2008 Second Sitting

2008B 01: 2 (40%) candidates passed this questions There were a number of possible factors that candidates could have selected. Examples include drug interactions (anticholinesterases, aminoglycoside antibiotics, local anaesthetics, steroids, antiarrhythmic drugs, anticonvulsants (phenytoin), diuretics, magnesium, lithium), hypothermia / hyperthermia, acidosis, [k+], burn injury, allergic reactions, gender, altered elimination due to renal or hepatic dysfunction and disease states (adrenocortical dysfunction, myasthenia, myopathies, denervation injury). Also extremes of age and pregnancy. Areas of weakness for the candidates were failure to include sufficient factual knowledge for their selected factors, and as a result, a failure to illustrate sufficiently the mechanisms by which the pharmacodynamic response of nondepolarising neuro-muscular blocking drugs may be affected. Syllabus: H2a 2 (c) Reference Text: Pharmacology and Physiology in Anaesthetic Practice / R K Stoelting

2008B 03: 3 (60%) candidates passed this question This question was generally well answered. Successful candidates illustrated their answer through the use of a table. For a good pass candidates were expected to include a definition of a buffer; mention the buffering capabilities of the differing buffering systems (bicarbonate, phosphate and protein buffers) in relation to the pKa; the area in the body where they are most effective and whether it was an open or closed system. The protein buffer system was the least well conveyed by candidates, despite approximately 60 to 70 per cent of the total chemical buffering of the body fluids being inside the cells, and most of this from the intracellular proteins. For a good answer it was expected that candidates also mention that, except for the red blood cells, the slowness with which H+ and HCO3- move through the cell membranes often delays for several hours the maximum ability of the intracellular proteins to buffer extracellular acid-base abnormalities. In addition to the high concentration of proteins in the cells, another factor that contributes to their buffering power is the fact that the pKas of many of these protein systems are fairly close to 7.4. Syllabus: F2b Reference Text: Guyton Chp 30

2008B 04: 3 (60%) candidates passed this question Metabolism is all the chemical reactions in all the cells of the body. Metabolic rate is usually described in terms of rate of heat liberation. Candidates often confused basal with metabolism during activity. A good answer was expected to outline conditions under which basal metabolic rate is measured (no food for 12 hours, after a night of restful sleep, person is at rest in reclining position for 30 minutes, all psychic or physical factors that cause excitement eliminated, at a controlled comfortable temperature), and the mention of and an explanation of the methods by which metabolic rate is measured (eg direct and indirect calorimetry). Any validated technique of determining the BMR was rewarded with marks, with oxygen consumption methods being the easiest to explain. No candidate mentioned any ‘normal’ value for the BMR. Candidates were expected to briefly mention and explain how factors affecting metabolic rate (eg exercise, specific dynamic action of protein after a meal is ingested,, age, thyroid hormone, sympathetic stimulation, fever, gender, hormonal, climate, sleep, chronic malnutrition, trauma, inflammatory response, etc). Questions with more than one part will have an indication of the proportion of the total mark that will be allocated to each part. It is important that candidates apportion their allocated time and content accordingly. Syllabus: K 2a, b Reference Text: Guyton Chp72

2008B 06: 4 (80%) candidates passed this question To achieve a pass in this question, candidates needed to state where and how CSF was formed, where it flows to after formation followed by a list of its functions. Additional credit was given for knowledge of rates of production and basic CSF composition. The fact that CSF production is constant whilst its absorption is pressure dependant was often overlooked. Thus candidates were expected to mention that there is ~ 150 ml of CSF in the adult, half within the cranium; about 60-70% of the CSF is formed by the choroid plexuses, the remaining 30-40% by the cerebral vessels lining the ventricular walls; in humans the CSF turns-over ~ 4 times/day; composition is essentially brain ECF; brain ECF normally occupies ~ 15% of brain volume; CSF flows out through the foramina of Magendie and Luschka and is absorbed through the arachnoid villi into the cerebral venous sinuses; absorption, being largely by bulk flow, is proportional to ventricular pressure [at normal pressure ~ 7.0-18.0 cmH2O (mean ~ 11), filtration = absorption, when pressure falls below ~ 7 cmH2O absorption ceases] and CSF Functions [buoyancy, constant metabolic environment, buffers CSF against rapid plasma changes in K+, Ca++, Mg++, transport of chemical messengers, sink for waste disposal]. A number of candidates embarked on long discussions of how CSF pH affects physiology to the exclusion of what was asked for in the question. Many answers did not adequately cover the three components asked for in the question. Syllabus: CNS 2d Reference Text: Guyton Chp 61

2008B 08: 1 (20%) candidate passed this question The clinical condition that results from this lesion is the so called Brown-Sequard syndrome. However only a very small proportion of points were given to mention of the latter, with the majority of points allocated to knowledge relating to spinal cord anatomy and physiology. The expected 4 main clinical features that are associated with this lesion are - 1. There is loss of pain and temperature sensation on the contralateral side below the level of the lesion due to interruption of ascending fibres in the crossed lateral spinothalamic tract. 2. There is loss of vibration, joint position and 2 point discrimination on the ipsilateral side below the level of the lesion due to interruption of ascending fibres in the posterior [dorsal] columns. 3. There is paralysis of voluntary movement on the ipsilateral side below the level of the lesion due to interruption of descending fibres in the lateral corticospinal [pyramidal] tracts. Initially the paralysis is flaccid, later it becomes hypertonic and hyperreflexic with extensor plantar response [upper motor neurone lesion]. 4. Finally there is segmental anaesthesia of the dermatome at the level of the lesion on the ipsilateral side due to damage of the nerve roots and anterior horn cells at this level. Some candidates described the clinical features of complete section of the spinal cord which was not asked for. Syllabus: G1 2b Reference Text: Guyton Sections IX and XI

2008B 09: 1 (20%) candidate passed this question This question was mainly about the metabolic consequences of an intravenous load of 25 grams of glucose. For a good pass the main areas that required description included: The transient glycosuria. The mechanism and time course of the biphasic release of insulin from pancreatic cells. The mechanism of the trapping of glucose within liver cells. The multiple actions of insulin which include inhibiting glycogenolysis and promoting glycgogen synthesis in the liver, promoting the uptake of glucose by muscle, fat and other cells, increasing the metabolism of glucose to fatty acids and triglycerides, inhibiting triglyceride breakdown and promoting protein synthesis. Additional marks were awarded for details of where these actions of insulin occurred and the enzymes that were stimulated or inhibited by insulin. Some candidates stated that this bolus of hypertonic glucose would produce a significant and prolonged increase in plasma osmolarity and then went on to produce detailed descriptions of the thirst and ADH mechanisms. In fact with a normal insulin response glucose is rapidly cleared from the blood

2008B 10: 4 (80%) candidates passed this question Candidates can benefit by having a system by which they approach topics that involve a broad and general topic such as that of the pharmacology of a particular drug or ideal agent. A good answer included the following logical subheadings: Desirable pharmacology – long shelf life, stable when drawn up and on exposure to light, cheap, mixes well with other agents in the central line lumen. Bacteriostatic. Desirable pharmacokinetics – Low volume of distribution, rapid clearance (context-sensitive half-life), clearance not affected by either renal or hepatic dysfunction. Little inter-individual variation in pharmacokinetics. (Availability of an antagonist). Desirable pharmacodynamics – Affects only CNS. Reliable dose – effect curve with little inter-individual variation in effect. Anxiolysis. (Analgesic properties). No effect on cardiovascular performance. Does not depress respiratory drive. Minimal side effects – No incidences of allergy / anaphylaxis. No idiosyncratic reactions. No tachyphylaxis. As indicated, 50% of the marks were allocated to mentioning how well propofol reflects these properties. Mention of ‘propofol infusion syndrome’ characterised by cardiac failure which can occur when propofol is used at >4mg/Kg/Hr for more than 24 hours also attracted marks. Syllabus: G2a 1&2 Reference Text: Pharmacology and Physiology in Anesthetic Practice / R K Stoelting

2008B 11: 2 (40%) candidates passed this question This question required the candidate to provide some detail why a given dose of intravenous anaesthetic administered for the purpose of induction may result in a variable response between individuals. A logical division into pharmacokinetic and pharmacodynamic factors pertaining to the drug and how these are impacted by patient physiology, citing appropriate examples, was expected. Extremes of age, pregnancy, low and high cardiac output states, sympathetic tone, body habitus and factors impacting on drug redistribution and elimination should have been addressed. Extra marks were awarded for relevant discussion of pharmacogenetics. Discussion of the “bolus effect” versus slow infusion of an induction drug, relative to these factors should have been included. Mention of drug interactions, idiosyncratic reactions and relevant pathophysiology impairing organ function reserve was appropriate. The consequences of variability in drug response in terms of over- / underdosing, haemodynamic compromise, respiratory depression, delayed recovery and allergic reactions needed emphasis to demonstrate understanding of the significance of predisposing factors. Effective answers to this question utilised either clear headings, or a tabular format, dividing what is a large topic into discrete areas. The lack of a structured approach to this question was invariably unsuccessful. Syllabus Ref: G2a 2.c,d,e,f,g Suggested Reading: Pharmacology and Physiology in Anaesthetic Practice / R K Stoelting – 4th ed - 2006. Chapters 4,6.

2008B 12 : 4 (80%) candidates passed this question This question was concerned with a very important physiological principle and was generally well answered. A good answer included a definition of autoregulation. In relation to the renal circulation, the kidneys extract only 10% of the available O2 supply and therefore the renal blood flow is high for the purpose of filtration and not metabolic demand, renal blood flow is autoregulated to remain constant against arterial blood pressures from 75 – 160 mmHg (an illustration helps explain this concept), Tubuloglomerular Feedback (including a description of the mechanism). A discussion about other mechanisms thought to play a role is important – eg intrinsic contractile response of smooth muscle to stretch (myogenic theory of autoregulation). Vasodilator substances tend to accumulate in active tissues, and these "metabolites" (decreases in O2 tension, increased CO2 tension and decreased pH) also contribute to autoregulation (metabolic theory of autoregulation). The sympathetic nerves innervate afferent and efferent arterioles. Renal autoregulation usually overrides mild to moderate degrees of sympathetic stimulation. Strong sympathetic stimulation however will constrict renal arterioles reducing flow to 10% of normal. GFR falls to a lesser extent than renal blood flow owing to a differential effect of sympathetic stimulation constricting the efferent arteriole to a greater degree than the afferent arteriole. Syllabus: C1f 2a, d D2i Reference Text: Guyton Chp 26

2008B 13: 3 (60%) candidates passed this question This question again highlighted the importance of candidates utilising a predetermined format or structure to their questions. Well structured responses were less likely to overlook important details, which was the predominate weakness for some candidates. A table format was one useful way of displaying a good answer, for example - Syllabus: C2c Reference Text: Goodman and Gillman Chp 34

2008B 15: 0 (0%) candidates passed this question This question sought an understanding of the physiological effects of thyroid hormones. The major area of weakness for candidates was a lack of detailed understanding of the physiological actions of thyroid hormones and/or providing an answer that predominately listed clinical manifestations. A good answer would have included the following points - Stimulation of Carbohydrate Metabolism - all aspects of carbohydrate metabolism, including rapid uptake of glucose by the cells, enhanced glycolysis, enhanced gluconeogenesis, increased rate of absorption from the gastrointestinal tract, and increased insulin secretion Stimulation of Fat Metabolism - all aspects of fat metabolism are also enhanced lipids are released from fat stores and increased oxidation of free fatty acids by the cells - decreases the concentrations of cholesterol, phospholipids, and triglycerides in the plasma, even though it increases the free fatty acids Increased Basal Metabolic Rate – increased CMRO2 Increased Requirement for Vitamins Increased vasodilatation, Cardiac Output, heart rate (not BP), contractility Increased Respiration – secondary to increased metabolism Increased Gastrointestinal Motility and secretions Excitatory Effects on the Central Nervous System, seizures and insomnia Effect on the Function of the Muscles – stimulates contractility and metabolism, but too much leads to the muscles become weakened because of excess protein catabolism. Also muscle tremor by increased reactivity of the neuronal synapses in the areas of the spinal cord that control muscle tone Effect on Other Endocrine Glands - . increases the rate of glucose metabolism everywhere in the body and therefore causes a corresponding need for increased insulin and glucagon secretion by the pancreas. Also, increase bone formation and, as a consequence, increases the need for parathyroid hormone. Thyroid hormone also increases adrenal glucocorticoid metabolism by the liver. Syllabus: N2e Reference Text: Guyton Chp 76

2008B 16: 3 (60%) candidates passed this question This question also highlighted the importance of candidates noting the way marks were proportioned. A good answer required the following points – Classification and examples - gram-positive cocci (Staphylococcus aureus, Streptococcus pyogenes or pneumoniae or agalactiae), gram-negative cocci (Neisseria meningitidis, N. gonorrhoeae), gram-positive bacilli (Bacillus anthracis, Listeria, corynebacteria, Clostridium difficile, etc), gram-negative bacilli (Escherichia Coli or E. Coli, Proteus, Yersinia, Salmonella, Shigella, Pseudomonas aeruginosa, Klebsiella pneumoniae, Legionella). Mechanisms of resistance include: a) Enzyme inactivation, beta-lactamase or Extended Spectrum Beta-lactamase b) Enzyme addition: enzyme produced by bacteria that add a chemical group to the antibiotic to inhibit its activity, aminoglycoside resistance by Staphylococcus aureus or Pseudomonas. c) Impermeability, anaerobes have no oxygen dependent transport mechanism which stops the penetration of aminoglycosides into the bacteria. d) Efflux mechanisms by acquisition of an inner member protein which actively pumps antibiotics out of the cell, E.Coli becomes resistance to tetracycline by this mechanism. e) Alternative pathway to circumvent the metabolic block impose by antibiotic, Some Staphylococcus aureus are resistant to methicillin by developing or acquiring the gene mecA which produces an alternative penicillin binding protein and hence they are not inhibited by methicillin. f) Alteration of the target site, rifampicin resistance by point mutations, insertions, or deletions in RNA polymerase gene. Syllabus: M2a, b, c Reference Text: Microbiology and Infection at a Glance by Gillespie & Bamford 3rd Ed, 2007 page 8-9,21.

2008B 17: 2 (40%) candidates passed this question Obesity is an increasing problem in the broader community and in Intensive Care practice. Hence it is important candidates understand the physiological and pharmacological consequences of obesity. This question confined its scope towards obesity and the respiratory system. Major area of weakness of candidates was a lack of depth and breadth in knowledge of this topic and in applying basic physiology. A good answer required the following points - Definition of morbid obesity (>200% ideal body weight or body mass index > 35) Upper airway effects: fat infiltration of pharyngeal soft tissues difficult airway, prone to airway obstruction eg OSA ↑ O2 consumption and CO2 production: due to ↑ total body fat, requires ↑ cardiac output and ↑ alveolar ventilation ↓ FRC mainly via ↓ ERV: due to mass loading and splinting of diaphragm, upright obese, closing capacity > FRC small airway closure, ↑ V/Q mismatch, ↑ venous admixture and arterial hypoxaemia, ↓ O2 stores ↓ total respiratory system compliance: ↓ chest wall compliance , subcutaneous and intra abdominal fat excess, ↓ lung compliance, ↑ airways resistance, ↑ work of breathing, ↓ resp muscle efficiency Altered ventilatory control: Obstructive sleep apnoea, Obesity hypoventilation syndrome Syllabus: B1k B1d2k Reference Text: Nunn’s Applied Respiratory Physiology / A B Lumb & J F Lunn - 6th ed

2008B 18: 3 (60%) candidates passed this question A good answer for this question required the description of the pathway of bilirubin production beginning with the breakdown of haemoglobin breakdown, then haem to biliverdin by biliverdin reductase, biliverdin to bilirubin, bilirubin transported to liver bound to plasma proteins, bilirubin monoglucuronide and diglucuronide by conjugation, secreted into bile. Secretion into bile is dependent on active transport and is the first to be impaired in inflammation of the liver. Bilirubis metabolized to stercobilinogen which is absorbed and excreted in urine as urobilinogen. The remaining part to this question flowed on from this point, ie Intrahepatic disease – increased conjugated bilirubin, urobilinogen and urine bilirubin, Posthepatic disease – increased conjugated bilirubin, no urobilinogen, increased urine bilirubin Syllabus: I2c Reference Text: Guyton Ch 70

2008B 07: 3 (60%) candidates passed this question A tabular format is a very desirable format for a response to this question. Again candidates who struggled to provide an organised response also failed to provide sufficient and succinct detail in their answer. A good answer would have included the following features. Syllabus: M2g Reference Text: Goodman and Gillman Chp 64

2008B 21: 0 (0%) candidates passed this question The renin-angiotensin system plays a central role in the pathophysiology of heart failure. Thus this question required integration of knowledge of the renin-angiotensin system and how pharmacological agents affect it in the treatment of cardiac failure. Candidates were expected to describe the pathway and the influence of these drug groups on cardiac failure and to recognise underlying basic physiological principles such as the interaction between AT1 and AT2 receptors along with awareness of production of Ang II by ACE-independent enzymes. A good answer was expected to contain the following points: Angiotensinogen is cleaved by kidney-derived renin to form the decapeptide angiotensin I (Ang I); ACE converts Ang I to Ang II; Ang II is a potent arterial vasoconstrictor and an important mediator of Na + and water retention through its effects on glomerular filtration pressure and aldosterone secretion; Ang II potentiates neural catecholamine release, is a secretagogue for catecholamine release from the adrenal medulla, promotes vascular hyperplasia and pathologic myocardial hypertrophy. ACE inhibitors suppress Ang II and aldosterone production, decrease sympathetic nervous system activity, and potentiate the effects of diuretics in heart failure. ACE is identical to kininase II, which degrades bradykinin and other kinins that stimulate production of NO, cyclic GMP, and vasoactive eicosanoids; these vasodilator substances seem to oppose the effects of Ang II on the growth of vascular smooth muscle and cardiac fibroblasts and on production of extracellular matrix. Thus, the increased levels of bradykinin that result from ACE inhibition may play a role in the hemodynamic and anti-remodeling effects of ACE inhibitors. An alternative means of attenuating the haemodynamic and vascular impact of the reninangiotensin system is through inhibition of angiotensin receptors. Most of the known clinical actions of angiotensin II are mediated through the AT1 angiotensin receptor. AT1 receptor antagonists may provide more potent reduction of the effects of angiotensin II than do ACE inhibitors.

2008B 22: 3 (60%) candidates passed this question Candidates were expected to cover the basic principles of gaseous diffusion across the placenta, with reference to: Both oxygen and carbon dioxide; Fick’s Law, including placental area and thickness, and relative gas tensions and solubilities; Changes in maternal and foetal blood flow approaching term; Approximate values for maternal and foetal gas tensions and content; The differences between foetal and maternal haemoglobin, quantitative and qualitative; The double-Bohr and double-Haldane effects; Relative maternal hyperventilation and it’s effects on arterial gas tensions and how these influence foetal transfer. A good answer would also include a description of the physical arrangement of maternal sinuses and foetal capillaries; labelled dissociation curves for O2 and CO2 detailing the differences between maternal and foetal Hb; a placental gas exchange diagram, showing foetal and maternal arterial and venous gas tensions and content values. Syllabus ref: O1 2d Suggested Reading: Review of Medical Physiology / W F Ganong – 22nd ed Chapter 32. Nunn’s Applied Respiratory Physiology / A B Lumb & J F Lunn - 6th ed

2008B 23: 2 (40%) candidates passed this question This question required the candidate to provide some detail why a given dose of intravenous anaesthetic administered for the purpose of induction may result in a variable response between individuals. A logical division into pharmacokinetic and pharmacodynamic factors pertaining to the drug and how these are impacted by patient physiology, citing appropriate examples, was expected. Extremes of age, pregnancy, low and high cardiac output states, sympathetic tone, body habitus and factors impacting on drug redistribution and elimination should have been addressed. Extra marks were awarded for relevant discussion of pharmacogenetics. Discussion of the “bolus effect” versus slow infusion of an induction drug, relative to these factors should have been included. Mention of drug interactions, idiosyncratic reactions and relevant pathophysiology impairing organ function reserve was appropriate. The consequences of variability in drug response in terms of over- / underdosing, haemodynamic compromise, respiratory depression, delayed recovery and allergic reactions needed emphasis to demonstrate understanding of the significance of predisposing factors. Effective answers to this question utilised either clear headings, or a tabular format, dividing what is a large topic into discrete areas. The lack of a structured approach to this question was invariably unsuccessful. Syllabus Ref: G2a 2.c,d,e,f,g Suggested Reading: Pharmacology and Physiology in Anaesthetic Practice / R K Stoelting – 4th ed - 2006. Chapters 4,6.

2008B 24: 4 (80%) candidates passed this question Most candidates quite correctly approached this from the perspective of “West’s zones of the lung. A clear description of the relationship between pulmonary arterial, venous and alveolar pressures producing the classical 3 zones was expected, along with situations which may alter the normal balance between the 3 zones, e.g. changing posture or airway pressure. Additional points were awarded for candidates describing ‘zone 4’ or alternate theories of V/Q distribution. Whilst most candidates described recruitment and distension with respect to changing pulmonary arterial pressure, candidates were also expected to correctly state that an increase in pulmonary artery pressure is only observed when these processes are exhausted, or in the setting of pulmonary vascular disease, then describing the subsequent effects of pulmonary hypertension on the heart and circulation. The vascular tree is distensible, that is, a change in pressure will produce a corresponding increase in dimension of the blood vessels: \[ Vascular \; distensibility \; = {{increase \; in \; volume} \over {Increase \; in \; pressure\; \times \; original \; volume}} \] Increased pressure delivered to the arterioles causes dilation and decreases resistance to flow, increasing flow by as much as twice what would be expected due to pressure alone The veins are 6 to 10 x as distensible as arteries owing to the structural differences in their respective walls. A notable exception is the pulmonary circulation where arteries are approximately ½ as distensible as veins; this buffers pressure changes transmitted to the alveolar capillaries and also permits the arteries to adopt a reservoir function. Pulmonary vascular resistance is also a function of lung volume. At extremes pulmonary capillaries are linearly stretched and collapse as may occur with hyperinflation. At very low lung volumes, extra-alveolar blood vessels become compressed and flow reduces (Zone 4). Use of appropriate graphs to illustrate some of the above points would have been desirable.. Syllabus Ref: B1i 2, B1k 2. a,c,i Suggested Reading: Nunn’s Applied Respiratory Physiology / A B Lumb & J F Lunn - 6th ed - Chapters 7,8 VIVAs A. Pharmaceutics B. Pharmacokinetics C. Pharmacodynamics D. Variability in Drug Response E. Cellular Physiology F. Respiratory Draw Capnograph tracing Collapse Lt Lung - processes contributing to hypoxia - V/Q, shunt, PVR, Pulse oximetry G. CVS NIBP vs Invasive BP monitor Noradrenaline - Physio, Pharm, PV loop changes, effect on Myocardial oxygen consumption, work and efficiency. Dobutamine infusion on PV loop H. Renal I. Body Fluids and Electrolytes J. Acid Base K. Neuro Cerebral blood flow, measurement, variations, Morphine Pharmacology of analgesic meds - Non-opioids, Opioids L. Musculoskeletal M. ANS N. Liver O. GIT Prokinetics, Laxatives, Octreotide P. Nutrition and Metabolism Q. Haematology R. Thermoregulation S. Immunology T. Microbiology U. Endocrine Insulin - Physio, Pharm, Refeeding syndrome V. Obstetrics W. Measurement and Monitoring X. Procedures