2025 Second Sitting

This question expected candidates to describe the four mechanisms of transmembrane signaling that are mediated by cell membrane receptors. These are: - Ligand gated ion channels that open and close in response to ligand binding - G protein coupled and G-protein mediated production of intracellular second messengers - Ligand regulated transmembrane enzymes whose intracellular enzymatic activity is allosterically regulated by a ligand binding to extracellular protein binding sites. - Transmembrane receptors that bind to and stimulate tyrosine kinase For each mechanism, a detailed answer would describe the receptor structure, location, an example of a natural ligands and an overview of the signaling pathway and physiological effects. An example would be: Ligand gated ion channels are part of a membrane-spanning complex of protein subunits forming a channel through the membrane. Binding of a ligand causes a conformational change allowing passage of an ion(s) down its concentration gradient resulting in a change in the resting membrane potential, depolarization or repolarization. For example; nicotinic acetylcholine receptors are pentameric structures comprising 5 sub- units. They are located at the neuromuscular junction and bind acetylcholine to cause opening of Na channels causing membrane depolarisation. Information on drug-receptor interactions such as agonism, antagonism, receptor affinity and intrinsic activity was not required.

. The question structure and mark allocation is a useful guide to the level of detail required for each section. a) The definition and components of dead space (apparatus, anatomical, alveolar and physiological) are relatively straightforward and were well answered. b) A useful structure for this section involved a description of the factors that affect each of the components of dead space outlined in the first section. It was expected that each factor would be correlated to its effect e.g., an increase in conducting airway volume (such as in the supine position or with larger patient size) leads to increased anatomical dead space. c) The major impact of increased dead space is a reduction in alveolar ventilation. Higher marks were gained by describing the consequences of this; changes in alveolar gas tension, compensatory changes in work of breathing and eventually respiratory failure once compensatory mechanisms are exhausted. d) Techniques used to measure dead space are well described in both Nunn’s and West’s respiratory physiology textbooks. Anatomical dead space is measured using the Fowler's method (nitrogen washout) and the Bohr equation with Enghoff modifications measures physiological or total dead space. Alveolar dead space is then derived by subtracting anatomical from physiological dead space. A brief description of these concepts was expected.

a) Descriptions of the action potentials of the SA node and cardiac myocyte are well described in most physiology textbooks and were relatively well answered. Shape, duration and ionic events were covered in good detail in most answers. b) An overview of the differences between the SA node and cardiac myocyte action potentials was required and then the implications of these differences. The differences expected to form a good answer included the absence of a true resting membrane potential in the SA node and differences in the duration of the action potentials, conduction velocities, action potential phases and refractory period.

. This question required a structured approach to cover its breadth. An example of a structure that worked well considered the functions of the kidney (regulation of water, electrolytes and systemic blood pressure; acid-base balance; excretion of metabolic waste; endocrine functions) and then a description of the consequences of renal failure on each. Each physiological effect required a reasonably detailed discussion of the mechanism(s) by which it occurs and the consequences on the body. For example: stating in endocrine dysfunction that “renal failure leads to erythropoietin (EPO) deficiency and anaemia” would score less than stating that “reduced O2 consumption by failing nephrons => reduced hypoxic stimulation of EPO production by kidneys => reduced RBC production => anaemia.

a) The definition of pain is relatively straightforward and was well answered. b) To assist in providing a comprehensive answer pain detection can be subdivided into the following; - Peripheral nociception – including classification and role of sensitisation - Transmission to spinal cord – including a description of fibre types and their characteristics - Spinal cord synapse and modulation – this required only an outline of what goes on here as this is complex and not well understood. A brief description of the receptors and neurotransmitters involved at the spinal cord level and the role of first order and second order neurons and inhibitory interneurons. - Transmission pathways from spinal cord to cortex – whilst spinothalamic was written by many the spinoreticular component of pain sensation and transmission was commonly missed. - Descending modulation – a brief outline of the central origin and neurotransmitters involved.

This question required a structured approach to cover the breadth. A common structure in most of the recommended resources includes classification of adverse reactions into - immune mediated haemolytic vs non-haemolytic immediate and delayed - non-immune mediated. acute reactions delayed reactions Not using a structured approach often resulted in the omission of whole sections. Other common omissions were in not briefly describing the mechanism of each reaction which was required to score well. Information on adverse effects related to storage lesions and massive transfusion also attracted marks.

. a) The synthetic, metabolic, immune and exchange functions of the placenta were generally well covered. Good answers addressed each of the synthetic, metabolic, exchange functions including and most importantly O2 and CO2 transport and the role of foetal Hb. Including a brief description on the exchange of electrolytes, glucose, nutrients, and waste products provided a comprehensive answer. b) Utero -placental blood flow has a uterine component and a foetal component. An understanding that maternal arterial blood pressure is key was required and a brief discussion of the limited autoregulation and sparse sympathetic innervation. A reasonable range for the value of uteroplacental blood flow at term was allowed. Placental blood flow is largely regulated by metabolic products as the foetus grows and requires only a simple reference to this to gain these marks.

. This question requires candidates to demonstrate their understanding of the safety considerations in performing a lumbar puncture. High scoring answers discussed the surface and bony anatomy including the spinal cord termination, adjacent structures, safe entry sites to perform the procedure and the layers traversed to reach the subarachnoid space. Diagrams were not always useful in demonstrating this information and needed to be well labelled and accurate to score marks.

. The question structure provides a guide to the level of detail required for each section. High scoring answers discussed the similarities and key differences between the drugs which may influence the use of one over the other. Both drugs are commonly used level two drugs in the syllabus. A detailed knowledge of the mechanism of action, pharmacodynamic and adverse effects was expected and well covered in pharmacology textbooks. In general, given these are both primarily anti-hypertensive agents the cardiovascular pharmacodynamics carried more weight than other system effects.

. Meropenem is a commonly used drug in ICU and information required to do well in this question is directly applicable to everyday practice. a) Mechanism of action was generally well answered and covered by candidates. b) The spectrum of activity required a statement of its broad spectrum including some examples of this. c) Indications for use were asking candidates to indicate the types of infections meropenem is preferred particularly as it is not usually the first antibiotic of choice, for example, hospital acquired infections, multi-microbial and necrotising infections, failure of first line therapy, melioidosis or any other reasonable example. d) This section required an explanation of how critical illness changes the way meropenem is handled and hence the need to adjust dosage not necessarily just a list of the general pharmacokinetics of meropenem. A comprehensive answer included the increased dosage required in high cardiac output states as high GFR ie. burns, sepsis due to the renal handling, or the effect of renal impairment. The changes to the volume of distribution for meropenem are seen in critical illness and the relative lack of concern in hepatic failure and thus the limited need to dose reduce in these circumstances.

. An ideal structure was represented in the breakdown of this question and gave an indication of the level of detail and time candidates should devote to describing the contribution of each to the control of breathing. This question was generally well answered. Good answers were able to integrate this sensor- controller- effector mechanism including the stimuli and effects. a) Sensors included a detailed description of the central and peripheral chemoreceptors and their relative primary and secondary stimuli. Better answers included other sensors such as pulmonary, skeletal, and baroreceptors and briefly touched on their contribution. b) This section required a brief description of the key areas that control breathing. These can be found in the medullary respiratory centre (CPG, VRG, DRG), the pons and the cortex. Their functions and primary effects needed to be listed. The role of PaCO2 (major determinant) and PaO2 was also required. c) Here only a brief description of the muscles that contribute to inspiration and expiration and the main nervous innervation would have constituted a good answer.

. a) This definition is straightforward and accounted for small proportion of marks. b) A good answer discussed the key changes in the right and left heart, pulmonary, systemic and coronary circulation and changes to the cardiac conduction pathways. The underlying mechanisms for these changes because of morbid obesity were expected.

. This topic is less commonly examined; however, it is well covered in the recommended physiology texts and was generally well done. The question breakdown provided a clear structure to approach this question and was mostly well utilised by candidates. Details that were commonly omitted included: - the contribution of starling forces to the production of lymph - differences between lymph and plasma - the difference in protein and fat content depending on the areas drained

. This question was best answered using the structure provided and ensuring the level of detail linked to the % of marks to be gained. It could be answered with the following simple information if presented with appropriate linking. a) Craniosacral outflow. CN III – eye, CN VII – parotid gland CN IX -submandibular glands, CN X – cardiac, pulmonary and abdominal organs; Sacral Outflow S2-4 = pelvic and sex organs. b) Preganglionic nerve fibres are long type B, partially myelinated and synapse on a ganglion close to the target organ. Post synaptic nerves are short type C unmyelinated. c) Preganglionic NT is ACh onto N2 ACh receptor which is a ligand gated ion channel allowing for Na and K movement. Post ganglionic NT is ACh onto Muscarinic receptors which are G protein coupled. - M1, M4 and M5 are in the CNS (Gq, Gi, Gq respectively) - M2 – heart and lung (Gi – inhibition of AC and decreased cAMP) - M3 stomach, gut and other organs (Gq – IP3/PLC).

. Again, the question breakdown provided a clear structure and expected level of detail for each section. Given the breadth of the question there was little time for candidates to give much more information other than a list of the roles under each category and a brief qualifying statement. This is all that was required to score well. High scoring answers included the following: b) an outline of carbohydrates, protein and lipid metabolism in the liver, including descriptions of catabolic and metabolic processes for each. c) an explanation of how the liver participates in drug biotransformation (phase 1+2 reactions and production of enzymes), lactate, ammonia, bilirubin and steroid hormone metabolism d) role in nutrient and vitamin storage, blood storage and bile secretion. e) role in phagocytosis, bacterial filtration in portal system and complement production.

. a) Many answers included a diagram and description of an ovoid intracellular organelle with inner and outer membranes, an intermembrane space, an inner matrix, and cristae (or folds) on the inner membrane to increase surface area. High scoring answers described the significance of these structures. b) This section requires a list of functions mentioning oxidative phosphorylation and any other functions. Descriptions were not expected. c) A detailed description of both the citric acid cycle and oxidative phosphorylation was expected and the metabolic processes involved in ATP production. A number of candidates provided a step-wise chemical representation of the citric acid cycle and the various proton generation steps, this level of detail was not required to do well in this question.

. a) The key components of the complement system are the C3 convertase, C5 convertase and membrane attack complex. These components are present as inactive precursors. b) Broadly speaking the activation pathways include the classical (activated by immune complexes) and alternate (activated by microbial polysaccharides or pattern recognition receptors). c) The main role of the complement system is to defend against bacterial infection. It is an important component of the innate immune system. The key functions are 9 opsonization and phagocytosis (via C3b), cell lysis, agglutination of microbes, chemotaxis (via C5a), modulation of B cell function, clearance of immune complexes and mast / basophil activation (via C3a, C4a and C5a). d) Control is achieved via the short half-life of the activated factors and specific complement inactivators.

. a) For a measurement question the correct units for any definitions are required. b) For this section candidates were expected to provide information on the following: Electrical thermometers - resistance thermometers; thermistor and thermocouple - infra-red thermometers. Nonelectrical thermometers include - liquid, dial and crystalline principles. The expected information to score well included an outline of each of the underlying principles and how it is used to measure temperature, an example of a type of thermometer, and advantages and disadvantages of each method.

. The information asked for in this question is the information directly relating to its safe use in intensive care. Phenytoin is an exemplar drug for multiple essential pharmacological principles that apply to the safe prescription of drugs in critical illness. The best answers succinctly demonstrated understanding of these concepts within the structure provided. In general, in the first part exam including in this question, more serious, important or more common side effects or pharmacological considerations ie. Cardiac S/E or the contribution of zero vs first order pharmacokinetics to the narrow therapeutic window, would be weighted higher in the mark distribution within their subsections.

. Given that heparin is the more commonly used drug and a level 1 drug, compared with bivalirudin which is level 2, a suggested way to answer this was to provide details on heparin for each subsection and then note the similarities and differences of bivalirudin. The low pass rate for this question largely reflected a limited knowledge of heparin not just bivalirudin.