2025 First Sitting

. The first part of the question required a definition of receptors and outline of their classification. Good answers described receptors as proteins or glycoproteins that are found on cell membranes, on membranes of intracellular organelles or in the cytosol / nucleus and contain a region to which a natural ligand or drug binds specifically (receptor site or recognition site) to bring about a conformational change and subsequent response. Receptors can be grouped into 3 classes depending on mechanism of action, altered ion permeability, production of intermediate messengers and regulation of gene transcription. Further descriptions of the different types of receptors/downstream messages were not required. The second part of the question is well covered in the outlined pharmacology textbooks namely Peck and Hill, Stoelting and Goodman and Gillman’s. This is best answered by applying receptor theory: namely that receptors can exist in two states, an active and inactive state. Agonists stabilise the receptor in the active state, partial agonists occupy (and block) the binding site but do not completely favour the active state, whilst inverse agonists stabilise the receptor in the inactive state. Antagonists simply block the binding site and prevent agonists from binding. A description then of affinity and intrinsic activity of each group would complete your answer.

. (a) The definition of closing capacity was well answered and is relatively straight forward. (b) (i) The main physiological factor is age (decreases from birth to 16 years and then increases to become higher than FRC in older adults). A discussion of the age at which it typically exceeds FRC in the supine and upright positions attracted marks. A mention of other factors that alter it like high expiratory flow rates and increased expiratory effort made for a comprehensive answer. (ii) This part of the question required candidates to cover how increases in closing capacity effect VQ mismatch and PaO2 by air-trapping, reduced compliance, cyclical atelectasis (resulting in lung injury), slower de-nitrogenation during pre-oxygenation and increased work of breathing. These changes are pronounced in situations where FRC is also reduced. This was the section most candidates struggled with given the breadth of effects required. (iii) Techniques used to measure closing capacity are well described in both Nunn’s and West’s respiratory physiology textbooks. One technique involves taking a vital capacity breath of 100% oxygen and then measuring exhaled nitrogen as the subject exhaled back to the residual volume. The closing capacity is the point at which the nitrogen concentration begins to rise above the alveolar plateau in phase III.

. (a) A definition of systemic blood pressure is found in most physiology textbooks and describes this as the pressure exerted on the arterial walls in the systemic circulation. It is a product of vascular resistance and blood flow. An expected formula would be: Pa-Pv (arterial venous pressure difference) = QR where Q is blood flow and R is peripheral arterial resistance. An alternative formula of MAP = CO X TPR was also accepted and provided a structure for the second part of the question. (b) This section required a more detailed discussion of the factors in the equation including determinants of cardiac output, arterial blood volume, arterial elastance and peripheral arterial resistance (based on the Poiseuille equation). Your discussion should include naming the factor and then providing a description of how that factor increases/decreases or contributes to systemic blood pressure relating this to the formula provided in the first part of the question.

. (a) A definition of a buffer such as that found in a general physiology textbook such as Power and Kam were required (i.e. “a solution consisting of a weak acid and it’s conjugate base which resists a change in pH when a stronger acid or base is added”). (b) The major buffer systems in the body are bicarbonate, haemoglobin, protein, phosphate and ammonia. Full marks were awarded for answers that included a description of each system, their pKa, whether they are ‘open’ or ‘closed’ and their relative importance.

. The most effective way to approach this question was to structure information into the headings provided and consider the mark allocation to determine the level of detail for each section. High scoring answers described the unique physical and biochemical features that make up the blood barrier (such as the capillary endothelial cells with tight junctions and numerous mitochondria), and relate these to its barrier and regulation functions. Part (c) required detailed information about the factors affecting permeability across the blood brain barrier and includes transporters and efflux pumps. Answers that provided examples of specific substances and how they move across the blood brain barrier scored best. When responding to the areas outside the blood brain barrier, answers that included not just the area but the rationale similarly scored higher.

. The explicit structure and mark allocation provides a guide to answering this question and was applied appropriately in most instances. There were no marks awarded for the structure-function relationship of red cells and this information may reflect awareness of past questions on the topic with a different emphasis. More detailed answers included information such as different site of production in the fetus, duration of time for erythropoesis (7 days), changes in aging red blood cells, and different clearance pathways [haemolysis (10%) and spleen and liver phagocytosis (90%)]. Haemoglobin breakdown in general was well answered and needed to include heme breakdown into iron and biliverdin and a description of the fate of each of these components.

. The hormones secreted from the anterior pituitary include TSH, ACTH, LH/FSH, prolactin and growth hormone. For each of these, marks were allocated for a list of the effects on target organs and the control. Better answers followed a clear structure that included the hormone, the target organ and immediate effect and the control/feedback. For example, TSH stimulates thyroid hormone (T3/T4) synthesis from the thyroid gland. TSH release is stimulated by TRH from the hypothalamus and inhibited by T3/T4 plasma levels.

. High scoring answers had a good structure utilising the following headings: location; femoral triangle boundaries; relations and contents including the femoral sheath; origin and tributaries; and the important surface anatomy for insertion of a femoral line. Commonly omitted were descriptions of the femoral sheath; the surface anatomy including the ideal puncture site; and anatomical pitfalls. A description of the procedure of central line insertion was not required for this question.

. High performing answers were structured according to the headings provided and used tables. They emphasised the shared features of milrinone and dobutamine under each heading, but also clearly pointed out the important differences and why they matter. Some candidates were unable to obtain sufficient marks as entire section/s of the answer were omitted. Milrinone & dobutamine are both level one medications in the syllabus and thus a detailed working knowledge of all content asked in the question was expected.

. (a) The dose of enteral feeds was generally well answered. Marks were awarded for the mention of methods used to estimate energy requirements (such as indirect calorimetry or the Harris- Benedict equation. (b) The composition of enteral feeds should include the macronutrients (fat, CHO, protein), micronutrients and water and what form they are presented in. The quantities of each constituent and the contribution of each to the daily caloric goal was also required. Mention of alternate formulations such as soy-based feeds or elemental feeds in pancreatic disease scored additional marks. (c) Adverse effects were well covered and included gastrointestinal, metabolic and long-term consequences. As noted, in the question, marks were not allocated for complications related to feeding tubes.

. This is a broad question that tested the application of knowledge regarding carbon dioxide transport and effect of ventilation on CO2 content. A structured approach to this question includes a description of how the production, carriage and elimination of CO2; including normal values where relevant and factors that may affect these, alter CO2 tension. Minute ventilation is the major mechanism of CO2 elimination and therefore a more detailed discussion of the control of minute ventilation was required to score well and accounted for half of the marks. This discussion includes the role of chemoreceptors and other factors that affect minute ventilation such as exercise, J receptor and baroreceptor stimulation.

. Parts (a) and (b) required a description of the general capillary structure (single cell layer, thin etc) with specific unique features relevant to capillary membranes (fenestrated, non-fenestrated and sinusoidal), and a discussion of water movement across capillary membranes via ultrafiltration primarily. Majority of marks were allocated for part (c), and the following headings provide a useful structure: hydrostatic pressure, oncotic pressure, net-filtration pressure and the filtration coefficient. The contribution of the Gibb’s Donnan effect to plasma oncotic pressure attracted a small amount of additional marks, as did the glycocalyx and its influence on fluid movement. The effect of arterial and venous tone on the capillary hydrostatic pressure was a common omission.

. (a) The expected information in this question included discussion of the sites at which glucose transport occurs (primarily glomerulus and proximal convoluted tubule) and the transport mechanisms involved including specific transporters. A discussion of the maximum transport concept was also required. (b) This section required a discussion of the glucose induced osmotic diuresis and subsequent electrolyte loss. Additional marks were available for answers which recognised that this diuresis was not able to be overcome by ADH.

. (a) Diagrams were useful for many candidates, however others chose to provide a detailed description and also scored well. High scoring answers outlined the structure of the neuromuscular junction (NMJ) including all key functional elements. (b) This section required a clear and ordered explanation from the arrival of a presynaptic action potential via motor axon until the restoration of a resting membrane potential in the post-synaptic motor endplate. Many answers ceased their description following the binding of acetylcholine to the nicotinic receptor and degradation by acetylcholinesterase omitting the final steps in returning the motor end plate to its resting state. Common errors arose from confusion between skeletal and cardiac myocyte action potentials.

. (a) This component of the question required a detailed discussion of the mechanical/anatomical factors, chemical factors, enterogastric nervous reflexes, and hormonal factors (both local and systemic) that affect gastric emptying. Given the mark allocation of 80% to this section a reasonably detailed discussion of the mechanisms involved with each of the factors was expected. (b) Erythromycin pharmacology knowledge was expected to address the headings provided. Descriptions regarding the mechanism of action of erythromycin in its antibiotic use was needed to score full marks. Adverse effects should be listed with a brief explanation or outline as to their mechanism when able.

. (a) The first part of this question required clear definitions of interthreshold range (ITR) and thermoneutral zone (TNZ), relating each to the body and environment respectively. Normal values were a common omission. (b) The second part of the question was best answered by explaining how the body detects and defends against a fall in environmental temperature using a sensor-controller-effector mechanism. Effector responses include mechanisms to reduce heat loss vs. those which generate heat and candidates were expected to explain vasomotor changes, shivering and non- shivering thermogenesis as a minimum. Discussion of other mechanisms (such as behavioral responses) attracted additional marks. Finally, candidates needed to explain how each component of the defense may be impaired in the neonate or elderly. High marks were awarded for answers that relate these explanations to the concepts of ITR and TNZ. Information about the response to warm environments or the physiological consequences of hypothermia was not required.

. (a) A good definition of innate immunity included the following information: present at birth, non- adaptive and responds to a limited set of foreign molecules. For full marks, it was expected that candidates would contrast this with the adaptive immune response including the requirement for sensitisation / pre-exposure and potential to respond to many unique antigens. (b) It was helpful to divide the components of the innate immune system into physiochemical, humeral and cellular elements. Physiochemical elements included skin, mucus, cilia and secretions such as gastric acid. Additional marks were allocated for answers which also mentioned how each component acts to prevent infection (i.e. skin forms a physical barrier which prevents bacterial translocation). This part was generally answered very well. For humoral elements marks were apportioned between complement, lysosymes and acute phase proteins / Negative phase proteins. A brief outline of each was desirable with full marks given for detailed description of their role in immunity including their sites of production Lastly a good description of cellular elements included neutrophils, macrophages/monocytes, mast cells and natural killer cells. For each a brief outline of their role and function attracted full marks.

. (a) The question involved describing the principles of measurement of arterial haemoglobin oxygen saturation i.e. provide a detailed account of this topic. The expected answer included describing the Beer Lambert Law correctly and describing the different absorption of light at different wavelengths by different haemoglobin species. Candidates were also expected to provide a description of the components and functioning of the components of a pulse oximeter such as LEDs, photodetectors and the algorithm used to provide the arterial Hb saturation and plethysmograph trace. (b) The second part of the question involved outlining the limitations of the pulse oximetry. This was generally well answered by candidates, outlining patient and equipment factors that limit the accuracy of this technique.

. (a) Opioids act on several receptors and a reasonable understanding of these is required to answer this question. A description of the intracellular events following ligand binding on G protein coupled opioid receptors, as well as pre and postsynaptic effects on calcium channels and potassium channels was required to score well in the first part. (b) A detailed description of the peripheral, spinal cord and supra-spinal opioid receptors including their activation and transmission pathways was required for a comprehensive answer. (c) Here the receptor, location and mechanism that brings about these common opioid side effects was needed to answer this component of the question.

. The question breakdown allowed for a simple but structured approach to this question. For common fungi like candida, full binomial names were required e.g. "candida albicans, candida glabrata". The mechanisms of actions were well outlined, and expected details included the target for the drug (e.g. enzyme or sterol), the effect on the cell membrane or wall, and whether it was fungicidal or fungistatic. A broad range of serious side effects were accepted for part b however specificity was required with respect to which drug is most likely linked to each.