2011 Second Sitting

2011B 01: 14 (56%) of candidates passed this question. It was expected answers would include a comment this would transiently increase the blood glucose and result in the stimulation of insulin production. Some detail was then required on the mechanism by which insulin production is increased and time frames over which this occurred, as well as mechanism by which glucose passes through to the urine. Other important points expected were the fate of glucose, once taken up by the cells, the inhibitory effects (and mechanisms) of insulin (ie inhibits glycogenolysis, triglyceride and protein breakdown, etc). A description of the physiological consequences of increased insulin production was required. This question has been asked before, in it’s current form. The pass rate on this occasion was higher. Candidates who did poorly did so due to a lack of detail and understanding of the topic.

2011B 02: 15 (60%) of candidates passed this question. This was a broad question that required some structure and organisation to score well. The issues around variability in both pharmacokinetics and pharmacodynamics, of which there are many, needed be covered. For example variability due to differences in organ function, age, metabolism, body composition, were just a few of the factors expected to be mentioned.

2011B 03: 13 (52%) of candidates passed this question. It was expected candidates would expand on the role of the kidney in the excretion of drugs and metabolites. A statement that referred to the classical features of drugs that undergo renal excretion (eg polarity, lipid solubility, size and protein binding, drug metabolites) and a definition of renal clearance was expected and would have provided an excellent introduction to any answer. It was then expected that candidates would mention, in some detail, the processes of filtration and secretion (both active and passive and both proximal and distal along the renal tubules). The question also asked for factors that affect renal drug excretion, for example, a reduction in GFR or alteration in protein binding. An approach to alterations of dosing would require some consideration of assessing degree of dysfunction (GFR estimation / calculation) then an understanding that it would not impact on loading doses but would influence subsequent dosing of renal cleared drugs. Plasma monitoring provides useful information for some drugs, particularly those with a narrow therapeutic index. Syllabus: II2d, D12h Recommended sources: Goodman and Gilman's the Pharmacological Basis of Therapeutics pgs10-14; Foundations of Anaesthesia Basic and Clinical Science, Hemmings pg107; Basic and Clinical Pharmacology, Katzung pgs 35, 48-49.

2011B 05: 2 (8%) of candidates passed this question. Monitoring and monitors are essential to Intensive Care practice, and is the reason why it is included in the syllabus. Unfortunately candidates have performed poorly in this question, as they have in previous measurement and monitoring questions. Future candidates need to be aware that such questions WILL get asked again. For a good answer it was expected that mention would be made of what an ECG monitors does (ie detects and amplifies the small electrical changes on the skin that are caused when the heart muscle depolarizes), how (ie use of 2 or more electrodes, typically being made of silver or silver chloride), the type of leads (ie unipolar and bipolar, and a description of the latter), the way the signal is handled (isolation, amplification, gain, filtering) and displayed. Methods to reduce artefact and improve signal:noise ratio, should have included skin conductive measures, minimising external interference (filters, earthing), common mode signal artefact rejection, high input impedance amplification and mention of diagnostic and monitoring modes. Syllabus: S2a Recommended sources: Davis and Kenny pgs 160-178, also Sykes & Vickers Principles in measurement and monitoring in Anaesthesia and Intensive Care, Chps 4, 5, 6, 23.

2011B 06: 15 (60%) of candidates passed this question. Renin and angiotensin are core components in the regulation of plasma volume and blood pressure regulation. It is unfortunate that many candidates presenting to this examination are not able to provide sufficient information for a pass. For a good answer, candidates were expected to mention what renin and angiotensin are and what they do, as well as briefly mention the place of angiotensin converting enzyme (converts Angiotensin I to Angiotensin II and inactivates bradykinin). Renin is a proteolytic enzyme cleaves angiotensinogen to angiotensin I, secreted by the juxtaglomerular cells of the kidney which are located in media of afferent arteriole and in close proximity to the glomerulus and the distal convoluted tubule (macula densa). Angiotensin II acts on cell surface AT1 and AT2 receptors. Major functions being to preserve of GFR & enhanced Na/H2O reabsorption in the setting of reduced renal blood flow (candidates expected to outline the mechanism by which this occurs), vasoconstriction, stimulate aldosterone secretion and increase thirst and ADH secretion. The better candidates also mentioned that it decreases sensitivity of baroreceptor reflex, increases secretion of ACTH and facilitates noradrenaline release from sympathetic nervous system as well as its fate (metabolized by blood/tissue peptidases). A good response for regulation would have been mentioning principally regulated via renin release (which in itself is influenced by renal sympathetic nervous system activity, intrarenal baroreceptors and macula densa sodium chloride delivery, ADH and intra-renal prostaglandins), negative feedback from angiotensin II. Syllabus: N2h Recommended sources: Textbook of medical Physiology, Guyton, Chp 26.

2011B 07: 9 (36%) of candidates passed this question. This is a core area of physiology that relates to everyday Intensive Care practice, thus it was expected that more than the observed number of candidates would have scored well. Candidates performed poorly purely from a lack of sufficient knowledge. Easy marks were to be gained purely by mentioning that compliance is defined by ∆V/∆P, the ∆P being the gradient from alveolar – intrapleural, normal values, static and dynamic compliance. Good answers would then include a mention of how static and dynamic compliance is measured (specifically how volume and pressures are measured. Syllabus: B1d 2b Recommended sources: Nunn Applied Respiratory Physiology, 6th Ed, Pgs 35-36

2011B 08: 3 (12%) of candidates passed this question. For a good answer candidates were expected to give a description of the lower oesophageal sphincter (the intrinsic and extrinsic sphincters and flap-valve), that it maintains a resting pressure of 15-25 mmHg above gastric pressure which prevents gastro-oesophageal reflux, which relaxes after swallowing, that the resting tone is maintained by myogenic and neurogenic mechanisms and the effects of hormones upon the sphincter (ie gastrin, motilin and α adrenergic stimulation increases and secretin, glucagon, VIP and GIP decrease tone). Syllabus: Q1 2f Recommended sources: Ganong Review of Medical Physiology Chp 26.

2011B 09: 8 (32%) of candidates passed this question. A portal system is an arrangement by which blood collected from one set of capillaries passes through a large vessel or vessels, to another set of capillaries before returning to the systemic circulation. The three portal systems are the - 1) system of blood vessels that link the hypothalamus and the anterior pituitary in the brain, which allows endocrine communication between the two structures. 2) within the liver, whereby venous blood from the GI tract drains into the superior and inferior mesenteric veins; these two vessels are then joined by the splenic vein to form the portal vein which enters the liver, drains into the hepatic sinusoids and then eventually into the hepatic veins which join the inferior vena cava, with the purpose of defending against by breaking down and metabolising most of what has been absorbed from the gastrointestinal tract (including an immunoprotective action). 3) within the kidney, whereby blood from the afferent arterioles enters the glomerulus (first capillary network), followed by the efferent arterioles, then the peritubular network (second capillary network) and eventually the venous system, with the purpose of stronger re-absorptive capacity for water from within long Loops of Henle that go deep within the renal medulla. Syllabus: N1 2c, I2d, D1 2a Recommended sources: Ganong Review of Medical Physiology Chps 18, 38, 29

2011B 11: 1 (4%) of candidates passed this question. For a good answer candidates were expected to mention that there were “essential” and nonessential proteins”, that protein synthesis draws on amino acids sourced from the common amino acid pool (because there is no cellular storage of amino acids) which is the combination of amino acids derived from gut absorption of digested dietary protein and also the continuous turnover of endogenous protein, amino acids filtered via the glomerulus are reabsorbed within the renal tubule and that in health losses are minor, but increases with illness. Protein synthesis is a semicontinuous activity, the rate of which varies considerably between cells under the influence of factors neuro- endocrine factors, substrate availability and energy availability. Proteolysis occurs within nuclear and cytoplasmic proteasomes, via peptide bond disruption catalysed by proteases, which are then processed further into amino acids being then available for release into the amino acid pool or utilised immediately for protein synthesis. In relation to starvation candidates were expected to mention that it results from a severe ongoing restriction of protein, energy and nutrient intake. That initially, glycogen stores from the liver and skeletal muscle are utilised after conversion to glucose and provide energy, thus sparing of fat and protein stores from use as an energy source for a period of less than a day, following which fats are increasingly utilised and finally protein catabolism accelerates, especially from the liver and skeletal muscle, with relative sparing of the heart and brain. Syllabus: K2c,f Recommended sources: Ganong Review of Medical Physiology Chp 2

2011B 12: 5 (20%) of candidates passed this question. A good response to this question required an ordered and well structured response. There are numerous important functions that the liver undertakes (eg bile formation, immunological, protein, lipid, glucose metabolism, storage, endocrine, etc), yet most candidates could not generate a sufficient list. In relation to paracetomol toxicity, a good response required candidates to mention that normal conjugating reactions in the liver are saturated and metabolism diverts to mixed function oxidases, which generate toxic metabolites. These in turn are inactivated by conjugation with glutathione. However when glutathione is depleted, toxic metabolites react with cellular nuclear material, thus causing liver necrosis. Toxic compound depletes sulphydril groups and also causes direct damage via lipid peroxidation. Regeneration of sulphydril groups and glutathione depends on availability of cysteine, thus the need to administer acetylcysteine. Syllabus: I2a, G2e2c Recommended sources: Gannong Review of Medical Physiology pg 485; Power and Kam Principles of Physiology for the Anaesthetist pg185; Stoelting Pharmacology and Physiology in Anesthetic Practice 4th edition pg 285; Rang & Dale Pharmacology 5th Ed pg 244.

2011B 13: 11 (44%) of candidates passed this question. Most candidates approached this question by defining cardiac output as stroke volume × heart rate and then discussing the determinants of cardiac output - preload, contractility, afterload and heart rate rather than focusing on the regulation of cardiac output. Under preload a brief description of the Frank Starling mechanism was required. Important was the concept that at rest cardiac output is controlled almost entirely by peripheral factors that determine venous return. These concepts were best illustrated by graphing vascular function (venous return vs right atrial pressure) and cardiac function (cardiac output vs right atrial pressure) curves. Then demonstrating on these curves the factors that affected preload, contractility and afterload such as changes in blood volume, sympathetic and parasympathetic stimulation and exercise as examples. Also important to demonstrate on these curves was the fact that venous return and cardiac output are equal at steady state. Most candidates tried to illustrate these cardiovascular concepts with a series of left ventricular pressure volume loops rather than use the vascular and cardiac function curves. They then went on to demonstrate via these pressure volume loops the effects of changes in preload, contractility and afterload on stroke volume. Candidates who took this approach were not penalised, if there were clear, correct diagrams with explanations indicating comprehension of these concepts. On the whole graphs were poorly drawn and were not well integrated into the answer. Some candidates also wasted time by unnecessarily describing excitation-contraction coupling and sympathetic nerve reflex pathways. Syllabus: C1c 2a,c,e,f,g Recommended sources: Guyton Textbook of Medical Physiology 11th edition pgs 241-243.

2011B 15: 5 (20%) of candidates passed this question. A good answer required a description of the sensory pathway(s) (eg nociceptors, Aδ and C fibres, spinal dorsal horn, spinothalamic, thalamic and cortical pathways), reflex arc (nocioceptive sensory fibres synapse with spinal inter-neurons that in turn synapse with peripheral motor neurons supplying the lower limb as well as inter-neurones that also synapse with motor neurons on the contra-lateral lower limb producing a crossed extensor response), central integration and the motor pathways (fibers from the contra-lateral motor (and pre-motor) cortex pass through the posterior internal capsule forming the lateral and ventral cortico-spinal tracts, the cortico-spinal tracts pass through the anterior brainstem, the lateral tract decussating in the caudal medulla, continue to synapse with spinal motor neurons in the ipsilateral lumbosacral anterior horn cells, passage via peripheral nerves and flexor muscle stimulated, extensors inhibited, resulting in withdrawal of the limb) Common mistakes included errors in naming nerve pathways and receptors. Another error was to confuse the polysynaptic pain response pathways with the monosynaptic stretch reflex. Very few candidates mentioned feedback regulation via cerebellar input and at spinal level from muscle spindles and Golgi tendon organs Syllabus: G12b Recommended sources: Ganong Review of Medical Physiology Chps 11 & 16

2011B 16: 12 (44%) of candidates passed this question. Graphical depictions of the effect of Mean Arterial Pressure, oxygen tension and carbon dioxide tension on cerebral blood flow were common and in general accurate. Mention of factors that affected, and regulation of, the MAP vs CBF graph was expected in order to pass this question well. The effect of propofol and ketamine on the CBF was well answered. Propofol and ketamine have an opposite effect on cerebral haemodynamic and metabolic rate. Propofol produces a dose dependent reduction in CBF with proportionate reduction in CMRO2, and thus a minimal change in cerebral venous O2 Sat. Propofol doesn’t affect the autoregulatory curve of CBF and the PaCO2 response. Ketamine produce a dose dependent increase in CBF and a mild increase in CMRO2. Syllabus: C1f 2c, G2a,2a. Recommended sources: Guyton Textbook of Medical Physiology Chp 61; Goodman and Gilman The pharmacological basis of therapeutics 11th edition pgs 350-352

2011B 17: 9 (36%) of candidates passed this question. Most candidates were able to classify the calcium channel blockers well (Type I : Phenylalkylamines eg verapamil, Type II : Dihydropyridines eg nimodipine and Type III : Benzothiazepines eg diltiazem) However, the comparison of the pharmacology of nimodipine and verapamil was in general answered poorly. Few candidates demonstrated an organised approach to this part of the question. The two drugs’ presentation, routes of administration, indications and dosing were poorly answered considering that nimodipine in particular is used frequently in intensive care units. Mode of action was well answered, but important principles relating to pharmacokinetics (such as a basic outline of protein binding, bioavailability, and metabolism) were expected, but common omissions. More knowledge than ‘metabolism in the liver’ is required. Few candidates mentioned interactions, adverse effects, or predictable effects of over dosage of these drugs. Syllabus: C2b 2d Recommended sources: Peck Hill and Williams Pharmacology for Anaesthesia and Intensive care 3rd Ed pgs 252-255.

2011B 18: 0 (0 %) of candidates passed this question. The majority of candidates were able to state that obstructive lung disease resulted in a reduction in the FEV1 and the FVC. Very few gave any indication of how much these parameters might be reduced in severe obstructive lung disease or that FVC is usually only slightly reduced, whereas the FEV1 is markedly reduced and therefore so is the FEV1/FVC ratio. Candidates were also expected to indicate that peak expiratory flow rate is also reduced (by 50% or more in severe disease), that carbon monoxide diffusing capacity is also reduced, and residual volume and total lung capacity are increased. A reasonable proportion of candidates commented that the forced expiratory flow (FEF) 25-50% being reduced and this results in a ‘scalloped’ flow volume loop. Accurately reproducing a normal flow volume loop and a flow volume loop of a patient with severe obstructive lung disease on the same graph could have depicted most of the above points and scored the majority of marks available. The second part of this question was poorly answered. Whilst the majority correctly stated that an increase in airways resistance was present, few stated what changes gave rise to this. Dynamic airway compression, was mentioned by many, but why this occurred was explained poorly. The effect of closing capacity rising above the FRC was seldom mentioned and why the FRC increased again was seldom mentioned or explained. A detailed knowledge of what is a core subject in intensive care medicine was expected. Syllabus: B1a 2a, b; B1j 2a Recommended sources: Respiratory Physiology: The Essentials. West 6th Ed pgs 26, 96-99, 131-142.

2011B 20: 13 (52%) of candidates passed this question. Platelets are small cells in blood, approximately 150,000 – 300,000 / microliter of blood with a half life of approximately 4 days. They have important membrane receptors (for collagen, vWF and fibrinogen) and intracellular contents (Actin, Myosin, Glycogen, Lysosomes, Dense granules, Alpha granules) and are involved in forming a platelet plug and clotting. Common omissions were to not give a normal platelet count or half life. Diagrams of the clotting cascade were not required. Clopidogrel is an oral, thienopyridine class antiplatelet agent (a prodrug activated in the liver by cytochrome P450 enzymes), used to inhibit blood clots in coronary artery disease, following stent placement, peripheral vascular disease, and cerebrovascular disease. Mechanism of action is: specifically and irreversibly inhibits the P2Y12 subtype of ADP receptor, which is important in aggregation of platelets and cross-linking by the protein fibrin and thus platelet aggregation, which is inhibited when binding blocks activation of the glycoprotein IIb/IIIa pathway. Elimination half-life of about 8 hours; rapidly absorbed after oral administration; undergoes rapid hydrolysis in liver and renal excretion; 95% protein bound. Important interactions/precautions include proton pump inhibitors, phenytoin, warfarin, heparin, danaparoid, enoxaparin and various thrombolytics. Greatest risk is bleeding. The best answers had a structured approach to describing a drug. Syllabus: J1 2f, J2 2d Recommended sources: Ganong Review of Medical Physiology pg 485; Goodman & Gillman. The pharmacological Basis of Therapeutics Chp 54.

2011B 21: 1 (4%) of candidates passed this question. A good answer required mentioning factors that affect systemic oxygen capacity and delivery (eg Hb, cardiac output, PaO2, etc), Hb-HBO2 dissociation and a description of the anatomy and regulation of renal medullary blood flow. 20 – 30% of nephrons have glomeruli deep in the cortex and long Loop of Henle that go deep into medulla. Here blood supply differs – long efferent arterioles from glomeruli into outer medulla and inner cortex that then divide into vasa recta deep in medulla. These vessels carry post glomerular blood so have less serum, mostly plasma, ie more viscous and concentrated. Factors that influence medullary blood flow include: Sympathetic stimulation – decrease (via efferent arteriolar constriction), Angiotensin II (via tubuloglomerular feedback) – decrease (via efferent arteriolar constriction), Endothelin – decrease (via efferent arteriolar constriction), Prostaglandins – increase, Bradykinin – increase, high protein meal – increase, high glucose levels – increase. Candidates performed poorly due to a lack of knowledge of the topic and/or failure to logically present their answer. Common mistakes were to give no value for renal blood flow, to discuss the function of the medulla which was not required and to not describe the factors that influence medullary blood flow. Syllabus: B1h 2a,b; C1f 2d Recommended sources: Guyton Medical Physiology Chp 26; Vander Renal Physiology Chps1, 5

2011B 23: 10 (40%) of candidates passed this question. The question consisted of three parts (production, release and fate of noradrenaline). The context was the sympathetic nerve terminal. The synthesis of Noradrenaline from Tyrosine was expected. Better answers mentioned the roles of Tyrosine Hydrolase, DOPA Decarboxylase and DOPA Beta-hydroxylase. Candidates were expected to describe the storage of Noradrenaline in vesicles and Ca++-mediated exocytosis in response to an action potential. Noradrenaline binds to post-synaptic and pre-synaptic receptors. Re-uptake, metabolism by MAO and COMT, and diffusion away from the synaptic cleft should have been discussed. An accurate diagram could be used to enhance the answer.