP: Nil<br />
GIT: Raised LFTs, nausea and vomiting and abdominal pain, pseudomembranous colitis <br />
HAEM: agranulocytosis<br />
RENAL: Interstitial nephritis<br />
IMMUNO: rash, allergy, anaphylaxis<br />
OTHER: less drug interactions, not a teratogen
| CNS: headache<br />
CVS: Prolonged QTc<br />
RESP: Nil<br />
GIT: Raised LFTs, nausea, vomiting, abdo pain<br />
HAEM: thrombocytopaenia, leukopaenia<br />
RENAL: Nil<br />
IMMUNO: rash, allergy, alopecia, anaphylaxis<br />
OTHER: Drug interactions (CYP450), teratogen
|}
 
 
 
<span id="examiner-comments-235"></span>
==== Examiner comments ====
 
<blockquote>8% of candidates passed this question.<br />
To pass this question each of the three components needed to be compared and contrasted for both agents. A tabulated answer helped in this regard but was not essential.<br />
Some answers included information that could not gain marks, as it was not directly relevant to the question asked (e.g. presentation and dose).<br />
In spectrum of activity, as well as what important organisms the agents were effective against, marks were also given for the important organisms that they were not effective against (e.g. MRSA and beta-lactamase producing organisms for penicillin G; and aspergillus for fluconazole).<br />
In general, of the two agents, fluconazole was the least well answered. For example, a common omission either in mechanism of action or in adverse effects was that fluconazole inhibits microsomal P450 enzymes.<br />
Some candidates confused fluoroquinalone with fluconazole.
</blockquote>
 
 
<span id="online-resources-4"></span>
==== Online resources ====
 
* [https://icuprimaryprep.files.wordpress.com/2015/01/q8-compare-and-contrast-the-mechanism-of-action-spectrum-of-activity-and-adverse-effects-of-benzyl-penicillin-metronidazole-and-clindamycin-march-2013.pdf ICU Primary prep]
* [https://jennysjamjar.com.au/syllabus/t/t2/t2i-16b23/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2016-2-23.pdf CICM Wrecks]
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2016-paper-2-saqs/question-23#answer-anchor Deranged physiology]
 
 
 
 
 
 
 
 
 
 
 
 
 
<span id="2015-1st-sitting"></span>
== 2015 (1st sitting) ==
 
 
 
<span id="question-10-12"></span>
=== Question 10 ===
 
 
 
<span id="question-237"></span>
==== Question ====
 
Compare and contrast the pharmacology of mannitol and hypertonic saline.
 
 
 
<span id="example-answer-235"></span>
==== Example Answer ====
 
{|
! Name
! Mannitol
! Hypertonic saline
|-
| '''Class'''
| Osmotherapy agent / osmotic diuretic
| Osmotherapy agent / concentrated electrolyte
|-
| '''Indications'''
| Temporary reduction in ICP / IOP<br />
Diuresis
| Temporary reduction in ICP / IOP<br />
Hyponatraemia
|-
| '''Pharmaceutics'''
| Clear colourless solution (10-25% conc)<br />
- 10% = 10g/100ml<br />
Precipitates at low temperatures
| Clear colourless solution (various concentrations)<br />
- 3% saline = 513 mmols Na + Cl (= osmolarity 1026)
|-
| '''Routes of administration'''
| IV
| IV (central)<br />
- Risk phlebitis, necrosis
|-
| '''Dose'''
| 0.25-1g/kg bolus (max 100g)<br />
repeated 3 hourly
| 3ml/kg (3% saline) bolus over 10 mins. Can be repeated to target Na 145-155
|-
| pKa
| 12.6
| 3.1
|-
| '''Pharmacodynamics'''
|
|
|-
| MOA
| ↑ osmolality of ECF &gt; ↓ volume of ICF (through osmotic shift) &gt; ↓ cerebral volume &gt; ↓ ICP. <br />
Also --&gt; freely filtered at glomerulus (but not reabsorbed) &gt; acts osmotically to ↓ H<sub>2</sub>O reabsorption.
| Increases osmolality of ECF &gt; decreases volume of ICF (through osmotic shift) &gt; decreases cerebral volume &gt; decreases ICP
|-
| Effects/side effects
| RENAL: osmotic diuresis, electrolyte disturbances (variable) <br />
CNS: increased osmolality of ECF &gt; osmotic fluid shifts out of cells &gt; decreased ICP/IOP<br />
CVS: initial rise in MSFP&gt;preload&gt;BP (fluid load) which then decreases with diuresis &gt; hypotension<br />
RESP: Pulmonary oedema (increased in ECF volume)
| Renal: Increases Na, Cl, NAGMA, osmolality<br />
MSK: necrosis/phlebitis if given peripherally/extravasates<br />
CVS: increased ECF &gt; overload<br />
RESP: pulmonary oedema (fluid overload)
|-
| '''Pharmacokinetics'''
|
|
|-
| Onset / duration
| Onset &lt;15 mins <br />
Duration = 4-6 hours
| Onset &lt;15 mins<br />
Duration = 1 hour
|-
| Absorption
| Given IV only (PO bioavailability - 0%)
| IV only
|-
| Distribution
| Does not cross BBB <br />
VOD = 0.2L / Kg<br />
75% becomes interstitial fluid, 25% intravascular
| Does not cross BBB <br />
VOD = 0.2L / Kg<br />
75% becomes interstitial fluid, 25% intravascular
|-
| Metabolism
| Nil (negligible hepatic metabolism)
| Nil
|-
| Elimination
| Renal elimination (unchanged) <br />
T 1/2 = 2-3 hours
| Renal elimination (unchanged)<br />
T 1/2 =
|-
| Monitoring
| Monitoring (osmolality, 320)
| Monitoring (Na 145-155)
|-
| Advantages
| Relatively cheap, as effective as HT saline
| Cheap, stable, small volumes<br />
No diuretic effect &gt; no hypoT<br />
Easily monitored
|-
| Disadvantages
| Unstable at low temps, leads to diuresis, more cumbersome to monitor
| Needs central access, can cause hypernatraemia,
|}
 
 
 
<span id="examiner-comments-236"></span>
==== Examiner comments ====
 
<blockquote>8 % of candidates passed this question.
 
A structured approach is important and a table worked best for most candidates, although a few attempted this in free text. Despite attempting a structured answer very few candidates provided information in regards to preparation, dose, monitoring of osmolarity, adverse effects or contraindications. Understanding of the action of these drugs was expected and factual inaccuracies were common with many candidates suggesting hypertonic saline acts as an osmotic diuretic. Better answers mentioned other potential mechanisms of action of mannitol. Many candidates failed to appreciate the impact on raised intracranial pressure.
</blockquote>
 
 
<span id="online-resources-5"></span>
==== Online resources ====
 
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2015-paper-1-saqs/question-10#answer-anchor Deranged physiology]
* [https://jennysjamjar.com.au/syllabus/i/i2/i2i-15a10-compare-and-contrast-the-pharmacology-of-mannitol-and-hypertonic-saline/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2019/04/2015-1-10.pdf CICM Wrecks]
 
 
 
 
 
<span id="2015-2nd-sitting"></span>
== 2015 (2nd sitting) ==
 
 
 
<span id="question-24-4"></span>
=== Question 24 ===
 
 
 
<span id="question-238"></span>
==== Question ====
 
Compare and contrast the pharmacology of valproic acid and carbamazepine
 
 
 
<span id="example-answer-236"></span>
==== Example Answer ====
 
{|
! Name
! Sodium valproate (valproic acid)
! Carbamazepine
|-
| '''Class'''
| Anticonvulsant
| Anticonvulsant
|-
| '''Indications'''
| - Migraine <br />
- Epilepsy (simple-complex and focal-generalised)<br />
- Status epilepticus
| - Epilepsy<br />
- Trigeminal neuralgia<br />
- Bipolar disorder
|-
| '''Pharmaceutics'''
| Enteric coated tablets, oral liquid <br />
Powder for reconstitution
| IR and MR tablets<br />
Oral liquid
|-
| '''Routes of administration'''
| IV, PO
| PO
|-
| '''Dose'''
| 15-30mg/kg in divided doses
| 400mg-1.2g in 2/3 divided doses
|-
| '''Pharmacodynamics'''
|
|
|-
| MOA
| Stabilises Na channels in their inactive state, thereby inhibiting the generation of further action potentials. Also by stimulating GABAergic inhibitory pathways
| Stabilises Na channels in their inactive state, thereby inhibiting the generation of further action potentials. Also by stimulating GABAergic inhibitory pathways
|-
| Effects
| CNS: Anticonvulsant, drowsiness, dizziness, ataxia <br />
GIT: Nausea, dyspepsia, liver failure, pancreatitis <br />
HAEM: thrombocytopaenia, neutropoenia <br />
Other: teratogen, hair loss
| CNS: Anticonvulsant, drowsiness, dizziness, ataxia, headache, diplopia <br />
GIT: Nz, Vz, Dz, raised LFTs<br />
HAEM: neutropoenia, thrombocytopaenia<br />
OTHER: severe skin reactions, teratogen
|-
| '''Pharmacokinetics'''
|
|
|-
| Onset
| TMax 2 hrs (PO), immediate (IV)
| TMax 1.5 hours PO
|-
| Absorption
| PO bioavailability = 90%
| PO bioavailability = 80%
|-
| Distribution
| Protein binding 90%<br />
VOD = 0.2L / Kg
| Protein binding = 75%<br />
VOD = 1L/kg
|-
| Metabolism
| Hepatic metabolism (glucuronidation) <br />
Active and inactive metabolites
| Hepatic (98%)<br />
CYP3A4<br />
Active metabolites
|-
| Elimination
| Renal elimination of metabolites (85%) <br />
T 1/2 = 12 hours
| Renal (70%) and faecal (30%) elimination<br />
T 1/2 = 14 hours (metabolites 30 hours)
|-
| '''Special points'''
| Monitor LFTs first 6 months given risk of liver failure
|
|}
 
 
 
<span id="examiner-comments-237"></span>
==== Examiner comments ====
 
<blockquote>6% of candidates passed this question.<br />
Both these agents are listed as “level B” in the syllabus pharmacopeia and as such a general understanding of each class and relevant pharmacokinetics and pharmacodynamics was expected. Most candidates had better knowledge of valproate than carbamazepine. Some description of the toxicological features for intensive care practitioners was expected.
</blockquote>
 
 
<span id="online-resources-6"></span>
==== Online resources ====
 
* [https://jennysjamjar.com.au/year/15b/15b24/ Jenny's Jam Jar]
* [https://cicmwrecks.files.wordpress.com/2017/04/2015-2-24-valproate-carbemazepine.pdf CICM Wrecks]
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2015-paper-2-saqs/question-24#answer-anchor Deranged Physiology]
 
 
 
 
 
 
 
 
 
<span id="2014-2nd-sitting"></span>
== 2014 (2nd sitting) ==
 
 
 
<span id="question-13-13"></span>
=== Question 13 ===
 
 
 
<span id="question-239"></span>
==== Question ====
 
Outline the pharmacology of amiodarone
 
 
 
<span id="answer-3"></span>
==== Answer ====
 
{|
! Name
! Amiodarone
|-
| '''Class'''
| Antiarrhythmic (Class III) <br />
- However, also has class I, II, and IV activity
|-
| '''Indications'''
| Tachyarrhythmias (e.g. SVT, VT, WPW)
|-
| '''Pharmaceutics'''
| 100-200mg tablets <br />
Clear solution in 150mg ampoules for dilution in dextrose
|-
| '''Routes of administration'''
| IV and PO
|-
| '''Dose'''
| IV: 5mg/kg, then 15mg/kg infusion / 24hrs.<br />
Oral: 200mg TDS (1/52) &gt; BD (1/52) &gt; daily thereafter
|-
| pKA
| 6.6
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| - Blocks K channels (Class III effects) prolonging repolarisation and therefore refractory period. <br />
- Decreases velocity of Phase 0 by Blocking Na channels (Class I effects) <br />
- Non-competitive inhibition of Ca channels prolonging depolarisation + AV nodal conduction time (Class IV effects) <br />
- Slows AV/SA nodal conduction via anti-adrenergic activity (Class II effects)
|-
| Effects
| Rhythm / rate control of tachyarrhythmias
|-
| Side effects
| Side effects worsen/increase with duration of therapy! <br />
RESP: pneumonitis, fibrosis <br />
CVS: bradycardia, QT prolongation <br />
CNS: peripheral neuropathy <br />
Thyroid: Hypo/hyperthyroidism <br />
LIVER: cirrhosis, hepatitis <br />
DERM: photosensitivity, skin discolouration
|-
| '''Pharmacokinetics'''
|
|-
| Onset / TMax
| Immediate (IV), 4 hours (PO)
|-
| Absorption
| PO bioavailability 40-60%
|-
| Distribution
| Highly protein bound (&gt;95%) <br />
V<sub>D</sub> ~70L /kg
|-
| Metabolism
| Hepatic (CYP3A4) with active metabolites (desmethylamiodarone)
|-
| Elimination
| T<sub>1/2</sub> = 1 month<br />
Faces, urine, skin elimination
|-
| '''Special points'''
| Many drug-drug interactions (e.g. digoxin and warfarin) due to high PPB and enzymatic system
|}
 
 
 
<span id="examiner-comments-238"></span>
==== Examiner comments ====
 
<blockquote>77% of candidates passed this question.
 
This was a repeat question and was generally answered well. Some candidates lost marks for being too approximate on the pharmacokinetics.
</blockquote>
 
 
 
 
 
 
 
 
 
 
 
 
 
 
<span id="question-17-12"></span>
=== Question 17 ===
 
 
 
<span id="question-240"></span>
==== Question  ====
 
Describe the pharmacology of Oxygen
 
 
 
<span id="answer-4"></span>
==== Answer ====
 
{|
! Name
! Oxygen
|-
| '''Class'''
| Naturally occurring gas (atomic number 8, atomic weight 16)
|-
| '''Indications'''
| Supplementation (i.e hypoxia)<br />
Prophylaxis (e.g. prior to intubation)<br />
CO poisoning<br />
Pneumothorax <br />
Decompression sickness
|-
| '''Pharmaceutics'''
| Diatomic gas, normally present at 21% in atmosphere<br />
Colourless, tasteless, odourless<br />
Stored in cylinders (various forms), flammable
|-
| '''Routes of administration'''
| Inhaled (variety of delivery devices)<br />
Intravenous (i.e. ECMO)<br />
External (hyperbaric oxygen therapy)
|-
| '''Dose'''
| 0.21 - 1.0 FiO<sub>2</sub> (generally targeting SaO2 &gt;94%; or 88-92% on CO<sub>2</sub> retainers; though exact target not entirely evidenced based)
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Oxygen is delivered to tissues for aerobic metabolism via oxidative phosphorylation
|-
| Effects
| '''RESP:''' improved oxygen saturations (may also improve DO2), decreased respiratory drive (very minimal), pulmonary toxicity (free radical generation), may worsen V/Q mismatch (impairs HPVC), drying of mucous membranes<br />
'''CVS:''' decreased pulmonary vascular resistance (vasodilation) due to reversal of HPV, increased HR/SV/SVR if hypoxic (via chemoreceptor reflex) &gt; increased CO and BP<br />
'''CNS:''' anxiety, nausea, visual changes (neonates), seizures (hyperbaric hyperoxia), decreased CBF (vasoconstriction)<br />
'''MET:''' oxidative phosphorylation &gt; ATP production
|-
| '''Pharmacokinetics'''
|
|-
| Absorption
| Diffusion across the alveolar capillary membrane.<br />
Rate of diffusion is governed by Fick's Law and is therefore proportional to the lung area, gas diffusion constant, partial pressure gradient and inversely proportional to membrane thickness
|-
| Distribution
| Bound to plasma Hb (98%)<br />
Dissolved in plasma (&lt;2%) - related to Henrys Law
|-
| Metabolism
| Metabolised in mitochondria during the Citric acid cycle, to produce ATP and generate CO2 and H2O
|-
| Elimination
| Exhalation of CO2 via lungs
|-
| '''Special points'''
|
|}
 
 
 
<span id="examiner-comments-239"></span>
==== Examiner comments ====
 
<blockquote>35% of candidates passed this question.<br />
Use of a general &quot;pharmacology&quot; structure to answer this question would help avoid significant omissions such as only discussing pharmacokinetics or only discussing pharmacodynamics. Oxygen has a well described list of pharmacodynamics effects that includes, cardiovascular, respiratory and central nervous system effects. Candidates’ knowledge of the pharmaceutics was limited for a routine drug. It was expected candidates would mention the potential for oxygen toxicity including a possible impact on respiratory drive in selected individuals, retrolental fibroplasia and seizures under some circumstances. Many candidates did not answer the question asked, and instead focussed on the physiology of oxygen delivery and binding of oxygen to haemoglobin
</blockquote>
 
 
<span id="online-resources-7"></span>
==== Online resources ====
 
* [https://derangedphysiology.com/cicm-primary-exam/past-papers/2014-paper-2-saqs/question-17#answer-anchor Deranged physiology]
* [https://cicmwrecks.files.wordpress.com/2019/04/2009-1-06.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/year/14b/14b17/ Jenny's Jam Jar]
 
 
 
 
 
<span id="2014-1st-sitting"></span>
== 2014 (1st sitting) ==
 
 
 
<span id="question-5-12"></span>
=== Question 5 ===
 
 
 
<span id="question-241"></span>
==== Question ====
 
Describe the pharmacological effects of paracetamol (40% marks). Outline its toxic effects and their management (60% marks).
 
 
 
<span id="example-answer-237"></span>
==== Example Answer ====
 
 
 
Pharmacological effects
 
* MOA
** Not entirely understood
** Analgesic effect thought to be related to
*** Decreased central prostaglandin synthesis by inhibition of COX-3
*** Modulation of 5-HT pathways (increased descending inhibition)
*** Activation of endocannabinoid (CB1) and capsaicin (TRPV1) receptors
** Antipyretic effect thought to be due to decreased PG synthesis in hypothalamus by COX-3
* Effects/side effects
** CNS: analgesia, antipyretic
** CVS: Hypotension (IV preparation, related to excipients)
** GIT: deranged LFTs, liver failure/damage in high doses/toxicity (below)
** Other: hypersensitivity reactions
 
 
 
Toxic effects
 
* Mechanism
** Paracetamol is normally hepatically metabolised
*** Principally it is conjugated (glucuronide and sulfate) &gt; eliminated
*** Small amounts undergo oxidation &gt; toxic metabolites (NAPQI)
** In regular amounts, the NAPQI can be neutralised by hepatic glutathione (anti-oxidant)
** In excess/toxicity, the conjugative pathways are saturated and there is increased oxidation &gt; increased NAPQI. The hepatic glutathione is exhausted &gt; build up of NAPQI &gt; liver damage
* Effects of toxicity:
** GIT: Liver failure / hepatitis, abdominal pain, nausea, vomiting
** HAEM: coagulopathy (related to liver failure)
** MET: impaired glucose homeostasis, lactataemia
** CVS: peripheral vasodilation &gt; shock
* Management
** Immediately post ingestion
*** activated charcoal
** N-acetylcysteine infusion
*** Converted to glutathione &gt; replenishes stores
*** Increased inactivation of the toxic metabolites (NAPQI) &gt; reduced liver damage
*** 200mg/kg over first 4 hours, then 100mg/kg over next 16 hours
** Supportive care
*** Fluids, antiemetics, etc
*** Complications of acute liver failure
*** Dialysis, ventilation etc
 
 
 
<span id="examiner-comments-240"></span>
==== Examiner comments ====
 
<blockquote>63% of candidates passed this question.<br />
This question was generally well answered with narrow variance; very few candidates discussed factors predisposing to hepato-toxicity or renal toxicity. Discussion of pharmacokinetics only gained marks when relevant to toxicity.
</blockquote>
 
 
<span id="online-resources-8"></span>
==== Online resources ====
 
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2014-paper-1-saqs/question-5#answer-anchor Deranged physiology]
* [https://cicmwrecks.files.wordpress.com/2017/04/2014-1-5-pkpd-paracetamol-and-toxicity.pdf CICM Wrecks]
* [https://jennysjamjar.com.au/syllabus/k/k4/k4i-14a05/ Jenny's Jam Jar]
 
 
 
 
 
<span id="question-17-13"></span>
=== Question 17 ===
 
 
 
<span id="question-242"></span>
==== Question ====
 
Classify local anaesthetic agents and give examples (30% marks). Describe the pharmacology of lignocaine (70% marks).
 
 
 
<span id="example-answer-238"></span>
==== Example Answer ====
 
 
 
Local anaesthetics
 
Classified according to the linkage between the hydrophilic and lipophilic groups
 
{|
!
! Esters
! Amides
|-
| '''Link'''
| Ester link
| Amide link
|-
| '''Examples'''
| Cocaine, tetracaine, procaine
| Lidocaine, bupivacaine, ropivacaine
|-
| '''Stability in solution'''
| Unstable
| More stable
|-
| '''Metabolism'''
| Plasma esterase's
| Hepatic (CYP450) dealkylation
|-
| '''Onset'''
| Slow
| Faster
|-
| '''Duration'''
| Shorter
| Longer
|-
| '''Toxicity'''
| Less likely
| More likely
|-
| '''Allergy'''
| Possible
| Very rare
|}
 
 
 
Lignocaine/Lidocaine
 
{|
! Name
! Lidocaine (lignocaine)
|-
| '''Class'''
| Amide local anaesthetic / Class 1b antiarrhythmic
|-
| '''Indications'''
| Local/regional/epidural anaesthesia, ventricular dysrhythmias, pain
|-
| '''Pharmaceutics'''
| Clear colourless solution (1%, 2%, 4%). <br />
Can come with/without adrenaline. Also available as cream/spray
|-
| '''Routes of administration'''
| SC, IV, epidural, inhaled, topical, PO
|-
| '''Dose'''
| Regional: Toxic dose 3mg/kg (without adrenaline), 7mg/kg (with adrenaline) <br />
IV use: 1mg/kg initially, then ~1-2mg/kg/hr
|-
| pKA
| 7.9, 25% unionised at normal body fluid pH
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Class 1b anti-arrhythmic: blocks Na channels, raising threshold potential + reducing slope of Phase 0 of action potential, shortened AP<br />
Local anaesthetic: binds to, and blocks, internal surface of Na channels
|-
| Effects
| Analgesic, anaesthetic, anti-arrhythmic
|-
| Side effects
| CNS: headache, dizziness, confusion, paraesthesia, reduced LOC, seizures, tinnitus, burred vision <br />
CVS: hypotension, bradycardia, AV Block, arrhythmia <br />
CC:CNS ratio = 7 (lower number = more cardiotoxic)<br />
Other: allergy, anaphylaxis, methaemaglobinemia,
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| Rapid onset (1-5 minutes)
|-
| Absorption
| IV &gt; Epidural &gt; subcut . <br />
Oral bioavailability ~35%. <br />
S/C Dependant on site of injection, blood flow, use of adrenaline.
|-
| Distribution
| 70% protein bound<br />
Vd ~0.9L/kg. <br />
Crosses BBB
|-
| Metabolism
| Hepatic (CYP450 dealkylation)<br />
Some active metabolites
|-
| Elimination
| Renal excretion (98%) of metabolites<br />
Half life ~90mins --&gt; Increased with adrenaline (SC). <br />
Reduced in cardiac/hepatic failure.
|-
| '''Special points'''
| Intralipid can be used in LA toxicity
|}
 
 
 
<span id="examiner-comments-241"></span>
==== Examiner comments ====
 
<blockquote>71% of candidates passed this question.<br />
The first part of this question was answered well by most candidates.<br />
Generally, the second part of the question was poorly organised by many candidates, the consequence being that many opportunities for picking up marks were lost. A brief statement as to what lignocaine is, its presentations and dose, some facts about PD and PK followed by a few lines on toxicity (CC/CNS ratio) was mostly what was required. Only a few candidates mentioned lignocaine toxicity.
</blockquote>
 
 
<span id="online-resources-9"></span>
==== Online resources ====
 
* [https://jennysjamjar.com.au/year/14a/14a17-classify-local-anaesthetic-agents-and-give-examples-30-marks-describe-the-pharmacology-of-lignocaine/ Jenny's Jam Jar]
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2014-paper-1-saqs/question-17#answer-anchor Deranged Physiology]
* [https://cicmwrecks.files.wordpress.com/2017/04/2014-1-17-local-anaesthetics-lignocaine.pdf CICM Wrecks]
 
 
 
 
 
 
 
<span id="question-20-13"></span>
=== Question 20 ===
 
 
 
<span id="question-243"></span>
==== Question ====
 
Describe the factors affecting drug absorption from the gastrointestinal tract
 
 
 
<span id="example-answer-239"></span>
==== Example answer ====
 
Drug factors
 
* Concentration of drug
** Increased concentration gradient = more rapid absorption
* Physical form of drug
** Liquid drug &gt; faster gastric transit time
** Ability to dissolve (e.g. enteric coatings) &gt; delays time
** MR preparations &gt; delayed absorption
* pKa of drug
** Weaker acids better absorbed
* Lipophilicity of the drug
** Lipophilic drugs better absorbed
* Size of the drug
** Smaller = faster/more readily absorbed
* Drug-drug interactions
** E.g. vitamin c increases absorption of iron
** activated charcoal prevents absorption of some drugs through chelation
 
 
 
Patient factors
 
* Gastric emptying time
** Diarrhoea, constipation, ileus will all influence this &gt; slow/fasten absorption
* Food intake
** Drugs can interact with food (e.g. iron absorbed better with orange juice due to vitamin C)
* Altered surface area of the GIT
** E.g. chrons or surgical short gut &gt; decreased absorption
* GIT blood flow
** Reduced blood flow &gt; decreased rate of absorption
* Biliary function
** Emulsifying effect of bile important for absorption of fat soluble vitamins and steroids
* Pancreatic function
 
 
 
<span id="examiner-comments-242"></span>
==== Examiner comments ====
 
<blockquote>45% of candidates passed this question.<br />
This is a very broad and open question. While a structured approach was useful, a sound knowledge of first principles or even being able to “think on the fly” would have provided candidates with enough opportunities to generate a pass.
</blockquote>
 
 
 
 
<span id="2013-1st-sitting"></span>
== 2013 (1st sitting) ==
 
 
 
<span id="question-1-12"></span>
=== Question 1 ===
 
 
 
<span id="question-244"></span>
==== Question  ====
 
List the different mechanisms of drug actions with examples
 
 
 
<span id="answer-5"></span>
==== Answer ====
 
{|
! Classification
! Mechanism
! Example
|-
| '''NON RECEPTOR'''
|
|
|-
| Physiochemical actions
| Drug exerts its effects due to its physiochemical composition
| Antacids (basic) which neutralise gastric acid &gt; decreased GORD symptoms
|-
| Colligative properties
| Drug exerts its effect due to the concentration of solute, not the identity of the solute
| Mannitol &gt; increased plasma osmolality &gt; diuresis
|-
| Actions on enzyme systems
| Decreased concentration of the substrate or product of the enzyme system
| ACE inhibitors &gt; decreased concentration of angiotensin II
|-
| Prodrugs
| Converted from inactive drug &gt; active drug following administration
| Levodopa &gt; dopamine
|-
| Alteration of a carrier protein
| Alter the normal function of a carrier protein
| Frusemide which inhibits NaK2Cl co transporter in LOH &gt; diuresis
|-
| Voltage gated ion channels
| Activated by changes in membrane potential near the ion channel
| Local anaesthetics &gt; block voltage gated Na channels
|-
| '''RECEPTOR'''
|
|
|-
| Binding to intracellular receptors
| Lead to changes in cell function by altering DNA/RNA transcription
| Steroids (nuclear receptor)
|-
| Binding to ionotropic receptors
| Lead to changes in cell function by allowing flow of ions down a concentration/electrical gradient
| GABA<sub>A</sub> receptor: GABA binds &gt; Cl channel opens &gt; hyperpolarisation &gt; inhibitory post synaptic potential
|-
| Binding to metabotropic receptors
| Bind to G protein coupled receptors and lead to changes in cell function through chemical second messenger systems
| Adrenaline binds to Gs PCR in myocardium &gt; activation of cAMP 2nd messenger pathway &gt; increased inotropy
|-
| Binding to enzyme coupled receptors
| Lead to changes in cell function through activation of an intracellular enzyme system
| Tyrosine kinase receptor (class II): insulin binds &gt; activates tyrosine kinases on intracellular domain &gt; phosphorylates IRS &gt; cellular cascade
|}
 
 
 
<span id="examiner-comments-243"></span>
==== Examiner comments ====
 
<blockquote>A good answer to this question required candidates to think broadly about how drugs act and have a system for classifying their actions. One possible classification is action via receptors or non-receptor actions. Many candidates used categories such as physiochemical, receptor and enzymes. Common problems were failure to mention a whole class of drug actions e.g. drugs acting via voltage-gated ion channels or gene transcription regulation. Candidates also gave far too much detail in some sections e.g. a description of zero order and first order kinetics is not required. Candidates often did not give examples of the drug action they described.
</blockquote>
 
 
<span id="online-resources-10"></span>
==== Online resources ====
 
<ul>
<li><p>[https://derangedphysiology.com/cicm-primary-exam/past-papers/2013-paper-1-saqs/question-1#answer-anchor Deranged physiology]</p></li>
<li><p>[https://cicmwrecks.files.wordpress.com/2017/04/2013-1-1-general-moas-for-drugs.pdf CICM Wrecks]</p></li>
<li><p>[https://jennysjamjar.com.au/syllabus/c/ciii-list-the-different-mechanisms-of-drug-actions-with-examples/ Jenny's Jam Jar]</p></li>
<li><p>[https://icuprimaryprep.files.wordpress.com/2015/01/q1-list-the-different-mechanisms-of-drug-actions-with-examples-march-2013.pdf Primary prep]</p>
<p></p></li></ul>
 
 
 
<span id="question-4-13"></span>
=== Question 4 ===
 
 
 
<span id="question-245"></span>
==== Question ====
 
Describe the pharmacology of tranexemic acid.
 
 
 
<span id="answer-6"></span>
==== Answer ====
 
{|
! Name
! Tranexamic acid (TXA)
|-
| '''Class'''
| Antifibrinolytic
|-
| '''Indications'''
| Trauma (within 3 hours)<br />
Cardiac/obstetric/orthopaedic/dental surgery<br />
Haemorrhage/Coagulopathy<br />
Hereditary angioedema<br />
Heavy menstrual bleeding<br />
Epistaxis
|-
| '''Pharmaceutics'''
| 500mg Tablets (PO) <br />
Clear colourless solution (100mg/ml) for injection (IV)
|-
| '''Routes of administration'''
| PO, IV, nebulised, topical, IM
|-
| '''Dose'''
| Trauma: 1 g (slow IV push) --&gt;infusion of 1g over 8 hrs (if needed)<br />
1g TDS/QID (PO) for most other conditions
|-
| pKA
| 10.2
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Competitive inhibition of plasminogen activation<br />
-&gt; binds to lysine binding sites of plasminogen<br />
-&gt; prevents the activation of plasminogen &gt; plasmin <br />
-&gt; decreases fibrinolysis
|-
| Effects
| HAEM: Decreased fibrinolysis &gt; prothrombotic complications in those patients with risk factors <br />
GIT: nausea, vomiting, diarrhoea<br />
CNS: seizures, headache, dizziness (dose related)<br />
CVS: hypotension (rapid administration)<br />
DERM: allergic skin reactions
|-
| '''Pharmacokinetics'''
|
|-
| Onset / duration
| Immediate (IV), 1 hour (IM), 2 hours (PO) <br />
Duration = 18-24 hours
|-
| Absorption
| PO bioavailability = 50%<br />
IM/IV bioavailability 100%
|-
| Distribution
| Protein binding: very low (&lt;5%) <br />
VOD = 0.3L / kg
|-
| Metabolism
| Minimal (&lt;5%) hepatic metabolism<br />
Inactive metabolites
|-
| Elimination
| Renal elimination of active drug (95% unchanged)<br />
T <sub>1/2</sub> = 2hrs (IV), 12 hrs (PO)
|-
| '''Special points'''
| Dose reduce in renal failure
|}
 
 
 
<span id="examiner-comments-244"></span>
==== Examiner comments ====
 
<blockquote>Tranexamic acid is a drug used to reduce bleeding in trauma or surgery. It is also used for hereditary angioedema and menstrual bleeding. It is being increasingly used in critically ill patients. As a Level B listed drug within the Primary Syllabus candidates would be expected to know it in some depth. Often basic information such as mechanism of action, pharmacokinetics and adverse effects was lacking.
</blockquote>
 
 
<span id="online-resources-11"></span>
==== Online resources ====
 
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2013-paper-1-saqs/question-4#answer-anchor Deranged physiology]
* [https://icuprimaryprep.files.wordpress.com/2015/01/q4-describe-the-pharmacology-of-tranexamic-acid-march-2013.pdf ICU Primary prep]
* [https://cicmwrecks.files.wordpress.com/2017/04/2013-1-4-tranexamic-acid.pdf CICM Wrecks]
 
 
 
 
 
 
 
 
 
<span id="question-13-14"></span>
=== Question 13 ===
 
 
 
<span id="question-246"></span>
==== Question  ====
 
Outline the effects of critical illness on drug pharmacokinetics
 
 
 
<span id="example-answer-240"></span>
==== Example answer ====
 
Absorption
 
* Oral
** Decreased CO &gt; decreased GIT blood flow &gt; decreased absorption PO drugs
** Ileus + uraemia &gt; decreased gastric emptying &gt; decreased absorption of PO drugs
** Diarrhoea &gt; fast transit time &gt; decreased absorption
** Change in gastric pH (e.g. with PPI) alters drug absorption
* Topical/IM/SC
** Vasoconstriction &gt; poor tissue perfusion &gt; decreased/slow absorption
* Inhalational
** Decreased MV / TV &gt; decreased delivery of aerosolised medications
 
 
 
Distribution
 
* Altered Vd
** Decreased CO (e.g. shock) &gt; slower redistribution
** Increased CO (e.g. hyperdynamic sepsis) &gt; faster residistribution
** Hypervolaemia (e.g. renal, cardiac, liver failure) &gt; increased Vd (vice versa)
** Critical illness &gt; muscle wasting &gt; alter lean mass percentage (alters Vd)
* Protein binding
** Decreased protein synthesis &gt; increased unbound fraction of drug &gt; increased Vd and activity
** Acid-base disturbances will alter free drug levels depending on drug pKa and the pH
* Inflammation &gt; impairs barrier function (e.g. BBB) &gt; increased penetration of meds (e.g. penicillins)
 
 
Metabolism
 
* Decreased CO &gt; decreased hepatic/renal blood flow &gt; decreased metabolism (e.g. propofol)
* Liver dysfunction &gt; Impaired phase 1 and 2 reactions and reduced 1st pass effect &gt; (e.g. labetalol, metoprolol)
* Renal dysfunction &gt; decreased renal metabolism &gt; prolonged drug effect (e.g. morphine)
* Hypothermia &gt; decreased metabolism &gt; Prolonged effect (e.g midazolam)
* Resp dysfunction &gt; Decreased resp metabolism of drugs (e.g. opioids) &gt; prolonged effect
 
 
 
Elimination
 
* Decreased CO (e.g. cardiogenic shock) = decreased GFR / HBF &gt; decreased clearance (e.g. gentamicin)
* Increased CO (e.g. hyperdynamic sepsis) &gt; increased GFR &gt; increased clearance
* Liver dysfunction &gt; impaired biliary excretion of drugs (e.g. vecuronium)
* Decreased GFR (e.g. AKI) &gt; decreased renal elimination drugs (e.g. Gentamicin, milrinone)
* Reduced MV &gt; decreased / slower clearance of volatile anaesthetics &gt; prolonged effect
 
 
 
<span id="examiner-comments-245"></span>
==== Examiner comments ====
 
<blockquote>Most candidates answered the question under the subheadings absorption, distribution, metabolism and elimination. However, they didn’t give any details of the direction or mechanism of change, often used vague statements without specifically addressing the question and failed to give examples. The impact of the shock state on different kinetic parameters including absorption from skin, tissue, muscles, enteral absorption and inhalational was often overlooked. Similarly, the consequences of changes in volume of distribution, protein binding (e.g. albumin and globulin, ionisation) was poorly understood as was alteration in liver and kidney function. Although this topic is very broad candidates were asked to only outline the details of this topic
</blockquote>
 
 
 
 
 
 
<span id="question-23-4"></span>
=== Question 23 ===
 
 
 
<span id="question-247"></span>
==== Question ====
 
How do chemical messengers in the extracellular fluid bring about changes in cell function? Give an example of a chemical messenger for each mechanism noted
 
 
 
<span id="example-answer-241"></span>
==== Example Answer ====
 
 
 
Chemical messengers (ligands) bind to receptors to elicit a response.
 
Receptors may be located on the cell surface or within the cell.
 
 
 
Intracellular receptors
 
* Proteins located in the cytosol or cell nucleus
* Activated by lipid soluble ligands (as they must be able to penetrate the lipid bilayer)
* Lead to changes in cell function by altering DNA/RNA transcription
* Example:
** Steroids (nuclear receptor) and milrinone (cytosolic receptor)
** Specific effects depend on the ligand and the receptor location
 
 
 
Ionotropic receptors
 
* Membrane spanning proteins
* Lead to changes in cell function by allowing flow of ions down a concentration/electrical gradient
* Examples:
** GABA<sub>A</sub> receptor: GABA binds &gt; Cl channel opens &gt; hyperpolarisation &gt; inhibitory post synaptic potential (drug example = benzos)
** nAChR receptor: acetylcholine binds &gt; non selective cation channel opening - Na/K/Ca &gt; depolarisation &gt; excitatory post synaptic potential (drug example is sux, which is agonist)
** NMDA receptor: glutamate binds &gt; non selective cations &gt; Na/K/Ca &gt; depolarisation &gt; excitatory post synaptic potential (drug example = ketamine which is an antagonist)
 
 
 
Metabotropic (G protein coupled) receptors
 
<ul>
<li><p>Transmembrane proteins with 7 regions</p></li>
<li><p>Lead to changes in cell function through chemical second messenger systems</p>
<ul>
<li><p>Activation of the extracellular domain &gt; conformation change in intracellular domain &gt; activation of G proteins &gt; second messenger pathway</p></li></ul>
</li>
<li><p>Three subtypes</p>
<ul>
<li><p>Gs (stimulatory; increased cAMP)</p>
<ul>
<li><p>Example: adrenaline (beta-1 receptor) &gt; increased inotropy</p></li></ul>
</li>
<li><p>Gi (inhibitory; decreased cAMP)</p>
<ul>
<li><p>Example: clonidine (alpha-2 receptor) &gt; decreased SNS outflow</p></li></ul>
</li>
<li><p>Gq (stimulatory; increased IP3)</p>
<ul>
<li><p>Example: noradrenaline (alpha-1 receptor) &gt; vasoconstriction</p></li></ul>
</li></ul>
 
<p></p></li></ul>
 
Enzyme coupled receptors
 
* Transmembrane protein receptor linked to an intracellular receptor
* Lead to changes in cell function through activation of an intracellular enzyme
* Example
** Tyrosine kinase receptor (class II): insulin binds &gt; activates tyrosine kinases on intracellular domain &gt; phosphorylates IRS &gt; cellular cascade
 
 
 
<span id="examiner-comments-246"></span>
==== Examiner comments ====
 
<blockquote>Overall answers lacked structure and depth, to what is a very fundamental topic. This topic is generally covered within the opening chapters of most physiology texts. Common errors were not answering the question, writing lists rather than describing and explaining, and poor categorisation. Candidates were expected to mention and give example for mechanisms such as hormones binding to cytoplasmic or intra-nuclear receptors, binding to transmembrane receptors coupled to G proteins, cAMP, cGMP, tyrosine kinase, etc.
</blockquote>
 
 
<span id="online-resources-12"></span>
==== Online resources ====
 
* [https://cicmwrecks.files.wordpress.com/2019/04/2013-1-23.pdf CICM Wrecks]
* [https://icuprimaryprep.files.wordpress.com/2015/01/q23-how-do-chemical-messengers-in-the-extracellular-fluid-bring-about-changes-in-cell-function_-give-an-example-of-a-chemical-messenger-for-each-mechanism-noted-march-2013.pdf Primary prep]
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2013-paper-1-saqs/question-23#answer-anchor Deranged physiology]
 
 
 
 
 
<span id="question-24-5"></span>
=== Question 24 ===
 
 
 
<span id="question-248"></span>
==== Question ====
 
Describe the mechanism of action and side effects of 3 classes of drugs that increase uterine tone and 3 classes of drugs that decrease uterine tone.
 
 
 
<span id="answer-7"></span>
==== Answer ====
 
 
 
INCREASE TONE
 
{|
! '''Class'''
! Oxytocin derivative
! Ergot derivative
! Prostaglandin
|-
| '''Example'''
| Syntocin
| Ergometrine
| Carboprost
|-
| '''MOA'''
| Binds to GqPCR in uterus &gt; IP3/DAG pathway &gt; uterine contraction
| Not fully understood
| Synthetic PGF2a analogue &gt; binds to PG receptor &gt; myometrial contraction
|-
| '''Effects'''
| - Uterine SM contraction <br />
- Weak antidiuretic effect
| - Uterine SM contraction
| - Uterine SM contraction
|-
| '''Side effects'''
| IMMUNO: Allergic reactions<br />
CVS: transient hypotension &gt; reflex tachycardia, arrhythmias, flushing<br />
CNS: headache<br />
GIT: nausea, vomiting
| CVS: Hypertension<br />
GIT: nausea, vomiting, abdominal pain
| CVS: Severe hypertension<br />
RESP: bronchospasm (rare)<br />
GIT: nausea, vomiting, abdominal pain<br />
OTHER: fever
|}
 
 
 
DECREASE TONE
 
{|
! Class
! Beta agonist
! CCB
! NSAIDs
|-
| '''Example'''
| Salbutamol
| Nifedipine
| Indometacin
|-
| '''MOA'''
| Activate B2 receptors (GsPCR), ↑ cAMP &gt; activates protein kinase A &gt; inhibition of MLCK &gt; relaxation
| Block L-type Ca2+ channels, causing relaxation of SM
| Inhibit prostaglandin synthesis (via inhibition of COX1/2) &gt; decreased uterine contraction
|-
| '''Effects'''
| Decrease uterine tone
| Decrease uterine tone
| Decrease uterine tone
|-
| '''Side effects'''
| CNS: headacge, hyperactivity<br />
CVS: tachycardia, palpitations<br />
CNS: Anxiety, tremor<br />
RENAL: hypokalaemia<br />
HAEM: lactatemia, hyperglycaemia
| CVS: hypotension, flushing, pulmonary oedema<br />
CNS: headache, dizziness<br />
GIT: nausea, vomiting
| Mother: gastritis, nausea, vomiting, platelet dysfunction, AKI<br />
Baby: premature closure of ductus arteriosus
|}
 
 
 
<span id="examiner-comments-247"></span>
==== Examiner comments ====
 
<blockquote>Candidates often appeared to have a sufficient awareness of the choice of drugs (e.g. oxytocin analogues, ergot alkaloids, beta-receptor agonists, calcium channel blockers, etc.), but then failed to produce sufficient depth of knowledge to adequately describe their mechanisms of action in respect to uterine tone. Candidates are reminded that if asked to mention side effects, mentioning side effects of greatest relevance to intensive care (e.g. bronchospasm) in addition to the more generic side effects (e.g. rash).
</blockquote>
 
 
<span id="online-resources-13"></span>
==== Online resources ====
 
* [https://icuprimaryprep.files.wordpress.com/2015/01/q24-describe-the-mechanism-of-action-and-side-effects-of-three-3-classes-of-drugs-that-are-used-to-increase-uterine-tone-and-three-3-classes-of-drugs-used-to-decrease-uterine-tone.pdf ICU Primary prep]
* [https://cicmwrecks.files.wordpress.com/2017/04/2013-1-24-uterine-tone.pdf CICM Wrecks]
* [Deranged physiology](
 
 
 
 
 
 
 
<span id="2013-2nd-sitting"></span>
== 2013 (2nd sitting) ==
 
 
 
<span id="question-6-12"></span>
=== Question 6 ===
 
 
 
<span id="question-249"></span>
==== Question ====
 
Describe the pharmacology of short acting insulin (actrapid).
 
 
 
<span id="answer-8"></span>
==== Answer ====
 
{|
! Name
! Short acting insulin (e.g. actrapid)
|-
| '''Class'''
| synthetic polypeptide hormone
|-
| '''Indications'''
| Diabetes / hyperglycaemia<br />
Hyperkalaemia (in conjunction with dextrose)<br />
B-blocker toxicity (high dose insulin therapy)
|-
| '''Pharmaceutics'''
| Clear colourless solutions (generally 100IU/ml)
|-
| '''Routes of administration'''
| SC, IV
|-
| '''Dose'''
| Variable, titrated to effect (generally bSL)
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| The same pharmacodynamic profile of endogenous insulin <br />
&gt; Insulin binds to the alpha subunit of the insulin receptor (tyrosine kinase receptor). Leads to activation of tyrosine kinases on intracellular domain &gt; phosphorylates IRS &gt; cellular cascade
|-
| Effects
| Increased: glucose uptake in cells, glycogenesis, protein synthesis <br />
Decreased: BSL, gluconeogenesis, lipolysis, proteolysis <br />
Cellular shift of potassium (intracellular) due to increased Na/K activity
|-
| Side effects
| Hypoglycaemia (excessive dosing) --&gt; decreased LOC, seizures, death<br />
Hyperglycaemia / DKA (inadequate dosing)<br />
Hypokalaemia --&gt; arrhythmias <br />
Weight gain (long term)
|-
| '''Pharmacokinetics'''
|
|-
| Profile (SC admin)
| Onset: 15-30 mins<br />
Peak: 1-2 hours<br />
Duration: 6-8 hours
|-
| Absorption
| No oral absorption (inactivated by GIT enzymes)<br />
SC administration is close to 100%
|-
| Distribution
| Protein binding &lt;10% <br />
VOD = &lt; 0.1 L/Kg
|-
| Metabolism
| Hepatic proteases
|-
| Elimination
| Renal elimination of inactive metabolites<br />
T 1/2B = 90 mins
|-
| '''Monitoring'''
| BSL levels (frequency depends on indication, glycaemic stability, route etc)
|}
 
 
 
<span id="examiner-comments-248"></span>
==== Examiner comments ====
 
<blockquote>In general candidates lacked a sufficient depth of knowledge for this commonly used drug. Some candidates confused actrapid with novo rapid. A structured approach (e.g. pharmaceutics, mode of action, pharmacokinetics, etc.) was expected.
</blockquote>
 
 
<span id="online-resources-14"></span>
==== Online resources ====
 
* [https://icuprimaryprep.files.wordpress.com/2015/01/q6-describe-the-pharmacology-of-short-acting-insulin-actrapid-sept-2013.pdf ICU Primary prep]
* [https://cicmwrecks.files.wordpress.com/2017/04/2013-2-6-pharmacology-of-actrapid.pdf CICM Wrecks]
* [Deranged physiology](
 
 
 
 
 
<span id="2012-2nd-sitting"></span>
== 2012 (2nd sitting) ==
 
 
 
<span id="question-5-13"></span>
=== Question 5 ===
 
 
 
<span id="question-250"></span>
==== Question ====
 
How does liver failure affect the pharmacology of drugs?
 
 
 
<span id="example-answer-242"></span>
==== Example answer ====
 
Absorption
 
<ul>
<li><p>Drugs which are absorbed orally are subject to first pass metabolism by the liver</p></li>
<li><p>Liver failure &gt; decreased first pass metabolism &gt; increased bioavailability &gt; potential for toxicity</p></li>
<li><p>oedema (from liver failure) &gt; impair subcut absorption </p>
<p></p></li></ul>
 
Distribution
 
* The liver is responsible for producing majority of the proteins that drugs bind to in plasma
* Therefore liver failure &gt; decreased plasma proteins
* Highly protein bound drugs (e.g. warfarin) are greatly affected by reduced plasma proteins
** Small decrease in plasma protein levels &gt; large change in the proportion of unbound (active) drug
 
 
 
Metabolism
 
* The liver is a primary organ of drug metabolism and biotransformation
** Phase 1 reactions by liver
*** Hydrolysis, Reduction, Oxidation
*** Small increase in hydrophilicity
** Phase 2 reactions
*** Glucuronidation, sulfation, conjugation, methylation
*** Significantly increased hydrophilicity (for renal excretion)
* Liver damage &gt; impaired metabolism / biotransformation &gt; accumulation &gt; toxicity (e.g. diazepam in liver failure)
* Portal hypertension &gt; shunting of blood &gt; decreased first pass metabolism &gt; accumulation
 
 
 
Elimination
 
* Liver failure &gt; decreased hepatic blood flow &gt; decreased elimination of drugs with high hepatic extraction ratio
* Liver failure &gt; decreased elimination of drugs with low hepatic extraction ratio (regardless of HBF)
* Liver failure &gt; decreased plasma proteins &gt; increased unbound fraction drug &gt; increased renal elimination of hydrophilic drugs
* Liver failure &gt; decreased elimination on lipophilic drugs excreted in biliary system
 
 
 
<span id="examiner-comments-249"></span>
==== Examiner comments ====
 
<blockquote>59% of candidates passed this question.<br />
Good answers were structured using pharmacokinetic and pharmacodynamics headings.<br />
They included some mention of changes in absorption, volume of distribution (an increase<br />
in Vd in liver failure), altered protein binding, altered metabolism and thus change in<br />
clearance, and changes in excretion (decreased biliary excretion of drugs). In respect to<br />
pharmacodynamics candidates could have mentioned increased sensitivity and prolonged<br />
action of sedative drugs, oral anticoagulants, etc. Good candidates also differentiated for<br />
acute (often hepatocellular dysfunction) and chronic liver failure (cirrhosis and changes in<br />
liver blood flow). Common problems were not using a logical structure to answer the<br />
question and stating an effect but not describing how this affected pharmacology. For<br />
example stating decreased albumin production but then not stating the consequence of this<br />
on drug distribution. Primary examination questions may often require candidates to<br />
integrate knowledge from across different sections of the syllabusor apply basic<br />
physiological or pharmacological principles.
</blockquote>
 
 
<span id="question-9-13"></span>
=== Question 9 ===
 
 
 
<span id="question-251"></span>
==== Question  ====
 
Classify the anti-arrhythmic drugs using the Vaughan-Williams classification (30% of marks). Compare and contrast the electrophysiological effects of Class 1 anti-arrhythmics (70% marks).
 
 
 
<span id="answer-9"></span>
==== Answer ====
 
{|
! Class
! Ia
! Ib
! Ic
! II
! III
! IV
|-
| Mechanism
| Blocks Na channels
| Blocks Na channels
| Blocks Na channels
| \beta-adrenergic blockade
| Blocks K+ channels
| Blocks Ca channels
|-
| Example
| Procainamide
| Lidocaine
| Flecainide
| Propranolol Esmolol, Atenolol Sotalol
| Amiodarone (also I,II,IV effects) Sotalol
| Verapamil Diltiazem
|-
| '''Effects on'''
|
|
|
|
|
|
|-
| Phase 0
| ↓
| -
| ↓
| -
| -
| -
|-
| Conduction velocity
| ↓
| -
| ↓
| ↓
| ↓
| -
|-
| ERP
| ↑
| ↓
| ↑
| ↓
| ↑
| -
|-
| APD
| ↑
| ↓
| -
| ↑
| ↑
| ↓
|-
| QRS duration
| ↑
| -
| ↑
| -
| ↑
| -
|-
| QTc
| ↑
| ↓
| ↑
| ↓
| ↑
| -
|}
 
Drugs not included
 
* Digoxin
* Adenosine
* Magnesium
 
 
 
<span id="examiner-comments-250"></span>
==== Examiner comments ====
 
<blockquote>Most candidates displayed a basic knowledge of the Vaughan-Williams classification and gave an example of each class. The remainder of the question lent itself very well to a tabular format. Better answers included the effect on the action potential (diagrams were useful here), channel dissociation kinetics (this was frequently omitted) and examples from each class of drug. There is an excellent table in Stoelting which answers this question nicely. Marks were not awarded for clinical effects. Overall, this question was generally well answered.
</blockquote>
 
 
 
 
<span id="question-13-15"></span>
=== Question 13 ===
 
 
 
<span id="question-252"></span>
==== Question ====
 
Describe the effects of obesity on drug pharmacology (70% of marks). Give examples of those drugs that illustrate those effects (30% of marks)
 
 
 
<span id="example-answer-243"></span>
==== Example answer ====
 
Obesity
 
* BMI &gt; 30
* Alters all aspects of pharmacology to varying degrees
 
 
PHARMACOKINETICS
 
 
 
Absorption
 
* Increased gastric emptying &gt; increased absorption
* Decreased subcutaneous blood flow (increased adiposity, no increase in vascularity) &gt; slow rate of SC absorption
* Difficulty with IM administration due to tissue (may lead to inadvertent SC injection)
* Increased CO &gt; delayed onset of inhalation anaesthetics
 
 
Distribution
 
* Increased body adiposity &gt; Increased volume of distribution of lipid soluble drugs (e.g. benzodiazipines, thiopentone)
* Small (relative to body fat) increased Vd for hydrophilic drugs e.g. gentamicin (due to increased blood volume, total body water).
* Generally lipid soluble drugs dosed on actual body weight, hydrophilic drugs on ideal body weight
 
 
Metabolism
 
* Increased hepatic blood flow (due to increased CO) = increased clearance of high extraction ratio drugs (flow dependant extraction) e.g. propofol
* Decreased hepatic blood flow (due to dysfunction, fatty infiltration) &gt; decreased hepatic extraction and metabolism
* Increased activity of plasma and tissue esterases &gt; increased metabolism/clearance of drugs using these systems (e.g. remifentanil)
* Increased pseudocholinesterase levels in obesity (sux to be doses on total body weight)
 
 
Elimination
 
* Increased GFR (due to increased CO) – increased renal clearance of hydrophilic drugs (e.g vancomycin)
* Decreased GFR due to diabetic nephropathy = decrease renal clearance
* Due to distribution, lipid soluble drugs may have increased elimination half life
 
 
PHARMACODYNAMICS
 
* Receptor resistance (e.g. insulin resistance in obesity)
 
 
 
<span id="examiner-comments-251"></span>
==== Examiner comments ====
 
<blockquote>36 % of candidates passed this question.<br />
This question could be approached by describing the effects of obesity on drug distribution,<br />
binding and elimination. Candidates that took this approach generally did better than those<br />
with a less structured approach. With obesity, fat body mass increases relative to the<br />
increase in lean body mass leading to an increased volume of distribution particularly for<br />
highly lipid soluble drugs, e.g. midazolam. However, the dosing of non-lipid soluble drugs,<br />
e.g. non-depolarising muscle relaxants, should be based on ideal body weight. An increase in<br />
blood volume and cardiac output associated with obesity may require an increased loading<br />
dose to achieve a therapeutic effect, e.g. thiopentone. Plasma protein binding of drugs may<br />
be decreased due to an increased binding of lipids to plasma proteins, resulting in an<br />
increased free fraction of drug. A reduction in plasma protein concentration due to an<br />
increase in acute phase proteins may also result in decreased plasma protein drug binding<br />
and increased free fraction of drug. Pseudocholinesterase levels are increased in obesity and<br />
therefore the dose of suxamethonium should be based on total body weight. Plasma and<br />
tissue esterase levels are increased resulting in the increased clearance of drugs by these<br />
enzymes e.g. remifentanil. Hepatic clearance is usually normal but may be impaired in liver<br />
disease caused by obesity. Renal clearance is usually increased due to increased body<br />
weight, increased renal blood flow and increased glomerular filtration rate. Renal clearance<br />
may be impaired in renal disease caused by obesity related diseases, e.g. diabetes. Insulin<br />
doses may be increased due to peripheral insulin resistance in type 2 diabetes caused by<br />
obesity. Most answers were deficient in examples of drugs to illustrate the effects of obesity<br />
on drug pharmacology.
</blockquote>
 
 
 
 
<span id="question-20-14"></span>
=== Question 20 ===
 
 
 
<span id="question-253"></span>
==== Question ====
 
What are drug enantiomers? (20% of marks). Explain the clinical relevance of enantiomers (60% marks). Give clinically relevant example (20% of marks)
 
 
 
<span id="example-answer-244"></span>
==== Example answer ====
 
Enantiomers
 
* A stereoisomer which has identical chemical formula and bond structure, but the relative positions of the functional groups in 3D space differ such that the molecules are not superimposable (they form mirror images of each other)
* Named according to their absolute configurations in 3D space
** R (rectus) atomic numbers descend clockwise
** S (sinister) atomic numbers descend anticlockwise
 
 
 
Example
 
* Ketamine is typically presented in a racemic mixture
* However, R- is less effective and has a higher incidence of adverse effects compared to S+ ketamine enantiomer.
 
 
Relevance
 
* Enantiomers, due to their different configurations in space, interact differently with receptors, transport proteins and enzymes &gt; differing pharmacokinetics and dynamics
* Pharmaceutics
** Enantiopure preparations are more expensive (hence racemic mixtures more common)
* Pharmacodynamics
** Will interact with receptors differently &gt; differing degrees of agonism/antagonism + also compete for receptors &gt; variable effects (R-ibuprofen 100X more portent inhibitor COX than S ibuprofen)
** Enantiopure preparations are more likely to include the most active or least toxic isomer (e.g. s-ketamine)
* Pharmacokinetics
** Absorption
*** No change in passive absorption
*** Active transport may favour one enantiomer over another (e.g methotrexate)
** Distribution
*** Stereoselectivity in protein binding which will also affect the Volume of distribution and proportion of active drug (e.g. propranolol)
** Metabolism
*** Stereoselectivity in metabolism due to varying degrees of interaction with enzymes (e.g. warfarin and CYP450)
** Elimination
*** Stereoselectivity in elimination (e.g. ibuprofen)
 
 
 
<span id="examiner-comments-252"></span>
==== Examiner comments ====
 
<blockquote>41% passed
 
Enantiomers refer to isomeric molecules with centres of asymmetry in 3 dimensions that are mirror images of each other but not superimposable. Enantiomers may be distinguished by the direction in which polarised light is rotated. Interactions involving weak drug-receptor bonds feature a dependence upon recognition of shape, i.e. stereochemical structure is often important. Frequently one enantiomer may bind to a given receptor more avidly than the other, thus pharmacodynamics, pharmacokinetics and toxicity may vary between enantiomers. Many drugs are supplied as racemic mixtures, the components of which have different activity. Clinically relevant examples that candidates could have mentioned, included bupivacaine, ropivacaine, ketamine and carvedilol.
</blockquote>
 
 
 
 
<span id="2011-1st-sitting"></span>
== 2011 (1st sitting) ==
 
 
 
<span id="question-14-12"></span>
=== Question 14 ===
 
 
 
<span id="question-254"></span>
==== Question  ====
 
Describe the mechanisms of action and adverse effects of pulmonary vasodilators that are administered via the inhalational route.
 
 
 
<span id="answer-10"></span>
==== Answer ====
 
 
 
Oxygen
 
* A pulmonary vasodilator in hypoxic patients (reverses hypoxic pulmonary vasoconstriction)
* MOA
** Initial phase HPVC: Decreased O2 (hypoxia) &gt; altered redox state in mitochondria of SM muscles &gt; inhibition of K channels &gt; depolarisation &gt; Ca influx &gt; vasoconstriction
** Prolonged hypoxia: maintains HPVC through decreased NO release +release of endothelin derived vasoconstrictors
** O2 therefore reverses this process of HPVC
* Effects
** RESP: improved oxygen saturations (may also improve DO2), decreased respiratory drive (minor), pulmonary toxicity (free radical generation), may worsen V/Q mismatch, absorption atelectasis, hypercapnoea (in chronic CO2 retainers)
** CVS: decreased pulmonary vascular resistance (vasodilation) due to reversal of HPV, increased HR/SV/SVR in setting of hypoxia (via chemoreceptor reflex) &gt; increased CO and BP, coronary vasoconstriction
** CNS: anxiety, nausea, seizures (hyperbaric hyperoxia)
** MET: oxidative phosphorylation &gt; ATP production
 
 
 
Nitric oxide
 
* Class:
** Pulmonary vasodilator / Inorganic gas
* MOA:
** Binds to guanyl cyclase &gt; Increases cGMP &gt; reduction in intracellular Ca &gt; relaxation of SM.
** As inhaled &gt; selectively vasodilates in regions of well ventilated alveoli
* Effects
** RESP: pulmonary artery vasodilation &gt; improves V/Q matching &gt; dec. WOB
** CVS: decreased pulmonary VR, decreased mPAP, decreased RHS, hypotension, rebound pHTN following cessation
** CNS: Increased CBF
** HAEM: thrombocytopaenia, methemoglobinemia
 
 
 
Prostacyclin
 
* Class
** Pulmonary vasodilator / prostacyclin analogue
* MOA:
** Binds to prostacyclin receptor (IP receptor) &gt; Activates GPCR &gt; increases cAMP &gt; decreased platelet activation and increased SM relaxation.
** If given inhaled &gt; local effects in regions of well ventilated alveoli only
* Effects
** RESP: pulmonary arterial vasodilation &gt; improve V/Q matching + oxygenation in patients with ARDS if inhaled (goes to ventilated regions only), but may worsen it if given intravenously (goes to all pulmonary blood vessels &gt; worsening shunt)
** HAEM: inhibition of platelet aggregation &gt; increased risk bleeding
** CVS: flushing, hypotension, reflex tachycardia, decreased pulmonary vascular resistance and mPAP &gt; decreased RV afterload (may improve CO in RHF)
** CNS: headache, increased CBF
 
 
 
<span id="examiner-comments-253"></span>
==== Examiner comments ====
 
<blockquote>Many candidates neglected to include oxygen which is also a drug with significant pulmonary vasodilating properties. Accurate detail concerning the receptor and second messenger effects of drugs was expected. The importance of V/Q matching and reduction in systemic effects via inhalational administration needed to be stated. Better answers included discussion of serious adverse effects such as methaemoglobinaemia, acute lung injury, systemic hypotension, rebound phenomena and heart failure.
</blockquote>
 
 
<span id="online-resources-15"></span>
==== Online resources ====
 
* [https://derangedphysiology.com/main/cicm-primary-exam/required-reading/respiratory-system/Chapter%20313/pharmacology-pulmonary-vasodilators Deranged physiology]
* [https://cicmwrecks.files.wordpress.com/2017/04/2011-1-14-pulmonary-vasodilators.pdf CICM Wrecks]
* [https://icuprimaryprep.files.wordpress.com/2012/05/q14-describe-the-mechanism-of-action-and-adverse-effects-of-pulmonary-vasodilators-that-are-administered-via-the-inhalational-route-march-2011.pdf Primary prep]
 
 
 
 
 
 
 
<span id="2010-2nd-sitting"></span>
== 2010 (2nd sitting) ==
 
 
 
<span id="question-5-14"></span>
=== Question 5 ===
 
 
 
<span id="question-255"></span>
==== Question ====
 
List the antiplatelet drugs and outline their mechanism of action, adverse effects, mode of elimination and duration of action
 
 
 
<span id="answer-11"></span>
==== Answer ====
 
{|
! Class
! Example
! Mechanism of action
! Elimination
! Reversibility
! Duration of antiplatelet effect
! Adverse effects
|-
| COX inhibitors
| Aspirin
| Inhibits COX on platelets &gt; ↓ thromboxane A2 &gt; ↓ platelet aggregation and activation
| Renal (100%)
| Irreversible inhibition
| Life of platelet (~7 days)
| -Haemorrhage<br />
- GIT ulcers<br />
- Allergy, angioedema, bronchospasm<br />
- AKI
|-
| ADP receptor antagonists
| Clopidogrel
| Binds to P2Y<sub>12</sub> subtype of the ADP receptor on platelets &gt; ↓ GP IIb/IIIa activation &gt; ↓ platelet activation
| Renal (50%) Faecal (50%)
| Irreversible inhibition
| Life of platelet (~7 days)
| - Haemorrhage<br />
- Non responder (CYP2C19 polymorphism)<br />
-CYP450 drug interactions<br />
- aplastic anaemia, thrombocytopaenia, anaemia, <br />
- GIT ulcers<br />
- Rash, urticaria, angioedema, TTP
|-
|
| Prasugrel
| As above
| Renal (70%)<br />
Faecal (30%)
| Irreversible inhibition
| Life of platelet (~7 days)
| - Haemorrhage<br />
- Rash, urticaria, angioedema, TTP
|-
|
| Ticagrelor
| As above (but binds to a different binding site)
| Faecal (70%)<br />
Renal (30%)
| Reversible inhibition
| 2-3 days
| - Haemorrhage<br />
- Dyspnoea<br />
- Rash, urticaria, angioedema, TTP
|-
| GP IIb/IIIa receptor antagonists
| Abciximab
| Directly bind to GP IIb/IIIa and block the final common pathway of platelet aggregation
| Renal
| Reversible inhibition
| 1-2 days
| - Haemorrhage<br />
- ↓ PLTs
|-
|
| Tirofiban
| As above
| Renal (70%)<br />
Faecal (30%)
| Reversible inhibition
| 4-6 hours
| - Haemorrhage<br />
- ↓ PLTs, TTP<br />
- Allergy
|-
| Phospho-diesterase inhibitors
| Dipyridamole
| Inhibits platelet adhesion to walls (by inhibiting adenosine uptake). Also inhibits phosphodiesterase activity &gt; increased cAMP &gt; decreased calcium &gt; inhibition of platelet aggregation
| Faecal
| Reversible inhibition
| 1-2 days
| - Haemorrhage<br />
- Hypotension<br />
- GIT upset (nausea, vomiting, diarrhoea)<br />
-Rash, urticaria
|-
| Prostacyclins
| Epoprostenol
| Binds to IP receptors &gt; increased cAMP &gt; ↓ calcium &gt; ↓ platelet aggregation
| Renal (70%), Faecal (15%)
| Reversible inhibition
| &lt; 5 mins
| - Hypotension, headache, flushing, Haemorrhage
|}
 
[[File:https://www.mja.com.au/sites/default/files/issues/178_11_020603/han10033_fm-1.gif|thumb|none]]
 
<span id="examiner-comments-254"></span>
==== Examiner comments ====
 
<blockquote>67% of candidates passed this question
 
Most candidates did reasonably well by including aspirin, ADP receptor blockade and glycoprotein 2b/3a blockade in their answers. The best approach to answer this type of question was to use a table with each anti-platelet agent within a column and headings for the rows such as mechanisms of action, adverse effects, mode of elimination and duration of action.<br />
Common omissions included the irreversibility of the blockade of the platelet function by many of these agents, renal toxicity and bronchospasm as side effects of aspirin, bone marrow toxicity of ADP receptor blockers, and dipyridamole as an anti-platelet agent. Some candidates classified clopidogrel as a glycoprotein 2b/3a blocker incorrectly and thought clopidogrel has a relative short duration of action on platelet function because of its half-life. Clopidogrel as a prodrug requiring activation by cytochrome P450 and hence significant potential drug interactions were not mentioned by any candidates.
</blockquote>
 
 
<span id="online-resources-16"></span>
==== Online resources ====
 
* [https://icuprimaryprep.files.wordpress.com/2012/05/q5-list-the-antiplatelet-agents-and-outline-their-mechanisms-of-action-adverse-effects-mode-of-elimination-and-duration-of-action-sept-2010.pdf ICU Primary Prep]
* [https://derangedphysiology.com/main/cicm-primary-exam/required-reading/haematological-system/Chapter%20221/antiplatelet-agents Deranged physiology]
* [https://ketaminenightmares.com/pex/saqs/pharmacology/haemostasis_drugs/2008B07_anti_platelets.htm Ketamine nightmares]
 
 
 
 
 
 
 
<span id="question-20-15"></span>
=== Question 20 ===
 
 
 
<span id="question-256"></span>
==== Question ====
 
Outline the pharmacokinetic consequences of old age. Illustrate your answer with examples
 
 
 
<span id="example-answer-245"></span>
==== Example answer ====
 
Absorption
 
* Decreased cutaneous blood flow &gt; slower/reduced absorption of transdermal (GTN patch) and subcut routes (e.g. heparin)
* Decreased intestinal absorptive capacity with age &gt; decreased PO absorption (e.g. digoxin)
* Decreased gastric emptying rate &gt; decreased PO absorption (e.g. digoxin)
* Decreased acid secretion &gt; increased pH gastric &gt; decreased absorption strong acids (e.g. amoxicillin)
 
 
Distribution
 
* Decreased TBW &gt; decreased Vd of hydrophilic drugs &gt; increased effect (e.g. ethanol, gentamicin)
* Increased fat / decreased muscle mass &gt; increased Vd of lipophilic drugs &gt; prolonged effect (e.g. amiodarone, diazepam)
* Decreased plasma proteins (e.g. albumin) &gt; increased unbound (active) drug &gt; increased redistribution and potency (e.g. phenytoin, warfarin)
* Reduced CO &gt; altered redistribution
 
 
Metabolism
 
* Decreased portal blood flow = increased oral bioavailability (e.g. labetalol)
* Decreased hepatic blood flow = decreased clearance (e.g. morphine) and phase 1 metabolism (e.g. ibuprofen)
* Decreased hepatic tissue mass = decreased Phase 1 reaction (e.g. ibuprofen)
 
 
Elimination
 
* Decreased renal mass / nephrons with age &gt; decreased GFR &gt; reduced clearance &gt; prolonged effects (e.g. vancomycin) or increased toxicity (e.g. gentamicin)
* Decreased hepatic blood flow / tissue mass &gt; impaired liver/GIT clearance of drugs (e.g. morphine)
 
 
 
<span id="examiner-comments-255"></span>
==== Examiner comments ====
 
<blockquote>53% of candidates passed this question.<br />
As the general population ages, and many elderly are admitted to intensive care units and/or<br />
encountered during intensive care ward consultations, this topic is highly relevant. Unfortunately<br />
candidate performance generally lacked sufficient depth and breadth in this area. Good answers<br />
were expected to mention changes in body compartments (eg total body water, lean body mass<br />
decrease, etc), consequences of changes in organ function (eg deteriorating glomerular filtration<br />
rate, reduced liver blood flow, etc), alterations in protein levels and binding, increased likelihood of<br />
drug interactions and the influence of disease states.
</blockquote>
 
 
<span id="question-24-6"></span>
=== Question 24 ===
 
 
 
<span id="question-257"></span>
==== Question ====
 
Classify anti-hypertensive agents by their mechanism of action with a brief outline of each mechanism and an example of a drug in each class.
 
 
 
<span id="answer-12"></span>
==== Answer ====
 
 
 
'''Sympatholytic's'''
 
{|
! Class
! Example
! MOA
|-
| Alpha blockers
| Prazosin
| <math display="inline">\alpha</math><sub>1</sub> antagonist &gt; arterial and venous vasodilation &gt; ↓ SVR &gt; ↓ BP
|-
| Beta blockers
| Metoprolol
| <math display="inline">\beta</math><sub>1</sub> antagonist &gt; ↓ inotropy and ↓ chronotropy &gt; ↓ BP
|-
| Centrally acting
| Clonidine
| Central <math display="inline">\alpha</math><sub>2</sub> agonist &gt; ↓ SNS tone (via ↓ NA release) &gt; ↓ BP
|}
 
 
 
'''RAAS inhibitors'''
 
{|
! Class
! Example
! MOA
|-
| ACE inhibitors
| Ramipril
| Block the conversion of angiotensin I to angiotensin II by ACE &gt; decreased AG2 &gt; ↓ SVR and ↑ natriuresis &gt; ↓ BP
|-
| ARBs
| Candesartan
| Same as ACEI (above) but blocks AG2 directly.
|}
 
 
 
'''Calcium channel blockers'''
 
{|
! Class
! Example
! MOA
|-
| Dihydropyridine
| Amlodipine
| Blocks L-Type calcium channels in SM &gt; ↓ intracellular Ca &gt; vasodilation &gt; ↓ SVR &gt; ↓ BP
|-
| Non-dihydropyridine
| Verapamil
| Same as dihydropyridines, but additionally preferentially acts on cardiac cells &gt; ↓ HR and ↓ contractility &gt; ↓BP
|}
 
 
 
'''Diuretics'''
 
{|
! Class
! Example
! MOA
|-
| Loop diuretic
| Frusemide
| Blocks to NK2Cl transporter in the aLOH&gt; ↓ Na,K, Cl reabsorption &gt; ↓ medullary tonicity + ↑ Na/Cl delivery to distal tubules &gt; diuresis &gt; ↓ BP. '''N.B Direct vasodilation effect - MOA unclear'''
|-
| Thiazide diuretic
| Hydrochlorothiazide
| Blocks Na/Cl cotransporter in DCT &gt; ↓ Na+ and Cl- reabsorption &gt; diuresis &gt; ↓ BP
|-
| Potassium sparing diuretic
| Spironolactone
| Competitive aldosterone antagonist &gt; ↓ Na reabsorption in DCT &gt; diuresis &gt; ↓ BP
|}
 
 
 
'''Vasodilators'''
 
{|
! Class
! Example
! MOA
|-
| Nitrates
| GTN
| Dinitrated to NO &gt; diffuses into SM &gt; binds to guanylyl cyclase &gt; ↑ GMP &gt; ↓ intracellular Ca &gt; vasodilation &gt; ↓ BP
|-
| Hydralazine
| Hydralazine
| Not fully understood. Though to also activate guanylyl cyclase &gt; ↑ GMP &gt; ↓ intracellular Ca &gt; arteriolar vasodilation &gt; ↓ BP
|}
 
 
 
 
 
<span id="examiner-comments-256"></span>
==== Examiner comments ====
 
<blockquote>67% of candidates passed this question.
 
There are many valid lists that can be used as a template to answer this question. One such list might broadly classify antihypertensive agents into sympatholytic agents, vasodilators, calcium channel antagonists, renin-angiotensin inhibitors and diuretics. Within each of these categories are a variable number of sub classes, for example diuretics might include thiazides, loop diuretics and potassium sparing diuretics. A good answer would include such a listing with a brief description of the mechanism of action with respect to the antihypertensive effect and the name of a typical drug that acts in the manner described. Most candidates were able to generate such a list and populate it as required by the question, thus being rewarded with good marks. Poorer answers lacked any logical classification system and were merely a random list of antihypertensive drugs and their actions. Candidates are reminded that organisation within an answer helps in answering the question and achieving marks.
</blockquote>
 
 
<span id="online-resources-17"></span>
==== Online resources ====
 
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2010-paper-2-saqs/question-24#answer-anchor Deranged Physiology]
* [https://icuprimaryprep.files.wordpress.com/2012/05/q24-classify-antihypertensive-agents-by-their-mechanism-of-action-with-a-brief-outline-of-each-mechanism-and-an-example-of-a-drug-in-each-class-sept-2010.pdf Primary Prep]
* [https://cicmwrecks.files.wordpress.com/2019/04/2010-2-24.pdf CICM Wrecks]
 
 
 
 
 
 
 
<span id="2009-2nd-sitting"></span>
== 2009 (2nd sitting) ==
 
 
 
<span id="question-5-15"></span>
=== Question 5 ===
 
 
 
<span id="question-258"></span>
==== Question  ====
 
Outline the kinetic characteristics and the mode of action of digoxin (75% marks). List the cardiovascular effects of digoxin (25% marks).
 
 
 
<span id="answer-13"></span>
==== Answer ====
 
 
 
Pharmacokinetics
 
* Onset/duration
** Onset; 2-3 hours (PO), 10-30mins (IV)
** Duration of action: 3-4 days
* Absorption
** Well absorbed from GIT
** 80% oral bioavailability
* Distribution
** Protein binding ~25%
** VOD 6-7L/kg
** High lipid solubility
* Metabolism
** Minimal hepatic metabolism (15%)
*** Oxidation and conjugation
*** Active and inactive metabolites
* Elimination
** Renal elimination (70% unchanged)
** Small amounts of faecal/biliary elimination &lt;15%
** T <sub>1/2</sub> = 48 hours
** Not readily dialysable
 
 
 
Cardiovascular effects
 
* Positive inotropy
** Inhibits Na/K ATPase &gt; Increased Na &gt; impairs Na/Ca exchanger &gt; increased intracellular Ca &gt; increased inotropy &gt; increased CO
* Negative chronotropy and dromotropy
** Increased PSNS release of ACh at M receptors &gt; decreases SA node firing (chronotropy) + prolongs AV conduction (dromotropy) &gt; increased diastolic filling time &gt; increased preload &gt; increased SV &gt; increased CO + BP
** Can also lead to bradycardia, AV block, bradyarrhythmia's
* Increased excitability
** Increases slope of phase 4 &gt; enhances automaticity of atrial, junctional, ventricular tissue &gt; arrhythmias
*** Not nodal tissue (due to vagal effects)
* ECG changes
** Shortens phase 2 &gt; shortened QT interval
** AV nodal inhibition &gt; prolonged PR interval
** Shortened Phase 2 &gt; repolarisation abnormalities (scooped ST, TWI)
 
 
 
<span id="examiner-comments-257"></span>
==== Examiner comments ====
 
<blockquote>0 (0%) of candidates passed this question.
 
The Syllabus for the Primary examination describes an outline to be “Provide a summary of the important points.” Thus candidates were expected to briefly mention the fundamental pharmacokinetic characteristics (eg highly lipid soluble, well absorbed from small intestine, oral bioavailability of 60 - 90%, protein binding of 20 - 30%, volume of distribution, half life, etc) and mode of action. This was poorly done and candidates’ answers often lacked structure. The question outlines the distribution of marks, being 25% for listing cardiovascular effects. Thus candidates were expected to broadly list the important cardiovascular effects relating to mechanical (eg increase intensity of myocardial contraction, direct venous and arteriolar constriction, etc) and electrical ( increase phase 4 slope &amp; automaticity, hyperpolarization, shortening of atrial action potentials, decrease AV conduction velocity and prolong AV refractory period, increase PR &amp; QT intervals, dose and baseline autonomic activity dependent actions, etc).
</blockquote>
 
 
 
 
<span id="question-17-14"></span>
=== Question 17 ===
 
 
 
<span id="question-259"></span>
==== Question ====
 
Explain the difference and clinical relevance between zero and first order kinetics (60% marks). Give an example that is relevant to intensive care practice (40% marks)
 
 
 
<span id="example-answer-246"></span>
==== Example answer ====
 
First order kinetics
 
* A constant proportion of a drug is eliminated per unit time
* Enzyme/elimination systems are working below their maximum capacity
* Therefore, elimination is proportional to drug concentration
** Increasing concentration of drug will increase elimination of drug
** Exponential concentration per time graph
* Most drugs eliminated in this way
 
 
 
Zero order kinetics
 
* A constant amount of drug is eliminated per unit time
* Enzyme/elimination systems are saturated/working at maximal capacity
** Increasing concentrations will not lead to increase in elimination
** Linear concentration vs time graph
* The transition from first order kinetics to zero order kinetics is described in the Michalis-Menten equation
* Only some drugs are eliminated this way
** Example: phenytoin, ethanol, salicylates
* Because of this, increasing concentrations &gt; increased risk of toxicity
* Phenytoin reaches the therapeutic range at the point at which it transitions from first to zero-order kinetics &gt; very narrow therapeutic range &gt; requires monitoring / dosage adjustment
 
 
 
<span id="examiner-comments-258"></span>
==== Examiner comments ====
 
<blockquote>
</blockquote>
 
 
 
 
<span id="2008-1st-sitting"></span>
== 2008 (1st sitting) ==
 
 
 
<span id="question-260"></span>
=== Question  ===
 
 
 
<span id="question-261"></span>
==== Question ====
 
Describe the role of the kidney in drug excretion and the factors affecting this. Briefly outline how you would alter the dosing of gentamicin in a patient with renal impairment
 
 
 
<span id="example-answer-247"></span>
==== Example answer ====
 
Renal excretion/elimination
 
<ul>
<li><p>Principle mechanism of drug elimination</p></li>
<li><p>Renal elimination is a balance between glomerular filtration, tubular secretion and reabsorption. </p>
<p></p></li></ul>
 
Factors affecting glomerular filtration
 
* GFR
** Increased GFR = increased filtration = increased clearance of hydrophilic drugs
* Drug size:
** Increasing drug size = decreased renal clearance
** Only drugs &lt;7kDa (weight) or &lt;30 Angstrom units (width) are able to pass the capillary BM
* Protein binding
** Only unbound drugs can pass the glomerular BM
*** Highly protein bound drugs are poorly filtered
* Charge
** Negatively charged molecules cannot readily pass BM (as it is also negatively charged)
 
 
Factors affecting drug secretion
 
* Protein binding and renal blood flow as per above
* Concentration: Increased concentration = increased secretion (until tubular transporters are saturated)
* Multiple substrates competing for the same transporters
 
 
Factors affecting drug reabsorption
 
* Can be active or passive (most are passive)
* Affected by charge (ionised drugs cannot pass through BM) and become trapped in the urine
* Concentration (as passive diffusion depends on concentration gradient)
* Lipophilicity - Lipophilic drugs are often reabsorbed
 
 
 
Gentamicin
 
* Basic pharm overview
** Bactericidal aminoglycoside, demonstrates concentration dependant activity
** Small volume of distribution (0.3L/kg), minimal protein binding (15%), not metabolised
** Renally excreted (GFR limited) unchanged with a normal T 1/2 of 3 hours
** Narrow therapeutic index
* Adjustments
** Loading dose
*** Loading dose is the same (though some antibiotic guidelines will recommend lower end-normal if reduced GFR)
** Ongoing therapy (if needed)
*** If CrCl &lt;40 strongly consider ongoing need
*** If ongoing need - stretch interval due to reduced renal clearance
*** Consider plasma concentration monitoring if therapy &gt; 48 hours needed
 
 
 
<span id="examiner-comments-259"></span>
==== Examiner comments ====
 
<blockquote>
</blockquote>
 
 
 
 
<span id="2008-2nd-sitting"></span>
== 2008 (2nd sitting) ==
 
 
 
<span id="question-8-13"></span>
=== Question 8 ===
 
 
 
<span id="question-262"></span>
==== Question  ====
 
Compare and contrast the pharmacology of sodium nitroprusside and glyceryl trinitrate
 
 
 
<span id="answer-14"></span>
==== Answer ====
 
{|
! Name
! Sodium nitroprusside
! Glyceryl trinitrate
|-
| '''Class'''
| Nitrate vasodilator
| Organic nitrate
|-
| '''Indications'''
| Hypertensive emergencies (or need for strict BP control)
| Hypertension, acute pulmonary oedema, angina, ACS/LV failure,
|-
| '''Pharmaceutics'''
| IV solution (50mg/2mL) <br />
Light sensitive
| Clear liquid (IV), Patch (transdermal), tablet (SL), spray (SL)
|-
| '''Routes of administration'''
| IV only (non PVC giving sets)
| Sublingual, intravenous, transdermal
|-
| '''Dose'''
| Titrated to effect (0-2mcg/kg/min)
| Patch: 5-21 mcg/hr<br />
SL: 400mcg PRN <br />
IV: titrated to effect
|-
| pKA
| 3.3
| 5.6
|-
| '''Pharmacodynamics'''
|
|
|-
| MOA
| Prodrug <br />
- Diffuses into RBCs and reacts with Oxy-Hb to produce NO <br />
- NO diffuses into cell &gt; incr cGMP &gt; decreased Ca &gt; SM relaxation
| Prodrug<br />
- Dinitrated to produce active nitric oxide (NO). <br />
- NO diffuses into smooth muscle cell &gt; binds to guanylyl cyclase &gt; increased cGMP &gt; decreased intracellular Ca &gt; SM relaxation &gt; vasodilation
|-
| Effects
| CVS: Arterial+venous vasodilation &gt; decreased BP + afterload <br />
RESP: impairs HPVC <br />
CNS: cerebral vasodilation <br />
GI: ileus <br />
Metabolic: acidosis
| CVS: systemic vasodilation (preferentially venodilation) &gt; decreased VR &gt; decreased stretch &gt; decreased O2 consumption, coronary arterial dilation<br />
CNS: Increased CBF &gt; inc ICP<br />
RESP: Bronchodilation, decreased PVR
|-
| Side effects
| headache, hypotension, rebound hypertension (abrupt withdrawal), cyanide toxicity (high doses), metabolic acidosis, hypoxia, raised ICP
| CVS: reflex tachycardia, hypotension<br />
CNS: Headache, increased ICP<br />
Derm: flushing<br />
|-
| '''Pharmacokinetics'''
|
|
|-
| Onset/offset
| Immediate onset + offset
| 1-3 mins (SL), &lt;1 min (IV), Patch variable.
|-
| Absorption
| 0% oral bioavailability
| Oral bioavailability 3% <br />
(hepatic - high first pass effect)
|-
| Distribution
| VOD 0.25L/Kg (confined intravasc). <br />
Nil protein binding
| 60% protein bound. <br />
Vd 3L/kg
|-
| Metabolism
| Nitroprusside &gt; cyanide &gt; prussic acid &gt; thiocyanate<br />
site: RBC (and liver secondarily)
| Hydrolysis into inactive compounds<br />
Site: liver + RBC cell wall + vascular cell walls.
|-
| Elimination
| Metabolites via urine (major)<br />
T 1/2 = 3 mins
| 80% urine. <br />
T 1/2 = 5 minutes.
|-
| '''Special points'''
|
| Can develop tachyphylaxis (depletion of sulfhydryl groups)
|}
 
 
 
<span id="examiner-comments-260"></span>
==== Examiner comments ====
 
<blockquote>80% of candidates passed this question
 
It was expected candidates would address specific aspects of pharmacology such as action, mechanism of action, half life and duration of effect, route of administration, potential toxicity and special precautions. These agents lend themselves to comparison and contrast as several distinct similarities and differences exist and credit was given for highlighting these. Specific comments should include that both agents result in blood vessel dilation with extra credit given for detailing the differences in the balance of arterial versus venous effects between them. For both agents the effect is mediated through nitric oxide and it was expected candidates would identify that nitroprusside releases NO spontaneously and GTN requires enzymatic degradation with the resultant effects on smooth muscle mediated via c GMP. They are both short acting agents when used intravenously and require careful titration to measured blood pressure for effect. Extra credit was given for mentioning that routes other than IV are available for GTN (topical / oral) but not for nitroprusside. Comments on special precautions such as Nitroprusside should be protected from light and GTN given via non PVC giving sets gained additional marks. In addition to the well described adverse effects of each agent, it was expected candidates would mention the potential for cyanide toxicity with nitroprusside and extra marks were awarded for an indication of usual doses.
</blockquote>
 
 
 
 
 
 
<span id="2007-2nd-sitting"></span>
== 2007 (2nd sitting) ==
 
 
 
<span id="question-2-12"></span>
=== Question 2 ===
 
 
 
<span id="question-263"></span>
==== Question  ====
 
Outline the sites and mechanisms of action of diuretics. Give one example of drug acting at each site and list two side effects of each drug.
 
 
 
<span id="example-answer-248"></span>
==== Example Answer ====
 
{|
! Site of action
! Example
! Mechanism of diuresis
! Side effects
|-
| Entire
| Mannitol
| Freely filtered at glomerulus (but not reabsorbed). Acts osmotically to ↓ H<sub>2</sub>O reabsorption
| - ↓ Na, K, Cl<br />
- Hypotension, hypovolaemia
|-
| PCT
| Acetazolamide
| Inhibits carbonic anhydrase in PCT &gt; ↓ reabsorption of filtered HCO3 + Na &gt; ↑ tubular osmolality &gt; diuresis
| - Metabolic acidosis (↓ HCO3)<br />
- ↓ Na, K, Cl
|-
| LOH
| Frusemide
| Binds to NK2Cl transporter in the thick ascending limb LOH &gt; ↓ Na,K, Cl reabsorption &gt; impairs counter current multiplier + ↓ medullary tonicity
| - ↓ Na, K, Cl<br />
- Metabolic alkalosis (↓ K, Cl)<br />
- Hypovolaemia, Hypotension
|-
| DCT
| HCT
| Inhibit Na+ and Cl- reabsorption (Na/Cl cotransporter) &gt; ↓ H<sub>2</sub>O reabsorption
| - ↓ K, Na, Cl<br />
- ↑ BSL, lipids<br />
- Metabolic alkalosis
|-
| CD
| Spironolactone
| Competitive aldosterone antagonist &gt; inhibition of ENaC &gt; ↓ Na reabsorption (and ↓K excretion) &gt; diuresis
| -↑ K and metabolic acidosis<br />
- Anti-androgen effects (decreased libido, menstrual irregularities, gynecomastica)
|-
| CD
| Amiloride
| Blocks ENaC &gt; ↓ Na/Water reabsorption
| - HypoNa (blocked ENaC)<br />
- HyperK (ENaC drives ROMK channels)
|}
 
 
 
<span id="examiner-comments-261"></span>
==== Examiner comments ====
 
<blockquote>Good answers to this question were those that had a tabular format to the structure of the answer — for example columns headed mechanism, sites, drug and side effects. Most common omissions were not to further describe how the different mechanisms of action of diuretics increased urine output, e.g. &quot;disruption of the counter current multiplier system by decreasing absorption of ions from the loop of Henle into the medullary interstitium, thereby decreasing the osmolarity of the medullary interstitial fluid&quot;. There was often little mention of increased urine solutes and the effect the electro chemical effect had in promoting a diuresis. Examples of drugs were well done
</blockquote>
 
 
<span id="online-resources-18"></span>
==== Online resources ====
 
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2007-paper-2-saqs/question-2#answer-anchor Deranged physiology]
* [https://derangedphysiology.com/main/cicm-primary-exam/past-papers/2007-paper-2-saqs/question-2#answer-anchor CICM Wrecks]
 
 
 
 
 
 
 
<span id="misc--not-previously-examined"></span>
== Misc / not previously examined ==
 
 
 
<span id="question-a"></span>
=== Question a ===
 
 
 
<span id="question-264"></span>
==== Question ====
 
Outline with examples the role of excipients in drug formulations.
 
 
 
<span id="example-answer-249"></span>
==== Example answer ====
 
Excipient
 
* Components of a drug preparation that do not exert the pharmacological effect
* Function: assists with optimal delivery of the active ingredient
* Ideally: nontoxic, inactive, and don’t interact with active ingredient
 
 
 
Preservatives
 
* Prevent/inhibit growth of microorganisms in the drug preparation
* Generally weak acids (pKa 4-5)
* Example: benzyl alcohol
 
 
Antioxidants
 
* Prevent/limit the degree of chemical breakdown due to oxidative reactions
* Example: ascorbic acid
 
 
Solvents
 
* A liquid (usually) substance which can dissolve another substance
* Water is the most common solvent (most drugs are water soluble to an acceptable degree)
* For non-water-soluble drugs, or drugs unstable in water, non-aqueous solvents are used (e.g. mannitol, propylene glycol)
 
 
Buffer
 
* A solution consisting of a weak acid and its conjugate base
* Maintains the pH of a drug preparation to maximise stability and/or maintain solubility
* Example: acetic acid / sodium acetate
 
 
Emulsifying agents
 
* Substances that stabilise emulsions which are typically unstable
* Example: soya bean oil / egg lethicin in propofol
 
 
Diluents
 
* Provide bulk and enable accurate dosing of potent ingredients
* E.g. glucose, lactose
 
 
Binders
 
* Bind tablet ingredients together for form/strength
* Example: starches, sugars
 
 
Flavours
 
* Added to increase compliance / ease of use
* Example: aspartame
 
 
Colouring
 
* Added for marketing purposes / compliance
* E.g. beta caroteine
 
 
Coatings/film
 
* Designed to make tablets easier to swallow, improve predictability of absorption, protect from environment e.g moisture
* Example: cellulose for enteric coating to delay release of agent
 
 
 
<span id="examiner-comments-262"></span>
==== Examiner comments ====
 
<blockquote>Not previously examined
</blockquote>
 
 
 
 
<span id="question-b"></span>
=== Question b  ===
 
 
 
<span id="question-265"></span>
==== Question ====
 
Describe the mechanism of action and effects of corticosteroid drugs with particular reference to asthma
 
 
 
<span id="answer-15"></span>
==== Answer ====
 
 
 
Asthma
 
* Asthma is an inflammatory condition of the airways characterised by airway narrowing, mucous secretion and expiratory airflow limitation.
 
 
 
Corticosteroids
 
* Steroid hormones normally produced by the adrenal cortex
* Two main classes of corticosteroids
** Glucocorticoids (secreted from zona fasciculata and reticularis)
** Mineralocorticoids (secreted from zona glomerulosa)
* Glucocorticoids are used in the treatment of asthma
** Systemic: Prednisone, Hydrocortisone
** Inhaled: Beclomethasone, Budesonide
* Note: prednisone and hydrocortisone also have some mineralocorticoid effect
 
 
 
Glucocorticoids
 
* Mechanism of action
** Lipid soluble hormone &gt; crosses cell membrane &gt; binds to intracellular steroid receptors &gt; translocate to nucleus &gt; alters gene transcription &gt; metabolic, anti-inflammatory &amp; immunosuppressive effects in tissue-specific manner
** The anti-inflammatory process is mediated by suppression of phospholipase A2 &gt; decreased arachidonic acid &gt; decreased PGs, TXA2, Leukotrienes
** Inhaled steroids (e.g. budesonide) at regular dosage tend to have only respiratory (local) effects, whereas systemic glucocorticoids (e.g. hydrocortisone, prednisone) exhibits effects at all sites.
* Effects on asthma
** RESP
*** Reduced airway oedema &gt; bronchodilation
*** Increased SM responsiveness to catecholamines and B2 agonists &gt; bronchodilation
*** Decreased mucous secretion &gt; reduced mucous plugging
*** Bronchodilation + decreased mucous secretion &gt; improved ventilation + oxygenation &gt; decreased work of breathing
** CVS
*** Increased BP (Due to mineralocorticoid effect on kidneys (increased H2O reabsorption) and increased alpha adrenergic responsiveness to endogenous catecholamines)
* Other effects of systemic steroids
** RENAL
*** Increased fluid reabsorption (Due to mineralocorticoid effect on kidneys &gt; increased Na/H20 reabsorption in DCT &gt; increased BP, oedema)
** Metabolic
*** Hyperglycaemia (Due to increased gluconeogenesis, protein catabolism, lipolysis)
*** Adrenal suppression (Due to negative feedback on the pituitary (inhibits ACTH) and hypothalamus (inhibits CRH))
** CNS
*** Sleep disturbance, mood changes, psychosis
** IMMUNE
*** Immunosuppression (particularly mast cells, eosinophils, T cells) &gt; decreased cytokines/pro inflammatory mediators
** GIT
*** GIT ulceration (inhibition of COX systems)
** MSK
*** Skin thinning and muscle wasting (due to increased protein/fat catabolism)
*** Osteoporosis
 
 
 
 
 
<span id="question-c"></span>
=== Question c ===
 
 
 
<span id="question-266"></span>
==== Question  ====
 
Pharmacology of aminophylline
 
 
 
<span id="answer-16"></span>
==== Answer ====
 
{|
! Name
! Aminophylline (and Theophylline)
|-
| '''Class'''
| Methylxanthine derivative
|-
| '''Indications'''
| Severe airway obstruction, including acute asthma (less commonly used nowadays)
|-
| '''Pharmaceutics''' (aminophylline)
| Complex of 80% theophylline (active component) and 20% ethylenediamine (improves solubility, no effect). Concentration of 25mg/ml in 10ml vials
|-
| '''Routes of administration'''
| IV (aminophylline) , PO (aminophylline and theophylline)
|-
| '''Dose''' (Aminophylline)
| Loading = 5mg/kg (slow injection)<br />
Maintenance = 0.5mg.kg.hr
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| - Non selective phosphodiesterase inhibitors &gt; increased cAMP &gt; decreased Calcium &gt; SM + bronchial relaxation<br />
- Also block adenosine receptors &gt; decreased inflammatory response
|-
| Effects
| Narrow therapeutic window<br />
RESP: Bronchodilation (via SM relaxation), increased respiratory centre sensitivity to CO2, improved diaphragm contractility<br />
CNS: headache, irritability, tremor, seizures<br />
CVS: palpitations, tachycardia, arrhythmia, increased inotropy/chronotropy <br />
GIT: Nausea, vomiting, diarrhoea<br />
RENAL: natriuresis
|-
| '''Pharmacokinetics'''
|
|-
| Absorption
| PO bioavailability &gt; 90%
|-
| Distribution
| V<sub>d</sub> = 0.5 L /kg<br />
Protein binding = 40%
|-
| Metabolism
| Hepatic metabolism (90%) via CYP450 mechanisms to active and inactive metabolites. 10% unchanged
|-
| Elimination
| Renal elimination of active and inactive metabolites <br />
Dialysable <br />
T <sub>1/2</sub> = 6-12 hours (longer in children)
|-
| '''Special points'''
| Therapeutic concentration 10-20mg/ml
|}
 
 
 
<span id="examiner-comments-263"></span>
==== Examiner comments ====
 
<blockquote>Not previously examined
</blockquote>
 
 
 
 
<span id="question-dnus"></span>
=== Question dnus ===
 
 
 
<span id="question-267"></span>
==== Question ====
 
Outline the pharmacology of metoclopramide.
 
 
 
<span id="answer-17"></span>
==== Answer ====
 
{|
! Name
! Metoclopramide
|-
| '''Class'''
| Antiemetic / Prokinetic
|-
| '''Indications'''
| - Nausea and vomiting <br />
- Prokinetic
|-
| '''Pharmaceutics'''
| Clear colourless solution (5mg/ml). <br />
Tablet (10mg)
|-
| '''Routes of administration'''
| IV, PO, IM
|-
| '''Dose'''
| 10mg TDS (adults) for short duration (max 5 days)
|-
| '''Pharmacodynamics'''
|
|-
| MOA
| Central D2 antagonism at chemoreceptor trigger zone &gt; reduced afferent input to vomiting centre in medulla
|-
| Effects
| GIT: Anti-emetic, Prokinetic (acceleration of gastric emptying)<br />
CNS: EPSE (akathisia, dystonia, tardive dyskinesia) in children, drowsiness, dizziness, headache, worsening of Parkinson symptoms<br />
CVS: arrhythmias
|-
| '''Pharmacokinetics'''
|
|-
| Onset
| Tmax &lt; 1 hour (PO), &lt;15 mins (IV)
|-
| Absorption
| PO bioavailability 80%
|-
| Distribution
| VOD = 3L / Kg <br />
Protein binding 30%
|-
| Metabolism
| Minimal hepatic metabolism (conjugation)
|-
| Elimination
| Renal elimination (85%)<br />
Active and inactive metabolites <br />
T <sub>1/2</sub> = 4 hrs
|-
| '''Special points'''
| - Contraindicated in pheochromocytoma (precipitates pheo crisis), Parkinson's (Blocks Dopamine receptors), GI obstruction/perforation (prokinetic), avoid in children &lt;20 years old (risk of EPSE)
|}

Revision as of 05:30, 13 February 2024

2022A 2021B 2021A 2020B 2020A 2019B 2019A 2018B 2018A 2017B 2017A 2016B 2016A Pre-2016

Retrieved from "http://ethans.wiki:80/index.php?title=Past_Questions&oldid=11"