2017A

2017 (1st sitting)

Question 1

Question

Outline the anatomy and physiology of the parasympathetic nervous system.

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 > nicotinic receptor
- Postganglionic neurons
  - Short
  - Neurotransmitter is ACh > muscarinic receptor

Anatomy + effects (based on "target" 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) CN IX (parotid)	-Submaxillary ganglion - Otic ganglion	M3	Salivation
GIT	Vagal nucleus Spinal cord	CN X 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

Examiner comments

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.

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Question 2

Question

Outline the components of dietary fat (20% of marks). Describe their possible metabolic fates (80% of marks).

Example answer

Examiner comments

21% of candidates passed this question
Almost all candidates interpreted "metabolic fate" to mean absorption, digestion and transport of 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.

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Question 3

Question

Classify and describe the mechanisms of drug interactions with examples

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 > decreased protein binding phenytoin > increased effect
Metabolism	Macrolides reduce metabolism of warfarin by outcompeting it for similar metabolic pathways (CYP450 enzymes) > increased duration of effect
Elimination	Probenecid decreases the active secretion of B-lactams and cephalosporins in renal tubular cells by competing for transport mechanisms > 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) > 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 Î± agonism

Examiner comments

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

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Question 4

Question

Describe the endocrine functions of the kidney.

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

Examiner comments

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

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Question 5

Question

Describe the regulation of plasma calcium concentration.

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 - Hypophosphatemia	- Hypocalcaemia - Hypophosphatemia - PTH	- Hypercalcaemia - Gastrin
Inhibitory factors	- Calcitriol - Hypermagnesemia - Hypercalca	- Hypercalcaemia - Dec. sun exposure - Dec. renal function	- Hypocalcaemia - Somatostatin
Effect on Calcium	Increases calcium	Increases calcium	Decreases calcium
Mechanism of effect on Ca	- Increased renal reabsorption (DCT) - Increased osteoclast activity - Increased production of calcitriol	- Increased GIT absorption (ileum) - Increased renal reabsorption (DCT) - Increased osteoclast activity	- Decreased renal reabsorption (DCT) - Inhibition of osteoclast activity

Examiner comments

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.

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Question 6

Question

Explain the meaning of the components of a Forest plot.

Example answer

Removed from primary syllabus

Examiner comments

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.

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Removed from primary syllabus

Question 7

Question

Compare and contrast the systemic circulation with the pulmonary circulation

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 >8um	Filters arterial blood in renal and hepatic vascular beds

Examiner comments

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.

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Question 8

Question

Describe the physiological consequences of decreasing the functional residual capacity (FRC) in an adult by 1 litre.

Example answer

Examiner comments

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 & units.

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Question 9

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)

Example answer

test	PT	APTT	ACT	TEG/ROTEM
Pathway	Extrinsic + common	Intrinsic + common	Intrinsic + common	Clot formation to lysis
Use	Warfarin monitoring Screening for coagulopathy	Heparin monitoring 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 > activates extrinsic pathway > wait until clot formation	Phospholipid added to plasma (+ activation agent) > stimulates intrinsic pathway > wait until clot formation	Blood added to kaolin clotting activator > stimulates intrinsic pathway > wait until clot formed	Blood distributed into cuvettes. Pin immersed in blood and either cuvette (TEG) or pin (ROTEM) spins. As blood clots > resists movement. TEG: toque exerted on the pin. ROTEM: impedance to rotation detected by optical system.
Normal	11-13 seconds (INR 0.8-1.2)	30-40 seconds	100-130	INTEM: similar to APTT EXTEM: similar to PT CT = time until 2mm amplitude A10 = amplitude at 10 mins MCF = time until maximal clot firmness ML: maximal lysis
Prolonged	Warfarin / vitamin K deficiency / factor II, VII, IX, X deficiency Liver disease Consumptive coagulopathy	Heparin Factor deficiency (II, IX, X, XI, XII) Liver disease Consumptive coagulopathy	Any coagulopathy (non specific) including systemic heparinisation	Hyperfibrinolysis Factor deficiency / inhibition Platelet deficiency / dysfunction Fibrinogen deficiency
Errors	Different thromboplastins in lab give different PT times > INR standardises	Inadequate mixing of blood Inadequate blood:citrate ratio	Underfilling shortens ACT Overfilling, prolongs ACT	Calibration of machine

Examiner comments

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.

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Question 10

Question

Describe the pharmacology of hydrocortisone.

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 > crosses cell membrane > binds to intracellular steroid receptors > alters gene transcription > metabolic, anti-inflammatory & immunosuppressive effects in tissue-specific manner
Effects/side effects	CNS: sleep disturbance, psychosis, mood changes CVS: Increased BP (mineralocorticoid effect + increased vascular smooth muscle receptor expression to catecholamines) RESP: decreased airway oedema, increased SM response to catecholamines RENAL: Na + water retention (mineralocorticoid effect) Metabolic: Hyperglycaemia, gluconeogenesis, protein catabolism, fat lipolysis and redistribution, adrenal suppression MSK: Osteoporosis, skin thinning Immune: immunosuppression + anti-inflammatory effects (decreased phospholipase, interleukins, WBC migration and function) 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 Small Vd (0.5L/kg)
Metabolism	Hepatic > inactive metabolites
Elimination	Metabolites excreted renally. Elimination T/12 = ~1 hour
Special points	Risk of reactivation of latent TB / other infections

Examiner comments

54% of candidates passed this question
Hydrocortisone is listed as a Class A drug in the syllabus and as such knowledge of its pharmacokinetics is expected. No marks were awarded for generic pharmacokinetic statements such as: "average bioavailability", "moderate protein binding", "bioavailability 100% for IV preparation" etc

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Question 11

Question

Outline the anatomical relations of the trachea relevant to performing a percutaneous tracheostomy.

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 --> 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 --> posterior)

Skin
Subcutaneous tissue
Fat
Pretracheal fascia
Fibroelastic tissue between tracheal cartilage rings
Trachea

Examiner comments

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.

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Question 12

Question

Describe the pharmacology of oxycodone

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 CVS: bradycardia/hypotension RESP: respiratory depression GIT: decreased peristalsis. N/V. constipation 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, VD = 3L/Kg, 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)

Examiner comments

53% of candidates passed this question
Few candidates covered the pharmacokinetic aspect of the question sufficiently. No marks were awarded for generic comments such as hepatic metabolism and renal excretion

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Question 13

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)

Example answer

Examiner comments

30% of candidates passed this question
The anatomy component of answers frequently lacked required detail. Many candidates listed the observed differences in the waveforms however an explanation for these differences was required.

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Question 14

Question

Define respiratory compliance (20% of marks). Describe the factors that affect it (80% of marks).

Example answer

Examiner comments

54% of candidates passed this question. This question was generally well answered with good structure.

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Question 15

Question

Outline the cardiovascular changes associated with morbid obesity.

Example answer

Obesity

Multisystem disorder defined by an increased BMI
- Overweight: BMI 25-30
- Obese: BMI >30
- Morbidly obese: BMI >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 > increased activation of renin-angiotensin-aldosterone system (RAAS) > increased Na and water reabsorption
Blood pressure
- Often increased (>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) > increased
- Fatty infiltration > increases risk of arrhythmias
- Fibrosis > leads to diastolic dysfunction
Pulmonary artery pressures
- Increased
- Due to hypoxic pulmonary vasoconstriction (obesity hypoventilation syndrome) and LV diastolic dysfunction from cardiac remodelling

Examiner comments

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.

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Question 16

Question

List the potential problems resulting from blood transfusion and methods used to minimise them

Example answer

Examiner comments

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.

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Question 17

Question

Compare and contrast the pharmacology of phenytoin and levetiracetam

Example answer

Name	Phenytoin	Levetiracetam
Class	Anticonvulsant	Anticonvulsant
Indications	- Seizure prophylaxis - Epilepsy (simple-complex and focal-generalised) - Status epilepticus	- Seizure prophylaxis - Focal partial seizures (monotherapy) - Partial/generalised seizures (adjunct) - 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 Target plasma level of 10-20mcg/ml	Load = 60mg/kg (Status epilepticus) 500-2000mg BD (maintenance)
Pharmacodynamics
MOA	Stabilises Na channels in their inactive state, thereby inhibiting the generation of further action potentials. Also decreases Ca entry > 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 GIT: Nausea, vomiting CNS: ataxia, confusion, nystagmus, visual disturbance Other: acne, hirsutism, blood dyscrasias, gingival hypertophy Pregnancy = teratogenic Many drug-drug interactions	CNS: irritability, agitation, anxiety, drowsiness, dizziness, headache, ataxia MSK: weakness/fatigue Other: allergy, angioedema, SJS
Pharmacokinetics
Onset	Slow oral absorption (1-3 hours onset)	< 1 hour (PO)
Absorption	PO bioavailability = 90%	Nearly 100% PO bioavailability
Distribution	VOD= 1L/kg Protein binding >90%	VOD = 0.5 L / Kg Protein binding = < 5%
Metabolism	- Hepatic hydroxylation by CYP450 system (saturable) - Wide patient variation (10% population are slow hydroxylators)	Enzymatic hydrolysis ~30% of dose to inactive metabolites
Elimination	Renal elimination of metabolites T 1/2 = 12 hours	Renal excretion - unchanged drug (70%) and metabolites (30%) T 1/2 = 6 hours
Monitoring	Phenytoin level 10-20ug/ml	Nil

Examiner comments

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.

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Question 18

Question

Outline the functional anatomy of the kidneys (40% of marks). Outline the regulation of renal blood flow (60% of marks).

Example answer

Examiner comments

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.

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Question 19

Question

Define mixed venous PO2 (20% of marks). Outline the factors that affect this value (80% of marks).

Example answer

Examiner comments

37% of candidates passed this question
This question was in two parts â€“ the first part was worth 20% and candidates were expected to provide a definition of mixed venous blood as well as the partial pressure of oxygen in mixed venous blood (including normal range). Good answers also provided the varying PO2 from different tissue beds that make up mixed venous blood, where the â€˜mixingâ€™ occurs (the right ventricle) and where it is sampled (pulmonary artery). For the second part of the question, worth 80% of the marks, good answers included the relationship between mixed venous PO2 and mixed venous O2 content (including the shape and position of the HbO2 dissociation curve); the variables encompassed in the modified Fick equation; arterial oxygen content and its determinants; oxygen consumption (VO2); and cardiac output (CO). Including an outline of how each affects the value of mixed venous PO2. A number of candidates wrote about mixed venous oxygen saturation. Other common errors were: missing a number of key factors that affect PO2; and using an incorrect form and/or content of the modified Fick equation.

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Question 20

Question

Describe the pharmacology of vasopressin (70% of marks) and its analogues (30% of marks).

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) - At lower doses has predominant V1 activity, V2 activity at higher doses
pKA	10.3
Pharmacodynamics
MOA / effects	Physiologically secreted by PVN of hypothalamus > stored in posterior pituitary > secreted in response to hypovolaemia + increased osmolality V1 receptor (blood vessels) agonism > Vasoconstriction > increased SVR > increased BP V2 receptor (collecting ducts of nephrons) agonism > increased water reabsorption > increased BP V2 receptor (endothelial cells) agonism > increased vWF release and Factor VIII activity
Side effects	CVS: reflex bradycardia, splanchnic vasoconstriction (possible ischaemia) HAEM: Excessive platelet aggregation / thrombosis RENAL: Hyponatraemia (increased water reabsorption > Na reabsorption) 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 Vd 0.2L/Kg
Metabolism	Extensive hepatic and renal metabolism by serine proteases and oxido-reductase enzymes > inactive metabolites
Elimination	Renal elimination of changed and unchanged drug T _1/2 15 minutes

Vasopressin analogues

Desmopressin (DDAVP)
- Indications: central diabetes insipidus, vWD, slowing correction of hyponatraemia
- Route: IV, IN, SC, PO, IM
- MOA: predominately V₂ mediated effects (limited V₁ effects) > increased H₂O 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 _1/2
Terlipressin
- Indication: variceal bleeding, hepatorenal syndrome
- Route: IV
- MOA: predominately V₁ mediated effects > splanchnic vasoconstriction > 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_1/2

Examiner comments

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.

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Question 21

Question

Explain the potential causes of a difference between the measured end tidal CO2 and the arterial partial pressure of CO2.

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 --> 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 > increased gradient

Examiner comments

30% of candidates passed this question.
Many candidates didnâ€™t distinguish between the different types of dead space. In general this topic was not well understood.

Online resources for this question

Question 22

Question

Outline the functions of the liver

Example answer

Examiner comments

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.

Online resources for this question

Question 23

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).

Example answer

File:/C:/Users/ethan/AppData/Roaming/Typora/typora-user-images/image-20210320173717612.png?lastModify=1707804095

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)

Examiner comments

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.

Online resources for this question

Question 24

Question

Outline the physiology of cerebral spinal fluid (CSF).

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

Composition relative to plasma

Similar: Na, osmolality, HCO3
Increased: Cl, Mg, CO2
Decreased: pretty much everything else (protein, potassium, calcium, glucose, pH)

Circulation

Circulation is driven by
- Ciliary movement of ependymal cells
- Respiratory oscillations and arterial pulsations
- Constant production and absorption
CSF flows from
- Lateral ventricles > foramen of Monro > 3rd ventricle > Sylvian aqueduct > 4th ventricle > cisterna magna (via foramen megendie and luschka) > spreads between spinal/cranial subarachnoid spaces

Reabsorption

Rate of ~24mls/hr
By the arachnoid villi
- Located predominately in the dural walls of the sagittal + sigmoid sinuses
- Function as one way valves, with driving pressure leading to absorption.

Functions

Mechanical protection
- The low specific gravity of CSF > decreased effective weight of the brain (1500g > 50g)
- With the reduced weight
  - Less inertia = less acceleration/deceleration forces
  - Suspended > 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

Examiner comments

67% of candidates passed this question
Better answers included details on CSF production (amount, site), reabsorption and factors which influences CSF and its circulation.

2017 (1st sitting)

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