Basic physiology

Question

Describe the structure and function of the mitochondrion. 

Report

Most candidates had at least a basic understanding of mitochondral function although some detail was required for a
pass and many did not provide this. A well labelled diagram was used by many candidates and scored marks.
Repetition of the same information illustrated on a labelled diagram in subsequent text was not required and did not
score additional marks.

It was expected answers would cover basic structure (double membrane structure with cristae and enzymes lining the
membrane and within the matrix), details of the electron transport chain, the citric acid cycle and beta-oxidation of
long chain fatty acids and mention the maternal origin of DNA. Better Answers provided some information on other
functions such as production of reactive oxygen species, role in calcium homeostasis and apoptosis, urea cycle,
haem synthesis and heat production 

Question

Explain the oxyhaemoglobin dissociation curve and the factors that may alter it.

Report

Marks were awarded for an appropriate curve with values, an explanation of the nature of positive cooperatively and
notes on those factors causing changes in the p50 or "shifts” in the curve.

Most candidates were able to provide the required sigmoid shaped curve with appropriate key value points (p50,
venous and arterial points). Better candidates were able to identify p50 as a measure of avidity or affinity for oxygen
and commented on T- Tense and R- Relaxed states, the role and production of 2,3 DPG , binding to the beta chains
(nature of the lack effect on foetal haemoglobin). Describing the mechanisms associated with factors shifting the
curve and commenting on changes in oxygen content over the steep and flatter parts of the curves gained additional
marks. Candidates are reminded to answer the question asked - no marks were awarded for a description of
dissolved oxygen delivery. Some answers confused the Bohr and Haldane effects. 

Question

Describe the formation and the metabolic fate of lactate. Outline its role in energy production. 

Report

It was expected that the answer would include comments on lactate generation from glucose via pyruvate and the
metabolic linkage of nicotinamide adenine dinucleotide (NAD). Lactate regenerates NAD+ (pyruvate is reduced to
lactate while NADH is oxidized to NAD+ ). The citric acid cycle and the electron transport chain occur in the
mitochondria of cells, and will only proceed in the presence of oxygen. One molecule of glucose produces 2 ATP
anaerobically (pyruvate to lactate) vs 26 aerobically (pyruvate enters TCA cycle) .Total production is about 1500
mmols/day with blood levels resting value of 1–1.5 mmol/L to a peak of 10–15 mmol/L. 

Lactate can be used in 3 ways:

1. Conversion to glucose via gluconeogenesis in the liver and release back into circulation
 (Cori cycle). This is the fate of 80 % circulating lactate from tissues low in oxygen (e.g. exercising muscle with low
pO2) or red blood cells (no mitochondria). The production from glucose in RBC’s is the Embden-Meyerhoff pathway.

2. Consumed as a fuel e.g. heart (20% of circulating lactate)

3. Mitochondria and oxygen

Oxidation back to pyruvate by well-oxygenated muscle cells, heart cells, and brain cells pyruvate is then directly used
to fuel the Krebs cycle (generating 28 mmols ATP)

Lactate generation from muscle is increased with B1 mediated stimulation e.g. from adrenalin. This topic is well
covered in Power and Kam Principles of Physiology for the Anaesthetist, 3rd

Edition, although some of the details are in several different sections.

Most candidates showed some understanding of the role of glucose in the production of pyruvate to lactate. However,
the differential ATP production, the role of NADH availability and how oxygen and the role of mitochondria were
involved was less well handled. Better answers described the normal generation of lactate in some tissues (e.g. RBC)
and role of muscle and liver in metabolism back to glucose (Cori cycle) and the role of lactate as a metabolic
substrate in some organs. Marks were awarded for normal production values and blood levels. 

Question

Describe the pharmacology of magnesium sulphate. 

Report

The standard “pharmacology template” approach would have served well to cover this question. Answers were
generally lacking in detail and focussed on extraneous physiology rather than pharmacology. Toxicity and side-effects
were important to emphasise, especially in the context of infusions for treatment of asthma and/or pre-eclampsia. 

Question

Describe the effects of ageing on the cardiovascular system.    

Report

Many candidates described the pathological processes which might affect the aging heart rather than the
physiological ones.

Recognition that aging reduces cardiovascular reserve followed up with an outline of the effects of aging on the heart,
the vasculature, endothelial function and the conducting system would be rewarded with a good mark.

Few answers quantified the decrease of cardiac output with age and only even fewer ventured into the contribution of
ventricular filling by atrial systole. No answer discussed endothelial changes with aging.

Some answers were repetitious. Some answers included a significant discussion of information that was not asked
for (Laplace law/Poiseuille's law). 

Question

Describe the physiology of skeletal muscle cell contraction. 

Report

This question required a description of excitation- contraction coupling. Marks were

gained for a brief outline of the structure of a sarcomere and how it facilitates
shortening. An explanation of membrane processes, receptor interactions and the
contraction processes was required. Mention of the role of ATP was also required and
marks were gained for commenting on the mechanism of return to the relaxed state.

Most candidates wrote extensively on the nerve action potential and neuromuscular
junction transmission, with minimal reference to events occurring within the skeletal
muscle cell membrane. They could not gain marks for this. Few candidates
demonstrated knowledge of the ATP dependent walk along processes of myosin heads
during contraction. 

Question

Describe, with the aid of a diagram, the structure of the cell membrane, (40% marks)
and transmembrane transport processes. (60% marks) 

Report

The structure of the cell membrane was generally well covered by most candidates.
Many had difficulties structuring an answer for the transmembrane transport processes.
Dividing this section into proteins (some receptors, channels etc.) and carbohydrates
(some receptors, immune reactions etc) followed by a very brief discussion of each type
of process would have aided candidates towards providing a good answer. 

Question

Explain the following laws:

Dalton’s

Boyles

Henry’s

Graham’s

Fick’s Law of Diffusion 

Report

The universal gas laws form the basis of oxygen therapy and delivery, pressure and volumetric monitoring as well as
a key to understanding the solubility of gases in blood.

All the equations and relationship are straightforward so this question provided a good opportunity to score marks.
Unfortunately many candidates were aware of the properties of the ideal gases but not the named laws. This led
many candidates to omit major sections of the answer and thus scored no marks. Several candidates wasted time
with complicated diagrams as well as equations and descriptions (scoring no additional marks). Many candidates
were unable to identify Grahams Law (rate of diffusion inversely proportional to the square root of the molecular
weight) but included it in an expanded Fick’s Equation. 

Question

Explain the role of the skin.   

Report

The skin is the largest organ of the body, accounting for about 15% of the total adult
body weight, with a rich, but tightly regulated blood flow. It performs many vital
functions, including the protection against external physical, chemical, and biologic
threats, the prevention of excess water loss from the body and thermoregulation. It is
composed of three principle layers, the epidermis, dermis and subcutaneous tissue,
each with their own purpose. In addition candidates were expected to describe those
aspects of the skin that play a role in physical protection, immune, sensory,
thermoregulatory and water regulation. Candidates lacked a sufficient breath and depth
of knowledge in this area and often digressed beyond areas specific to the skin (e.g.
thermoregulation not specific to the skin). 

Question

How do chemical messengers in the extracellular fluid bring about changes in cell
function? Give an example of a chemical messenger for each mechanism noted.

Report

Overall answers lacked structure and depth, to what is a very fundamental topic. This
topic is generally covered within the opening chapters of most physiology texts.
Common errors were not answering the question, writing lists rather than describing and
explaining, and poor categorisation. Candidates were expected to mention and give
example for mechanisms such as hormones binding to cytoplasmic or intra-nuclear
receptors, binding to transmembrane receptors coupled to G proteins, cAMP, cGMP,
tyrosine kinase, etc.

Question

Describe transport mechanisms across cell membranes. Give an example of each.

Report

Candidates were able to list types of transport across cell membranes but frequently
described them incorrectly or gave an incorrect example. In a number of answers, there
was confusion between facilitated diffusion and secondary active transport. Though
diagrams were not required, several Candidates used a diagram of the cell very
effectively to illustrate the mechanisms of transport across the membrane. For a good
answer, some mention and description of exocytosis, endocytosis, ion channels,
facilitated diffusion, passive diffusion, primary and secondary active transport was
expected.

Question

Describe the processes of excitation and contraction within a smooth muscle cell
(60% of marks). Briefly outline the mechanism by which nitric oxide affects
smooth muscle cell activity (40% of marks). 

Report

Insufficient breadth and depth of knowledge limited candidates’ performance to this

question. Candidates were expected to mention mechanisms of muscle cell membrane
activation (e.g. Ca2+ channel mediated action potential, Pacemaker potential, etc),
sources of rise in intracellular Ca2+, intracellular Ca2+ binding to calmodulin in
cytoplasm Ca2+calmodulin complex binding to, and activation of myosin light chain
kinase, energy dependent myosin cross bridges and cycling and mechanism of smooth
muscle relaxation. 

Nitric Oxide (NO) activates guanylyl cyclise which in turn catalyzes the
dephosphorylation of GTP to cyclicGMP which in turn induces smooth muscle
relaxation, and the various mechanisms by which this occurs.. 

Question

Describe the production and metabolism of lactate

Report

 Lactate is constantly produced from pyruvate via the enzyme lactate dehydrogenase
(LDH). Lactate is produced during normal metabolism and in increased quantities during
anaerobic metabolism. Candidates were expected to further describe this physiological
processes.

A good answered required quantification of lactate production during normal aerobic

metabolism, during anaeorobic metabolism, the pathways involved (Glucose to
Pyruvate, Pyruvate to Citric Acid cycle in presence of Oxygen, Pyruvate + NADH to
Lactate + NAD+ without Oxygen) associated ATP production, site of intracellular
production, why red blood cells differ and lactate metabolism (eg oxidation to pyruvate
by well-oxygenated muscle cells which is then directly used to fuel the citric acid cycle
conversion to glucose via the Cori cycle in the liver through the process of
gluconeogenesis). Good answers illustrated the loss of energy potential with the
production of lactate and discussed the situations that would lead to an inbalance
between production and metabolism of lactate.
Candidates who did poorly in this question did so due to a lack of depth and breadth for
this topic. For example, even though the Cori Cycle was often mentioned, it was poorly
described in relation to lactate metabolism.
Syllabus: K2g References: Textbook of Medical Physiology, Guyton Chp 67

Question

Discuss the important factors in exchange of gases and substrates between capillaries
and tissue cells

Report

Good answers were based around Fick’s Law, Starling forces and the Gibb’s Donnan
effect.
It was expected that candidates would give Fick’s equation and describe the
components :
Fick’s Law J = -DA dc/dx
Candidates were also expected to describe Starlings equation and the equation for
Osmotic Pressure. Starling Equation:
Fluid movement = k[(Pc-Pi) – s(πp – πi)] Osmotic pressure : sRT(Ci-Co).
Gibb’s Donnan effect and, other mechanisms of transport (filtration and pinocytosis)
was also expected for a good answer.
Syllabus: A combination C1c2.d, C21 2.e, C2b2.c, C2b2.e References: Pharmacology
and Physiology in Anesthetic Practice, Stoelting pgs 294-300, 322- 325

Question

Define basal metabolic rate and describe factors that influence it (70% of marks).  How
could you measure metabolic rate?

Report

 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.

Cardiovascular pharmacology

Question

Compare and contrast the mechanisms of action and toxicity of sodium nitroprusside and glyceryl trinitrate (GTN). 

Report

Some excellent responses to this question showed a clear understanding of the pharmacology of these agents – the
differing mechanisms of action involving both involving nitric oxide. Better answers were able to use this to explain
the altered vascular specificity.

Toxicity was similarly well prepared for with a good understanding of the role of cyanide in SNP and the low rates of
toxicity with GTN. This question was best handled in a tabular format which minimised omissions.

Some candidates focused on pharmaceutics, indications and side effects which were not allocated any marks.

'Compare & contrast' means the similarities; differences & unique features need to be related to each other. Several
candidates confused ‘nitrous oxide’ with nitric oxide. 

Question

Compare and contrast the pharmacology of noradrenaline and dobutamine. 

Report

The best answers used tables and key pharmacological headings for comparisons, and avoided long sentences/
paragraphs. 

An answer that correctly considered the following sections would be awarded a very good pass: Presentation,
pharmacodynamics, mechanism of action, organ effects, side effects and pharmacokinetics.

Many candidates failed to identify agents as natural / synthetic catecholamines.

Few answers correctly mentioned the available preparations of these drugs or considered the structure activity
relationships. Only 3 candidates commented that dobutamine is a racemic mixture.

Intracellular second messenger pathways were often incorrectly recounted or not mentioned at all. Pharmacodynamic
effects on all organ systems, and all CVS parameters (HR, inotropy, PVR, SVR, SBP/DBP/MAP, regional
circulations) should be considered. Metabolic fate and clinical dosage ranges were frequently incorrectly quoted. 
Question

Classify anti-arrhythmic drugs by mechanism of action, giving examples of each (75% of marks). Describe the
electrophysiological and ECG effects of sotalol (25% of marks). 

Report

Most answers displayed a good knowledge of the Vaughan Williams classification, classes I to IV and the relevant
electrophysiological characteristics of the classes.

Answers should also have included mention of other antiarrhythmics, such as digoxin, magnesium and adenosine.
The second part of the question required comment about K ion blockade and its effects. It was helpful to mention
prolongation of QT and risk of torsade. Most answers omitted reference to its being a racemic mixture, with different
actions of the isomers. 

Question

Provide a detailed account of the side effects of Amiodarone. 

Report

The question asked for a detailed account and the expected marks were spread across a range of systemic side
effects, not just the cardiovascular and pulmonary side effects. Many candidates provided irrelevant and lengthy
descriptions of the mechanisms of action of amiodarone which was not asked for in the question and gained no
additional marks. Most successful answers used an organ systems approach to include the many side effects of
amiodarone.

Many candidates failed to mention skin side effects, neurological side effects, GI/hepatic side effects, pregnancy and
breast feeding considerations, and interactions with other highly protein bound drugs. The predominant mechanism
for hypotension with rapid IV administration of amiodarone was incorrectly given in a number of answers. 

Question

Outline the pharmacology of sodium nitroprusside (50% of marks). Discuss the

mechanisms of toxicity and their management (50% of marks). 

Report

Most candidates presented a structured answer and exhibited a good understanding of the pharmacology of sodium
nitroprusside. Few candidates demonstrated an understanding of the mechanisms of SNP toxicity and details on
management of cyanide toxicity were lacking. Cobalt EDTA is no-longer recommended as initial therapy in the
management for cyanide toxicity.

More specific detail was expected beyond a generic comment on "mechanisims of toxicity" such as potentially causes
of respiratory, renal, hepatic or CNS failure.

Few candidates mentioned adverse effects other than that of cyanide toxicity. Many candidates also failed to outline
the management of sodium nitroprusside toxicity. 

Question

Classify commonly used inotropic agents. (40% of marks) Outline four different mechanisms of action for inotropic
agents. (60% of marks) 
Report

This question was generally well answered. The poorer answers suffered for want of a useful classification system
that enabled them to separate the various drug classes. 

Question

Outline the pharmacology of amiodarone. 

Report

This was a repeat question and was generally answered well. Some candidates lost
marks for being too approximate on the pharmacokinetics. 

Question

Classify calcium channel blockers, and give an example for each classification. (30% of
marks) Describe the pharmacology of verapamil. (70% of marks) 

Report

Most candidates managed to provide a classification of calcium anatagonists. The

pharmacology of verapamil was less well understood. The structure for answering a
pharmacology question was often poor and there was commonly a lack of precision in
pharmacokinetics. We suggest that candidates look at a general pharmacokinetic
structure when answering these questions. One approach would be a structure that
covers drug name and description, pharmaceutics (chemistry/ ampoule contents),
Pharmacokinetics, Pharmacodynamics (Think CNS/CVS/Resp/GIT etc. if relevant),
Dose and Side effects then Indications and Contraindications can help organize the
information. 

Question

Classify local anaesthetic agents and give examples. (30% of marks) Describe the
pharmacology of lignocaine. (70% of marks) 

Report

Generally, the second part of the question was poorly organised by many candidates,
the consequence being that many opportunities for picking up marks were lost. A brief
statement as to what lignocaine is, its presentations and dose, some facts about PD
and PK followed by a few lines on toxicity (CC/CNS ratio) was mostly what was
required. Only a few candidates mentioned lignocaine toxicity. 
Question

Compare and contrast the mechanism of action, pharmacokinetics, pharmacodynamics,

and adverse effects of digoxin and levosimendan. 

Report

This question provided candidates with a clear structure and headings that were often
ignored. Candidates wasted time on pharmaceutics, derivation (“foxglove” mentioned
often) and dosing – these were not requested and scored no marks. Superficial answers
such as “cardiac glycoside” or “calcium sensitiser” were not adequate. Responses such
as “modest” for Vd are inadequate – marks could be gained for identifying at least the
direction of the difference between the two agents. Likewise “hepatic metabolism and
renal excretion” is inadequate. Both agents had quantitative and qualitative
differences in outcome of metabolic products and the renal elimination of active drug.
Confusing diagrams with inadequate labelling, arrows with two heads and the use of
uncommon abbreviations without definition all served to confuse the examiners rather
than help the candidate. Candidates should read the questions carefully. 

Question

Outline the pharmacokinetics and mechanism of action of carvedilol and spironolactone.

Report

Carvedilol and spironolactone are common drugs used in the management of cardiac
failure. They have different mechanisms of action and pharmacokinetics. Both are drugs
listed in the Syllabus as Level B and thus candidates are expected to have a general
understanding of their pharmacology. Many candidates gave class specific information
about beta blockers rather than demonstrating an understanding of carvedilol`s
particular properties. Most candidates were able to score marks by commenting upon
the results of aldosterone antagonism suggesting an understanding of the physiology of
this hormone but appeared to know little more about the pharmacology of
spironolactone. Overall there was insufficient information provided by most candidates
for both drugs.

Question

Describe the actions of endogenous vasopressin. (60% of marks) List the vasopressin
analogues and their uses. (40% of marks)

Report

Overall the first section was not answered in sufficient detail. Aspects such as the anti-
diuretic effects of vasopressin were often overlooked. Some candidates spent more
time on outlining the clinical contexts in which vasopressin is used (which did not score
marks), rather than the physiology (which did score marks). DDAVP was the most
common analogue mentioned, with the others often being omitted (e.g. terlipressin,
ornipressin, etc.).

Question

Classify the anti-arrhythmic drugs using the Vaughan-Williams classification (30% of

marks). Compare and contrast the electrophysiological effects of Class 1 anti-
arrhythmic drugs (70% of marks).

Report

Most candidates displayed a basic knowledge of the Vaughan-Williams classification

and gave an example of each class. The remainder of the question lent itself very well
to a tabular format. Better answers included the effect on the action potential (diagrams
were useful here), channel dissociation kinetics (this was frequently omitted) and
examples from each class of drug. There is an excellent table in Stoelting which
answers this question nicely. Marks were not awarded for clinical effects. Overall, this
question was generally well answered.

Question

List the properties of the ideal inotrope (50%ofmarks). How does adrenaline compare
with respect to these ideal properties? (50% of marks).

Report

Inotropes are drugs that increase the force and velocity of myocardial contraction
resulting in increased contractility and stroke volume and hence cardiac output. Good
answers were those that adopted a systematic approach, such as providing a coherent
list of ideal properties that included pharmaceutical, pharmacokinetic and
pharmacodynamics characteristics, and then contrasted adrenaline against that list. The
area less well covered was that of those aspects of adrenaline that made it less than an
ideal inotrope, e.g. it increases myocardial oxygen consumption, causes
tachyarrhythmias, tolerance may develop, hyperglycaemia, lactic acid production, etc.

Question

Compare and contrast adrenaline and levosimendan    

Report

A basic and fundamental question which required candidates to present their answer in
a coherent fashion (a table worked best), as well as demonstrate sufficient knowledge.
The majority of candidates did so, and so scored well. Candidates tended to struggle
most with levosimendan. Candidates also confused the use of the terms “elimination”
and “metabolism”, often using them interchangeably. 

Question

Compare and contrast the pharmacology of dobutamine and milrinone

Report

Many candidates presented their information in a tabular form and this worked well as it
allowed direct comparison between the two drugs. Most candidates did not mention that
dobutamine was a racemic mixture of [+] and [-] isomers. Also that the [+] isomer was a
potent 

antagonist, while the [-] isomer was an alpha1 agonist. The administration of the racemic
mixture

results in the overall beta1 agonism responsible for its activity and also its mild beta2
agonism effect.

While most candidates stated that milrinone was an inodilator details on its mechanism
of action as a selective phosphodiesterase type III inhibitor were on the whole vague.
Within the cytoplasm of the cardiac myocyte milrinone inhibits the enzyme PDE 3 which
results in the inhibition of the breakdown of cyclic AMP which in turn results in elevated
cellular levels of cAMP. These elevated levels of cAMP in turn activate cAMP
dependant protein kinases with a resultant increase in the influx of Ca2+ into the cell via
the sarcolemma. Also uptake of Ca2+ by the sarcoplasmic reticulum is increased. The
overall effect is an increase in intracellular Ca2+ which increases myocardial
contractility. Milrinone also has lusitropic action, inducing left ventricular relaxation. This
probably occurs as a result of the inhibition of SR membrane bound PDE3. Milrinone
also causes peripheral vasodilatation by inhibiting PDE3 in vascular smooth muscle
cells which again results in elevated cAMP levels. In vascular smooth muscle cAMP
normally inhibits myosin light chain kinase the enzyme that is responsible for
phosphorylating smooth muscle myosin and causing muscle contraction.

Many candidates did not emphasize how very different the pharmacokinetics of these
two drugs were. Milrinone has a much longer half life than dobutamine and because of
its predominant renal excretion accumulates in renal failure.

Question

Classify the calcium channel blockers and provide one example of a drug for each class
(20% marks). Compare and contrast the pharmacology of nimodipine and verapamil
(80% marks).
Report

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.

Question
 Compare and contrast the pharmacology of Noradrenaline and Vasopressin
Report
A straightforward question that was reasonably answered, with most candidates using a methodical tabular approach to
explaining the differences in pharmacology between noradrenaline and vasopressin. The benefits of adhering to a well-
organised system of columns showing direct comparisons of the various relevant drug characteristics was clear, with
candidates who chose this approach covering most of the necessary information in a clear and comprehensive manner.
Some candidates managed to provide a great deal of relevant detail within the allocated time as would be expected in this
relatively uncomplicated question. Simple definitions were often lacking and failing to provide this basic introductory
information resulted in lower marks for this question. While most candidates were able to discuss the effects of each drug on
the cardiovascular system, not as many were able to give outline other physiological effects in sufficient detail. For example,
many candidates made little mention of important renal, metabolic and haematological effects. While some candidates
discussed pharmacokinetics well, many provided only a very superficial outline of this aspect. The important area of adverse
reactions could also have been covered in greater detail.

Syllabus: C2d, 2a and N2, 2f Recommended sources: Basic and Clinical Pharmacology, Katzung, Chp 9 and 37

Question
 Compare and contrast the pharmacology of digoxin and amiodarone
Report

 This question required a structured approach to a comparative description of the pharmacology of two commonly used and encountered
drugs in intensive care practice. Candidates who did not gain a sufficient mark, did so because of a poor knowledge of this topic, as well as a
critical failure to structure their answer.

 
Syllabus: C2c,2b References: Stoelting, Pharmacology and Physiology in Anaesthetic Practice pg 280 and 339, Peck Hill and
Williams, Pharmacology for Anaesthesia and Intensive Care, pgs 224, 232
Question
 Classify antihypertensive agents by their mechanism of action, with a brief outline of each mechanism, and an example of a drug
in each class.
Report

 There are many valid lists that can be used as a template to answer this question. One such list might broadly classify antihypertensive
agents into sympatholytic agents, vasodilators, calcium channel antagonists, renin-angiotensin inhibitors and diuretics. Within each of these
categories are a variable number of sub classes, for example diuretics might include thiazides, loop diuretics and potassium sparing
diuretics.
 
A good answer would include such a listing with a brief description of the mechanism of action with respect to the antihypertensive
effect and the name of a typical drug that acts in the manner described. Most candidates were able to generate such a list and
populate it as required by the question, thus being rewarded with good marks. Poorer answers lacked any logical classification
system and were merely a random list of antihypertensive drugs and their actions. Candidates are reminded that organisation within
an answer helps in answering the question and achieving marks.
 
Syllabus: C2b,2e References: Berne & Levy, Physiology, Ch 2-3
Question

Classify the commonly used inotropic agents and describe their mechanism of action

Report

This question required a classification based on chemical structure and class action.
Sympathomimetics, phosphodiesterase inhibitors, calcium sensitizers and cardiac
glycosides should have been mentioned. Additional detail was expected, subdividing
Sympathomimetics into catecholamines (naturally occurring and synthetic), and non-
catecholamines (direct and indirect acting). Further classification based on peripheral
vasomotor action demonstrated greater understanding.

Better answers included diagrams illustrating the mechanism and point of action on the
cardiac myocyte. Discussion of receptors, second messengers, and the role of calcium
was essential.
The question was aimed at “commonly used” agents, although some marks were
awarded for discussion of calcium, glucagon and other rarely used drugs. Insufficient
detail regarding mechanisms of action was a common observation.
Syllabus: C2d 2 References: Pharmacology and Physiology in Anaesthetic Practice,
Stoelting 4th Ed p293-320. Basic and Clinical Pharmacology Katzung 10th Ed p121-
198. Pharmacology Rang & Dale 6th Ed p168-187, 290-291

Question

Define the mechanisms of action and adverse effects of metoprolol and glyceryl
trinitrate when used to manage myocardial ischaemia

Report

 For a good answer candidates were expected to make some mention of the link
between myocardial O2 demand / heart rate / contractilty. This was often overlooked,
and candidates who did tended to not respond to what the question was asking, that is
“when used to manage myocardial ischaemia”.
Good answers had a structured response. For a good answers candidateswere
expected to mention metoprolol effects of reducing left ventricular wall stress ,
decreased C AMP / mechanism, decreased hear rate, contractility, resultant decreased
O2 demand as well as adverse effects include Bradycardia / heart block / hypotension /
bronchconctriction, etc. In relation to Glyceryl trinitrate, to mention dilation via nitric
oxide, predominately venodilatation, decreased venous return, LVEDP, Wall stress,
decreased demand O2 demand and increased supply via coronary vasodilation and
adverse effects include hypotension / tachycardia tolerance / headache. Candidates are
reminded that if they are to use non standard abbreviations, then those abbreviations
must be defined somewhere within their answer.
Syllabus: C1c, 2d, C2b, 2e, C2a, 2d References: Goodman and Gilman's the
Pharmacological Basis of Therapeutics, Chp 32

Question

Outline the kinetic characteristics and the mode of action of digoxin (75% of marks). 
List the cardiovascular effects of digoxin (25% of marks).

Report

the syllabus for the primary examination describes and outline to be "Provide a
summary of the important points".  Thus, candidates were expected to briefly mention
the fundamental pharmacokinetic characteristics (eg highly lipid soluable, well absorbed
from small intestine, oral bioavailability of 60-90%, protein binding 20-30%, volume of
distribution, half life etc) and a mode of action.  This was pooorly done and candidates
answers often lacked structure.

The question outlines the distribution of marks, being 25% for listing cardiovascular
effects.  Thus, candidates were expected to broadly list the important cardiovascular
effects relating to mechanical (eg increase intensitiy of myocardial contraction, direct
venous and arteriolar constriction etc) and electrical (increase phase 4 slope and
automaticity, hyperpolarisation, shortening of atrial action potentials, decrease AV
velocity and prolong AV refractory period, increase PR and QT intervals, dose and
baseline autonomic activity dependent actions etc)

Question

Outline the pharmacology of noradrenaline.

Report

Candidates should expect that questions relating to the "pharmacology of....." are likely
to be common.  Thus, candidates should have prepared a structured response to any
such question.  For example, one that includes predefined major categories such as
pharmacodynamics and pharmacokinetics and subcategories such as mechanism of
action, absorbtion, preparations, bioavailability, volume of distribution, metabolism,
elimination, adverse effect, clinical indications, precautions / interactions etc. and the
information relevant to each category.  Failuire to take a structured approach to such
questions, as was observed amongst some candidates within this exam, risks
omissions of vital facts (and not gaining marks) or errors.  Noradrenaline is such a
common drug within intensive care practice and so candidates would be expected to
know it in great detail.  There are many references for it.

Question

Outline the ideal properties of a colloid intravenous fluid (25% of marks).  Compare and
constrast gelatins, Hydroxyethyl starch and 4% albumin solutions (75% of marks).

Report

The ideal properties of a colloid include : stability at room temperature, long shelf life,
lack of complications such as antiginicity, toxicity, pyrogenicity, disease transmission, or
other adverse effects (eg coagulopathy) and plasma volume expansion lasting several
hours.  Candidates performed well in this section.

Marks were equally divided between each colloid and this part of the answer was well
suited to table format.  Candidates were expected to compare and contrast fluid source,
infection and antigenic risk, cost and resource issues, packaging and ease of
administration, duraction of effect, tonicity and properties which determine their side
effect profile etc.  Common errors were omission of adequate detail for each colloid and
not being aware that Dextran is no a Hydroxyethyl starch.

Question

Outline the pharmacology of amiodarone

Report

Successful candidates applied, a systematic approach/format to answer questions that

refer to outlining pharmacology of select drugs. A number of useful mnemonics are
suggested in the recommended texts for use when answering such a question. All
candidates correctly stated what amiodarone is used for but most were not structured
methodically and thus suffered from significant omission. Amiodarone is an important
class III anti-arrhythmic (with some characteristics of all 4 Vaughan-Williams classes).
For a good pass candidates were expected to actions of amiodarone (eg blocks
inactivated Na channels, decreases Ca current, non- competitive adrenergic blocking
effect, blocks myocardial K channels which contributes to slowing of conduction and
prolongation of refractory period in AV node, prolongs refractory period in all cardiac
tissues, prolongs cardiac action potential duration) and it’s pharmacokinetics (eg
bioavailability, large volume of distribution, high protein binding, complex metabolism
and long elimination half life – 29 days) 
Question

Classify antiarrhythmic drugs, including their mechanisms of action, and give an

example of one drug from each group

Report

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

NB: Many agents have effects in more than 1 class. Various agents do not fit into this
classification, therefore some add a ‘Class V’ = other, e.g. digoxin.

Question

Compare and contrast the pharmacology of sodium nitroprusside and glyceryl trinitrate

Report

It was expected candidates would address specific aspects of pharmacology such as

action, mechanism of action, half life and duration of effect, route of administration,
potential toxicity and special precautions. These agents lend themselves to comparison
and contrast as several distinct similarities and differences exist and credit was given for
highlighting these. Specific comments should include that both agents result in blood
vessel dilation with extra credit given for detailing the differences in the balance of
arterial versus venous effects between them. For both agents the effect is mediated
through nitric oxide and it was expected candidates would identify that nitroprusside
releases NO spontaneously and GTN requires enzymatic degradation with the resultant
effects on smooth muscle mediated via c GMP. They are both short acting agents when
used intravenously and require careful titration to measured blood pressure for effect.
Extra credit was given for mentioning that routes other than IV are available for GTN
(topical / oral) but not for nitroprusside. Comments on special precautions such as
Nitroprusside should be protected from light and GTN given via non PVC giving sets
gained additional marks. In addition to the well described adverse effects of each agent,
it was expected candidates would mention the potential for cyanide toxicity with
nitroprusside and extra marks were awarded for an indication of usual doses.

Question

Outline the pathophysiological basis for the use of angiotensin converting enzyme
inhibitors and angiotensin receptor blockers in congestive cardiac failure
Report

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
renin- angiotensin 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.

Question

Classify the commonly used inotropic agents and list their mechanisms of action.

Report

Candidates could use a number of different classifications, however were required to

include all the major groups of agents.  Most made some mention of the
sympathomimetics, however failed to sub-classify these, or confused catecols versus
non-catecols, or naturally occurring versus synthetic agents.  Other agents, such as
phosphdiesterase inhibitors, calcium sensitisers, cardiac glycosides or calcium itself
received minimal attention.

Mechanisms of action required more than listing adrenergic receptor types.  Some
listing or discussion of the subcellular mechanisms were necessary.  Comment about
 intracellular calcium being the final common end point would have scored additional
marks.

Question

Compare and contrast the pharmacology of sodium nitroprusside and glyceryl trinitrate
for the treatment of acute hypertension,.

Report

It was expected candidates would address specific aspects of pharmacology such as

action, mechanisms of action, half life, and duration of effect, route of administration,
potential toxicity and special precautions.  These agents lend themselves to comparison
and contrast as several distinct similarities and differences exist and credit was given for
highlighting these.  Specific comments should include that both agents result in blood
vessel dilation with extra credit given for detailing the differences in the balance of
arterial versus venous effects between them.  For both agents the effect is mediated
through nitric oxide and it was expected candidates would identify that nitroprusside
releases NO spontaneously and require careful titration to measured blood pressure for
effect.

Extra credit was given for mentioning that routes other than IV are available for GTN
(topical or oral) but not nitroprusside.  Comments on special precautions such as
nitroprusside should be protected from light and GTN given via non-PVC giving sets
gained additional marks.  In addition to the well described adverse effects of each
agent, it was expected candidates would mention the potential for cyanide toxicity with
nitroprusside and extra marks were awarded for indication of usual doses.

Question

Compare and contrast the pharmacology of noradrenaline and vasopressin.

Report

This was best answered using a table.  The main points expected were:

 both are naturally occurring substances

 direct acting via receptors
 mechanisms by which both increase mean arterial pressure
 metabolism
 uses in intensive care, septic shock, vasodilatory shock and diabetes insipidus
 side effects related to intense vasoconstriction and for vasopressin possible coronary ischaemia and sodium and
water retention
Question

List the potential clinical uses of an alpha 2 adrenoceptor agonist.  Outline the
limitations of clonidine for each use.
 Report

Producing a list that included the following was required :

 to treat hypertension and substance withdrawal

 to provide anxiolysis, sedation, analgesia and sympatholysis

A brief discussion of the abilities of clonidine in each of these areas would have rounded
off a good answer

Many candidates only listed a couple of uses of these agents then followed this with a
comparison of clonidine and dexmeditomidine.  Most answers did not include sufficient
information to achieve a pass mark

Question

Compare and contrast the cardiovascular effects of an induction dose of propofol and
ketamine.

Report

The key words in this question were "compare and contrast", "cardiovascular effects"
and "induction dose".  Some candidates described aspects of both drugs other than the
cardiovascular effects but gained no marks for this.  Better answers used a combination
of a table plus some explanation to contrast the cardiovascular effects of the two drugs
concentrating on aspects such as heart rate, cardiac output, vascular resistance and
blood pressure.

Many candidates were confused by the direct versus the indirect cardiovascular effects
of both drugs.

Propofol probably has no direct negative inotropic effect.  Ketamine has a direct
myocardial depressant function but this effect is overridden by the centrally mediated
sympathetic action of the drug.  The effect of both drugs on the baroreceptor response
alone is a difficult area as there is significant interplay between the direct cardiovascular
effects of the drug and their effect on the baroreceptor reflex.  Allowance was made for
this in the marking.  Propofol resets the baroreceptor reflex producing a slower heart
rate for a given level of blood pressure.  Overall, both drugs depress the baroreceptor
reflex.

Comparisons of the effects on cerebral, coronary, renal and hepatic blood flow earned
extra marks.

Cardiovascular physiology
Question

Compare and contrast the systemic circulation with the pulmonary circulation. 

Report

This question encompasses a wide area of cardiovascular physiology. As a compare and contrast question this
question was well answered by candidates who used a table with relevant headings. Comprehensive answers
included: anatomy, blood volume, blood flow, blood pressure, circulatory resistance, circulatory regulation, regional
distribution of blood flow, response to hypoxia, gas exchange function, metabolic and synthetic functions, role in acid
base homeostasis and filter and reservoir functions.

A frequent cause for missing marks was writing about each circulation separately but comparing. For example: many
candidates stated 'hypoxic pulmonary vasoconstriction', but did not contrast this to 'hypoxic vasodilation' for the
systemic circulation. Frequently functions of the circulations were limited to gas transport / exchange. 

Question

Outline the cardiovascular changes associated with morbid obesity. 

Report

Many candidates did not include enough detail in their answers.

Higher scoring answers included more depth such as the following: blood volume, left ventricular changes, arterial
blood pressure, pulmonary artery pressures, risks of ischaemia, arrhythmias etc. 

Question

Draw and label a left ventricular pressure volume loop in a normal adult (40% of marks). List the information that can
be obtained from this loop (60% of marks). 

Report

Many candidates lost marks for poor quality diagrams with inaccurate labelling. An accurate diagram was required.
Many answers lacked sufficient detail regarding contractility and afterload. 

Question

Describe the physiological factors that affect pulmonary arterial pressure (65% of marks). Write short notes on the
use of inhaled nitric oxide as a pulmonary vasodilator (35% of marks). 

Report

Pressure in a system is generated by the interaction between flow and resistance. A structured approach to defining
and describing the many factors that influence fluid flow and resistance was required to score well. Poiseuille’s law
describes the determinants of resistance to laminar fluid flow and provides a useful answer structure. It is also
necessary to describe factors that determine flow. This includes factors that determine venous return, as well right
and left heart output.
A standard structured answer to the pharmacology of nitric oxide enabled concise and high scoring answering of this
question. 

Question

Compare and contrast the supply and demand of oxygen for the right and left ventricle. 

Report

An integrated answer to supply and demand of oxygen was expected, as a comparison between the right and left
ventricles. Many candidates concentrated on differences not similarities. Myocardial oxygen demand was in general
poorly described. 

About 85 - 90% of oxygen demand is for internal work (major determinants wall tension 30 - 40%, heart rate 15 -
25%, myocardial contractility 10 - 15%, basal metabolism 25%). 10 - 15% of oxygen demand for external work or
pressure volume work, determined by MPAP x CO.

It was expected answers would comment on the phasic nature of coronary blood flow which differs between left and
right and the consequence of this to subendocardial oxygen supply during systole usually. Coronary blood flow is
affected by coronary perfusion pressure (determined by aortic pressure and RV pressure) & coronary vascular
resistance (determined by autoregulation, metabolic factors, humoral factors, nervous control interacting with local
endothelial factors)

Generally, coronary blood flow is tightly coupled to oxygen demand/consumption due to high basal oxygen
consumption (8 - 10 ml/ min/100g) and high oxygen extraction ratio (75%). Better answers noted that oxygen supply
can only be increased to cope with increased demand only by increased coronary blood flow. 

Question

Compare the action potentials of a sino-atrial node cell and a myocardial cell. 

Report

A good answer included a well labelled sketch with a description of ion channels and relative directional flow. When
using sketches in an answer they should be correctly labelled, and when used as a comparison with another sketch,
the differences should be clear e.g. shape, duration and voltage difference. 

Question

Draw a labelled diagram of both the aortic root and radial artery pressure waveforms in a young adult using the same
axis (60% of marks). Explain the factors that account for the differences between these two waveforms (40% of
marks). 

Report

A well labelled diagram drawn clearly to demonstrate the salient features of the aortic and radial arterial pulses was
expected. This would include the different systolic pressure, the absence of a dicrotic notch in the radial pulse
(instead a diastolic hump), the narrowness and the delay of the radial pulse, garnered many marks.

Marks were lost for insufficient explanation such as the distance needed to travel for the pressure wave accounting
for the delay, the sharper rise and decline of the radial pulse due to loss of the WIndkessel effect and the different
compliance and the loss of the dicrotic notch due to summation and damping out of high frequency components of
the pressure wave. 
Question

Describe how Starling forces determine fluid flux within the pulmonary capillary bed. 

Report

The equations for nett fluid flux and for nett filtration pressure were incorrect in many answers.

Better answers presented the equations and discussed each of the elements as relevant to the pulmonary capillary
bed, including difference from systemic capillary beds.

Mention of the role of lymphatics and of the effect of surfactant, left atrial pressure, gravity and posture gained marks,
also. 

Question

Describe the essential components of an ECG monitor (80% of marks). Outline the methods
employed to reduce artefact (20% of marks). 

Report

The ECG device detects and amplifies the small electrical changes on the skin that are
caused when the heart muscle depolarizes (0.5 – 2 mV). This is reflected as rises and
falls in the voltage between two electrodes placed either side of the heart which is
displayed either on a screen or on paper. Usually more than 2 electrodes are used and
they can be combined into a number of pairs (For example: Left arm (LA), right arm
(RA) and left leg (LL) electrodes form the three pairs LA+RA, LA+LL, and RA+LL). The
output from each pair is known as a lead. Each lead is said to look at the heart from a
different angle.

Electrodes are commonly made of silver or silver chloride components that are attached
to the main unit of the machine. Most ECG machines use 12 electrodes. Better answers
made mention of the two lead types: unipolar and bipolar.

Methods to reduce artefact include improving signal detection (conductive paste, skin
preparation (dry, no hair, etc.)) and minimizing external electrostatic forces (common
earthed environment, diathermy, etc.,) or patient environment (avoid shivering). 

The amplifier has three essential functions: High input impedance so as to minimize signal loss and reject
interference (50 – 60 Hz), differential amplification, (to amplify the potential difference detected by the skin
electrodes), and high common mode rejection (e.g. > 50Hz) to aid eliminating muscle artefact or electrical
interference from the power grid.).

Vector analysis is not a component of the ECG machine and so was not required to answer the question. 

Question

Describe the cardiovascular effects of a sudden increase in afterload. 

Report

It was expected the answer would start with a definition of afterload and then proceeded to indicate what effects this
increase in afterload would have on ventricular end-systolic pressure, ventricular end-diastolic pressure, left atrial
pressure, cardiac output, myocardial oxygen demand and myocardial work, coronary blood flow and systemic blood
pressure.

Most candidates who failed to pass this question submitted answers that were just too brief, only including a small
subset of the material required. Very few candidates included any mention of myocardial oxygen demand or
myocardial work or the impact upon the cardiac output. A number of candidates included a detailed description of the
Sympathetic Nervous System and the Renin-Angiotensin system, material which was not asked for. There were quite
a number of incorrect perceptions about what effect a sudden increase in afterload would have on the systemic blood
pressure. Candidates who mentioned the baroreceptor response and the stretch receptor response where rewarded
with additional credit. 

Question

Outline the determinants of oxygen delivery to the tissues. 

Report

An opening statement such as oxygen delivery = cardiac output x oxygen content then allowed a more detailed
description of the determinants of both oxygen content and cardiac output. It was expected candidates could detail
the formula for Oxygen Content = Sat O2 % x 1.34 x Hb x 10 (depending on units) + PaO2 x .003, or x .03 (units) and
accurately describe each element. Determinant of cardiac output completed the answer, often starting with CO = HR
x SV while discussing the importance of preload, afterload and contractility.

Many candidates spent little time on cardiac output which cost valuable marks. Some candidates provided a lot of
detail on how oxygen is managed within the lung, the majority of which was not required as part of the answer. Some
candidates answered the question describing the oxygen cascade only which was not sufficient to score well. 

Question

Compare and contrast renal and hepatic blood flow, and their regulation. 

Report

It was expected candidates would describe the salient features of the anatomy, distribution and content of blood flow
and influences on each circulation. Answers with a clear organisation and context for the normal influences of blood
flow on the functioning of each organ system scored highly. Anatomy was often sufficiently covered, but candidates
often did not take advantage of that by linking the anatomical features to the functional concepts. Figures should be
clearly and accurately labelled to score well. Many answers failed to demonstrate a depth of understanding of key
concepts. For example tubuloglomerular feedback, relationship between hepatic arterial and portal venous flows and
autoregulation within both those systems was often poorly described. 

Question

Define cardiac preload and describe its determinants. 

Report

This question required synthesis and application of knowledge derived from multiple sources rather than regurgitation
of a published list in a text. Many candidates failed to recognise that venous return is not the only determinant of
preload. Most candidates failed to discuss determinants of venous return. Factors such as contractility, afterload or
chamber filling and emptying can all impact preload. In addition to listing determinants the question required an
explanation of their relationship with preload (e.g. the direction of change).

A discussion about the determinants of cardiac output was not asked for as did not score marks. 

Question

Describe the adult coronary circulation (50% of marks) and its regulation (50% of
marks). 

Report

This question was generally well answered. Some candidates did not mention the
factors which are peculiar to the coronary circulation and answered in a generic
manner, as if for any vascular bed. The coronary circulation has a high O2-ER and flow-
dependence. Many candidates seemed to lack a perspective that metabolic demand
dominates control of the coronary arterial flow. The phasic nature of flow was best
shown with a diagram and whilst "publication-level" graphs are not expected, the graph
drawn must be factually correct and convey the principal similarities and differences.
While this topic is covered in both Guyton and Ganong, additional detail can be found in
the Mosby physiology monograph series: Cardiovascular Physiology, 10th Edition by
Pappano and Wier,( the replacement of Berne and Levy). 

Question

Describe baroreceptors and their role in the control of blood pressure. 

Report

This is a core topic and a detailed knowledge was expected. Baroreceptors are stretch
receptors located in the walls of the heart and blood vessels and are important in the
short term control of blood pressure. Those in the carotid sinus and aortic arch monitor
the arterial circulation. Others, the cardiopulmonary baroreceptors, are located in the
walls of the right and left atria, the pulmonary veins and the pulmonary circulation. They
are all stimulated by distention and discharge at an increased rate when the pressure in
these structures rises. Better answers provided some detail on the innervation for these
receptors. It was expected candidates would describe that increased baroreceptor
discharge inhibits the tonic discharge of sympathetic nerves and excites the vagal
innervation of the heart. This results in vasodilation, venodilation, a drop in blood
pressure, bradycardia and a decreased cardiac output.

Some candidates had a major misunderstanding around the purpose of "low pressure
baroreceptors" with many believing that these are the ones that respond to lower blood
pressures, while the "high pressure baroreceptors" respond to higher blood pressures. 
Question

Describe the factors that determine right and left ventricular afterload. 

Report

This is a big question and required some structure to cover the material required. A
Definition of afterload, factors specific to left ventricle, right ventricle and both were
required. The question asked to describe and not merely list factors affecting afterload.

Marks were not given for describing pathologies rather than physiological processes
that affect afterload. Candidates seemed to lack depth and understanding on this topic. 

Question

Outline the motor and sensory pathways involved in withdrawing the lower limb from a
painful stimulus. 

Report

It was expected that candidates would outline both motor and sensory pathways and
mention a reflex arc and conscious pathways. 

Question

Describe autoregulation within peripheral circulations. 

Report

Most candidates failed to fully comprehend the question. Candidates displayed some
difficulty in differentiating regulation at a local level (which is what the question asked
for) from that of central regulation (e.g. sympathetic nervous system activity, cardiac
output, etc.), which was not what the question asked for. Other omissions were a failure
to define and explain autoregulation. Most candidates mentioned the myogenic and the
metabolic theories, but failed to provide sufficient details as to their mechanisms. It was
expected candidates would provide some detail as to locally acting factors. Adenosine
and nitric oxide were mentioned on occasions but others such as endothelin and
prostacyclin were often omitted. 

Question

Define cardiac output. (10% of marks) Outline the factors that affect cardiac output.
(60% of marks) Briefly describe the thermo dilution method of measuring cardiac output.
(30% of marks) 
Report

This is a core question. It was expected candidates could provide a definition (heart rate
x stroke volume) and then move on to outline factors that affect it (afterload, preload,
contractility). Additional marks were awarded for descriptions of the relationship to mean
systemic filling pressure and other influences beyond this.

Most candidates described a thermodilution cardiac output curve but almost all
described the technique as based on the “Fick equation or method” (which is used to
estimate cardiac output from oxygen consumption). Very few candidates correctly
identified the Stewart Hamilton equation as the integration method used to relate
cardiac output (flow) to temperature change as an example of indicator dye dilution.

Candidates seemed to lack depth and understanding on this topic. 

Question

Describe the various rapidly acting cardiac reflexes that influence cardiac function and
the mechanisms by which they act. 

Report

Cardiac reflexes are fast-acting reflex loops between the heart and central nervous
system that contribute to regulation of cardiac function and maintenance of physiologic
homeostasis. It was expected candidates would include within their answer a mention of
the stimulus and how it is sensed, the reflex arc and the resultant effect. Thus
candidates could have mentioned the Baroreceptor Reflex/Carotid Sinus Reflex,
Chemoreceptor, Bainbridge, Cushing, Oculocardiac and Bezold-Jarisch (involves
response to ventricular stimuli, sensed by receptors within the LV wall that trigger vagal
afferent type C fibers and the resultant triad of hypotension, bradycardia, and coronary
artery dilatation) reflexes. 

Question

What is the Valsalva manoeuvre? Explain the cardiovascular response and include
graphs in your answer.

Report

A good answer to this question required attention to detail and an ability to describe
changes in many variables at each stage e.g. intrathoracic pressure, blood volumes,
baroreceptor firing and the subsequent cardiovascular response (e.g. heart rate and
blood pressure). Using graph(s) is a useful way to assist the explanation and was
required as part of the answer. Dividing the response into four stages makes answering
the question much easier. Overall there was a deficiency in a deep understanding of the
integrated physiology associated with the Valsalva manoeuvre. The most common
mistakes were describing a change but not saying why it happened, not considering
each element at each stage and confusing terms e.g. saying increased cardiac output
when the response was increased mean arterial pressure. Very few candidates drew
accurate graphs. Graphs required were those of the changes in intrathoracic pressure,
the pulse pressure response and the heart rate response.

Question

Describe and compare the action potentials from cardiac ventricular muscle and the
sinoatrial node.

Report

A fundamental aspect of cardiac physiology, that overall was well answered. The
majority of candidates used figures to good effect. Candidates are reminded that all
figures must be correctly labelled (e.g. X and Y axis, phases of action potential, etc.).
Common omissions were those that reflected an adequate depth of knowledge (e.g.
some of the current flows).

Question

Define myocardial contractility and briefly describe dP/dT, the end systolic
pressure volume (ESPV) relationship and the ejection fraction (EF).

Report

Contractility represents the performance of the heart at a given preload and afterload. It
is the change in peak isometric force (isovolumic pressure) at a given initial fibre length
(end diastolic volume). All indices of myocardial contractility are dependent on preload
or afterload to a varying degree. The dP/dT is the maximum rate of change in left
ventricular pressure during isovolumetric contraction, after mitral valve closes and
before the aortic valve opens. It is preload dependant and afterload independent. A
diagram of a pressure- volume loop is very helpful when describing the ESPV. Absence
of a diagram (correctly labelled and scaled) was a weakness in many answers.
Candidates were then expected to at least explain that, as preload is increased a new
pressure volume loop is generated. Each new PV loop has a new end systolic point that
is at a slightly higher pressure and volume than the previous end systolic point. The line
connecting the end-systolic points is called the linear ESPVR. The slope of the ESPVR
or Emax is used as an index of myocardial contractility. Ejection fraction is the
percentage of the ventricular end diastolic volume (EDV) which is ejected with each
stroke volume (SV). Ejection fraction = stroke volume/end diastolic volume X 100
(Normal range 55 to 70%). Only a minority of candidates achieved the depth of
knowledge required for a Level 1 topic.
Question

Outline the mechanisms that control regional skeletal muscle blood flow

Report

Candidates were expected to present the cellular mechanisms underlying the control of
skeletal muscle blood flow. Many candidates correctly identified a role for sympathetic
nervous system, metabolic (e.g. vasodilator metabolites such as CO2, H+, K+, lactate
and adenosine), vasoactive substances released by endothelium (nitric oxide,
prostacyclin, endothelin 1, etc.) and autoregulatory control but failed to present any
details of direction and magnitude of control. Better answers also mentioned humeral
(e.g. catecholamines, vasopressin, ANP, angiotensin II, histamine, serotonin, etc.) or
myogenic control (i.e. when the pressure within a smooth muscle blood vessel is
suddenly increased, the vascular smooth muscle is stretched.

Question

Describe the changes to cardiovascular physiology in a healthy elderly person.    

Report

It is clearly stipulated in the syllabus that candidates would be expected to understand

physiology as it applies at the extremes of age. In the past, questions have been asked
relating to foetal and neonatal physiology as well as for the elderly. This question was
poorly answered as candidates lacked a detailed and coherent knowledge of this topic.
For a good answer candidates were expected to at least mention the effects on the
heart, e.g. increases in size due to concentric ventricular hypertrophy (LVH),
hypertrophy of myocytes but a decrease in the number of myocytes, cardiac output
decreases, the increase in cardiac output in response to severe exertion is attenuated,
ventricular filling is particularly dependent on diastolic relaxation which is impaired,
greater contribution of atrial contraction, increase in left ventricular afterload, effects on
vasculature, e.g. intima and media thickening result in less distensibility, effects on
endothelial function, e.g. nitric oxide release is decreased, effects upon autonomic and
integrated responses, e.g. decline in receptor numbers, down regulation of post-
receptor signalling and decreased receptor density and impaired baroreceptor reflexes. 

Question

Define afterload and describe the physiological factors that may affect afterload   

Report

Definitions for afterload vary slightly amongst common physiology textbooks, and
candidates were expected to mention any one commonly accepted definition.
Essentially afterload is the resistance to ventricular ejection - the "load" that the heart
must eject blood against and is related to ventricular wall stress (Law of Laplace,
T=Pt.r/u). Candidates were expected to mention aortic valve and systemic vascular
resistance, aortic impedance, blood viscosity, intathoracic pressure and relationship of
ventricular radius and volume. Candidates generally did well, but few substantially good
answers, with a lack of detail being the biggest limiting factor. 

Question

Define a Portal System. Describe the anatomy and function of three portal systems in
the body.

Report

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.

Question

Discuss the regulation of cardiac output. Illustrate your answer by using a graph to
describe the important physiological relationships.

Report

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.

Question
 Describe the factors that affect the output of the right ventricle
Report

 An approach that covered the main determinants of right ventricular cardiac output including heart rate, right ventricular
preload, contractility, afterload and the relationship with left ventricular output, ventricular interdependence, and the
respiratory system would have provided the framework for a good answer. Some candidates used this approach but
described more features of left ventricular than right ventricular output. The observation that the right ventricle is relatively
thin walled and its output is very sensitive to changes in right ventricular preload and afterload particularly was central to this
question. The unique shape of the right ventricle and its contraction characteristics involving ventricular interdependence
were rarely mentioned. Also details on right ventricular afterload and the importance of factors affecting pulmonary vascular
resistance were lacking in most answers.

Question
 Relate the surface electrocardiogram (ECG) to the events of the cardiac cycle (60% of marks). Briefly describe the
mechanism of the effects of digoxin, and the mechanism of the effects of amiodarone, on the ECG (40% of marks)
Report

 Candidates were expected to provide sufficient detail in answers. Extra marks were awarded for diagrams relating the ECG
accurately to pressure events during the cardiac cycle. Time intervals, units of measurement and clear labels were essential
for diagrams.

 
Mechanisms pertaining to ion flux and ion channels needed to be specifically explained. Discussion of mechanisms
needed to be accurate and relevant to the effect on the ECG. For example, better answers noted that AV conduction was
depressed by Digoxin, predominantly due to an increase in Vagal tone
Question
 Explain the physiological processes involved in the development of tissue interstitial oedema.
Report

 The question required an accurate statement of Starling’s Equation, including the filtration and reflection co-efficients, and
definitions of terms. Marks were awarded for numerical values pertaining to hydrostatic and oncotic pressure gradients and
net filtration in a 24 hour period.
 
A satisfactory answer explained the factors which cause imbalance in Starling’s relationship including; precapillary
vasodilation, increased venous pressures, gravity / posture, fall in plasma protein concentration, changes to capillary
permeability and lymphatic obstruction.
Question
 Briefly describe the cardiovascular events that occur during ventricular diastole.
Report

 One possible way to answer this question is to offer a definition of the diastolic period then to split the events up for
description into mechanical events, ECG events and electrical/ionic events. Few candidates defined the diastolic period, and
whilst many talked about opening and closing of valves, there was generally a poor understanding of the sequence of events
whereby the left ventricle comes to be filled with blood. The better answers included a description of the ionic events that
occurred at the various stages of diastole. Many answers lacked any reference to the ECG events in diastole.

 
The major weakness in answers was again the failure to include sufficient information to achieve a pass mark. This was
probably as a result of the lack of a systematic approach when answering a question of this nature.

Question
 Outline the various cardiac reflexes and the mechanisms by which they maintain physiological homeostasis.
Report

 This question required candidates to provide an answer that integrates their knowledge of various aspects of cardiovascular physiology.
Cardiac reflexes are fast-acting reflex loops between the heart and central nervous system that contribute to regulation of cardiac function
and maintenance of physiologic homeostasis. This was often overlooked by many candidates. For a good answer it was expected that at
least the chemo and baroreceptor, Bainbridge (elicited by stretch receptors located in the right atrial wall and the cavoatrial junction),
Cushing (result of cerebral medullary vasomotor centre ischemia), oculocardic (provoked by pressure applied to the globe of the eye or
traction on the surrounding structures), Bezold-Jarisch (responds to noxious ventricular stimuli sensed by chemoreceptors and
mechanoreceptors within the LV wall) reflexes be mentioned and described.

Question
 Describe the ionic events associated with a ventricular cardiac action potential (80% of marks). Outline how the action potential
relates with the mechanical events of the cardiac cycle (20 % marks)
Report

 To achieve a good pass in this question, candidates needed to outline the ionic events associated with Phase 0 to phase 4 of the ventricular
action potential followed by a description of excitation – contraction coupling. The second part of the question was best answered using a
ventricular pressure-volume loop and overlaying the phases of the ventricular action potential.

 
Description of the ionic events associated with the action potential phases was generally well done, but this was as far as many
answers went in answering this question. Few candidates included a description of excitation-contraction coupling in there answer
and few candidates considered an answer to the second part of the question. The use of illustrations helped answer this question.
 
Question

Describe the cardiovasculare changes that occur following the loss of 1000ml of blood
in an adult

 
Report

A structured approach that included mentioning that 1000mls of blood was substantial –
being approximately 20% of the blood volume of a 70 kg person was required for a
good answer. Candidates were expected to also include changes in systolic and
diastolic blood pressure, pulse pressure, heart rate, cardiac output and the neuronal (eg
sympathetic nervous system response on the various circulations) and hormonal
responses (eg renin aldosterone, Anti-Diuretic Hormone, catecholamines, etc).
Candidates were also expected to discuss differences in responses according to rate of
blood loss. Flow diagram could have been used to illustrate some of these concepts.

Question

Define preload and describe the determinants of preload

Report

 A definition based on stretch of the isolated myocyte prior to contraction, and

extrapolation to the human heart, was expected. Surrogate measures of preload used in
clinical practice needed to be explained and related to the definition (for example, end-
diastolic volume and central venous pressure). The Frank-Starling Law was relevant to
discussion of the significance of preload to cardiac performance.
A diagram illustrating the interaction of important factors would have been helpful in
answering this question. At a minimum, detail should have included atrial contractility,
diastolic filling time, ventricular compliance, and the determinants of venous return.
Better answers included discussion of the effects of afterload, arrhythmias, and valvular
pathology. A distinction between the factors determining left and right ventricular
preload would have demonstrated a more sophisticated understanding of the
physiology.

Question

Describe the physiological consequences and responses after an acute haemorrhage of

2.0 litres in a healthy 70kg adult if there is no immediate fluid resuscitation.

Report

To adequately answer this question, candidates must be able to demonstrate that they
recognised this to be a major haemorrhage.  When a weight and a volume are supplied
it is expected the percentage blood loss would be calculated and the shock graded or
the haemorrhage at least described as severe.  Often the consequences were omitted.
Consequences were best described in organ systems eg CVS, renal, metabolic.  Many
candidates failed to mention the patient would be hypotensive and tachycardic.

 
 A good answer should include mention, and provide explanations, of the mechanisms
for the following compensatory responses:

 Activation of both baroreceptors and chemoreceptors and their consequences

 the sympathetic nervouse system response
 fluid shifts
 renal effects - most candidates mentioned the urine output would be decreased but did not provide a mechanism for
this

Endocrine effects eg secretion and actions fo ADH, ACTH / Cortisol

Question

Describe the adult coronary circulation (50% of marks).  Describe the physiological
control of the coronary circulation

Report

For a good pass candidates were expected to cover at least the following areas -
Anatomy of the coronary arteries and their supply, variations in supply and venous
circulation Other unique features - coronary sinus saturation <30%, the diastolic aortic
pressure, Tachycardia reduces the coronary blood flow through a reduction in diastolic
time, left ventricle perfused mainly during diastole and right ventricle perfused mainly
during systole, different pattern of left and right ventricular coronary perfusion (drawing
a figure of Rt and Lt coronary blood flow), lack of capacity for the myocardium to
increase its extraction ratio Physiological control: The most important mechanism
through which coronary blood flow can be changed is by autoregulation which changes
the coronary vascular resistance to maintain constant flow in response to different
coronary perfusion pressure and changing metabolic demand. Important mediators are
adenosine, nitric oxide, and opening of the ATP- sensitive K+ channels, prostaglandins,
carbon dioxide, lactic acid or hydrogen ion. Sympathetic stimulation to heart increases
coronary blood flow.
Overall the greatest deficiency by candidates was lack of detail, use of illustrations and
clarity in their response. It is important that candidates take note of the distribution of
marks given within the question. 

Question

Describe the hormonal response to hypovolaemia following the acute loss of one litre of
blood in an adult. Include changes that occur in the first 24 hours following the blood
loss.  

Report

 Candidates were expected to know the different hormonal responses to hypovolaemia

The possible approach to this question can be either by explaining the hormonal
response in terms of time sequence or by different hormonal systems.
 Good answers to this question included how different hormonal responses are activated
and mediated.
The common omissions were secretion of erythropoietin within 24 hours of
haemorrhage, role of macula densa and juxtaglomercular apparatus, interactions
between baroreceptors and sympathetic nervous system with the secretion of ADH,
cortisol, glucagon and catecholamines.

Question

Draw and label a left ventricular pressure loop in a normal adult.  List te information that
can be obtained from this loop.

Report

Candidates were expected to draw and label a diagram showing the relationship
between pressure and volume during the different phases of the left ventricular
contraction and relaxation (or systole and diastole)
Good answers to this question consisted of a well-labelled graph with appropriate scale
on both x and y-axes showing all the important events during systole and diastole of the
left ventricle.
The common omissions were rapid and slow ejection phase during systole, when aortic
valve closes, stroke volume, ejection fraction, end-systolic pressure volume line
showing the contractility of the left ventricle.
Some candidates appeared to have confusion about which line shows contractility and
which line shows left ventricular after load.

Question

Explain the role of the baroreceptors in the control of blood pressure.

Report

Good answers included the following

 description of and types of baroreceptors (eg stretch receptors)

 their locations (eg walls of the aorta, carotid sinuses, the atria)
 the stimulus they respond to (eg pressure, volume)
 short term and long term responses, alteration to set points, impulse frequency / pressure curve
 a brief description of the afferent and efferent pathways and the resultant efferent effects (eg alterations to heart rate,
blood pressure etc)
Question

Describe the effects of tachycardia on myocardial oxygen supply and demand in a

normal heart.
Report

The main points expected were the determinants of myocardial oxygen supply.  THese
include arterial oxygen content and coronary blood flow.  Coronary blood flow depends
on coronary perfusion pressure and coronary vascular resistance and that most left
coronary blood flow occurs in diastole.  Tachycardia reduces diastolic time and hence
left coronary blood flow.  In comparison, blood flow in the right coronary artery is
continuous both in systole and diastole and is little affected by heart rate.  A correctly
labelled diagram of left and right coronary blood flow attracted extra marks.
Unfortunately most diagrams were inaccurate, not labelled and had no units on the
axes.  Systolic compression particularly reduces blood supply to the left ventricular
subendocardium which is most susceptible to ischaemia.  Extra marks were given for
describing metabolic autoregulation , the high oxygen extraction, explaining that oxygen
supply cannot be increased by increasing oxygen extraction in the coronary circulation
describing the driving pressure differences in both coronary arteries in systole and
diastole.

A description of the determinants of myocardial oxygen demand was also required) eg

left ventricular, preload, contractility, afterload and tachycardia.  This part of the
question was particularly poorly answered.

Question

Explain how oxygen supply is maintained to the tissues in chronic anaemia.

Report

Candidates were expected to base their answer around the variables involved in the
equations that describe oxygen content in blood and oxygen delivery.  Although most
candidates mentioned changes in haemoglobin that increase oxygen carriage, a more
complete discussion of the changes that influence cardiac output and the peripheral
circulation was often omitted.

CNS pharmacology

Question

Compare and contrast the pharmacology of phenytoin and levetiracetam. 

Report

A table was useful to answer this question. Comparing and contrasting the pharmacology was required to score well
rather than listing various aspects of pharmacology. The key properties of the drugs which demonstrate their
importance to ICU was required.
Question

Compare and contrast the pharmacokinetics and adverse effects of morphine and fentanyl 

Report

This question is best answered in a tabular form, comparing absorption, distribution, metabolism, excretion and the
adverse effects.

Common omissions were lack of details on distribution, and not relating lipid solubility to effect. A description of the
relative adverse effects was expected, e.g., more histamine release, less bradycardia, rather than listing similar
adverse effects, e.g. respiratory depression.

Comparisons of pharmaceutics and pharmacodynamics did not attract any additional marks. 

Question

Describe the pharmacology of propofol. 

Report

Those candidates who did poorly lacked any structure for answering a pharmacology question. Pharmacokinetics
was generally poorly handled and many answers revealed a lack of knowledge about this drug. Adverse effects and
mechanism of action were generally well known. Doses of the drug were often incorrectly stated.

Important aspects such as dose or pharmacodynamics were often omitted and a structured approach helps avoid
this. 

Question

Compare and contrast the pharmacology of valproic acid and carbamazepine. 

Report

Both these agents are listed as “level B” in the syllabus pharmacopeia and as such a general understanding of each
class and relevant pharmacokinetics and pharmacodynamics was expected. Most candidates had better knowledge
of valproate than carbamazepine. Some description of the toxicological features for intensive care practitioners was
expected. 

Question

Describe the pharmacodynamic effects and indications for the use of anticholinesterase
drugs. 

Report

It was expected the answer would provide a structured approach to describing the pharmacodynamics (what the drug
does to the body) of this discreet class of drugs. A brief acknowledgement of the drugs in this class followed by a
catalogue of the various clinical uses of this class of drugs would be a good start. If this was followed up with a
description of the effects of these drugs on the CVS, GIT, Salivary glands, eye, NMJ and the lungs a good mark
would have been awarded.
A number of candidates described the actions at the receptors in detail which did not attract marks. The extensive
range of clinical uses for this class of drugs was poorly appreciated.

Few answers demonstrated any understanding of the PD effects of the drug class. There was generally a good
knowledge of representative drugs within this class. Failing to achieve a pass mark reflected scant/brief answers that
just did not cover enough of the expected material. 

Question

Compare and contrast dexmedetomidine and ketamine    

Report

The majority of candidates were able to describe the mechanism of action, uses, dose and some side effects of each
drug. The better answers were in a table format. It is of course possible to include much of the relevant information
without using a table; however without the visual prompt of a table it makes it likely sections will be omitted.

When comparing two drugs it would be useful to note that though they both provide sedation with analgesia they are
used in different circumstances. In ICU, dexmedetomidine is mainly used for sedation peri-extubation and may be
continued post-extubation but this was not often mentioned.

The pharmacodynamic effects often omitted the cardiovascular and respiratory effects of ketamine (particularly
bronchodilation).

The pharmacokinetic information required was not detailed but only minimal marks can be awarded for ‘administered
IV with 100% bioavailability, liver metabolism and renal excretion’ which was a common answer. Noting
dexmedetomidine is metabolised to inactive metabolites and ketamine is metabolised to norketamine gained marks,
specific pathways were not required. Both drugs are licenced for administration intravenously (and ketamine may be
administered IM); however other routes of administration are emerging in clinical practice for both drugs. 

Question

Describe the pharmacology of Phenytoin (75% of marks) and Levetiracetam (25% of

marks). 

Report

The knowledge of phenytoin was often superficial and many answers were too brief and
didn’t adequately cover the required material. The knowledge around levetiracetam
seemed very limited with many candidates guessing (incorrectly) what the
pharmacokinetics might be. Most answers demonstrated a structured approach to this
type of question.

Better answers were able to distil major issues such as the narrow therapeutic window
for phenytoin or the potential clinical impact of differing ordered kinetics or altered
metabolism. Candidates are reminded to read each question carefully; levetiracetam
should not be confused with levosimendin. 
Question

Outline the mechanisms that potentiate the action of non-depolarising muscle relaxants
and give examples. 

Report

A structured approach would work well for this question but was often lacking. Many
answers were superficial providing short lists of factors affecting NDMRs without
reference to mechanism. Candidates failed to differentiate factors which potentiate
NDMRs from those which inhibit the action of the drugs. Some confusion also existed
confusing speed of onset kinetics with potentiation kinetics. Candidates who structured
their answer into pharmacokinetic and pharmacodynamic factors generally scored
better marks. Candidates who used pre-post synaptic type structure tended to omit
kinetics completely from their answers. Incorrect facts were common. 

Question

Compare and contrast the pharmacology of haloperidol and diazepam. 

Report

These are both commonly used agents and a tabulated format worked well.
Subheadings covering the “general” pharmacology approach ensured core areas were
addressed. Vague terms such as "good" or "moderate" did not allow a detailed
comparison between the agents. Repetition of facts between sections such as uses,
pharmacodynamics, effects and adverse effects did not gain further marks. 

Question

Describe the mechanism of action of the analgesic effect of opiates. (70% of marks)
Explain the mechanism by which morphine causes respiratory depression and
constipation. (30% of marks) 

Report

This question was poorly answered with a low pass rate; which was unexpected for this
core topic. In general, completed answers demonstrated good understanding of the
analgesic mechanisms of opiates, but only superficial understanding of respiratory
depression and constipation. Better answers explained the decreased responsiveness
of the respiratory centre to CO2, and the effects of opiates on the enteric nervous
system and peristalsis. 

Question

Describe the pharmacology of suxamethonium.    

Report

This question was generally well answered. A structured approach that included
headings such as pharmaceutics, mechanism of action, pharmacodynamics, kinetics,
dose and side effects was associated with a good answer. 

Question

Compare and contrast the mechanism of action, pharmacokinetics and central nervous
system effects of morphine and tramadol. 

Report

In general candidates either lacked a depth of knowledge, or a deep enough

understanding of the drugs so as to apply their knowledge specifically to the central
nervous system (CNS). Mechanism of action and pharmacokinetics for morphine was
better understood, in comparison to tramadol. Mention of the non-CNS effects of
morphine and tramadol, was not expected, did not score marks, and would have wasted
valuable exam time. 

Question

Describe the pharmacology of propofol.   

Report

A high level of knowledge was expected as it is a commonly used drug in intensive

care. Overall most candidates performed very well. Areas of weakness were those
relating to propofol pharmacokinetics and pharmacodynamics. 

Question

Describe the pharmacology of naloxone

Report

Naloxone is a commonly used intravenous opioid antagonist, which acts as a

competitive antagonist with high affinity for the mu, kappa, delta and sigma opioid
receptors. It is used to ameliorate or reverse opioid effects at these sites. It has a
shorter effect site and plasma half-life than most opiates so levels will fall before the
opioid agonist it is being used to treat, thus a repeat dose maybe required to maintain
opioid reversal. Overall candidates lacked sufficient depth of information to achieve high
marks for this question.
Question

Suxamethonium is a non-competitive partial agonist. Explain what is meant by

this statement using definitions of the underlined terms (50% of marks). List the
advantages and disadvantages of suxamethonium within Intensive Care practice
(50% of marks).

Report

For a good answer candidates were expected to mention that an agonist is a drug that
elicits a maximal response on binding to a receptor. A partial agonist has intrinsic affinity
with only partial efficacy and hence is unable to elicit a maximal response. A competitive
drug acts at the same binding site of a receptor as an endogenous ligand (e.g.
acetylcholine at the neuromuscular junction) and its action therefore is surmountable
with increasing concentrations of drug and how this concept relates to suxemethonium.
For the remainder of the question, Candidates were expected to mention the
advantages and disadvantages of suxamethonium within Intensive Care practice. Good
answers included a systematic approach and use of tables and/or well organised lists.

Question

Classify the 5HT receptors and give examples of pharmacological agents that affect
them (60% of marks). Outline the pharmacology of ondansetron (40% of marks).

Report

The 5HT (5 Hydroxytryptamine or serotonin) receptor is a monoamine neurotransmitter

synthesized from tryptophan, and is an important receptor in the body.. It is found in the
CNS, gastrointestinal tract, platelets and mast cells. There are 7 main receptor subtypes
(G- Protein coupled are 5HT1, 5HT2, 5HT4 and 5HT7 and ligand-gated ion channel
5HT3). Drugs may affect them by acting on serotonergic transmission (degradation
inhibitors - MAOI e.g. selegiline, storage inhibitors- amphetamine, reuptake inhibitors -
SSRI’s or tricyclic antidepressants), serotonin agonists (selective-5HT1B, 5HT1D e.g.
triptans for migraine, non-selective, e.g. ergotamine), serotonin antagonists (ketanserin,
clozapine, ondansetron). Ondansetron is a commonly used anti-emetic. Candidates
were expected to mention, that it is a selective antagonist at the 5HT3 receptor centrally
and peripherally. To outline “pharmacology” it was also expected that answers would
mention that it comes in a variety of formulations and to outline its fundamental
pharmacokinetic properties.

Question

Describe the factors that increase the risk of systemic toxicity of the amide local
anaesthetics.
Report

The amide group of local anaesthetics consist of lignocaine, prilocaine, ropivacaine and
bupivacaine. The systemic toxicity primarily relates to toxic plasma levels and the
factors that influence this. The main factors expected can be categorized under drug
factors (including kinetics), patient factors, site of injection and external factors. Many
candidates omitted important details such as pKA, lipid solubility and addition of
vasoconstrictors. For example, absorption is affected by drug pKA, (the closer to
physiological pH the more rapid the absorption), use of vasoconstrictors and the drugs
own vasoactive properties, site of injection (intercostal>epidural>brachial
plexus>subcutaneous infiltration). Distribution is dependent on physicochemical
properties of the amide. The rate of metabolism, mechanism of action (bupivacaine, in
comparison to lignocaine has stronger binding to inactivated resting sodium channels
and a slower rate of dissociation) and external factors (e.g. systemic acidosis) are other
factors that should have been mentioned, and expanded upon with relevant detail.

Question

Describe the pharmacology of phenytoin    

Report

Many candidates scored well in this question by using a standardised approach such
as: Pharmacoceutics, Pharmacokinetics and Pharmacodynamics. This topic is well
covered in the reference texts and a high degree of content was expected. 

Question

Compare and contrast the pharmacology of dexmedetomidine and propofol.    

Report

A basic and fundamental pharmacology question which required candidates to present

their answer in a coherent fashion (a table worked best) as well as demonstrate
sufficient knowledge. The majority of candidates did so, and so scored well. Candidates
tended to struggle with the pharmacokinetic properties of these drugs. 

Question
 Compare and contrast the pharmacology of intravenously administered atropine and glycopyrrolate
Report

 Most candidates exhibited a structural approach with reasonable understanding of the pharmacology of atropine although
there was a lack of precision (anticholinergic is correct, competitive muscarinic antagonist is more precise). Some answers
did not contrast glycopyrrolate adequately. The phrase ‘hepatic metabolism, renal excretion’ needed to be accompanied with
detail if marks were to be awarded.
Question
 Describe the pharmacology of suxamethonium
Report

 Most candidates presented a structured answer and demonstrated reasonable understanding of the pharmacology of
suxamethonium. This is however a core subject and candidates should be able to answer this question in depth.

Question
 Compare and contrast the pharmacology of morphine, fentanyl and remifentanil.
Report

 The question asked for a comparison of the pharmacology (pharmacokinetics and pharmacodynamics) of three commonly
used opiates. Better answers made use of a well constructed table with headings including chemistry, protein binding, lipid
solubility, half-lives, context sensitive half-time, volume of distribution, metabolism, active metabolites, oral bioavailability,
and clearance. A distinction should have been clearly drawn between onset, peak, and duration of effect. CNS stimulant
effects as well as depressant effects, were expected to be listed.

 
Syllabus: G2d, 2d Recommended sources: Anaesthesia, Miller Chp 11 and Pharmacological Basis of Therapeutics,
Goodman and Gillman, Chp 21
Question
 List the adverse properties of Propofol and Ketamine
Report

 This question was not well answered by many candidates. Candidates included advantages of these sedative / analgesic agents in their
answers when they were not asked for in the question. The best approach to answer this question is to use a table listing their potential
adverse properties in categories such as pharmaceutical and chemical properties, pharmacodynamic properties in different body systems,
and pharmacokinetics.

 
The common weaknesses observed included the side effects of ketamine, including its side effects on intracranial pressure,
myocardial contractility and oxygen consumption, and hallucinations or delirium. Some adverse properties of propofol including
bacterial contamination and pain on injection were also not well covered by many candidates.
Question
 List the adverse properties of Propofol and Ketamine.
Report

 This question was not well answered by many candidates. Candidates included advantages of these sedative / analgesic agents in their
answers when they were not asked for in the question. The best approach to answer this question is to use a table listing their potential
adverse properties in categories such as pharmaceutical and chemical properties, pharmacodynamic properties in different body systems,
and pharmacokinetics.

 
The common weaknesses observed included the side effects of ketamine, including its side effects on intracranial pressure,
myocardial contractility and oxygen consumption, and hallucinations or delirium. Some adverse properties of propofol including
bacterial contamination and pain on injection were also not well covered by many candidates.
Question

Describe the mechanism of action of the analgesic effect of opiates (70%)  Explain the
mechanism by which morphine causes respiratory depression and constipation.
Report

 This was a multi-part question, for which many candidates failed to apportion their time
as indicated by the question. Most patients who enter Intensive Care receive opioid
analgesia so candidates were expected to have detailed knowledge about the
mechanics of action of opiates. For a good answer candidates were expected to
mention that opiate agonists produce analgesia by binding to Mu receptors (which are G
protein coupled) in the central and peripheral nervous system and spinal cord and their
cellular mechanism of action eg presynaptic neurone - close voltage gated Ca channels
and prevent neurotransmitter release and post synaptic neurone - hyperpolarise and
inhibit post synaptic neurone. The fact that opiates also affect emotional side of pain
and cause euphoria which may help with pain perception was often omitted.
Mechanism of respiratory depression is mediated via mu receptor. It occurs at normal
analgesic doses, and decreases the chemosensitivity of the respiratory centre to
PaCO2

Mechanism of constipation results from increased tone and decreased motility of the
GIT via action on visceral smooth muscle mediated by intramural nerve plexus and all
three opioid receptors.
Many candidates had poor organisation and poor knowledge of all aspects of this
question.

Question

Describe the pharmacology of Phenytoin

Report

A structured approach was expected addressing both the mechanism of action and
pharmacokinetics. Candidates were expected to outline relevant mechanisms of action
(such as sodium channel blockade) and how they relate to its use as an anticonvulsant
agent. Additional credit was given for discussing other potential mechanisms and other
uses such as pain management and antiarrhythmic properties.
Phenytoin is illustrative of several key concepts in pharmacology and mention of these
was expected. Failure to address these key concepts or provide sufficient detail was a
common omission. Candidates were expected to discuss that phenytoin is highly protein
bound, changes from first to zero order kinetics with escalating doses and is
metabolised by the cytochrome p450 enzyme system. Some discussion of the
significance of these points was expected and extra credit was awarded for more
detailed explanations, comments on enzyme induction and examples of drug
interactions that are well known and clinically relevant. Candidates were expected to
comment on the mode of delivery and compare oral and intravenous dosing. It was
expected that the need for a loading dose followed by maintenance dosing would be
mentioned and extra credit was given for highlighting the potential hazards of rapid
intravenous administration. Additional credit was given for mentioning the importance of
a narrow therapeutic index and the need for clinical monitoring. Well organized answers
such as those with an ordered list of subheadings were rewarded.

Question

Describe the factors that influence the speed of ONSET of neuromuscular blockade

Report

The better candidates had an organised approach to their answer.  For example, factors
could be broadly classified as pharmacokinetic and pharmacodynamic factors of patient
and drug factors.  For example, pharmacokinetic factors could include dose, the use of
a priming dose, patient's volume status, cardiac output, muscle group and skeletal
muscle blood flow.  Pharmacodynamic factors expected were those of mechanism of
blockade, receptor affinity, agent potency, neuromuscular disorders, age, drug
interactions and electrolyte disorders.

Many answers listed factors which affect the DURATION of neuromuscular blockade
instead of the ONSET.  Marks were not allocated for information provided by candidates
that did not address the question asked.  It is important that candidates provide an
answer specific to the question asked.  Many candidates applied Fick's Law
inappropriately.  Lipid soluability and pKa are not relevant as these drugs do not cross
the nerve membrane.

Question

Describe the blood brain barrier. (50% of marks).  What characteristics does a drug
need to effectively penetrate into the CNS? (50% of marks).

Report

Candidates were expected to state the purpose of the BBB, define what constituted the
BBB, what its function is, and what parts of the brain lie outside of this barrier (and
why).  Further, candidates should have mentioned what substances cross the BBB and
how this is achieved.

Common omissions included not mentioning the presence of astrocyte foot processes in
addition to the tight junctions between the capillary endothelial cells, the presence of
active pumps for sugars, amines and some ions, and what parts of the brain lay outside
the BBB.

 
Characteristics of a drug that will penetrate the BBB included low molecular weight,
good lipid soluability, a low volume of distribution, low potency and low protein binding. 
Also expected was a discussion of Fick's Law and the drug features that would allow a
high concentration gradient in the cerebral blood vessels to be achieved and a high
diffusion coefficient and mention of drugs that resemble natural ligands for active
transport mechanisms.

Question

Outline three factors which alter the pharmacodynamic response of non-depolarising

neuromuscular blocking drugs and describe the mechanism by which they may occur

Report

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 non-
depolarising neuro-muscular blocking drugs may be affected.

Question

Outline the pharmacological properties of an ideal agent for sedating patients

undergoing mechanical ventilation in intensive care (50% of marks).  Describe how
propofol compares with the "ideal agent"

Report

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. 

Question

Compare and contrast the pharmacology of midazolam and dexmedetomidine when

used for sedation

Report

This question was also well suited to be answered in a preset format. For example a
tabular format that had headings such as mechanism of action, preparations, dosing,
pharmacokinetics, metabolism and excretion, pharmacodynamics, drug interactions and
side effects.
A good answer was expected to include the following points. Under mechanism of
action, mention that both drugs produce sedation by hyperpolarizing CNS nerve
membranes and act on different receptors (Midazolam binds the benzodiazepine
receptor and dexmedetomidine being selective for the a2 receptor). Also mention of
other effects for each drug, eg anxiolytic, anticonvulsunt, analgesia, etc. A similar
approach would be required for other key areas such as metabolism and excretion,
(including alterations with age, organ failure, disease, etc), drug interactions,
pharmacodynamics, particularly in relation to important physiological effects (eg CNS
and CVS effects).
A brief summary of the similarities and differences which influence the clinical use of
these agents gained more marks and showed the candidate had applied knowledge of
these drugs. The common omissions were lack of explanation of mechanism of action
and failure to mention pharmacodynamic effects, drug interactions and specific
advantages for each agent. 

Question

Describe the physiological basis for the mechanism of action of three commonly used
anticonvulsant groups.  Give and example of a drug for each mechanism of action.

Report

The three main anticonvulsant mechanisms required were :

 Sodium channel blockers.  These promote the inactive state of voltage activated Na channels.  Sodium channels are
unable to open for a period of time making the neurone more refractory to action potential generation.  Rapid
repetitive firing is diminished and spread of electrical activity to adjacent brain areas is suppressed.  Examples -
phenytoin, carbamazepine, lamotrigine, Na valproate
 Drugs that enhance GABA mediated synaptic inhibition.  This increases the influx of chloride ions into the cell and
hyperpolarizes the neurone.  3 mechanisms - act on GABA receptor eg benzos, barbiturates; inhibition of GABA
transporter and reduce neuronal GABA reuptake, example tiagabine; promote GABA release - gabapentin
 Drugs that inhibit calcium channels.  Limit activation of voltage activated Ca channel known as the T current.
Example : Na valproate
Other mechanisms of action with examples if described earned extra marks.  These
included glutamate / NMDA receptor inhibition eg magnesium

Question

Compare and contrast ibuprofen and tramadol as analgesic agents in intensive care.

Report

Ibuprofen - inhibition of the cyclo-oxygenase (COZ) and synthesis of prostaglandins,

which are important mediators for peripheral sensitisation and hyperalgesia.  Act
peripherally and spinal COX - nonselective.  Oral and PR only.  Associated with a
number of side effects, including decreased haemostasis, renal dysfunction,
gastrointestinal haemorrhage and effects on bone healing and osteogenesis.

Tramadol - is a synthetic opioid that exhibits weak mu agonism activity and inhibits re-
uptake of serotonin and noradrenaline.  Analgesic effects primarily through central
mechanisms, it may exhibit peripheral local anaesethetic properties. 

Tramadol is comparable in analgesic efficacy to ibuprofen.  Common side effects

(overall incidence 1.6-6.1%) include dizziness, drowsiness, sweating, nausea, vomiting,
dry mouth, and headache.  Tramadol should be used with caution in patients with
seizures or increased intracranial pressure and in those taking monoamine oxidase
inhibitors.  IV and oral preparations.  No bleeding, GIT or renal complications.  More
expensive.

Both have advantage of lack of respiratory depression, major organ toxicity and
depression of GIT motility and have a low potential for abuse.

CNS PHYSIOLOGY

Question

Outline the anatomy and physiology of the parasympathetic nervous system. 

Report

An efficient way to answer this question was to describe the anatomy and physiology of both cranial and sacral
sections together. High scoring answers included an outline of the relevant nerves, the various ganglia,
neurotransmitters and physiological effects. Some candidates described the cellular basis of Nicotinic, Muscarinic
and M1-M5 receptors which didn't attract marks. 

Question

Outline the physiology of cerebral spinal fluid (CSF). 

Report

Better answers included details on CSF production (amount, site), reabsorption and factors which influences CSF
and its circulation. 

Question

Discuss the determinants of intracranial pressure (80% of marks). Outline how it can be measured (20% of marks). 

Report

It was expected answers would include an explanation of the Monro-Kellie Doctrine. Many candidates gave
insufficient details of compensatory mechanisms especially regarding decreased total cerebral blood volume
(primarily venous) in response to increased intracranial pressure.

Most candidates had all the information but had difficulty synthesising the information to write a cohesive answer.
Factors affecting ICP could be divided into factors affecting CBV, factors affecting CSF and factors affecting brain
tissue. Under factors affecting CBV the effect of blood gases, autoregulation, temperature, metabolism, drugs and
venous obstruction could have been detailed. 

Question

Describe the factors that influence intracranial pressure. 

Report

A structure approached works well for “describe the factors ...” questions. Better answers provided a definition of ICP,
explained the Monro-Kellie doctrine and then detailed the factors which affect the volume of each of the components -
cerebro spinal fluid (CSF), cerebral blood flow and brain parenchyma. Some candidates focused only on factors
which cause intracranial hypertension and were thus unable to score full marks. Many candidates stated that CSF
production was ICP dependant which is incorrect. 

Question

Describe the methods of temperature measurement. 

Report

A good answer included a definition of temperature and a classification of the methods of measuring temperature
such as electrical, non-electrical and infrared. There followed a brief description of the physical principles of
thermistors, thermocouples and resistance thermometers; mercury and alcohol thermometers, bimetallic strips; and
of infrared methods. Candidates who did well reproduced the content of the chapter on temperature measurement in
the recommended text book. Candidates who were not familiar with this material attempted to answer the question by
falling back on clinical experience of measuring temperature in different sites or occasionally referring to concepts of
thermoregulation. Neither approach gained credit.

Some candidates interpreted “methods” incorrectly as "site of measurement" so scored poorly. 

Question

Compare and contrast the anatomy and physiology of skeletal and smooth muscle. 
Report

It was expected answers would describe in detail the role of troponin, tropomyosin and calmodulin in mediating
muscle contraction. Detail on the structure (histology) of the skeletal and smooth muscle cells was often lacking.
Many answers omitted the mechanism of muscle relaxation. 

Question

Describe the stages of sleep (50% of marks). Describe the respiratory physiological changes that occur in sleep (50%
of marks). 

Report

Few candidates demonstrated a good knowledge of this topic. Few answers described the EEG changes associated
with the stages of sleep. Respiratory changes in sleep were more commonly known though many candidates made
no reference to the change in resistance associated with reduction in upper airway tone.

Confusion existed about the tidal volume changes in sleep. The question asked specifically for respiratory changes
and marks were not awarded for discussion about cardiovascular or metabolic responses. 

Question

Describe the structure and function of the blood brain barrier.    

Report

There was general lack of understanding of the conceptual framework of the blood brain
barrier (BBB) and its function. To attain a pass, candidates were required to describe
the concept of BBB as a physical and a transport barrier, describe the role of tight
junctions and glial cells and identify important barrier functions with some examples of
things commonly transported across or excluded.

Question

Describe the physiology of cerebrospinal fluid.

Report

Most candidates answered the question well. The most common mistake was incorrect
CSF composition. Better answers also discussed raised ICP and CSF’s role in
the compensation for raised ICP.

Question

Describe the physiology of cerebrospinal fluid.

Report

Most candidates answered the question well. The most common mistake was incorrect
CSF composition. Better answers also discussed raised ICP and CSF’s role in
the compensation for raised ICP.

Question

Describe the anatomy of the sympathetic nervous system.    

Report

A definition of the sympathetic system, followed by a systematic description of the central sympathetic centres; what
happens at the spinal cord; the anatomy of the pre and post ganglionic fibres would have been awarded with a pass
mark. Additional information about the sympathetic ganglia and the neurotransmitters involved would have rounded
off a good answer.

Many answers lacked anatomical detail and described the actions (function) of the sympathetic system which was not
asked for.

Most answers lacked any structure. The most common reason for not passing this question was that significant
sections of the anatomy from central to peripheral were not mentioned. Most had a simple sketch understanding of
the question asked but could not add enough of the next layer to be awarded a pass mark. 

Question

Outline the anatomy and physiology of the parasympathetic nervous system. 

Report

Generally there was a lack of detailed knowledge, incorrect facts and at times confusion
between the sympathetic and parasympathetic nervous system functions. A lack of
anatomical detail was common (the origin of preganglionic cell bodies was not
described clearly, and parasympathetic ganglia were not often named and located). It
was expected an answer would mention the central role of Acetylcholine as a
neurotransmitter at preganglionic and post ganglionic neurons in the parasympathetic
system. Target organs were identified correctly but the exact action was not specified
e.g. pupillary constriction vs. dilatation, GI sphincter/bladder - contraction vs. relaxation.
Detail concerning receptor physiology was not required.

This is a question covering a core topic that no candidate passed. An overview of the
arrangement and function of the autonomic nervous system is provided in several core
physiology texts, including Ganong and Guyton. 

Question

Discuss the factors that may potentially influence the speed of onset of neuromuscular
blockade. 
Report

Speed of onset is related to how quickly an effective dose reaches the neuromuscular
junction, the type of interaction with the receptor and the margin of safety of the
receptors. Examples of parameters that increase speed of onset include a high drug
rate of delivery (high CO, high muscle group blood flow, and fast injection rate), high
drug concentration (higher dose, low potency, higher ED 95, lower protein binding) or a
depolarising block. A good answer would include a list of these factors, with a brief
explanation. Mention of other factors such as electrolyte disturbances gained additional
marks. It was expected that the direction of an effect would be clearly indicated (e.g.
“potency” would not score a mark unless the candidate wrote – “low potency increases
speed of onset”, etc.). These drugs are charged molecules which do not cross cell
membranes and have a low volume of distribution. Absorption from GIT, Lipid solubility,
pKa, metabolism and clearance have minimal relevance to speed of onset. 

Question

Using a diagram, explain the effect of PaO2, PaCO2 and MAP (Mean Arterial Pressure)
on cerebral blood flow (CBF). (60 % of marks) Outline the effects of propofol and
ketamine on CBF and cerebral metabolic requirement for oxygen (CMRO2). (40% of
marks) 

Report

This question was well answered. It is a structured question that guides candidates
through exactly what is required. Well drawn graphs were a particularly effective means
of scoring marks. 

Question

Define pain. (10% of marks) Describe the anatomical and immediate physiological
components of the response to pain arising from the insertion of an arterial line. (90% of
marks) 

Report

The pain pathways following arterial line insertion involve sensing the stimulus and
transmitting the sensation to the central nervous system. It was expected candidates
could provide some detail about the major features along this pathway including a
description of sensors, nerve types, spinal cord input and decussation with subsequent
projection to higher centres. Better answers provided additional details about
modulation and descending pathways. The question also required a description of the
physiology with some discussion of the mediators involved and explanation of how a
stimulus or tissue may result in the perception of pain. Common omissions included
insufficient detail of the pain pathway and limited or no discussion of the physiological
components. 
Question

Describe the blood brain barrier (50%ofmarks). What characteristics does a drug need
to effectively penetrate the blood brain barrier? (50% of marks)

Report

The BBB is the separation of the blood from the brain extracellular fluid and serves to
maintain consistent internal environment in the brain and protect the brain from large
harmful substances and microorganisms. Most answers displayed some knowledge of
the structure of the BBB but many answers did not include its function. Better answers
included substances to which the BBB is permeable, how permeability changes with
age and a mention of the circumventricular organs and their significance (i.e. are
outside the BBB). Most candidates correctly identified the characteristics of drugs that
cross the BBB. Marks were also allocated for giving examples.

Question

Outline the respiratory and cardiovascular consequences of an acute complete spinal

cord transection at C6.

Report

The main respiratory consequences of an acute C6 transection include the effects on

the inspiratory muscles, the expiratory muscles, lung volumes, effects of changes in
posture and effects on gas exchange. Sparing of the phrenic nerve, the main muscle of
inspiration (C3 - 5), but paralysis of the external intercostal muscles innervated by
thoracic nerve roots results in paradoxical inward movement of the chest wall on
inspiration. Paralysis of all the expiratory muscles including the internal intercostal
muscles innervated by thoracic nerve roots and the abdominal wall muscles, which are
innervated by lower thoric and lumbar nerves. Many candidates did not mention these
muscles or their innervation in their answers. While expiration is normally passive these
muscles are required for manoeuvres involving forced exhalation like coughing. Forced
expiratory lung volumes (FEV1 and FVC) are reduced. Work of breathing is increased.
Static lung volumes reveal a restrictive lung defect with most lung volumes decreased
but in particular expiratory reserve volume (ERV) is significantly reduced. The reduction
in FRC leads to airway closure, atelectasis and pathologic low V/Q and shunt and
hence hypoxemia. These mechanisms can result in significant hypoxemia but were not
described by many candidates.

The second part of the question concerning the cardiovascular consequences of C6

transection was better answered. Areas that required mention in this section included
the early massive sympathetic outflow and hypertension via the release of
catecholamines from the adrenal medulla. Neurogenic shock is also seen due to
interruption of the sympathetic outflow and impaired reflex vasoconstriction secondary
to hypotension of any cause. Finally the loss of sympathetic innervation of the heart (T1-
T4) results in unopposed parasympathetic cardiac stimulation and bradycardia and
bradyarrthymias.

Question

Describe the physiology of cerebrospinal fluid (CSF). (70% of marks) Describe the
anatomy relevant to the performance of a lumbar puncture. (30% of marks)

Report

Most candidates performed well in this question. The physiology of cerebrospinal fluid
(CSF) required candidates to write about CSF formation, circulation and absorption,
compare the composition of CSF to plasma and describe normal volumes and
pressures. The functions of CSF also need to be listed. Some candidates described the
displacement of CSF when intracranial pressure rises as a function of CSF. No marks
were given for this.

The best approach to the anatomy of a lumbar puncture was to describe the lumbar
intervertebral space at which the lumbar puncture is done and then describe the
anatomical structures that the needle would traverse from the skin to the subarachnoid
space. Mentioning the indications for a lumbar puncture was not required.

Question

Outline the physiological consequences of therapeutic hypothermia at 32 degrees

Celsius 

Report

It is well documented and often stressed that the Primary Exam is focused upon the
basic sciences that underpin clinical Intensive Care. It will examine a candidates
understanding of, for example, the physiology associated with a clinical circumstance.
Many candidates discussed why we use therapeutic hypothermia after cardiac arrest
rather than outline the physiological consequences of hypothermia at 32 degrees
Celsius, for which they would not have scored any marks. A good answer was expected
to outline changes in metabolism as well as specific organ responses such as
cardiovascular (e.g. bradycardia; vasoconstriction; decreased cardiac output, etc),
respiratory (decreased minute volume; haemoglobin-oxygen dissociation curve moves
left; increased anatomical dead space; diminished HPV; increased pulmonary vascular
resistance, etc), renal (e.g. diuresis, changes to GFR, etc) as well as other organs.
Again candidates failed to synthesize a coherent and detailed answer. 

Question

Outline the motor and sensory pathways involved in withdrawing the lower limb from a
painful stimulus.
Report

A good answer required a description of the sensory pathway(s) (eg nociceptors, A-

delta

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

Question

Using a diagram, explain the effect of PaO2, PaCO2 and MAP (mean arterial pressure)
on cerebral blood flow (60% marks). Outline the effects of propofol and ketamine on
cerebral blood flow (CBF), cerebral metabolic requirement for oxygen (CMRO2), and
cerebral venous oxygen saturation (40% marks).

Report

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.

Question

Outline the production, release, and fate of noradrenaline at the sympathetic nerve
terminal.
Report

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 exucytosis in
response to an action potential. Noradrenalin 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.

Question
 Outline the consequences of mild hypothermia in a patient following major surgery
Report

 This is another very important, and not an infrequently seen, aspect of almost daily intensive care practice which was poorly understood by
candidates. For a good answer candidates were expected to outline pharmacological (eg alteration in drug behaviour), physiological (eg
shivering, vasoconstriction, impaired coagulation, etc) consequences. Additional points such as poor wound healing, discomfort also
attracted a small number of marks. Candidates would have benefited by illustrating their answers with examples, eg prolonged recovery from
anaesthesia and duration of neuromuscular blokade.

Question

Describe the physiology of intracranial pressure and the physiological mechanisms that
limit a rise in intracranial pressure 

Report

Candidates who did well in this question used graphs to describe the various concepts,
described normal physiology and covered the breadth of the topic. A good answer made
mention of normal values of ICP, it’s variation with respiration and blood pressure and
illustrated a trace of the ICP. An explanation of the Monroe Kelly doctrine was expected,
CSF production and absorption and it’s relationship to raised ICP as well other
compensatory mechanisms for a high ICP (eg displacement of CSF into spinal canal,
displacement of venous blood into the jugular veins, rise in ICP leads to ischaemia if the
brain. Critical ischaemia invokes the Cushing reflex.
Major omissions by candidates was the use of diagrams, description of normal variation
and only a superficial knowledge of compensatory mechanisms.

Question

Describe the formation, circulation and functions of cerebrospinal fluid

Report

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. 

Question

Describe the clinical findings you would expect to see in a patient who underwent acute
hemisection of the spinal cord at the upper thoracic level

Report

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. 

Question

 Outline the physiological factors that influence cerebral blood flow.

Report

The main points expected for a pass were : 

 Description of the relationship of CO2, O2, MAP and cerebral metabolism with cerebral blood flow.  The use of
graphs, correctly labelled and associated free text would be an effective means of portraying this information
 the effect of other factors such as intracranial pressure, cerebral venous pressure, vascular calibre, blood viscosity
and regional blood flow differences
Question

Describe the formation, flow and absorption of cerebrospinal fluid.

Report
The main points expected for a pass were :
 CSF is formed by ultrafiltration and secretion
 CSF volumes and turnover
 Flow through the ventricles and subarachnoid spaces
 Absorption through the arachnoid villi
 Relationship between absorption and pressure
This is not a question about intracranial pressure so no points were given for Munroe Kellie doctrine etc.  Also, no
points were functions of CSF.
Diagrams need to have the axes labelled correctly.