2021A

2021 (1st sitting)

Question 1

Question

Describe the pharmacology of adrenaline.

Example answer

Name	Adrenaline
Class	Naturally occurring catecholamine
Indications	Haemodynamic support, anaphylaxis, bronchoconstriction/airway obstruction
Pharmaceutics	Clear solution, light sensitive (brown glass), 1:1000 or 1:10,000
Routes of administration	IV, IM, INH, ETT, Topical, subcut
Pharmacodynamics
MOA	Non-selective adrenergic receptor agonist. At low doses B effects dominate, at high doses alpha dominate. Adrenaline > a-1 receptor > increased IP3 (2nd messenger) > increased Ca Adrenaline > B1,B2,B3 receptors > increased cAMP (second messenger)
Effects	CVS: vasoconstriction (high doses), vasodilation (low doses), increased inotropy + chronotropy RESP: bronchodilation, increased minute ventilation METABOLIC: hyperglycaemia (glycogenolysis, lipolysis, gluconeogenesis) CNS: increased MAC GIT: decreased intestinal tone/secretions
Side effects	Extravasation > tissue necrosis, pHTN due to increased PVR, hyperglycaemia, tachyarrhythmias,
Pharmacokinetics
Absorption	Zero oral bioavailability due to GIT inactivation. variable/erratic ETT absorption.
Distribution	Poor lipid solubility, doesn't cross BBB, crosses placenta
Metabolism	Metabolised by MAO (mitochondria) and COMT (liver, blood, kidney) to VMA and metadrenaline
Elimination	T 1/2: ~2 mins (due to rapid metabolism) Metabolites (above) are excreted in the urine

Examiner comments

90% of candidates passed this question.
Adrenaline is a level 1 drug and is commonly used in intensive care. A comprehensive explanation of the drugs MOA, PK, PD and side effect were expected. Candidates who scored well generally provided a factually accurate, detailed and well-structured answer. Overall, the quality of answer provided for this question was of a high standard.

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Question 2

Question

Describe the work of breathing and its components.

Example answer

Work of breathing

Energy used by the respiratory muscles during respiration
Work of breathing (joules) = pressure x volume
Normally ~0.35 J/L (approx 2% BMR)
Can be represented using pressure-volume curves

Components

Elastic work (~70%)
- Force required to overcome the elastic forces of the chest wall, lung parenchyma, and alveoli surface tension
- Elastic resistance increases with increasing tidal volumes
- Energy is stored as elastic potential energy and used on expiration
- Factors increasing elastic work:
  
  e.g. obesity, chest wall deformities, circumfrential burns etc.
  
  e.g. loss of surfactant in ARDS
Non elastic (resistive) work (~30%)
- Derived from airway resistance (majority; 80% of non elastic work) and viscous tissue resistance (e.g. lung sliding over chest wall)
- Airway resistance increases with increased RR (frequency dependence of work of breathing) or smaller airway diameter (e.g. bronchospasm)
- Energy is lost as heat

Work of breathing during a tidal volume breath (ref to fig below)

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Examiner comments

24% of candidates passed this question.
This is a core topic within respiratory physiology. There was a very low pass rate for this question. Expected components of the answer included: a definition of WOB as a product of pressure and volume or force and distance including the units of measurement; followed by a detailed explanation of the following three broad components â€“ elastic resistance, viscous resistance and airflow resistance. Further marks were awarded to situations where the energy for expiration increases beyond stored potential energy as well as the impact of respiratory rate and tidal volume on different aspects of the WOB. For example, the changes in TV will have relatively greater impact on the elastic component, whereas RR will impact the resistance component. Additional marks were awarded for describing the efficiency of breathing. A common area where candidates missed out on marks was producing a diagram of WOB without a description; many diagrams were often incorrectly drawn or had no axes labelled. There were many incorrect definitions or respiratory equations provided without any link to the written answer. Factual inaccuracy and limited depth of knowledge were also prevalent in poorly performing answers. Marks were not awarded for a description of the control of breathing.

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Question 3

Question

Outline the formation, structure, and function of the platelet.

Example answer

Formation/fate

Produced via thrombopoiesis
- Within the bone marrow, common myeloid progenitor cells differentiate into megakaryocytes
- Megakaryocytes are the largest cell of the bone marrow (50-150um), have multiple (up to 8) nuclei. They produce pro-platelets in their cytoplasm which break up into numerous smaller functional platelets. Each megakaryocyte produces ~5000 platelets each
- Thrombopoiesis takes ~10 days
- Thrombopoietin (produced primarily in the liver) stimulates the differentiation and release of plts
- Process regulated by negative feedback loop based on platelet count
Normally 150-400 x 10^9/L
Lifespan is 7-10 days
Utilised during clotting or removed by the reticuloendothelial system in the spleen or liver

Structure

Not true cells, but fragments of the Megakaryocyte cytoplasm
1-4 um in size, Irregular, No nucleus.
External glycocalyx later
Contain:
- Mitochondria
- Dense granules (ATP, ADP, calcium)
- Alpha granules (vWF, thrombin)
- Contractile elements (microtubules)

Function

Main function of platelets is haemostasis
Platelets are important for formation of the platelet plug (primary haemostasis)
- Platelet adhesion
  - Damage to blood vessel wall exposes vWF in the subendothelium
  - Glycoprotein receptor complex (GP1b-IX) on platelets bind to vWF (adhesion)
- Platelet activation
  - When exposed to Tissue Factor, collagen, and vWF the platelets become activated
  - Activated platelets
    - Change shape (Swell, become irregular, develop pseudopods) to enable aggregation
    - Release molecules (Thromboxane A2, ADP, Serotonin) which activates further platelets + vasoconstricts
  - Platelet aggregation
    - Activated platelets bind to fibrinogen and vWF to form a soft platelet plug
Platelets are also central to the cell based model of secondary haemostasis
- Initiation (less relevant to platelets)
- Amplification
  - Surface of activated platelets is primed with factors V, VIII, XI
  - Small amount of thrombin produced during initiation activates V, VIII and XI
  - XIa activates IX to IXa, which leads to formation of tenase complexes (accelerate thrombin production at platelet surface)
- Propagation
  - Begins with formation of tenase complexes on platelet surfaces (IXa-VIIIa)
  - Leads to increased rate of Factor X activation
  - The large amounts of Xa interacts with factor Va forming prothrombinase complex (Va-Xa)
  - Va-Xa catalyses the conversion of prothrombin to thrombin

Examiner comments

79% of candidates passed this question.
This question was divided in three sections to help candidates formulate an answer template. The first section required a brief outline of the formation of platelets from pluripotent stem cells via megakaryocytes. The second section required an outline of platelet structure highlighting the special features such as, an absence of a nucleus, the presence of an external glycocalyx layer, specific surface receptors, contractile proteins, dense tubular system and granules. The third section was about platelet function where the expected focus was on the role of platelets in haemostasis. This required outlining the mechanism of platelet plug formation by adhesion-activation-aggregation, interactions with the coagulation cascade and role of platelets in clot contraction as well as fibroblast invasion. Although many candidates were able to answer the first section reasonably well, there was a noticeable knowledge deficit in the latter two sections. A significant proportion of answers had missing information on platelet structure and lack of structure in outlining platelet function

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Question 4

Question

Outline the dose (10% marks), composition (60% marks) and side effects (30% marks) of total parenteral nutrition (TPN).

Example answer

Overview

TPN is the delivery of nutrients into the venous circulation to replace enteral requirements

Indications

Patients who are unable to be fed via enteral route for prolonged periods of time (e.g. >72 hours)
May include patients who fail trial of enteral feeding or other contraindications (e.g. GI obstruction, severe pancreatitis, short gut syndromes)

Daily nutritional requirements (major)

Nutrient	Requirement (kg/day)
H2O	30mls
Energy	25-30 kcal
Protein	1g (higher in critically ill, 1.5g)
Glucose	2g
Lipids	1g
Na	1-2 mmol
K	1mmol
Ca / Mg	0.1mmol
PO4	0.4 mmol

Note

Requirements vary according to physiological (e.g. age, gender, body size, activity levels) and pathological (e.g. burns, sepsis, renal failure, hepatic failure) factors

Composition of TPN (note many formulations of this)

Glucose
- Typically supplies around 60-70% of daily caloric needs (~1400KCal)
- Typically 50% dextrose used (3.4 kCal/mil - 824mls)
Lipid
- Typically supplies around 30-40% daily caloric needs (~600Kcal)
- Can be olive oil, soybean, fish oil based
Protein (Amino acids)
- Will contribute to energy source + provides essential amino acids
- L-amino acids used only
- Typically 1.5g/kg/day in critically ill (~100g protein / day)
Electrolytes (Na, K, Mg, Ca, Cl, PO4)
- TPN solutions can come with/without electrolytes and adjusted
Vitamins, trace elements
- Micronutrients are added in appropriate amounts to the bag for adequate daily intake
- Thiamine, folic acid and vitK are vulnerable to depletion and additional may be needed
Water
- In solution, though insufficient for daily requirements
- Hyperosmolar solution due to above nutrients

Side effects / complications

Delivery device / vascular access related
- Infection, pneumothorax, thrombosis, air embolism
Fluid/elextrolyte disturbances
- Fluid overload
- Electrolyte derrangements, shifts and refeeding syndrome
- Acid base disturbances
Metabolic disturbances
- Hypoglycaemia, hyperglycaemia (dose related issues due to over/under feeding)
- Hyperlipidaemia

Examiner comments

59% of candidates passed this question.
The pharmacology of enteral and parenteral nutrition is a level 1 topic in the first part syllabus. The TPN dose in terms of daily calorie and other nutritional requirements were key expectations in first part of the question. A detailed list of all macro and micronutrients was required under TPN composition. Expected information about macronutrients were their forms in the TPN solution (e.g., carbohydrate in the form of glucose, protein in the form amino acids), their relative calorie contributions and their essential components (e.g., the names of the essential amino acids). Identification of potential variability in composition and dose based on specific patient factors scored extra marks. Side effects included metabolic derangements (refeeding syndrome, over or under-feeding, hyperglycaemia, hyperlipemia), biochemical disturbances (fluid and electrolyte imbalances), organ injury (liver, pancreas) and vascular access related complications. Limited breadth and depth of information as well as incorrect facts were prevalent in the answers that scored lower marks.

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Question 5

Question

Outline the factors that determine central venous pressure (60% marks) and explain how it is measured (40% marks).

Example answer

Overview

CVP is the venous blood pressure (of the great veins) measured at or near the right atrium
Normally 0-6mmHg in spontaneously breathing non ventilated patient

Measurement

Non invasive
- Echocardiography can provide non invasive estimations off the CVP
- Visual inspection of the height of the JVP can provide some bedside clinical insight
Invasive
- Most commonly measured using central line
- Central line tip sits at or near the right atrium
- CVC is connected to a pressure transducer via incompressible tubing with flush solution
- Transducer is zeroed to the atmospheric pressure and levelled at the height of the right atrium

Factors determining CVP

<math display="inline"> \Delta CVP \; = \; \frac {\Delta Volume}{\Delta Compliance}</math>
Thus factors determining CVP related to those that influence compliance and volume
Central venous blood volume
- Increased total blood volume (e.g. renal failure) = increased CVP
- Decreased CO (e.g. LV failure) > blood backs up > increased thoracic blood volume > increased CVP
Central venous vascular compliance
- Increased vascular tone central veins (e.g. noradrenaline) > decreased compliance > increased CVP
- Decreased myocardial/pericardial compliance > increased CVP
- Decreased pulmonary arterial compliance (e.g. PAH) > increased CVP
Tricuspid valve function
- TV regurg > increased CVP (retrograde transmission of RV systolic pressure)
- TV stenosis > increased CVP (increased resistance to RV inflow)
Intrathoracic pressure
- ITP is transmitted to the central venous compartment
- Thus, increased PEEP, IPPV, or a tension pneumothorax will lead to increased CVP
Measurement technique
- Level of the transducer will clearly influence the CVP measured

Examiner comments

57% of candidates passed this question.
This question examined a core area of cardiac physiology and measurement. Considering this, candidates overall, scored poorly in this section. There was a common misunderstanding around the relationship between cardiac output and CVP. A decrease in cardiac output (e.g. due to either decreased stroke volume or heart rate) will cause an increase in CVP as blood backs up in the venous circulation, increasing venous volume as less blood moves through to the arterial circulation; the resultant increase in thoracic volume increases central venous pressure. Several candidates confused the direction of their arrows, for example "increased right atrial compliance increases CVP". Double negatives were used by several candidates which then resulted in the incorrect relationship described. (e.g., "arrow down compliance and arrow down CVP"). The measurement section should have included an explanation of the components of an invasive pressure monitoring system relevant to the measurement of CVP.

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Question 6

Question

Describe the pharmacology of vecuronium, including factors that prolong its action of neuromuscular blockade.

Example answer

Name	Vecuronium
Class	Aminosteroid
Indications	Muscle relaxant; intubation, control of ICP, assist ventilation,
Pharmaceutics	Potentially unstable in solution Comes in powder (10mg), dissolved in water (5ml) for use
Routes of administration	IV
Dose	Intubation: 0.1mg/kg
ED95
Pharmacodynamics
MOA	Non depolarising muscle relaxant; Competitive antagonism of ACh at N2 receptors on PSM of NMJ
Effects	MSK: NMJ blockage (paralysis) CVS: nil RESP: Apnoea
Side effects	MSK: prolonged use can lead to myopathy Rare for histamine release (anaphylaxis, hypotension)
Pharmacokinetics
Onset/duration	90-120s; 30-45 minutes
Absorption	IV only
Distribution	Doesn't cross BBB; VD 0.23L/kg
Metabolism	20% hepatic de-acetylation
Elimination	70% biliary, 30% urinary
Reversal	Can be reversed with sugammadex

Factors prolonging action

Electrolyte disturbances
- Hypokalaemia, Hypermagnesemia and hypocalcaemia potentiates non depolarising NMBA
Acidosis
- Increased affinity for ACh receptor
Hypothermia
- Reduced metabolism of muscle relaxant > prolonged effects
Hepatic/renal disease
- Prolonged metabolilsm/elimination of active metabolites
Drug interactions
- e.g. lithium, diuretics, volatile anaesthetics, aminoglcosides

Examiner comments

13% of candidates passed this question.
Vecuronium is a commonly available and regularly used amino-steroid neuromuscular blocking agent. It is a level 1 drug in the 2017 syllabus. A simple template utilising the headings; pharmaceutics, PK, PD, uses in ICU and adverse reactions with associated relevant important facts would have scored well. Expected information regarding the factors prolonging neuromuscular blockade included electrolyte abnormalities, drug interactions and patient factors. Overall, the level of understanding and knowledge demonstrated in the answers was below an expected standard for a level 1 drug.

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Question 7

Question

Outline the anatomy of the blood supply (arteries and veins) of the gastrointestinal system (oesophagus to anus)

Example answer

Arterial supply

The aorta (and its branches) supplies the entire arterial supply to the GIT
The oesophagus is supplied by various arterial branches
- Cervical portion- inferior thyroid artery
- Thoracic portion - bronchial arteries
- Abdominal portion - left gastric, inferior phrenic arteries
The abdominal aorta then has three main branches which supply the remainder of the GIT
- Celiac trunk
  - Arises from abdominal aorta immediately below aortic hiatus at T12/L1
  - Divides into left gastric artery, splenic artery, common hepatic artery
    - Left gastric a. (supplies stomach)
    - Splenic a. (supplies spleen, pancreas)
    - Common hepatic, divides into
      - Hepatic a. proper (supplies liver)
      - Gastroduodenal (supplies pancreas, duodenum, stomach)
      - Right gastric (supplies stomach)
- Superior mesenteric artery (SMA)
  - Arises from abdominal aorta immediately inferior to coeliac trunk (L1)
  - Multiple branches (15-20) which join in an arcade
  - Supplies the midgut structures (from duodenum to 2/3 transverse colon)
- Inferior mesenteric artery (IMA)
  - Arises from abdominal aorta ~L3
  - Multiple branches (including Left colic, sigmoid, superior rectal arteries), join in arcade
  - Supplies the hindgut (distal 1/3 transverse colon - rectum)

Venous drainage

For the most part, the venous drainage of the GIT is via veins which accompany the arterial system
They return via the portal vein
- Portal vein
  - Combination SMV and splenic vein
  - Receives drainage from forgut structures
- Splenic vein
  - Travels along with the splenic artery + drains corresponding regions (foregut)
  - Combines with SMV to form portal vein
- Superior mesenteric vein (SMV)
  - Travels along with the SMA + drains corresponding regions (midgut)
  - Combines with splenic vein to form portal vein
- Inferior mesenteric vein (IMV)
  - Travels along with the IMA + drains corresponding regions (hindgut)
  - Drains into the splenic vein

Examiner comments

48% of candidates passed this question.
This question was answered best if the main arteries and veins were discussed first and then their corresponding supply outline in reasonable detail. Very few candidates were able to achieve this. Listing the names of vessels with no context and in a random non-sequential order did not attract many marks. The physiology of the blood supply to the liver also did not attract marks.

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Question 8

Question

Describe renal handling of potassium (60% marks), including factors that may influence it (40% marks).

Example answer

Renal handling of potassium

Potassium is freely filtered at the glomerulus
- Serum K = 4.2mmols/L, with 180L filtered / day (assuming GFR 125mls/min)
- Thus most of filtered K needs to be reabsorbed in the kidney
Proximal convoluted tubule (PCT)
- ~60% of K reabsorbed
- Reabsorbed passively by solute drag (coupled to water reabsorption) + concentration gradient
- Water absorption is driven by the Na/K ATPAse on basolateral membrane > drives Na reabsorption
Loop of henle (LOH)
- 30% reabsorbed in thick ascending LOH
- NK2Cl cotransporter drives transcellular reabsorption (via basolateral K channels) + paracellular reabsorption (due to negative charge generated by Cl reabsorption)
- Active/secondary active transport
DCT + CD
- 0-10% reabsorbed
- Secretion and absorption
  - Principle cells in DCT and CD: secrete potassium
  - Type A intercalated cells: reabsorb potassium
- Net effect depends on the K state at the time
  - With normal intake or excessive intake, net effect is secretion
  - With low intake the net effect is reabsorption

Regulation / factors influencing renal handling K

Aldosterone
- Increases Na-K ATPase activity primarily in the principle cells > increasing secretion of K
Vasopressin
- Increases ROMK channels, increasing K secretion (balanced by decreased urinary flow rate)
Acid base disturbances
- Metabolic alkalosis
  - Potassium secretion increases (increased Na/K ATPase activity due to low H+)
- Metabolic acidosis
  - Potassium secretion decreases (opposite of above)
K intake
- Increased intake > Increases ROMK channels > increasing K secretion

Examiner comments

33% of candidates passed this question.
This question covers a core physiology topic. The detail required is well described in the recommended reference texts. Generally, this question was poorly answered. From an answer template perspective, a "describe question" in this context involves both the stating the relevant potassium handling mechanism and then giving a description of how it occurs and how this system is regulated. Many answers that scored poorly simply listed sites of potassium handling but excluded the details surrounding the specific receptors and channels involved as well as the processes that exist to perpetuate and regulate these biological processes. Simple identification as to whether the potassium was being secreted or reabsorbed as well as the location as to where this may occur within the nephron, were often not specifically detailed or used interchangeably. Such answers scored poorly

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Question 9

Question

Outline the mechanisms by which normal body temperature is maintained and regulated

Example answer

Overview

Human 'core temperature' is the 'deep body' temperature of the internal organs and viscera
- Core temperature ~ 37Â°C <math display="inline">\pm</math> 0.4Â°C, despite changes in ambient temperature
- Rectal, bladder, oesophageal, central vascular temperatures are often used as approximations.
Peripheral temperatures are variable and generally less than the core temperature
Significant hypothermia (e.g. <35Â°C) or hyperthermia (e.g. >40Â°C) can lead to multi-organ dysfunction
Humans have multiple thermoregulatory mechanisms to resist change in core body temperature
- In general, heat is lost by 4 mechanism: conduction, convection, evaporation, radiation
- In general, heat is gained by 5 mechanisms: conduction, convection, evaporation, radiation, metabolism

Thermoregulatory system & regulation

Sensor
- Peripheral:
  - Skin thermoreceptors (cold= bulbs of Krause; warm=bulbs of Ruffini)
  - Travels via spinothalamic tract to hypothalamus
- Central:
  - Thermoreceptors (hypothalamus and spinal cord)
Integrator/controller
- Hypothalamus
  - Functions as the thermostat (temperature kept around a thermoneutral zone, TNZ)
  - Stimulation of anterior hypothalamus leads to heat loss (temp above TNZ)
  - Stimulation of the posterior hypothalamus leads to heat conservation/generation (below TNZ)
Effector/Response
- Response to cold
  - Shivering -> involuntary muscle contractions that generate heat (ATP hydrolysis)
  - Peripheral vasoconstriction (ANS) --> decreased cutaneous blood flow --> decreased heat transfer from ambient air
  - Increase metabolic rate, thyroid hormone secretion, Non shivering thermogenesis (brown fat paeds, skeletal muscle adults) -> increased heat generation
  - Behavioural changes (seek warmth)
  - Piloerection (unimportant in humans)
- Response to heat
  - Peripheral vasodilation (ANS) --> increased cutaneous blood flow > increased heat loss
  - Sweating --> evaporative heat loss
  - Behavioural changes (seek cool)

Examiner comments

59% of candidates passed this question. This question was relatively well answered by most candidates. There was significant variation in the temperatures expressed as normal and few candidates mentioned CORE temperature as a concept. Several candidates gave a detailed description of thermo-neutrality for which there were no marks.

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Question 10

Question

How does warfarin exert its pharmacological effect (40% marks)? Write brief notes on the pharmacology of the agents that can be used to reverse the effects of warfarin (60% marks).

Example answer

Name	Warfarin
Class	Oral anticoagulant
Indications	Systemic anticoagulation, e.g. in prophylaxis/treatment of thromboembolism
Pharmaceutics	Racemic mixture of two enantiomers R and S, with the S isomer more biologically active.
Routes of administration	Oral
Dose	Varies; titrated to INR generally
Pharmacodynamics
MOA	Inhibits the synthesis of vitamin K dependant clotting factors (II, VII, IX, X). Specifically, inhibits vitamin K epoxide reductase (VKORC1) from converting VitK from the oxidised to reduced form, which prevents carboxylation (activation) of clotting factors listed above (as well as protein C and S)
Effects	Anticoagulation
Side effects	Haemorrhage, teratogenicity (1st trimester), foetal haemorrhage (3rd trimester), drug interactions
Pharmacokinetics
Onset	Peak onset is 72 hours (as existing clotting factors not affected by warfarin)
Absorption	100% oral bioavailability
Distribution	99% protein bound, small VD 0.14L/Kg
Metabolism	Complete hepatic metabolism
Elimination	Renal elimination of metabolites
Reversal	Vitamin K, FFP, Prothrombinex, cessation+time

Reversal (in more detail)

Cessation + time
- Stopping warfarin, will lead to normalisation of the INR generally in 4-5 days (but varies according to initial INR, comorbidities etc)
- Mechanism: drug washout
- Con: slow, risk of bleeding
- Pro: decreased risk thrombotic events from over/rapid correction
Vitamin K
- can be given IV/IM/PO
- Higher doses, IV doses can reverse more rapidly
- Mechanism: replenishes the substrate
Fresh frozen plasma
- Mechanism: Contains all necessary clotting factors - hence rapid reversal
- Blood product, with all the risks associated with this (fluid overload, infection, allergic responses)
- Dose: 2-4 units (varies)
- Con: require crossmatch, time for thawing etc
Prothrombinex
- Mechanism: Contains factors II, IX, X (Aus) 500IU each- hence immediate reversal
- Dose: 25-50 u/kg
- Pro: immediate effects, smaller fluid volume, immediately available for use
- Con: Factor 7 absent, expensive

A general approach, adapted from Red Cross Blood Service

Not bleeding
- INR not too high (<4.5) and/or low bleeding risk = expectant management
- INR high >4.5 and/or moderate-high bleeding risk = oral/IV Vit K
Bleeding
- Life threatening: IV Vit K 10mg , Prothrombinex 50u/kg (or FFP if not available)
- Clinically significant: IV VitK 5-10mg, Prothrombinex 25u/kg (or FFP if not available)
- Minor bleeding: IV VIt K

Examiner comments

43% of candidates passed this question.
Warfarin is listed as a level 1 drug in the 2017 syllabus and as such a detailed knowledge of its mechanism of action would be expected from candidates sitting the exam. The reversal agents for warfarin are collectively classed as level 2 drugs and hence the knowledge required would be at a write short notes level. The following topics were expected: what drugs may be used, how they work, in what dose, any common side effects, why/when would one be used in preference to others etc. The use of reversal agents for warfarin is a common practice in ICU. Generally, answers demonstrated a lack of a precise and detailed knowledge with respect to warfarinâ€™s mechanism of action and had a very superficial knowledge with incorrect facts regarding the reversal agents

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Question 11

Question

Describe the buffer systems in the body

Example answer

Buffers

A solution consisting of a weak acid and its conjugate base
Main function is to resist change to pH, with the addition of stronger acids/bases, through reversible binding of H+ ions
Effectiveness depends on the buffer pKa, the pH of the solution, the amount of buffer present, whether the system is open or closed
All buffers participate in equilibrium with each other in defence of pH (Isohydric principle)

Main buffering systems in ECF

Bicarbonate-carbonic acid buffering system
Protein buffering system (includes Hb buffering system)
Phosphate buffering system

Bicarbonate-carbonic acid system

pKa of 6.1
Weak acid (H₂CO3) and base (HCO₃ salt)
Via reaction: <math display="inline"> CO_2 \; + H_2O \; \leftrightarrow \; H_2CO_3 \; \leftrightarrow \; HCO_3^- \; + H^+</math>
Increased acid > increased CO₂ (excreted via lungs)
Increased base > increased HCO₃ (excreted via kidneys)
OPEN system - hence most important - responsible for 80% of the ECF buffering

Protein buffering system

Include haemoglobin (150g/L) and plasma proteins (70g/L)
- Hb has pKa of 6.8. Weak acid (HHb) and weak base (KHb)
H+ binds to the histadine residues on imadazole side chains, the HCO3 diffuses down concentration gradient into ECF
Hb is quantitatively 6 times more important than plasma proteins, as the concentration is double and there are three times as many histadine residues in Hb

Phosphate buffering system

Overall pKa 6.8
Tribasic (HPO₄, H₂PO₄, H₃PO₄) though only the H₂PO₄ has a physiological pKa to be useful
Overall contribution is minimal to the blood due to the low concentration of phosphate. However more important in the urine where the concentration is higher
closed system

Examiner comments

57% of candidates passed this question.
This is a core physiology topic; a detailed knowledge of buffering and the available buffer systems is crucial to ICU practice. A candidate presenting for the first part exam should have a detailed understanding of all aspects of the buffer systems. Higher scoring answers provided both technical details of the buffer systems, the context for their normal function and their relative importance. Efficient answers dealt with the buffers by chemical rather than by site, but many answers categorising buffers by site also scored well. Many low scoring answers simply failed to provide detail, some provided incorrect information. Very few candidates demonstrated an understanding of the isohydric principle

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Question 12

Question

Describe the pharmacology of oxycodone.

Example answer

Name	Oxycodone
Class	Semi-synthetic opioid (phenanthrene)
Indications	Analgesia
Pharmaceutics	White tablet (IR, MR) +/- naloxone - various conc Oral solution (1mg/ml) Clear, colourless, solution (10mg/ml)
Routes of administration	PO, IV, SC, IM
Dose	Depends - Example: PO 5-10mg PRN 4hrly, IV 1mg 5 minutes PRN
Morphine equivalence	1.5 x morphine (10mg oxycodone = 15mg morphine )
Pharmacodynamics
MOA	MOP receptor (Gi PCR) in cerebral cortex, basal ganglia, periaqueductal grey Weak KOP / DOP receptor activity
Effects	CNS: Analgesia, sedation, euphoria, dyspho CVS: bradycardia, hypotension RESP: respiratory depression (reduces chemoreceptor sensitivity to CO2), depressed cough reflex GIT: decreased peristalsis > constipation, nausea, vomiting MSK: pruritis, muscle rigidity GU: urinary retention EYE: miosis
Pharmacokinetics
Onset	Peak 5 mins, duration 4 hrs
Absorption	80% oral bioavailability
Distribution	~50% protein bound VOD = 3L/Kg Crosses placenta
Metabolism	Hepatic metabolism (CYP3A4) - extensive Oxidation > demethylation Active metabolites: noroxycodone, oxymorphone
Elimination	Renal elimination Active metabolites T _1/2 = 2-4hrs (IR)
Reversal	Naloxone (100mcg IV boluses, PRN 3 minutely)

Examiner comments

54% of candidates passed this question.
There were many exceptional answers which provided extensive detail on the drug. The best of these gave context for the drug characteristics, such as by referring to oxycodone relative to other opioid drugs that might be chosen, or to considerations for safe and effective administration. Some answers, however, provided generic information on opioid drugs, which could not gain all the available marks.

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Question 13

Question

List the cell types in the anterior pituitary gland. Outline their secretions, control and target organ effects.

Example answer

Anterior pituitary connected to the hypothalamus via the hypophyseal portal system

Anterior pituitary cell types

Chromophils (granular secretory cells)
- Acidophils (80%)
  - Red staining
  - Includes lactotropes (prolactin) and somatotropes (GH)
- Basophils (20%)
  - Blue staining
  - Includes gonadotropes (FSH, LH), thyrotropes (TSH) and corticotropes (ACTH)
Chromophobes (agranular secretory cells)
- inactive/degranulated secretory cells
- Weakly staining, no longer secrete hormones

Anterior pituitary hormones and their effects

Hormone	Increased release (stimulation)	Decreased release (inhibition)	Effects
ACTH	Corticotrophin releasing hormone (CRH): stress, catecholamines, ADH	Cortisol (negative feedback)	Acts on adrenal cortex to increase release and synthesis of glucocorticoids and androgens
TSH	Thyrotropin releasing hormone (TRH) from hypothalamus	Negative feedback (T3/T4), somatostatin	Increased synthesis and secretion of T3/T4 from thyroid cells Hyperplasia and hypertrophy of thyroid follicular cells
GH (somatotropin)	Somatotropin releasing hormone from hypothalamus. Stress, starvation, hypoglycaemia	- Somatostatin - Negative feedback (IGF-1)	- Releases IGFs (anabolic action; growth and differentiation of cells) - Increases protein, fat, carbohydrate metabolism/utilisation in liver, adipose/muscle tissues.
FSH, LH	Gonadotropin releasing hormone from hypothalamus	Negative feedback (FSH, LH)	LH: ovulation (females), testosterone secretion (males) FSH: ovarian follicle development (females), spermatogenesis (males)
Prolactin	Thyrotropin releasing hormone (TRH), suckling	Prolactin inhibiting hormone, dopamine, negative feedback	Promotes mammary gland and ductal development (during pregnancy) Promotes lactation, amenorrhoea (following delivery)

Examiner comments

40% of candidates passed this question.
Few candidates described cell types as chromophils and chromophobes. There were many errant references to chromaffin cells which are found mainly in the adrenal medulla, and to staining on H&E. Chromophil cells stain by absorbing chromium salts. Few candidates mentioned that the hormones secreted by the anterior pituitary are peptides. Most candidates outlined the hypophyseal-portal system well. Knowledge of TSH and ACTH control and target organ effects were good. Similar knowledge for LH, FSH, PRL and GH was much more sporadic.

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Question 14

Question

Describe the pharmacology of sodium bicarbonate.

Example answer

Name	Sodium Bicarbonate
Class
Indications	Severe NAGMA, alkalinisation of urine (salicylate toxicity), hyperkalaemia, TCA overdose (Na channel blocking effects)
Pharmaceutics	Tablet (varying doses e.g. 300mg) Clear colourless solution (various concentrations e.g, 4.2%, 8.4%) which can be given hypertonic or isotonic
Routes of administration	PO, IV
Dose	1mmol/kg IV = 1ml/kg of 8.4% (cardiac arrest due to hyperK)
Pharmacodynamics
MOA	Dissociates into Na and HCO3. The HCO3 functions as a buffer in the bicarbonate-carbonic acid buffering system (raising pH). The Na increases the strong ion difference in plasma (raising pH)
Effects	Increases pH, alkalinisation of urine
Side effects	Hypokalaemia, hypocalcaemia, hypernatremia Fluid overload (Large doses IV) Extravasation tissue injury (IV) Metabolic alkalosis (overdose)
Pharmacokinetics
Onset	Immediate
Absorption	NA
Distribution	Intravascular space
Metabolism	<math display="inline"> CO_2 \; + H_2O \; \leftrightarrow \; H_2CO_3 \; \leftrightarrow \; HCO_3^- \; + H^+</math>
Elimination	Renal (bicarbonate), lungs (as CO₂)
Special points	Incompatible with calcium /magnesium salts (precipitates)

Examiner comments

29% of candidates passed this question.
This question was best answered with a structured approach as per any pharmacology question. It nonetheless required good understanding of various aspects of physiology. Many candidates failed to gain marks by omitting to mention facts which could have been prompted by a defined structure. A good response mentioned the pharmaceutic features including formulation and the hypertonicity of IV bicarbonate, pharmacodynamics including indications for use, mode of action, adverse effects (systemic and local), pharmacokinetics and dose. Pleasingly a few candidates stated that sodium bicarbonateâ€™s mechanism of action to cause alkalosis involved increasing the strong ion difference in plasma. Credit was also given for stating the mechanism of action as providing bicarbonate ions to augment the extracellular buffer system

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Question 15

Question

Explain perfusion limited and diffusion limited transfer of gases in the alveolus.

Example answer

Gas diffusion

Rate of diffusion of gasses is given by Fick's Law

<math display="block">Diffusion = \frac {A \times D \; \times \Delta P}{T }</math> Where: A= lung area, D = diffusion constant of the gas, <math display="inline">\Delta</math>P = partial pressure gradient of gas, T=thickness of membrane. Diffusion constant is influence by the Temperature of the gas, the density of the gas and the size of the molecules

Gas diffusion at the level of the alveolus can either be perfusion or diffusion limited.

Perfusion limited gases

Rapidly equilibrates between alveolus and capillary
Equilibration time is less than the capillary transit time
Thus for the majority of the RBCs time travelling through the capillary, there is no further diffusion
As a result this gas is 'perfusion limited' because increasing the blood flow (perfusion) will increase gas transfer, but increasing the rate of diffusion will not
Examples
- Oxygen (under normal conditions)
  - Due to the large partial pressure gradient (100 > 40)
  - Equilibrates within 0.25s (pulmonary capillary transit time 0.75s)
- Carbon dioxide
  - While a smaller partial pressure gradient (46 > 40), the diffusivity of CO₂ is 20 X greater than O₂
  - Equilibrates within 0.25s
  - Actually ventilation limited - as you need to blow off CO2 to ensure gradient
- Nitrous oxide
  - Relatively insoluble and doesn't bind to Hb, therefore struggles to equilibrate

Diffusion limited gasses

Does not rapidly equilibrate between alveolus and capillary
Equilibration time is greater than the capillary transit time
Thus for the entirety of the RBCs time in the capillary there is ongoing diffusion occurring
As a result this gas is 'diffusion limited' because increasing the rate of diffusion will increase the rate of gas transfer, but increasing the blood flow (perfusion) will not.
Examples
- Carbon monoxide
  - Slowly diffuses
  - CO binds to Hb so avidly that there is virtually none in the plasma
  - Therefore the equilibrium is never reached and further gas exchange could occur with a greater diffusivity
- Oxygen
  - Typically perfusion limited under normal circumstances.
  - Under extreme conditions it may become diffusion limited
    - Increase altitude > decreased PAO2
    - High cardiac output > reduced capillary transit time
    - Alveolar membrane disease > decreases rate of diffusion

Examiner comments

36% of candidates passed this question.
This question required detail on those factors affecting gas exchange at the level of the alveolus. A description of the components of the Fick equation was expected - and how this related to oxygen and carbon dioxide transfer at the alveolar capillary membrane. The rapid rate of equilibration (developed tension) was the limiting factor in of blood/alveolar exchange that rendered some gases perfusion limited (examples - N2O, O2 under usual conditions but not all) and the slower rate of others diffusion limited (examples CO and O2 under extreme conditions e.g., exercise, altitude). Estimates of time taken for each gas to equilibrate relative to the time taken for the RBC to travel across the interface was also expected for full marks. CO2 despite rapid equilibration and higher solubility was correctly described as perfusion limited (unless in disease states). Better answers described CO2 as ventilation limited. Some answers also correctly included the component of interaction with the RBC and haemoglobin. Ventilation/perfusion inequalities over the whole lung were not asked for and scored no marks

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Question 16

Question

Describe the pharmacology of piperacillin-tazobactam

Example answer

Name	Piperacillin-tazobactam
Class	Semi-synthetic penicillin (piperacillin) B-lactamase inhibitor (tazobactam)
Indications	Pseudomonal infection Broad spectrum antimicrobial cover of severe infections/sepsis
Pharmaceutics	Powder, reconstitutes in water/NaCl/glucose
Routes of administration	IV/IM
Dose	4g/0.5g 8hrly 4g/0.5g 6hrly (pseudomonas cover); dose reduced renal failure
Pharmacodynamics
MOA	Piperacillin: bactericidal - inhibits cell wall synthesis by preventing cross linking of peptidoglycans by replacing the natural substrate (D-ala-D-ala) with their B-lactam ring Tazobactam: B lactamase inhibitor (prevents piperacillin degradation)
Antimicrobial cover	Broad spectrum coverage of gram positive bacteria, gram negative bacteria, anaerobes. Covers pseudomonas. Doesn't cover: MRSA, VRE, ESBL, atypical
Side effects	GIT: diarrhoea, nausea, vomiting Renal: AKI Allergy (up to 10%), rash most common, skin eruptions/SJS and anaphylaxis (<1/10,000)
Pharmacokinetics
Absorption	Minimal oral absorption > IV Peak concentrations immediately after dose.
Distribution	Very good tissue penetration (minimal CNS without active inflammation) Low protein binding (<30%)
Metabolism	Piperacillin: not metabolised Tazobactam: metabolised to M1, an inactive metabolite
Elimination	Renal (80% unchanged)
Special points	Removed by haemodialysis

Examiner comments

62% of candidates passed this question.
Most candidates used a structured approach with the usual major pharmacology headings. Mechanism of action was well described by most, with better answers including mechanisms of resistance. Higher scoring candidates included an explanation as to the combination of the drugs. Likewise, better answers included detailed information on spectrum of activity beyond â€œgram positive and gram negativeâ€, including relevant groups of organisms which are not covered. There also seemed to be some confusion about coverage for anaerobes, which piperacillin tazobactam covers well. Specific detail about adverse reactions, other than â€˜allergy, rash, GI upset, phlebitis, etcâ€™, is expected for commonly used antibiotics.

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Question 17

Question

Describe the principles of measurement of arterial haemoglobin O2 saturation using a pulse oximeter (60% marks). Outline the limitations of this technique (40% marks).

Example answer

Definition

Non invasive spectrophotometric technique to measure O2 saturation in arterial blood
Normal: typically 95-100% (for young health individuals)

Components

Two light sources (LEDs): emit light at 660nm and 940nm
Light detector (photodiode)
Opaque housing unit (minimises ambient light)
Signal amplifier, noise filter
Microprocessor
Connectors , user interface and alarm system

Physical principles

Utilises the principles of the Beer-Lambert law: <math display="inline">A = Îµ \; l \; c</math>
- Absorption (A) of light passing through a substance is directly proportional to
  - The optical path length (Lambert's law; l)
  - The concentration of attenuating species within the substance (Beers Law; c)
  - The absorptivity of the attenuating species ( Îµ )

Utilises the different absorption spectra of Oxy- and deoxy-Hb
- Deoxy-Hb absorbs far more light in the red spectra (660nm)
- Oxy-Hb absorbs far more light in the near-infrared spectra (940nm)

How it works

Pulsatile blood (arterial) is isolated and Hb saturation calculated
- During pulsatile flow, there is expansion and contraction of the blood vessels
- This alters the optical distance (Lamberts law), changing the absorption spectra
- Non pulsatile elements (e.g. venous blood) are excluded from the pulsatile elements (arterial blood) by creating a ratio of absorbances (R)
- Whereas the ratio of absorbances at different spectra (660nm vs 940nm) utilised to calculate saturation of Hb

<math display="block">R = \frac {Pulsatile_{660} \; / \; Non-pulsatile_{660}}{Pulsatile_{940} \; / \; Non-pulsatile_{940}}</math>

Empirical correlation with SaO2
- The relationship between R and SpO2 was derived empirically by comparing arterial oxygen saturations (from ABGs) at different R values in healthy volunteers
There are important corrections in modern pulse oximeters
- Correction for Hb concentration using isosbestic points
- Correction for ambient light using rapid cycling of the light source (up to 1000 hz)

Limitations

Requires detectable pulsatile flow (shock, poor perfusion, hypothermia, ECMO, CPB)
Bodily movements (e.g. shivering, seizure) confound readings
Not accurate nor calibrated at low saturations (progressive decline in accuracy as SaO2 decreases)
Not all devices are created equal (device accuracy ranges; generally within 1-5% of ABGs)
Ambient light contamination (effects minimal due to rapid cycling as described above)
Interference: nail polish, oedema, intravascular dyes (methylene blue)
False readings: carbon monoxide poisoning, MetHb
Racial bias in pulse oximetry: tested predominately on white population. A study demonstrated 3x as many black patients had occult hypoxemia compared to white patients.

Examiner comments

74% of candidates passed this question.
Most candidates provided a reasonable structured sequence of how a pulse oximeter generates a value. Nearly all candidates described the Beer-Lambert laws correctly, but few specifically described the basic principles of absorption spectrophotometry. Most candidates had a reasonable list of extrinsic factors that can interfere with pulse oximeter performance, but few described the intrinsic/inherent limitations of the device that can cause SpO2 to be different to SaO2, such as functional versus fractional saturation.

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Question 18

Question

Outline the pharmacology of intravenous magnesium sulphate

Example answer

Name	Magnesium sulphate
Indications	HypoMg, eclampsia/pre-eclampsia, severe asthma, arrhythmias (including TdP), analgesia
Pharmaceutics	Clear colourless solution, various concentrations
Routes of administration	IV, IM
Dose	5mmol bolus (torsade's). 4g (16mmols) bolus > 1g/hr thereafter (eclampsia, PET)
Pharmacodynamics
MOA	Essential cation - Essential cofactor in hundreds of enzymatic reactions - Necessary in several steps of glycolysis (ATP production) - NMDA receptor antagonism (increasing seizure threshold) - Inhibits Ach release at NMJ (muscle relaxation) - Smooth muscle relaxation (Inhibits Ca L-type channels)
Effects	CNS: anticonvulsant (NMDA effect) Resp: Bronchodilation (CCB effect > SM relaxation) CVS: Anti-arrhythmic ( decreased conduction velocity due to CCB effect)
Side effects	Related to speed of administration + degree of HyperMg Toxicity generally occurs > 4mmol/L CVS: Hypotension, bradycardia CNS/MSK: hyporeflexia, muscle weakness, CNS depression, potentiates NMBs RESP: respiratory depression GIT: Nausea, vomiting
Pharmacokinetics
Onset	Immediate
Absorption	N/A
Distribution	30% protein bound
Metabolism	Not metabolised
Elimination	Urine; clearance is proportional to GFR and plasma concentration
Special points	Incompatible with calcium salts > precipitation Drug interaction with NMB agents (potentiation)

Examiner comments

57% of candidates passed this question.
The best answers appropriately addressed the pharmacology of magnesium sulphate, rather than diverting into physiology. They noted that the question concerned intravenous magnesium sulphate and did not discuss other routes. They included pharmaceutics, important examples of the wide-ranging indications, listed potential modes of action and considered the full range of body systems affected including potential adverse effects. Drug interactions, such as potentiation of neuromuscular blocking agents, and pharmacokinetics (including stating that magnesium is not metabolised) were described

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Question 19

Question

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

Example answer

Vascular anatomy

Coronary arteries arise from the sinuses of valsalva at the aortic root
- Left coronary artery (LCA)
  - LAD
    - Branches: D1, D2 arteries
    - Supplies: anterior 2/3 of the IV septum, anterior LV, LA
  - LCx
    - Branches: OM1, OM2
    - Supplies: inferolateral LV wall, SA node (40%), AV node (20%)
- Right coronary artery
  - Branches: Right marginal branches
  - Supplies: RA, RV, SA node (60%), AV node (80%)
- PDA
  - Continuation of RCA (~70%), LCx (~15%), or both (~15%)
  - Supplies: posterior inferior LV
Coronary veins
- Majority (85%) of venous drainage is via the coronary sinus
  - Great cardiac vein (follows LAD)
  - Middle cardiac vein (follows PDA)
  - Small cardiac vein (follows RCA)
- Remainder (15%)
  - Anterior cardiac veins --> RA
  - Thebesian veins (drains into cardiac chamber directly)

Coronary blood flow

CBF ~250mls/min (5% CO)
Oxygen extraction near maximal (70%) --> Increased CBF is needed for increased O2 demand.
RCA: blood flow is constant, pulsatile and higher flow rate during systole
LCA: blood flow is intermittent, pulsatile, and higher flow rate during diastole

Regulation of flow

Autoregulation
- Metabolic autoregulation
  - Anaerobic metabolism > increased vasoactive substances (lactate, adenosine, CO2, NO) > vasodilation > increased flow
  - Predominant means of autoregulation
- Myogenic autoregulation
  - CBF is autoregulated over a wide range of BPs (perfusion pressure 50-120mmhg)
  - Increased transmural pressure > vasoconstriction > flow reduction
  - Modest means of autoregulation
Direct autonomic control
- Weak effect
- a1 activation > vasoconstriction; B/muscarinic activation > vasodilation
Indirect autonomic control
- Increase / decrease HR to alter time in diastole/systole which will lead to increased/decreased flow
- i.e. Increased PSNS activity > decreased HR > increased diastolic time > increased CBF

Examiner comments

62% of candidates passed this question.
Good candidates described normal blood flow to the coronary circulation, including differences between the right and left ventricles. Coronary artery anatomy was outlined, including the regions of the heart supplied and the concept of dominance. In addition to epicardial vessels, strong answers also outlined penetrating arteries, subendocardial supply and venous drainage. Regulation of coronary blood flow required an explanation of flow-dependence of the heart given its high oxygen extraction rate. Metabolic autoregulation and its mediators needed to be described, along with the physical factors driving coronary blood flow. Less important mechanisms such as the role of the autonomic nervous system were also described, with an emphasis on indirect effects over direct effects.

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Question 20

Question

Outline the physiological factors that influence cerebral blood flow

Example answer

Cerebral blood flow (CBF)

~15% CO (~750mls/min) under normal resting conditions
High demand due to high metabolic rate
Brain is very sensitive to interruptions (due to high demand and inability to store energy)

Factors effecting CBF

Related to blood pressure, vessel characteristics, rheological factors per Hagan-Poiseuille eqn.
- <math display="inline">CBF \; = \; \frac {\Delta P \pi R^4}{8 \eta L}</math>
- Where: Î”P represents the driving pressure (i.e. CPP), R is the radius of the blood vessels, Î· is blood viscosity, L is the length of the tube.

Pressure effects
- Cerebral perfusion pressure (CPP) = MAP - ICP (or CVP whichever is higher)
- Normally CBF is kept constant across a wide range of CPP (approx 50-150mmHg)
- Able to do this via cerebral autoregulation
  - Predominant means is myogenic autoregulation
    - Increased CPP > Inc. stretch > inc. wall tension > vasoconstriction > decreased CBF
- Outside autoregulatory ranges (e.g. MAP <50mmhg or >150mmHg)
  - CBF becomes pressure passive (any increase in CPP = increase CBF, vice versa)
Vessel radius effects
- Myogenic autoregulation (per above)
- PaCO₂
  - CO2 is a cerebral vasodilator = increased CBF
  - Linear increase in CBF for increase CO2 between 20-80mmHg
- PaO2
  - Within normal physiological limits does not effect CBF
  - Exponential increase in CBF with hypoxia (e.g. PaO2 <50-60) due to vasodilation
- Metabolism/metabolic autoregulation
  - Linear increase in CBF for any increase in mebtaolism (flow metabolism coupling)
  - Controlled by local vasoactive mediators (H+, adenosine, NO)
- Neurohormonal
  - Minimal impact of hormones (e.g. adrenaline) on vessel radius
  - Minimal impact of ANS mediated vasoconstriction
Rheological factors
- Minimal effect, does not rapidly change
- Mostly dependant upon HCT
- Increased HCT = increased resistance = reduced blood flow
Vessel length
- Would not change = no effect

Examiner comments

19% of candidates passed this question. Overall, this question was poorly answered with a high failure rate. A good answer gave a normal value, iterated that CBF is held relatively constant by autoregulation, and proceeded to divide factors affecting CBF into categories with an explanation/description of each. Those factors with the greatest influence were expected to have more accompanying information (e.g., pressure/myogenic autoregulation, metabolic). Systemic factors such as MAP, O2, CO2 were expected to be mentioned with detail of the impact (i.e., key values, relationships demonstrated with a description and/or labelled graph). Local factors within the brain such as H+ concentration/pH, metabolic activity (including the impact of temperature, inclusion of mediators, regional variation based on activity & grey versus white matter) were also expected to be mentioned. Few answers mentioned impact of pH change independently of CO2. Few answers mentioned how CO2 changes the pH of CSF and that over time, this impact is buffered/reduces. The role of the sympathetic nervous system was required to be mentioned although not explored in detail (although many answers overstated the importance of the SNS on CBF or gave a simplistic concept such as increased SNS activity increases CBF). Many answers focussed on descriptions of the Monro-Kelly doctrine and ICP to the exclusion of the aforementioned factors or included detail on factors influencing MAP which were not required (and irrelevant when within the autoregulation range). Many answers were simplistic: e.g., increase MAP increase CPP therefore increase CBF, or by stating CO2/O2 without mentioning a relationship or the limits/patterns of the relationship. Many answers failed to separate the effect of systemic PaO2 and PaCO2 from metabolic autoregulation.

2021 (1st sitting)

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