View source for 2021B

<span id="2021-2nd-sitting"></span>
== 2021 (2nd sitting) ==

<span id="question-1"></span>
=== Question 1 ===



<span id="question-1"></span>
==== Question ====

Describe the regulation of body water



<span id="example-answer-1"></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-1"></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-1"></span>
==== Online resources for this question ====

* CICM Wrecks
* Deranged Physiology
* Jenny's Jam Jar



<span id="similar-questions-1"></span>
==== Similar questions ====

* Question 8, 2008 (1st sitting)
* Question 4, 2015 (1st sitting)
* Question 9, 2018 (2nd sitting)





<span id="question-2"></span>
=== Question 2 ===



<span id="question-2"></span>
==== Question ====

Describe the pharmacology of lidocaine



<span id="example-answer-2"></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-2"></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-2"></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-2"></span>
==== Similar questions ====

* Question 17, 2014 (1st sitting)
* Question 1, 2019 (1st sitting)





<span id="question-3"></span>
=== Question 3 ===



<span id="question-3"></span>
==== Question ====

Discuss the physiological determinants of cardiac output



<span id="example-answer-3"></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-3"></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-3"></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-3"></span>
==== Similar questions ====

* Question 8, 2011 (1st sitting)
* Question 13, 2011 (2nd sitting)
* Question 19, 2014 (1st sitting)





<span id="question-4"></span>
=== Question 4 ===



<span id="question-4"></span>
==== Question ====

Compare the pharmacology of fluconazole and amphotericin



<span id="example-answer-4"></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-4"></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-4"></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-4"></span>
==== Similar questions ====

* ?Nil





<span id="question-5"></span>
=== Question 5 ===



<span id="question-5"></span>
==== Question ====

Write detailed notes on angiotensin, including its synthesis, role within the body and regulation



<span id="example-answer-5"></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-5"></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-5"></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-5"></span>
==== Similar questions ====

* Question 18, 2009 (2nd sitting)
* Question 6, 2011 (2nd sitting)





<span id="question-6"></span>
=== Question 6 ===



<span id="question-6"></span>
==== Question ====

Describe the functions of the placenta (80% marks). Outline the determinants of placental blood flow (20% marks). 



<span id="example-answer-6"></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-6"></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-6"></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-6"></span>
==== Similar questions ====

* Question 9, 2018 (1st sitting)







<span id="question-7"></span>
=== Question 7 ===



<span id="question-7"></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-7"></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-7"></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-7"></span>
==== Online resources for this question ====

* CICM Wrecks
* Deranged Physiology
* Jenny's Jam Jar



<span id="similar-questions-7"></span>
==== Similar questions ====

* Nil





<span id="question-8"></span>
=== Question 8 ===



<span id="question-8"></span>
==== Question ====

Describe the anatomy of the internal jugular vein including surface anatomy landmarks relevant to central venous line insertion.



<span id="example-answer-8"></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-8"></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-8"></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-8"></span>
==== Similar questions ====

* Question 23, 2017 (2nd sitting)





<span id="question-9"></span>
=== Question 9 ===



<span id="question-9"></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-9"></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-9"></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-9"></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-9"></span>
==== Similar questions ====

* Question 14, 2019 (2nd sitting)





<span id="question-10"></span>
=== Question 10 ===



<span id="question-10"></span>
==== Question ====

Describe the ventilation / perfusion (V/Q) relationships in the upright lung according to Westâ€™s zones (40%). Explain the physiological mechanisms responsible for these relationships (60%)



<span id="example-answer-10"></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-10"></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-10"></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-10"></span>
==== Similar questions ====

* Nil





<span id="question-11"></span>
=== Question 11 ===



<span id="question-11"></span>
==== Question ====

Provide a detailed account of the side-effects of amiodarone.



<span id="example-answer-11"></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-11"></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-11"></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-11"></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"></span>
=== Question 12 ===



<span id="question-12"></span>
==== Question ====

Explain the physiological factors that affect airway resistance



<span id="example-answer-12"></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-12"></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-12"></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-12"></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"></span>
=== Question 13 ===



<span id="question-13"></span>
==== Question ====

Describe the factors that affect mixed venous oxygen saturation



<span id="example-answer-13"></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-13"></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-13"></span>
==== Online resources for this question ====

* CICM Wrecks
* Deranged Physiology
* Jenny's Jam Jar



<span id="similar-questions-13"></span>
==== Similar questions ====

* Question 10, 2008 (1st sitting)
* Question 19, 2017 (1st sitting)
* Question 8, 2019 (1st sitting)





<span id="question-14"></span>
=== Question 14 ===



<span id="question-14"></span>
==== Question ====

Describe the production, action and regulation of thyroid hormones. 



<span id="example-answer-14"></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-14"></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-14"></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-14"></span>
==== Similar questions ====

<ul>
<li><p>Question 17, 2016 (1st sitting)</p>
<p></p></li></ul>



<span id="question-15"></span>
=== Question 15 ===



<span id="question-15"></span>
==== Question ====

Classify and describe the mechanisms of drug interactions with examples.



<span id="example-answer-15"></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-15"></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-15"></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-15"></span>
==== Similar questions ====

* Question 3, 2017 (1st sitting)
* Question 9, 2015 (1st sitting)





<span id="question-16"></span>
=== Question 16 ===



<span id="question-16"></span>
==== Question ====

Classify the anti-psychotic drugs (25% marks). Outline the pharmacology of haloperidol (75% marks).



<span id="example-answer-16"></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-16"></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-16"></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-16"></span>
==== Similar questions ====

* Question 21, 2014 (2nd sitting)





<span id="question-17"></span>
=== Question 17 ===



<span id="question-17"></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-17"></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-17"></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-17"></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-17"></span>
==== Similar questions ====

* Question 5, 2011 (2nd sitting)
* Question 9, 2016 (1st sitting)





<span id="question-18"></span>
=== Question 18 ===



<span id="question-18"></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-18"></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 (Vestibuloâ€“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-18"></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-18"></span>
==== Online resources for this question ====

* CICM Wrecks
* Deranged Physiology
* Jenny's Jam Jar



<span id="similar-questions-18"></span>
==== Similar questions ====

* ?Nil





<span id="question-19"></span>
=== Question 19 ===



<span id="question-19"></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-19"></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-19"></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-19"></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-19"></span>
==== Similar questions ====

* Question 4, 2013 (1st sitting)
* Question 19, 2015 (2nd sitting)





<span id="question-20"></span>
=== Question 20 ===



<span id="question-20"></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-20"></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-20"></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-20"></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-20"></span>
==== Similar questions ====

* Question 24, 2011 (1st sitting)