2020B

2020 (2nd sitting)

Question 1

Question

Describe and compare the action potentials from cardiac ventricular muscle cells and the sino-atrial node.

Example answer

Pacemaker vs myocyte action potential

	Myocyte	Pacemaker
Resting potential	-90 mV	No set RMP but minimum potential is around -60 mV
Threshold potential	-70 mV	-40 mV
Phases of AP
Phase 4	- Resting membrane potential (-90mV) - Maintained by inward rectifying K current	- Slow depolarisation (drift) to threshold (-40mv) -Funny current Na influx, slowing K efflux
Phase 0	- Rapid depolarisation at threshold (-70mV) - Fast voltage gated Na opens (influx) > depolarisation -Peak around +40mV	- Depolarisation (slower relative) - L type Ca channels open (influx) -Peak around +20mV
Phase 1	- Partial repolarisation - Na close (stops influx), K opens (efflux)	No Phase 1
Phase 2	- Long Plateau (100-200ms) - L type Ca channels opens (influx) which balances K efflux	No phase 2, no plateau
Phase 3	- Rapid repolarisation to membrane potential (~-90mv) - L type Ca channels close, continued K efflux	- Rapid repolarisation -K open (efflux), Ca close (stops influx)

File:Https://derangedphysiology.com/main/sites/default/files/sites/default/files/old image pile/Neurocritical-care/images/comparison of ventricular myocyte and pacemaker action potentials 3.jpg

image-20220202114143450image-20220202114127372

Examiner comments

72% of candidates passed this question.

This question details an aspect of cardiac physiology which is well described in multiple texts. Comprehensive answers included both a detailed description of each action potential and a comparison highlighting and explaining any pertinent differences. The question lends itself to well-drawn, appropriately labelled diagrams and further explanations expressed in a tabular form. Better answers included a comparison table with points of comparison such as the relevant RMP, threshold value, overshoot value, duration, conduction velocity, automaticity, ion movements for each phase (including the direction of movement) providing a useful structure to the table. Incorrect numbering of the phases (0 â€“ 4) and incorrect values for essential information (such as resting membrane potential) detracted from some responses

Online resources for this question

Question 2

Question

Define functional residual capacity (10% marks). Outline the functions (70% marks) of the functional residual capacity and the factors affecting it (20% marks).

Example answer

Functional residual capacity

The volume of gas in the lungs at end-expiration during tidal breathing
Typically ~30mls/kg (or ~2.1L in 70kg adult)
Sum of the residual volume and expiratory reserve volume
Represents the point at which the elastic recoil force of lung, and the expanding elastic force of the chest wall are equal

Functions/role of FRC

Oxygen reservoir
- Maintains an oxygen reservoir > maintains oxygenation between breaths / periods of apnoea
- Prevents rapid changes in PaO2
Maintains small airway patency
- At FRC, the airway resistance is low
- Normally FRC > closing capacity (prevents atelectasis)
Reduces work of breathing
- At FRC, lung compliance is maximal and airway resistance is low
Minimises cardiac workload
- At FRC, pulmonary vascular resistance is minimal
Important starting point for measuring lung volumes

Factors effecting FRC

Lung size
- Increasing lung size = increasing FRC
- Thus affected by
  - Height (Taller FRC > shorter)
  - Age (adult FRC > children)
  - Gender (Male FRC > female)
Respiratory compliance
- Increase in compliance
  - e.g. emphysema, increased PEEP
  - Leads to increased FRC
- Decrease in compliance
  - E.g. ARDS, obesity, pregnancy
  - Leads to reduction in FRC
Age (increasing age generally increases FRC)
Anaesthesia
- Reduces FRC (multifactorial)
Posture
- FRC decreases when going from erect to supine position

Thus if FRC is reduced we will get

Reduction in
- Lung compliance
- oxygen reserves
- tidal volumes
Increase in
- airway resistance
- pulmonary vascular resistance
- atelectasis
- work of breathing
- V/Q mismatch

Examiner comments

79% of candidates passed this question.

This question was in two parts with the percentage of marks allocated an indication of the relevant time or detail expected per part. The second part of the question also contained two distinct headings which should have been used in the answer. As an outline question, dot points with a brief explanation of each point were expected. Most candidates drew diagrams, few of which added value. For a diagram to add value it should be accurate, have labelled axes, a scale with numerical values and units. As a general rule, diagrams should also be explained and help to illustrate or relate to a written point.
For factors affecting FRC, to score full marks, it should be clearly stated if the factor causes an increase or decrease in FRC. This topic is well covered in the recommended respiratory texts.

Online resources for this question

Question 3

Question

Describe the pharmacology of hydrocortisone.

Example answer

Name	Hydrocortisone
Class	Glucocorticoid (endogenous)
Indications	Glucocorticoid insufficiency, allergy/anaphylaxis/asthma, severe septic shock, immunosuppression (e.g. transplant, autoimmune dz)
Pharmaceutics	Tablet, white powder diluted in water
Routes of administration	IV, PO
Dose	50-200mg QID (commonly in ICU population)
Bio-equivalence	100mg hydrocort = 25mg pred = 20mg methypred = 4mg dex
Pharmacodynamics
MOA	Lipid soluble > crosses cell membrane > binds to intracellular steroid receptors > alters gene transcription > metabolic, anti-inflammatory & immunosuppressive effects in tissue-specific manner
Effects	CNS: sleep disturbance, psychosis, mood changes CVS: Increased BP (mineralocorticoid effect + increased vascular smooth muscle receptor expression to catecholamines) RESP: decreased airway oedema, increased SM response to catecholamines RENAL: Na + water retention (mineralocorticoid effect) Metabolic: Hyperglycaemia, gluconeogenesis, protein catabolism, fat lipolysis and redistribution, adrenal suppression MSK: Osteoporosis, skin thinning Immune: immunosuppression + anti-inflammatory effects (decreased phospholipase, interleukins, WBC migration and function) GIT: Increased risk of peptic ulcers
Pharmacokinetics
Onset	Peak effect 1-2 hours, duration of action 8-12 hours
Absorption	50% oral bioavailability
Distribution	90% protein bound, small Vd (0.5L/kg)
Metabolism	Hepatic > inactive metabolites
Elimination	Metabolites excreted renally. Elimination T/12 = ~1 hour
Special points	Risk of reactivation of latent TB / other infections

Examiner comments

69% of candidates passed this question.

Hydrocortisone is a level 1 drug in the syllabus. Most answers were well structured, many used key headings. In general, detailed information specific to hydrocortisone was lacking. Answers that focused on the mechanism of action, pharmacodynamic effects and pharmacokinetics effects which were detailed and accurate scored well. It was expected that significant detail be included in the sections with relevance to clinical practice for example, the mechanism of action and pharmacodynamic effects including the side effect profile. An indication/appreciation of the timelines of such was also represented in the marking template.

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Question 4

Question

Outline the role of the liver in the metabolism of fat (â…“ marks), carbohydrate (â…“ marks) and proteins (â…“ marks).

Example answer

Carbohydrate metabolism

Glycolysis
- Metabolises glucose to generates ATP + pyruvate.
- Pyruvate is converted to Acetyl Coa and enters the TCA cycle (aerobic) or is converted to lactate (anaerobic)
- Catabolic role
Glycogenesis
- The liver can store up to a 100g of glucose in the form of glycogen
- Stimulated by insulin (released from the pancreas) when BSLs are HIGH
- Anabolic role
Glycogenolysis
- Liver can mobilise stored glycogen to produce glucose via glycogenolysis
- Stimulated by glucagon (released from pancreas) when BSLs are LOW
- Catabolic role
Gluconeogenesis
- Liver can synthesise glucose from non-carbohydrate precursors (amino acids, lactate, glycerol)
- Stimulated by glucagon (released from pancreas) when BSLs are LOW
- Anabolic role

Fat metabolism

Lipid breakdown (B oxidation)
- In the liver, free fatty acids undergo B-oxidation to Acetyl CoA
- Acetyl Coa then enables energy production by entering Krebs Cycle
- Catabolic role
Lipid synthesis
- Lipids, including cholesterol, are synthesised in liver from Acetyl CoA
- Anabolic role
Lipid processing
- Apolipoproteins are synthesised in the liver and are responsible for processing of VLDL, LDL, HDL

Protein metabolism

Protein synthesis
- Liver is responsible for synthesis of most plasma proteins (except immunoglobulins)
- Anabolic role
Deamination
- Individual amino acids have their amino groups removed by liver > a keto acids > TCA cycle
- Catabolic role
Amino acid synthesis
- Keto-acids can be transformed into non-essential amino acids by transamination, forming new amino acids.
Urea formation
- Ammonia (end product of amino acid degradation) is converted to urea > excretion in urine

Examiner comments

54% of candidates passed this question.

This question relates to basic hepatic physiology and is well described in the recommended texts. The mark allocation and division of time was indicated in the question. Better answers used the categorisation in the question as an answer structure. Many candidates gave a good description of beta oxidation, the formation of Acetyl Co A and ketone synthesis. A description of the synthesis of cholesterol, phospholipids, lipoproteins and fatty acid synthesis from proteins and carbohydrates mainly using glycogen, glucose and lactate also received marks. Candidates seem to have a better understanding of fat and glucose metabolism than protein metabolism. Higher scoring candidates appreciated the anabolic and catabolic processes of each component.

Online resources for this question

Jenny's Jam Jar
CICM Wrecks
Basic Physiology for the Anaesthetist (simplest overview)

Question 5

Question

Describe the anatomy (70% marks) and effects (30% marks) of the sympathetic nervous system.

Example answer

Sympathetic nervous system (SNS)

Portion of the autonomic nervous
Provides involuntary control of many bodily functions

Anatomy of SNS

Preganglionic component
- Short, myelinated, preganglionic neurons
- Originate in the lateral horn of the spinal cord between T1 and L3 (thoracolumbar outflow)
- Travel via ventral roots and white rami communicantes to synapse in the ganglia
- Neurotransmitter is acetylcholine > nicotinic receptor
Ganglionic component
- Two types (prevertebral ganglia and paravertebral ganglia)
  - Paravertebral ganglia form the two sympathetic chains which extend along the vertebral column
  - Prevertebral ganglia are located in abdominal cavity around branches of aorta (e.g.. coeliac ganglia)
- Preganglionic neurons can synapse at ganglia above, below, at same level or directly to prevertebral ganglia
Post ganglionic component
- Long, unmyelinated, postganglionic neurons
- Leave the ganglia through the grey matter communicantes > effector tissue/organ
- Neurotransmitter is noradrenaline > adrenergic receptor
- There are exceptions e.g. Adrenal medulla: directly innervated by preganglionic neurons (ACh)

Effects of SNS

Organ	SNS
Heart	Increased chronotropy (B1) and inotropy (B1), increased lusitropy
Arterioles	Vasoconstrict (a1, a2)
Lung	Bronchodilation (B2)
GIT	Inhibition of peristalsis (predominately a1,a2)
Liver	Glycogenolysis (B2)
Renal	Increased renin release (B1)
Pupils	Dilation (a1)
Salivary glands	Inhibition of salivation
Adrenal gland	Release of norad and adrenaline
Bladder	Detrusor relaxation (B2), sphincter contraction (a1)
Sweat gland	Sweat (ACh)

Examiner comments

51% of candidates passed this question.

Most candidates had a suitable structure to their answers, those without a clear organisation of thought tended to gain fewer marks. In many cases incorrect information or limited detail, particularly around the anatomical organisation prevented higher marks.

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Question 6

Question

Classify the oral hypoglycaemic drugs (20% marks); include their mechanism of action (40% marks) and their most significant side effects (40% marks).

Example answer

Hypoglycaemic agents

Drug class	Example	Mechanism of action	Important side effects
Commonly used
Biguanides	Metformin	Multiple mechanisms of action. 1) Inhibits hepatic+renal gluconeogenesis 2) increases insulin sensitivity (increases GLUT4 receptors to increase peripheral utilisation), 3) Delayed glucose uptake from GIT	Lactic acidosis (higher risk with renal/liver impairment) due to increased glycolysis and impaired gluconeogenesis leading to lactatemia GIT upset (diarrhoea, nausea, vomiting)
Sulfonylureas	Gliclazide	Increase insulin secretion from pancreatic B cells , reduce insulin sensitivity	Risk of hypoglycaemia, GIT upset, blood dyscrasias
DPP-4 inhibitors	Sitagliptin	Inhibit DPP-4 (which normally breaks down GLP-1). GLP-1 stimulates insulin release from pancreas, reduces appetite, delays gastric emptying	Risk of hypoglycaemia Risk of pancreatitis
SGLT-2 inhibitors	Empagliflozin	Inhibits SGLT-2 receptors > decrease glucose reabsorption in the PCT	Osmotic diuresis (Polyuria, polydipsia, dehydration), euglycemic diabetic ketoacidosis, risk of hypoglycaemia, UTIs
Not commonly used
Alpha glucosidase inhibitors	Acarbose	Slows/prevents carbohydrate breakdown and absorption	GIT upset
Thiazolidineodiones	Pioglitazone	Increases insulin sensitivity via PPAR receptors in fat cells	Increased risk of heart failure
Meglitinides	Repaglinide	Similar to sulfonureas, though different receptor	Hypoglycaemia, sig. interaction with antifungals > high levels > hypos

GLP-1 agonists

Commonly given S/C
New oral agents are becoming available - not yet widely used in AUS

Examiner comments

37% of candidates passed this question.

High scoring answers most often started with a strong and logical structure and focused on the requested categories of information. Many candidates gave good answers across the wide range of drugs. Several candidates could have scored more highly by giving more correct information on biguanides and sulphonylureas.

Online resources for this question

Question 7

Question

Compare and contrast external ventricular drains and intraparenchymal fibreoptic pressure monitors.

Example answer

	External ventricular drain (EVD)	intraparenchymal catheter (e.g. codman)
Location/anatomy	Sits in the lateral ventricle. Inserted 2-3cm lateral midline ~10cm posterior to the nasion (Kochers point) aiming away from motor cortex	Sits in the brain parenchyma (2cm depth)
Method of measurement	Pressure transmitted to wheatstone bridge via fluid filled non compressible tubing.	Pisoelectric strain gauge pressure sensor, connected to monitor via fibreoptic cable
Calibration	Yes, can be zero'd post insertion to atmosphere	No, cannot be zeroed post insertion
Diagnostic (ICP)	Yes, gold standard.	Yes
Diagnostic (CSF sample)	Yes, can sample CSF	No, cannot sample CSF
Therapeutic (drain CSF)	Yes	No, cannot drain CSF
Sources of error	Migration of catheter tip, blockage of EVD, incorrect levelling to tragus, damping/resonance	Drift, only measures local ICP (not global ICP)
Advantages	Diagnostic (CSF sample, ICP) and therapeutic (high ICP), can be re-zeroed, cheaper	Easier to insert with less expertise, less complications (infection, haemorrhage)
Disadvantages	Increased risk of: trauma, infection, misplacement	Decreased risk of trauma, infection, haemorrhage. Not therapeutic. Cannot be recalibrated and prone to drift. More expensive. measures local ICP only

Examiner comments

22% of candidates passed this question.

This question is ideally suited to a tabular format, where candidates are expected to highlight the significant similarities and differences as well as why a certain monitor may be chosen in preference to another rather than compile two lists written next to each other. To score well in this question, a statement of what could be measured (ICP: global vs local), a description of the measurement principles, along with other measurement related information like calibration and sources of error was required. Also sought was information regarding anatomical placement (e.g., lateral ventricle for EVD) and method of placement.
Furthermore, a comparison with each other (e.g., higher infection/bleeding risk with EVD, greater risk of trauma due to size and insertion, expertise to insert, cost, therapeutic benefit, risk of blocking) was required for completion. Candidates who structured these elements into advantages and disadvantages were generally able to elucidate this information and score better.

Online resources for this question

Jennys Jam Jar
[chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/viewer.html?pdfurl=https%3A%2F%2Fcicmwrecks.files.wordpress.com%2F2021%2F05%2F2020-2-07.pdf&clen=256304&chunk=true CICM Wrecks]
Deranged Physiology

Question 8

Question

Describe the cough reflex.

Example answer

Cough

Complex, sudden expulsion of air from the airways
- Can voluntarily cough, however the cough reflex = involuntary

Purpose of cough reflex

Airway protective function
- Helps clear foreign material/noxious stimuli from the airway
N.B: Useful clinically in brain death testing

COUGH REFLEX

Sensors

Rapidly adapting mechanoreceptors, slowly adapting mechanoreceptors, and c-fibres

Stimulus for cough

Chemical, mechanical, noxious stimuli in the airways (larynx, trachea, carina, bronchi)
- e.g. leukotrienes, histamine, bradykinin, foreign bodies

Afferents

Afferents from the internal laryngeal nerve (br. of vagus nerve)

Integrator/controller

Vagal afferents synapse in the medullary respiratory centre (NTS)

Efferents

Diaphragm (via phrenic nerve)
Abdominal muscles (via spinal motor nerves)
Larynx (via laryngeal branch of vagus nerve)

Effector / mechanism

Coordinated action of respiratory, pharyngeal, abdominal muscles
Phase 1: inspiratory phase
- Deep inspiration to near vital capacity (muscles of inspiration, including diaphragm)
Phase 2: compressive phase
- Closure of the cords+epiglottis, contraction of the abdominal and intercostal muscles
- Leads to dramatic rise in intrapleural pressure (>100cmH₂O)
Phase 3: expulsive phase
- Sudden partial opening of the cords and epiglottis
- Leads to violent expiration of turbulent air removing foreign material

Examiner comments

62% of candidates passed this question.

Overall, this question was reasonably well answered. Those that performed well had suitably detailed knowledge and structured their responses which generally included a definition and purpose of the reflex as well as the identification and a description of the afferent, integrator/controller, and efferent limbs of the reflex. This structure allowed a logical platform for the elucidation of the detail required in the answer, including types of stimulus, receptors, nerves (for both limbs of the reflex) and the muscles used in the phasic response to be clearly articulated.

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Question 9

Question

Outline the daily nutritional requirements, including electrolytes, for a normal 70 kg adult.

Example answer

Energy intake

Most guidelines recommend around 25-30 kcal/kg of energy / day
- Approx 2000 kcal / day for average adult
Met with a combination of carbohydrates, protein, fats
Critically unwell patients, may need more due to increased energy expenditure.

Carbohydrates

Preferred substate for energy production
Average intake (adult) ~350g / day
- Minimum recommended intake >2g.kg.day
1g carbs = 4 kCal energy

Fats

Provides essential fatty acids (e.g. Omega 6 + 3 fatty acids)
Essential for synthesis of cell membranes and for fat soluble vitamins (A,D,E,K)
Recommended intake = 1g.kg.day (i.e. ~70g / day)
1g fat = 9kCal energy
Ideal carb : fat ratio not empirically known, but in practice we use ~70:30

Protein

Replaces essential amino acids (e.g. phenylalanine, valine, leucine) which cannot be produced in vivo
Recommended intake (healthy adult) = 1g.kg.day
- Critically ill patients will need more (1.5- 2g.kg.day - i.e. 100-140g/day)
1g protein = 4 kCal energy
Not typically included in the resting energy expenditure

Water / electrolytes

Water: 30ml/kg/day
Sodium: 1-2mmol/kg/day
Potassium: 1mmol/kg/day
Calcium: 0.1mmol/kg/day
Magnesium: 0.1 mmol/kg/day
Phosphate 0.4mmol/kg/day

Vitamins

Organic compounds that the body is unable to synthesise, though needs for cellular function
- Commonly enzyme cofactors, antioxidants, metabolic regulators
- Required in small amounts
Fat soluble
- A,D,E,K
- Excessive intake > toxicity
- Stored largely in liver
Water soluble
- E.g. vitamin C, B1, nicotinic acid, B12, folate
- Not readily stored - readily excreted in urine > less likely to be toxic

Trace elements

E.g. zinc, copper, iron, selenium, iodine
Needed for daily functioning in trace amounts

Examiner comments

40% of candidates passed this question.

This topic is well covered in the recommended physiology textbooks. Many answers unfortunately simply listed the various components without providing sufficient detail; outline questions require some context around the key points as opposed to just a list.
Most candidates had a good estimate for the basal energy requirements of a resting adult. Good candidates were able to outline the g/kg daily protein requirements and the distribution of remaining energy intake between carbohydrates and lipids and included how this may change during periods of stress. They also stated the energy derived per gram of each of those food groups. Few candidates mentioned the need to include essential amino acids. Similarly, with fat intake, few candidates mentioned the need for essential fatty acids. A definition of â€œvitaminâ€ would have received credit. Most candidates were able to classify vitamins as water soluble or fat soluble. Most candidates mentioned trace elements (with an abbreviated list) and mentioned bone minerals. A daily intake requirement for Na and K was expected, though not for bone minerals or trace elements.

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Question 10

Question

Describe the pharmacology of suxamethonium.

Example answer

Name	Suxamethonium (succinylcholine)
Class	Depolarising muscle relaxant
Indications	Facilitate endotracheal intubation during anaesthesia (i.e. RSI)
Pharmaceutics	Clear colourless solution (50mg/ml), needs refrigeration (4Â°C) or else lasts only a couple of weeks at room temp
Routes of administration	IV, IM
Dose	1-2 mg/kg (IV), 2-3 mg/kg (IM)
Pharmacodynamics
MOA	Binds to the nACh receptor on motor end plate > depolarisation. Cannot be hydrolyed by Acetylcholinesterase in NMJ > sustained depolarisation (i.e. Na channels remain in open-inactive state) > muscle relaxation
Effects	Flaccid paralysis.
Side effects	Major: anaphylaxis, suxamethonium apnoea, malignant hyperthermia Minor: hyperkalaemia, myalgia, bradycardia/arrhythmia Pressure: increased IOP, ICP, intragastric pressure.
Pharmacokinetics
Onset	Onset 30s - 60s, duration <10 mins
Absorption	-
Distribution	30% protein bound Vd = 0.02 L/Kg
Metabolism	Rapid hydrolysis by plasma cholinesterase's (~20% reaches NMJ)
Elimination	Minimal renal elimination (due to rapid metabolism)
Special points	May have prolonged duration of action with congenital or acquired (e.g. liver, renal, thyroid disease) pseudocholinesterase deficiency Treatment of malignant hyperthermia is with dantrolene (+ cooling + supportive care)

Examiner comments

63% of candidates passed this question.

This was a level 1 pharmacology question, and it represents core knowledge. The mechanism of action of suxamethonium and the interactions at the neuromuscular junction as well as pharmaceutics were areas that often required further detail. Few candidates mentioned the effects of suxamethonium on the autonomic nervous system. Another common omission related to the factors that reduce plasma cholinesterase activity beyond genetic deficiency (such as liver disease, renal failure, thyrotoxicosis). Pleasingly, there was generally a good understanding of role, dosing, side effect profile, pharmacokinetics and of special situations and limitations of use pertinent to this drug.

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Question 11

Question

Describe the changes in the circulatory system that occur during exercise.

Example answer

Exercise

Leads to increased oxygen demand (predominately skeletal muscle) and increased metabolic waste products which need to be cleared
Leads to many circulatory changes:

Cardiac output

Increased oxygen demand > increased CO (as CO is the main modifiable component of the oxygen delivery equation - Hb, Sats, PaO2 not readily changeable)
Most of the increased CO goes to skeletal muscle beds
Due to a combination of increased HR/SV
Increases 5-6x - from 5L/min up to 30L/min

Heart rate

Increased HR due to SNS mediated chronotropy
Max = 220-age

Stroke volume

Increased SV initially is due to
- Reduced afterload (skeletal muscle vasodilation > decreased peripheral vascular resistance)
- Increased preload (peripheral venoconstriction > increased venous return)
- SNS mediated inotropy

With increasing HR, SV will begin to decrease (due to reduced diastolic filling time)
- Plateaus at ~50% VO2max

Redistribution of blood flow

Vasodilation in skeletal muscle beds
- Mediated by local factors (hypoxia, CO2, Lactate, adenosine) which lead to vasodilation (to decrease resistance, thus increase blood flow)
- Also mediated by autonomic factors: SNS activation > B2 stimulation > vasodilation
Vasoconstriction of non working tissues
- SNS mediated vasoconstriction of GIT, Kidneys > blood flow directed to "working tissues"
Coronary blood flow
- Increases by metabolic autoregulation due to increased demand from increased inotropy/chronotropy
Cerebral blood flow
- Remains constant (autoregulation) - no increase in metabolic demand. Increased BP > myogenic vasoconstriction.

Increased oxygen extraction

Increased CO₂ and H+ and temperature in working skeletal muscle beds > right shift of the oxygen-Hb dissociation curve > increased O2 extraction (Bohr effect)

Blood pressure/s

Increased SBP (due to increased inotropy > increased CO)
Decreased DBP (due to reduced SVR from skeletal vasodilation)
Widened pulse pressure (increased SBP, decreased DBP)
Overall increase in MAP (increase in CO is greater than reduction in PVR)

Other haemodynamics

Increased venous return > increased CVP and PCWP

Examiner comments

22% of candidates passed this question.

This is an applied physiology question. Better answers categorised the changes in some manner and included a measure of the degree of change as applicable (e.g., what increases, what decreases and what may stay the same). The question was to describe the changes so that the detail behind the mechanisms enabling these changes to occur was expected (e.g., neurohumoral, local factors). Marks were also awarded for any regional variation that occurs

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Question 12

Question

Describe the physiology (50% marks) and pharmacology (50% marks) of albumin.

Example answer

Albumin physiology

Structure
- Human plasma protein
- 69kDa
Synthesis
- Synthesised in the liver (~10-15g/day)
- Decreased synthesis: liver disease, protein malnutrition, sepsis/infection (prioritises other Acute Phase Reactants)
Distribution
- Accounts for ~50% plasma proteins
- 40% intravascular, 60% extravascular (skin, muscle, liver)
Functions
- Osmotic pressure - accounts for majority (80%) of plasma oncotic pressure
- Transport / drug binding (mainly acidic drugs)
- Acid-base buffer (protein-buffering system)
- Detoxification role
Breakdown
- Broken down by cysteine protease into amino acids
- Half life ~20 days
Elimination
- Elimination half life 16 hours
- Increased loss with renal dysfunction (e.g. nephropathy)

Albumin Pharmacology

Name	Albumin
Class	colloid (human plasma protein)
Indications	Intravascular volume replacement, low albumin, hepatorenal syndrome, SBP
Pharmaceutics	4% or 20% concentrations. Hypotonic -Collected by blood donation (whole blood, plasma apheresis) > fractionated > pasteurised > partitioned > stored.
Routes of administration	IV
Pharmacodynamics
MOA	Related to volume of fluid (i.e. volume expansion) and role of albumin (oncotic, transport, etc)
Side effects	No risk of bacteria/parasite infections (destroyed during processing), but risk of blood borne viruses (HIV, HepB, HCV) remains. Allergy, fluid overload.
Pharmacokinetics
Absorption	IV only (0% oral bioavailability)
Distribution	Rapid distribution within intravascular space. Small Vd - about 5% leaves per hour
Metabolism	Cellular proteolysis by cysteine protease
Elimination	Degradation by liver and reticuloendothelial system
Special points	- May worsen outcomes in TBI - No need for blood cross matching

Examiner comments

19% of candidates passed this question.

The question required an equal treatment of the physiology and pharmacology of albumin. The physiology discussion needed to include synthesis, factors affecting synthesis, distribution in the body (including the proportion divided between the plasma and interstitial space), functions, breakdown, and elimination half-life. Discussion of the pharmacology should have included available preparations (4% and 20% Albumin) and pharmaceutics, distribution, elimination (both the protein and crystalloid components), mechanism of action to expand the plasma compartment, longevity in the plasma compartment, indications, and adverse effects. Oedema, circulatory overload, immunological reactions, and relative contraindication in brain injury were important to mention. There was some confusion regarding the infectious risks of albumin. An outline of the manufacturing process from donated plasma and pasteurisation was expected.

Online resources for this question

Deranged Physiology
Jennys Jam Jar
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Question 13

Question

Describe the anatomical (20% marks) and physiological (80% marks) features of the pulmonary circulation.

Example answer

Anatomical features (pulmonary circulation)

Low pressure, low resistance, high capacitance, high flow system
- Thus --> vessel walls are highly elastic + have less muscle + much thinner than systemic circulation
Circulation
- RV > Pulmonary trunk > R/L pulmonary artery > progressively smaller pulmonary arteries > capillaries > progressively larger pulmonary veins > pulmonary veins x4 > LA
- Arteries and veins travel with respective bronchi, nerves and lymphatics in bronchovascular bundle

Physiological features (pulmonary circulation)

Low pressure system
- Normal PA
  - Systolic pressure 15-25mmHg
  - Diastolic pressure 8-15mmHg
  - Mean pressure 10-15mmHg
- Pulmonary venous pressure ~8-10mmHg
Low resistance system
- ~100-200dynes/sec/cm-5
- ~10% of systemic circulation
- With further flow (e.g. increased CO during exercise) can maintain low resistance by recruitment of additional capillaries
High flow system
- Pulmonary arterial flow = cardiac output
- Needs capacity to expand (highly elastic) with increasing CO
Volume
- Contains ~10% circulating blood volume (~500mls)
- Has capacity to expand (highly elastic, recruit additional capillaries)
Regional distribution of blood flow
- Right lung receives 55% CO, left lung 45% CO
- Flow distributed according to hydrostatic and alveolar pressure (west zones)
- Hypoxic pulmonary vasoconstriction can redirect blood flow away from poorly ventilated regions
Regulation
- Minimal capacity to self regulate (except for hypoxic vasoconstriction) with weak autonomic activity
- Response to hypoxia: vasoconstriction
- Response to hypercapnia: vasoconstriction
Functions
- Main function is gas exchange: Absorbs O2, releases Co2
- Other functions: filtration clots/debris, source of ACE, metabolism of PGs

Examiner comments

25% of candidates passed this question.

The examiners consider that an understanding of the pulmonary circulation is core area of the syllabus. In general, the anatomy section was better answered than the physiological features. As well as a description of the gross anatomy of the pulmonary circulation tracking it from the pulmonary valve to the left atrium, some mention of the microscopic anatomy was required (e.g., that the pulmonary arteries are thin walled with little smooth muscle).
For the second part of the question, a breadth of knowledge was required. Candidates were expected to address the following physiological features of the pulmonary circulation: volume, pressure, resistance, regulation and regional distribution and function. Marks were apportioned to each section, so it was important to write something on each section. Focussing on one section in detail (e.g., a very detailed description of Westâ€™s Zones) usually came at the expense of missing one or more of the other sections, most commonly the functions of the pulmonary circulation. Indeed, candidates that scored well provided information on each section and for the functions of the pulmonary circulation mentioned more than gas exchange.

Online resources for this question

Question 14

Question

Describe the anatomy of the larynx.

Example answer

General anatomy
- Located at the levels of C3- C6
- Serves as a connection between the oropharynx and the trachea
- Lined by pseudostratified columnar ciliated epithelium below cords, stratified square epithelium above
General functions
- Respiration (conductive airway)
- Swallowing and protection of airway from GI tract
- Phonation
- Cough reflex
Cartilages
- 3 Paired: arytenoid, corniculate, cuneiform
- 3 unpaired: thyroid, cricoid, epiglottis
Extrinsic muscles
- Infrahyoid and suprahyoid muscles
- move the larynx as a whole (elevates, depresses)
Intrinsic muscles
- Move individual laryngeal components
- Grouped into: adductors/abductors (e.g. cricoarytenoids, oblique arytenoids), tensors/relaxors (e.g. cricothyroid, thyroarytenoid) and the vocalis muscle (minute adjustments vocal cord)
Vocal ligament
- Attaches to thyroid cartilage (ant) to arytenoid cartilage (post)
- Opening forms the Rima Glottis
- Produces phonation
relations
- Skin/fascia (anterior)
- Thyroid gland (anterior, lateral and inf.)
- pharynx/oesophagus (posterior)
- Carotid arteries (lateral), jugular veins (lateral)
- Vagus and laryngeal nerves (lateral)
Innervation
- Motor: All laryngeal muscles are supplied by the RLN except the cricothyroid which is supplied by the External branch of the superior laryngeal nerve
- Sensory: internal branch of the superior laryngeal nerve (above cords), RLN (below cords)
Arterial supply
- Upper half: Superior laryngeal artery (br. from the superior thyroid artery)
- Lower half: Inferior laryngeal artery (br. of the inferior thyroid artery)
Venous drainage
- Superior and inferior laryngeal veins which drain into respective thyroid veins
Lymphatics
- Above the vocal cords: superior deep cervical LNs
- Below the vocal cords: inferior deep cervical LNs

Examiner comments

40% of candidates passed this question.

For this question, candidates were expected to address the location of the larynx, its relations, the cartilages (single and paired), ligaments, muscles (intrinsic and extrinsic), innervation (sensory and muscular) and blood supply (including venous drainage). Marks were apportioned to each section, so whilst some detail was required, breadth of knowledge was also important. Most candidates had a grasp of the gross anatomy, the main relations and at least the innervation provided by the recurrent laryngeal nerve. However, an understanding of the functional anatomy of the cartilages was not always apparent. It should be noted that not every single muscle needed to be named (especially for the extrinsic muscles), but an understanding of the major muscle groups should have been included

Online resources for this question

Question 15

Question

Compare and contrast the pharmacology of dobutamine and levosimendan.

Example answer

Name	Dobutamine	Levosimendan
Class	Synthetic catecholamine (inodilator)	Calcium sensitizer (Inodilator)
Indications	Increase inotropy in cardiogenic shock, cardiac stress testing	Increase inotropy in cardiogenic shock
Pharmaceutics	Clear colourless solution (12.5mg/ml) Diluted in water	Diluted in glucose, clear-yellow
Routes of administration	IV	IV, PO
Dose	Infusion (0.5-20 ug/kg/min)	Load, then infusion
pKA	10.4	6.3
Pharmacodynamics
MOA	B1 and B2 agonist (B1>> B2)	- Sensitises troponin C to calcium > increases contractility (without impairing relaxation) - Activates ATP-sensitive K channels in smooth muscle > vasodilation
Effects	CVS: increased inotropy, increased chronotropy, increased lusitropy, increased dromotropy, decreased SVR, increased BP, increased risk arrhythmias, increased myocardial oxygen requirement RESP: bronchodilation, CNS: Increased CBF RENAL: Increased RBF	Increased chronotropy, increased inotropy, coronary vasodilation, decreased afterload, increased SV and CO, decreased SVR, decreased blood pressure and myocardial oxygen consumption, hypotension, arrhythmias, GIT upset, dizziness
Pharmacokinetics
Onset	Immediate	1 hour
Absorption	0% oral bioavailability	85% oral bioavailability
Distribution	Small Vd (0.2L/Kg) Unknown protein binding	Small Vd (0.3L/kg) 99% protein bound
Metabolism	Hepatic and tissue metabolism COMT/MAO > inactive metabolites	By liver into inactive metabolites (95%) and active metabolites (5%)
Elimination	Renal (70%) and faecal (20%) excretion of metabolites T 1/2 = 2mins	Renal elimination of metabolites (active metabolites last as long as 80 hours)
Special points	Does not require SAS approval	Requires SAS approval in AUS

Examiner comments

41% of candidates passed this question.

The objective of this question was that candidates relay a detailed knowledge of both drugs with respect to their individual pharmacology highlighting the important clinical aspects of each drug (e.g., mechanism of action, metabolism, duration of effect). Then an integration of this knowledge was in the contrast section where the better candidates highlighted features of the drug that would influence when or why one may use it with respect to the second agent. Tabular answers of the pharmacology of each drug without any integration or comparison scored less well. A detailed knowledge of both agents was expected to score well.

Online resources for this question

Question 16

Question

Describe the formation of gastric acid (50% marks) and the regulation of gastric acid secretion (50% marks).

Example answer

Gastric acid

Gastric acid (HCl, pH 1.6) is one component of gastric secretions
Other components include: Gastrin, pepsinogen, IF, mucous
~2L of gastric secretions produced per day
Gastric acid is important for innate immunity, pepsin activity, iron absorption etc.

Formation of gastric acid

Produced by the parietal cells in the stomach
Mechanism of HCl production
- CO2 diffuses into parietal cells from blood
- CO2 reacts with water to give H2CO3 (catalysed by CA)
- H2CO3 dissociates into H+ and HCO3
- At the basolateral membrane: HCO3 is exchanged for Cl (Cl in, HCO3 out)
- Cl then passively diffuses down concentration gradient into secretory canaliculi
- At the apical membrane: H-K ATPase pumps H+ into secretory canaliculi (against concentration gradient)

Stages of secretion

Cephalic
- ~30% of gastric secretions as a result of this phase
- Due to thought / taste / sight / smell of food
- Leads to increased PSNS (vagal) activity
Gastric
- ~60% of gastric secretions during this phase
- Due to the mechanical stretch of the stomach by the food
- Leads to increased PSNS activity and gastrin release
Intestinal
- <10% of gastric secretions during this phase
- Distention of small intestine --> release of secretin
- Increased acid load in duodenum --> release of somatosatin

Regulation of gastric acid secretion

Histamine
- Most important stimulus for gastric acid secretion
- Synthesised and stored in neighbouring ECL cells
- Binds to H2 receptors on parietal calls > HCl release
- Stimuli: PSNS activity + gastrin
PSNS (vagal) activity
- Vagal nerve stimulation of M3 receptors (Ach) on parietal cells > increased release HCl
- Vagal stimulation of ECL cells > increased release histamine
Gastrin
- Released from G cells
- Indirectly leads to increased release of histamine from ECL cells
- Activated by vagus, Inhibited by secretin
Somatostatin
- Released from D cells
- Inhibits gastrin
Secretin
- Released from S cells
- Inhibits gastrin

Examiner comments

26% of candidates passed this question.

The is question was divided into two sections offering equal marks. The first section required a description of the generation and transport of both H+ and Cl- into the stomach lumen by the parietal cell. The contributions of basolateral and luminal ion channels, the role of carbonic anhydrase and accurate description of the net flux was expected for full marks. The second section required comments on the roles of neural and endocrine regulation. Increased acid secretion via acetylcholine (via muscarinic M3), histamine (via H2) and gastrin were expected as was reduced secretion via secretin and somatostatin. Better responses were able to combine and integrate these into cephalic, gastric, and intestinal phases. The nature and function of other gastric secretions and the role of pharmacologic agents was not asked for and therefore not awarded any marks.

Online resources for this question

Question 17

Question

Describe the pharmacology of inhaled nitric oxide (NO).

Example answer

Name	Nitric oxide
Class	Inorganic gas / inhaled pulmonary vasodilator
Indications	ARDS, Right heart failure, pHTN
Pharmaceutics	Colourless gas (100ppm NO, 800ppm N2) in aluminium cylinders
Routes of administration	Inhaled (via the inspiratory limb of an ETT)
Dose	Typically 5-20ppm - titrated to minimal effective dose
Pharmacodynamics
MOA	Stimulates cGMP > reduction in intracellular Ca > relaxation of SM. As inhaled > selectively vasodilates well ventilated alveoli
Effects	RESP: Inhibits HPV, improves V/Q matching, CVS: decreased pulmonary vascular resistance, CNS: Increased CBF
Side effects	Methaemoglobinaemia hypotension Rebound pHTN following abrupt cessation Thrombocytopaenia
Pharmacokinetics
Onset	Seconds
Absorption	Rapidly absorbed in pulmonary circulation due to high lipid solubility
Distribution	Minimal systemic distribution
Metabolism	Reacts with oxyHb to produce methaemaglobin and nitrates. T 1/2 5 seconds
Elimination	Metabolites (main metabolite = nitrate) are renally excreted
Special points

Examiner comments

24% of candidates passed this question.

Nitric Oxide (NO) is an inorganic colourless and odourless gas presented in cylinders containing 100/800 ppm of NO and nitrogen. Many candidates mentioned oxygen instead of nitrogen. The exposure of NO to oxygen is minimized to reduce formation of nitrogen dioxide and free radicals. Hence it is administered in inspiratory limb close to the endotracheal tube. Many candidates did not mention the contraindications/caution for NO use. Candidates generally did well in mentioning the impact on improving V/Q mismatch by promoting vasodilatation only in the ventilated alveoli and reducing RV afterload. Many candidates did not mention the extra cardio-respiratory effects. The expected adverse effects of NO were nitrogen dioxide related pulmonary toxicity, methemoglobinemia and rebound pulmonary hypertension on abrupt cessation. Pharmacokinetics of NO carried a significant proportion of marks. It was expected that the answers would involve mention of location of delivery of NO in inspiratory limb and reason behind it, the high lipid solubility and diffusion, the dose (5-20ppm), very short half-life of < 5 seconds and combination with oxyhemoglobin to produce methaemoglobin and nitrate. The main metabolite is nitrate which is excreted in urine.

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Question 18

Question

Define afterload (10% marks) and describe the physiological factors that may affect afterload on the left ventricle (90% marks).

Example answer

Afterload

Isolated muscle: The external force required to be generated before the myocardial sarcomere can begin to shorten in the isolated muscle.
Intact heart: the forces impeding ejection of blood from the ventricle during contraction

Change in afterload

Decreased afterload --> increased LV stroke volume --> increased CO
Increased afterload --> reduced LV stroke volume --> reduced CO

Factors effecting afterload

Broadly, the factors effecting afterload can be broken up into factors effecting
- Mycocardial wall stress
- Impedance to flow

MYOCARDIAL WALL STRESS (governed by the law of LaPlace)

Transmural pressure
- Negative intrathoracic pressure > increased transmural pressure > increased afterload
- e.g. inhalation (more pronounced in asthma)
Ventricular size
- Increased radius of ventricle > increased wall stress > increased afterload
- e.g. ventricular dilation
Myocardial wall thickness
- Increased thickness > reduced wall stress (more sarcomeres share tension) > reduced afterload
- e.g. LV hypertrophy

IMPEDENCE TO FLOW

Arterial compliance
- Poorly compliance vessels > increased afterload
- e.g. in pathology such as atherosclerosis
Arterial resistance/impedance
- Related to (Hagen-Poiseuille equation)
  - the length of the arterial system (fixed)
  - blood viscosity (e.g. HCT, changes slowly)
  - Vessel radius (most important factor, changes readily)
- E.g. profound vasoconstriction of capacitance vessels (e.g. norad infusion) > increased resistance > increased afterload
Outflow tract impedance
- Leads to increased afterload (increased forced required for ejection)
- E.g. valvular disease (AS), SAM, LVOT

Examiner comments

53% of candidates passed this question.

Afterload can be defined as factors resisting ventricular ejection and contributing to myocardial wall stress during systole. Most answers utilised the law of Laplace to expand upon factors affecting ventricular wall tension. Systemic vascular resistance was commonly mentioned, but less frequently defined. Aortic and left ventricular outflow tract impedance were commonly referred to. Effects of preload and neurohumoral stimuli were less well outlined. Description of factors affecting right ventricular afterload and depictions of left ventricular pressure volume loops earned no extra marks unless directly referenced to the question.

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Question 19

Question

Explain how the kidney handles an acid load.

Example answer

Acid production

Normal biproducts of cellular function and metabolism
'Fixed acids'
- Body produces ~1mmol/kg/day
- Fixed acids, except for lactate, are eliminated by the kidneys
'volatie acids' (i.e. CO2)
- Body produces ~15-20moles/day
- Eliminated by the lungs

Mechanisms of acid-base regulation by kidneys

Secretion of H+ / Reabsorption of HCO3
- H+ activately secreted into the urine
  - Na-H exchanger (PCT, LOH)
  - H+ ATPase (DCT)
  - H-K ATPase (CD)
- HCO3 is freely filtered at glomerulus (needs to be reabsorbed)
- H+ and HCO3 combine to form H2CO3
- H2CO3 converted to H2O and CO2 (by apical carbonic anhydrase)
- H2O aand CO2 diffuse into cell and converted back to H2CO3 by CA
- H2CO3 then dissociates into HCO3 and H+ (HCO3 reabsorbed, H+ is secreted once more)
- This allows for all HCO3 to be reabsorbed

Combination with titratable acids
- Excess H+ combines with filtered buffers (e.g. phosphate, sulphate)
- Phosphate is most important and is responsible for eliminating ~40% of excess fixed acid load / day
  - H+ combines with HPO4 > H2PO4 (ionised, not reabsorbed)
- Minimal capacity to increase
Ammonium mechanism
- Excess H+ can bind to ammonia > excreted
  - in PCT/DCT: metabolism of glutamine > releases new HCO3 and excess NH4
  - In CD: secretion of NH3 binds to H+ > NH4 (ionised and cannot be reabsorbed)
- Accounts for remainder of excess fixed acid load,
- Has capacity to greatly expand when there is excess H+

Examiner comments

51% of candidates passed this question.

This question required candidates to understand the renal response to an acid load. It was expected that candidates would answer with regard to recycling of bicarbonate in the proximal tubule, excretion of titratable acid via the phosphate buffer system and generation of ammonium and its role in acid secretion. Many candidates had a good understanding of the bicarbonate system but used this to explain the secretion of new acid.

Online resources for this question

Question 20

Question

Describe the pharmacology of intravenous sodium nitroprusside.

Example answer

Name	Sodium nitroprusside
Class	Nitrate vasodilator
Indications	Hypertensive emergencies (or need for strict BP control)
Pharmaceutics	IV solution (50mg/2mL) Light sensitive
Routes of administration	IV only
Dose	Titrated to effect (0-2mcg/kg/min)
pKA	3.3
Pharmacodynamics
MOA	Prodrug Diffuses into RBCs and reacts with Oxy-Hb to produce NO NO diffuses into cell > incr cGMP > decreased Ca > SM relaxation
Effects	CVS: decreased BP, afterload RESP: impairs HPVC CNS: cerebral vasodilation GI: ileus metabolic: acidosis
Side effects	headache, hypotension, rebound hypertension (abrupt withdrawal), cyanide toxicity (high doses), metabolic acidosis, hypoxia, raised ICP
Pharmacokinetics
Onset/offset	Immediate onset + offset
Absorption	0% oral bioavailability
Distribution	VOD 0.25L/Kg (confined intravasc). Nil protein binding
Metabolism	Nitroprusside > cyanide > prussic acid > thiocyanate
Elimination	Metabolites via urine
Special points

Examiner comments

49% of candidates passed this question.

This was a straightforward pharmacology question relating to a relatively common and archetypal intensive care medication. The structure of the question was well handled by most of the candidates; easily falling into the classic pharmaceutics, pharmacokinetic and pharmacodynamics framework. Many candidates had a superficial knowledge of the presentation and formulation of the drug, aside from its light sensitivity. Better answers detailed the drug according to the above-mentioned framework but also accurately highlighted specific points relevant to the ICU practise such as the metabolic handling of sodium nitroprusside and relating this to the consequences of the various metabolic products.

2020 (2nd sitting)

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