2024 First Sitting SAQs

A good answer provided a definition of a receptor as a protein/glycoprotein that undergoes a conformational change upon ligand binding. They then gave an overview of where these are found and the mechanisms of activation/downstream processing. A definition of each type (agonist, antagonist, partial agonist and inverse agonist) was expected with reference to the intrinsic activity at the receptor and the affinity for the receptor. A good answer also touched upon law of mass action (D+R=DR) and how this equilibrium is altered by each. Concepts such as reversible and irreversible binding and its implications as well as competitive and non-competitive antagonism would elevate the answer.

(a) This part of the question required candidates to provide a definition of venous admixture and provide detail on the sources. This would include anatomical (including atelectasis/closing capacity) and V/Q Mismatch or Scatter. V/Q Scatter was commonly omitted from answers. The use of the verb “describe” implies that further details are required beyond a simple list of the sources (such as a description of their mechanism and relative importance). (b) This part required the effect supplemental oxygen on the many causes of arterial hypoxaemia to be explained. This would require the effect that this has on areas of true shunt and different degrees of shunt fraction and also on V/Q scatter. Information for this can be found on Nunn's Respiratory Physiology.

This question was specific to the left ventricle only. Good answers provided information on immediate changes in LV Volumes and Pressures and how compensatory mechanisms largely within the LV itself eventually lead to restoration of stroke volume. Marks were allocated for a description of the Frank Starling mechanism, baroreceptor reflex and anrep effect. Good answers also discussed the effect of increased SVR on LV myocardial work and oxygen consumption and coronary perfusion. Common errors included focusing on definitions and determinants of SVR and providing LV PV loops without relating this to the situation of an increased SVR or without adequately labelling or explaining what they were demonstrating with the graph. This question required the integration of a number of physiological principles and is challenging.

(a) Good answers divided this section into haemodialysis and haemofiltration and answered in two parts. Included information expected that candidates would cover the principles of haemodialysis, solute movement across a semipermeable membrane by diffusion and its dependency on the solute characteristics (size, charge, protein binding, volume of distribution) the dialysis membrane properties (porosity, thickness, surface area), the concentration gradient of substance in dialysate to blood and the rate of solute delivery (blood flow vs dialysate rate). Haemofiltration, solute movement across semipermeable membrane by diffusion and required a discussion of the effect of transmembrane pressure, blood flow, effluent/ultrafiltration rate, plasma oncotic pressure,solute concentration in plasma water and the Sieving coefficient on the clearance. (b) This part of the question required a brief representation of the substances found in renal replacement fluids including major electrolytes at near physiological concentrations (sodium, potassium, calcium, magnesium, and phosphate) and when these might be varied i.e. no calcium in citrate anticoagulation, less potassium in hyperkalaemia. Also the inclusion of a buffer (such as bicarbonate, lactate or citrate), water and the absence of colloid was also expected.

The question provided the headings that candidates would be expected to provide information on and those that used these headings to structure their answers provided good overall responses. A definition of the SNS and effects of activation was not required. Candidates were expected to outline SNS anatomy with respect to origin (pre-ganglionic neurons in the grey matter of the lateral horn of the spinal cord, T1 to L2), fibre types including a description of short pre-ganglionic myelinated b fibres, the sympathetic chain and the long post-ganglionic unmyelinated C fibres. Receptors and neurotransmitters included nicotinic Ach receptors in the ganglion and adrenergic alpha and beta receptors on target organs/vessels. A brief discussion of the arrangement at the adrenal medulla was also expected.

(a) This part required candidates to demonstrate their knowledge of the fibrinolytic pathway with details of the relevant mediators and inhibitors. Candidates where then required to apply their knowledge of both the coagulation cascade and fibrinolysis, with detail of how the pathways are simultaneously activated by the same stimuli to ensure balance between bleeding and clotting. An example would be endothelial damage stimulating both the clotting cascade through collagen exposure and thromboplastin activation (faster response) as well as fibrinolysis through t-PA activation (slower response). (b) This section of the question required a detailed description of the mechanism of action of alteplase, recombinant t-PA. A comparison to endogenous t-PA helped illustrate this action and the subsequent bleeding and the non-bleeding effects.

This question required candidates to discuss the role of the pancreas and liver in the homeostasis of blood glucose. This included how the pancreas senses high or low glucose levels, the mechanism of secretion of insulin and glucagon and subsequent effects on the liver. The response in early fasting when glucagon stores are depleted was expected as well as the role of other organs in this setting such as muscle glycogen and hypothalamus driven satiety. A brief mention other hormonal responses in the setting of hypoglycaemia was also expected (including ACTH, cortisol, adrenaline, growth hormone and thyroid hormones).

Anatomical questions are best answered with a standard structure that details the location; the boundaries (anterior/posterior, superior/inferior, medial/lateral); a description of the contents of that area and layers; and the relevant surface anatomy. For this question a description of the femoral triangle and boundaries, the origin and termination of femoral vein along with its tributaries, the relationship of the femoral vein to different structures in the triangle and information about femoral sheath and its contents was expected. Marks were also awarded for detailing the surface anatomy of femoral vein relevant to cannulation. This was an anatomy question as such details of femoral vein cannulation technique, complications and the risks associated with femoral venous access was not required.

This question is essentially a compare and contrast question. It was worded specifically to encourage candidates to describe the pharmacokinetics of the drugs in question (in particular the relative lipid solubilities, volume of distribution, pka/ionisation, plasma protein binding, and metabolism) and then use these features to discuss the clinically relevant implications. In part (c) a brief definition of what is meant by the context sensitive half time followed by how these pharmacokinetic differences influence the CSHT of each was required.

(a) This question required an explanation of the process of contraction in smooth muscle, as well as specific information pertaining to the smooth muscle of the uterus. Specific information included: stimuli for contraction (i.e., hormones such as oxytocin, oestrogen, and prostaglandins and stretch); possessing an unstable membrane potential which plays a greater role than nervous input; as well as the uterus smooth muscle functioning as a syncytia and having baseline tone. The key steps of contraction (influx of calcium, formation of calcium-calmodulin formation, activation of MLCK, creation of myosin-actin cross bridges with utilisation of ATP) are those generic to any smooth muscle and marks were awarded accordingly. Descriptions of striated muscle did not attract marks. A description or explanation was required rather than a list of steps (e.g., the sources of calcium rather than a simple statement of calcium influx occurring). (b) Use of these drugs as tocolytics is acknowledged as a less common reason for their utilisation - the fractionation of this question was to breakdown into more achievable parcels of information. This allowed candidates to score more marks for relating the mechanism of action specifically to the uterus. Higher marks in this section were awarded for specific unwanted effects relevant to use as a tocolytic e.g., foetal tachycardia for salbutamol as result of crossing the placenta. Marks were awarded to doses for these drugs when used as a tocolytic, as opposed to for other indications (i.e., salbutamol infusion rather than nebulised).

A good response included normal values of the partial pressures of both oxygen and carbon dioxide including the arterial and venous contents. Methods of carriage (haemoglobin, dissolved and other forms), haemoglobin binding characterisitcs (co-operative binding and affinities); and impact on loading/off loading at tissues and lungs for both oxygen and carbon dioxide was included. Correctly labelled diagrams with a brief accompanying explanation could be used to convey some of these concepts.

(a) A detailed description of the ionic events of the phases of the sino-atrial node AP was expected. A diagram of the sino-atrial node potential which included the phases and labelled x and y axis was helpful in this description. Some comparison with other cardiac action potentials added depth to answers, as did a brief description of the influences on the action potential such as the autonomic nervous system. (b) This section required a detailed explanation of impulse propagation both between cardiac myocytes and across the myocardium. Safety mechanisms to be mentioned included anatomical insulation, refractory periods and rate.

A good answer included an explanation of the purpose of the countercurrent mechanism followed by a detailed description of the functional and anatomical relevance of the Loop of Henle, vasa recta and urea recycling. A diagram if included required some explanation as it is not sufficient to completely replace text alone.

The first part of this question required a list of the normal values for cerebral blood flow including differential flow to grey and white matter. For the second part, an answer structured around the cerebral perfusion/cerebral vascular resistance formula worked well to ensure breadth. Factors influencing flow include autoregulation of pressure (via the myogenic reflex), metabolic autoregulation and local acidity, arterial levels of CO2 and O2, temperature and a minor role for the sympathetic nervous system. Many answers were augmented effectively with graphs of cerebral blood flow versus CPP, PaO2 and PaCO2. A detailed discussed of ICP and factors effecting this was not required.

A good answer should cover the following points: normal range, how and why the value is affected by liver failure and potential con-founders. As an example in the case of albumin; the normal range is 35-50g/L; it is produced in the liver and thus the measured value will decrease in synthetic liver dysfunction; the half life of albumin is long (20 days) and therefore it is a better marker of chronic dysfunction; potential con-founders include inflammation (negative phase protein), malnutrition and increased loss (nephrotic syndrome etc). Marks were not allocated for information not relevant to the question asked (such as the function of albumin).

(a) The definition of temperature and heat varies considerably in texts, so reasonable leeway was granted in marking this part. (b) In this section the following information was expected; body temperature range; thermoneutral zone; sensors (including receptors, fibres, and tracts); central processing (the role of the hypothalamus including anterior and posterior portions); interthreshold range; and a detailed description of the efferent responses for either increasing or decreasing body temperature.

Expectations for a high scoring answer were: (a) a definition of innate immunity featuring its presence since birth, the non-specificity and lack of memory when compared with the adaptive immune system, (b) an outline of different components of innate immune system including; physicochemical (skin, mucus, cilia, gastric acid), humoral (lysosome, complement, acute phase proteins) and cellular (neutrophils, macrophages, natural killer cells, mast cells). In addition to listing a number of these examples, a brief explanation (“outline”) of their function should be included.

This question required an accurate explanation of the mechanism of measurement for each device. A head to head comparison of the differences and similarities in utility, accuracy, global versus regional measurements, calibration, drift and dampening should follow. A comparison of potential complications was also expected.