2019B

2019 (2nd sitting)

Question 1

Question

Describe the physiological consequences of the oral ingestion of 1 litre of water in a young adult.

Example answer

Handling of oral water ingestion

Absorption
- Near complete absorption of water occurs in the proximal small intestine (85%), with 10% in large bowel, 5% in rectum.
- Most of the diffusion is transcellular and driven by osmosis (due to active absorption of other electrolytes, including sodium)
Distribution
- Absorbed water distributes equally amongst all body fluid compartments, proportional to size
  - ~66% into the ICF (~667mls)
  - ~33% into the ECF (~333mls)
    - ~75% of which is interstitial fluid
    - ~21% of which is intravascular
    - ~4% of which is transcellular fluid
Elimination
- Water is eliminated predominately by renal excretion
- Filtered water at the glomerulus is highly regulated

Physiological consequences of oral water ingestion

Decrease in osmolality
- ~2.5% decrease in osmolality for 1L of oral water
- Sensed by osmoreceptors (hypothalamus) which have sensitivity of ~2% > decrease in secretion of vasopressin from the posterior pituitary gland
- Decreased vasopressin > decreased luminal aquaporin channel insertion in collecting ducts of nephrons > decreased water reabsorption > diuresis
Decrease in plasma Na concentration
- Leads to release of angiotensin and aldosterone > increased Na reabsorption in nephron
Small increase in blood volume
- For 1L oral ingestion of water > leads to ~70mls of intravascular water (33% of 1L goes to ECF, 21% of which is intravascular)
- This change is below the sensitivity threshold of the cardiovascular regulatory reflexes > no change in blood pressure/HR of a normal healthy individual

Examiner comments

28% of candidates passed this question.

It was expected candidates would provide details the consequences of water ingestion from its rapid absorption in the small intestine to the resultant impact on plasma osmolarity and the minimal impact of plasma volume of this volume. Some detail on the mechanisms of absorption (transcellular vs osmosis) was expected and the distribution of water across body fluid spaces. Many candidates accurately described the small drop in plasma osmolarity that is sufficient to trigger osmoreceptors with better answers providing details of the locations and mechanisms involved. The physiological consequences of inhibition of ADH, including the renal effects of decreased water permeability in distal renal tubules and collecting ducts. The volume load after distribution would be lower than the plasma volume triggers for the circulatory reflex responses.

Online resources for this question

Question 2

Question

Describe renal blood flow and its regulation (80% of marks). Outline the impact of adrenoreceptor agonists on renal blood flow (20% of marks).

Example answer

Renal blood flow (RBF)

Approximately 20-25% of cardiac output (1-1.25L/min)
Majority of blood flow is distributed to the renal cortex (95%) compared to renal medulla (5%)
Renal blood flow far exceeds metabolic requirements --> to support the filter function of th ekidney

Anatomy of RBF

Renal arteries > interlobar arteries > arcuate arteries > interlobular arteries > afferent arterioles > glomerulus > efferent arterioles > peritubular capillaries > venous system
Venous system similarly named in reverse

Regulation of RBF

Autoregulation
- Kidneys have the capacity to autoregulate (cortical nephrons can, juxtamedullary nephrons cant)
- Can maintain a constant RBF across a wide range in MAP (70-170mmHg)
- Two main mechanisms: myogenic autoregulation, tubuloglomerular feedback
- Myogenic autoregulation
  - Intrinsic contraction of the afferent arterioles in response to increased transmural pressures via release of vasoactive mediators
- Tubuloglomerular feedback
  - Increased RBF > increased GFR > increased Na/Cl sensed by macula densa > releases adenosine > constriction of afferent arterioles > decreased RBF
  - Decreased RBF > decreased GFR > decreased Na/Cl at macula densa > releases NO > dilation > increased RBF
SNS
- Activation of adrenoreceptors > constriction of arterioles > decreased RBF
Hormonal response
- Renin is released by B1 stimulation and decreased GFR
- AG2 constricts afferent and efferent arterioles > decreased flow

Impact of adrenoreceptor agonists on RBF

As mentioned, kidneys are innervated by SNS (adrenergic receptors)
Massive SNS stimulus (e.g. shock, high dose adrenergic agonists) can override autoregulation
Efferent arterioles constrict greater than afferent arterioles > decrease in RBF, but the GFR is proportionally less effected (greater perfusion pressure)
Effect of alpha adrenergic agonists
- Will act as renal vasoconstrictors > decrease renal blood flow / GFR
- Examples: phenylephrine, metaraminol
Effect of beta adrenergic agonists
- Will lead to increased RBF (vasodilator)
- Example: isoprenaline
Non-selective adreneergic agonists
- Greater proportion of alpha > beta receptors.
- Mixed agonists (e.g. adrenaline) will predominately lead to decreased flow (alpha predominance)

Examiner comments

64% of candidates passed this question.

This question was well answered by most candidates. The description of renal flow involves a brief comment of the anatomy including interlobar, arcuate, interlobular arteries, then afferent and efferent arterioles â€“ 2 sets of capillaries and then corresponding veins and better answers made the distinction better cortical and medullary flow and went on to detail the consequence of this. Renal blood flow is autoregulated and most candidates describe well the various mechanisms around myogenic and tubuloglomerular feedback. Additional marks were gained with by discussing renal vascular resistance and how this may be varied. The impact of adrenoreceptor agonists is varied but generally sympathomimetic agents will vasoconstrict and therefore increase renovascular resistance and result in a decrease renal blood flow. The relative impact on afferent vs efferent arteriolar tone may alter glomerular perfusion pressure.

Online resources for this question

Question 3

Question

Describe the relationship between muscle length and tension (50% of marks). Outline the physiologic significance of this relationship in cardiac muscle (50% of marks).

Example answer

Length-tension relationship

The tension generated within a single muscle fibre is related to its length
Total tension = passive tension + active tension
Passive tension
- Increases with increasing muscle length (modelled as a non-linear spring)
Active tension
- Also varies with muscle length, but is described by the sliding filament model and has an optimal length at which maximal tension is generated
- The physiological basis of this is due to different number of actin-myosin cross bridges formed at the different muscle lengths
- The optimal myocardial sarcomere length is ~2.2 um (greatest overlap of actin-myosin filaments)
The resting muscle length is often close to the optimal length for active tension

Cardiac muscle

The muscle length-tension relationship forms an important part of the Frank-Starling law (strength of myocardial contraction is dependant on the initial muscle fibre length)
With increase in diastolic filling of the heart > increase stretch (preload) > increased muscle length (increased cross bridge formation) > increased force of contraction > increased stroke volume
- Note: this mechanism is within limits. When the muscle length is too great, there is actually a reduction in cross bridge formation > decreased SV
Importance
- Ensures venous return = cardiac output (else pooling would occur)
- Allows beat-beat adjustments to variation in preload

Examiner comments

41% of candidates passed this question.

Some detail was expected on a general description that tension is variable with the length of muscle. It was expected answers would describe that there is a resting length at which tension developed on stimulation is maximal. Many candidates omitted that differences exist between muscle types with smooth muscle behaving differently. Additional credit was given for the distinction about active tension vs resting tension. It was expected a description of the potential mechanism would be included with discussion of sliding filament theory, overlapping fibres and optimal sarcomere length. Some candidates utilised a diagram effectively to convey understanding and more detail was rewarded with additional marks.
The second half of the question involved describing how this relationship is particularly important in cardiac muscle and underpins the Frank Starling relationship and all the cardiac physiology that follows. Initial length of fibres is determined by the diastolic filling of the heart, so pressure developed is proportionate to the total tension developed. The developed tension increases as diastolic volume increases to a maximum (the concept of Heterometric regulation). Better answers appreciated that the physiology may be different for a whole heart rather than isolated muscle fibres.

Online resources for this question

Question 4

Question

Outline the pharmacology of intravenously administered 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, IO
Dose	10-20mmols
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 - Smooth muscle relaxation (Inhibits Ca L-type channels)
Effects	CNS: anticonvulsant Resp: Bronchodilation CVS: Anti-arrhythmic
Side effects	Related to speed of administration + degree of HyperMg (dose dependant) CVS: Hypotension, bradycardia CNS/MSK: hyporeflexia, muscle weakness, CNS depression RESP: respiratory depression GIT: Nausea, vomiting
Pharmacokinetics
Onset	Immediate
Absorption	N/A
Distribution	30% protein bound
Metabolism	Nil
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

55% of candidates passed this question.

Overall answers were well structured. However, a lack of detail and inaccurate pharmacokinetics was common. Better answers included a discussion of the mechanism of action of Mg++ including Ca++ antagonism, presynaptic cholinergic effects and NMDA receptor antagonism. Adverse effects were not discussed in detail by many candidates and contraindications were commonly omitted.

Online resources for this question

Question 5

Question

Describe the anatomical course and relations of the trachea and bronchial tree (to the level of the segmental bronchi).

Example answer

Trachea

10-12cm long fibromuscular tube
Continuation of the larynx (at ~C6) and divides into the left and right main bronchi at the level of the carina (~T5)
Relations
- Superior: larynx
- Anterior: manubrium, thyroid, brachiocephalic trunk, thymus
- Posteriorly: oesophagus, recurrent laryngeal nerve
- Right lateral: thyroid, right common carotid a., right vagus nerve, azygous vein. Eventually the right lung and pleura,
- Left lateral: thyroid, left common carotid, arch of aorta, left subclavian artery, left recurrent laryngeal nerve. Eventually the left lung and pleura,

Bronchi

Left main bronchi
- 5cm long, courses leftward
- More horizontal and smaller diameter than right main bronchi
- Relations: azygos vein, right pulmonary artery (ant), pulmonary veins, oesophagus (post)
Right main bronchi
- 2.5cm long, courses rightward
- More verticle and larger in diameter than left main bronchi
- Relations: pulmonary hilum - aortic arch, descending aorta, left pulmonary artery, left pulmonary veins

Lobar bronchi

Each main bronchi gives rise to lobar bronchi
- Right: upper, middle and lower lobe bronchi
- Left: upper and lower lobe bronchi
Each lobar bronchi gives rise to segmental bronchi
- 10 segmental bronchi on each side (left / right) corresponding to the 'bronchopulmonary segments'
- Left
  - LUL: Apical, Superior, Inferior, Anterior
  - LLL: Anterior, Lateral, Posterior, Superior
- Right
  - RUL: Apical, Posterior, Anterior
  - RML: Lateral, Medial,
  - RLL: Superior, Medial, Anterior, Lateral, Posterior
Relations: predominately alveoli, pleura and accompanying pulmonary arteries/veins at this stage

Addit: mnemonics for remembering bronchopulmonary lung segments

Right lung
- 'A PALM Seed Makes Another Little Palm'
  - RUL: Apical, Posterior, Anterior
  - RML: Lateral, Medial,
  - RLL: Superior, Medial, Anterior, Lateral, Posterior
Left lung
- 'ASIA ALPS'
  - LUL: Apical, Superior, Inferior, Anterior
  - LLL: Anterior, Lateral, Posterior, Superior

Examiner comments

24% of candidates passed this question.

Better answers included details of the significant structures related to the cervical and mediastinal trachea and bronchi. The lobar branches and bronchopulmonary segments requiring naming to attract full marks. Many answers lacked sufficient detail or contained inaccuracies regarding vertebral levels and key structural relations. Some candidates discussed the general anatomy of the airway, including the larynx, structure of the airways, blood supply and innervation. This did not attract marks.

Online resources for this question

Question 6

Question

Outline the factors that determine central venous pressure and explain how it is measured.

Example answer

Overview

CVP is the venous blood pressure measured at or near the right atrium
Normally 0-6mmHg in spontaneously breathing non-ventilated patient
Measurement taken at end-expiration

Measurement

Most commonly measured using central venous catheter (CVC)
- CVC 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
Echocardiography can provide non-invasive estimations off the CVP
Visual inspection of the height of the JVP can provide some bedside clinical insight

Factors determining CVP

Central venous blood volume
- Increased total blood volume (e.g. renal failure) = increased MSFP > 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 > 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, PPV, or a tension pneumothorax will lead to increased CVP
Measurement technique
- Level of the transducer will clearly influence the CVP measured
- Timing of the measurement with respiratory cycle

Examiner comments

18% of candidates passed this question.

It was expected that answers include central venous blood volume, central venous vascular compliance, intrathoracic pressure and tricuspid valvular function. Good answers outlined how each of these factors determine CVP and whether it was increased or decreased. Many candidates incorrectly described the effect of venous return.

Online resources for this question

Question 7

Question

Define closing capacity (10% of marks). Describe the factors that alter it (30% of marks), its clinical significance (30% of marks) and one method of measuring it (30% of marks).

Example answer

Closing capacity

The point in expiration when the small airways begin to collapse
Small airway closure occurs because the elastic recoil of the lung overcomes the negative intrapleural pressure keeping the airway open.
More likely to occur in dependant parts of the lung where airways are smaller (due to effects of gravity).
Closing capacity = residual volume + closing volume

Significance of closing capacity

If closing capacity exceeds the FRC then small airway collapse occurs during tidal respiration
- This leads to shunt > V/Q mismatch > impairs oxygenation > hypoxaemia
- This also leads to gas trapping > reduced compliance
High CC will therefore also
- Decrease the effect of anaesthetic pre-oxygenation
- Increases dependant atelectasis.
  - Cyclic opening/closing of airways due to increased atelectasis > lung injury

Factors affecting closing capacity

Age
- Normally CC is less than FRC at a young age
- Increasing age > increasing closing capacity
  - At age 44, supine FRC = closing capacity
  - At age 66, erect FRC = closing capacity
Expiratory gas flow
- Increase flow > increased closing capacity
Pathology
- Parenchymal/airway disease (e.g. COPD) > loss of tissue available for radial traction > (closing capacity > FRC)
- Decreased surfactant > increased surface tension > increasing collapsing pressure > increased CC
- Increased pulmonary blood volume (e.g. CCF) > increased weight compressing small airways > increased CC

Measurement of CC

Closing capacity = closing volume + residual volume
Closing volume
- Measured using the single breath nitrogen washout test
- Subject exhales to residual volume
- Pure oxygen inhaled to TLC
- Subject breaths out through a nitrogen sensor (records N2 concentration vs time curve)
- Phase 4 of this curve indicates the closing volume.
Residual volume
- Cannot be directly measured
- FRC is first calculated by body plethysmography (or other methods)
- ERV measured using spirometry
- Residual volume is the difference between FRC and ERV

Examiner comments

49% of candidates passed this question.

Many candidates confused the factors that affect closing capacity (CC) with factors which affect functional residual capacity (FRC). Some candidates confused airway closure with expiratory flow limitation secondary to dynamic airway compression. A good answer would have included the following:
Small airway closure occurs because the elastic recoil of the lung overcomes the negative intrapleural pressure keeping the airway open. Thus, airway closure is more likely to occur in dependant parts of the lung where airways are smaller. Normally closing capacity is less than FRC in young adults but increases with age. Closing capacity becomes equal to FRC at age 44 in the supine position and equal to FRC at age 66 in the erect position. Closing capacity is increased in neonates because of their highly compliant chest wall and reduced ability to maintain negative intrathoracic pressures. In addition, neonates have lower lung compliance which favours alveolar closure. Closing capacity is also increased in subjects with peripheral airways disease due to the loss of radial traction keeping small airways open.
The consequences of airway closure during tidal breathing include shunt and hypoxaemia, gas trapping and reduced lung compliance. In addition, cyclic closure and opening of peripheral airways may result in injury to both alveoli and bronchioles. Closing volume (CV) may be measured by the single breath nitrogen washout test or by analysis of a tracer gas such as xenon during a slow exhaled vital capacity breath to residual volume. Residual volume (RV) cannot be measured directly but is calculated as follows: the FRC is measured using one of three methods: helium dilution, nitrogen washout or body plethysmography. The expiratory reserve volume (ERV) may be measured using standard spirometry. Using the measured FRC and ERV we may calculate RV from the equation:
RV = FRC â€“ ERV. Then CC = RV + CV.

Online resources for this question

Question 8

Question

Outline the pharmacology of drugs used to treat asthma.

Example answer

Oxygen

Increases FiO2 > increased SaO₂ (by increasing P_AO₂ as per Alveolar gas equation).
Given by numerous devices (nasal prongs, masks, NIV, ETT)
Dose titrated to SaO₂
- Hypoxemia is harmful (but optimal target SaO₂ unclear)
- Generally titrated to Sats 94-98% (with caveats for some subgroups of patients)
- Hyperoxia may lead to hypercapnia, worsening of V/Q mismatch (through alteration of HPVC), lung damage

Beta-adrenergic agonists

Long acting B2 selective agonists (e.g. salmeterol) are used in prevention
Short acting B2 selective agonists (e.g. salbutamol) are preferred first line therapy for exacerbation
Nonselective adrenergic agonists (e.g. adrenaline) can also be used in severe exacerbations
SABAs can be given inhaled (via spacer), nebulised or via IV infusion (if unresponsive to inhaled)
Example: Salbutamol
- Short acting B2 agonist
- MOA: Acts on B₂ receptors (Gs protein coupled receptors) in bronchial smooth muscle cells > activates activates adenyl cyclase-CAMP system > increase cAMP > decreased intracellular Ca > SM relaxation / bronchodilation
- Side effects: Tachycardia, Anxiety, tremor, Hypokalaemia, lactic acidosis

Anticholinergics

Example: ipratropium bromide
Routes: Inhaled, nebuliser
MOA: Competitive antagonism of muscarinic ACh receptors > bronchodilation + decreased secretions
Side effects: dry mouth, N/V, headache, blurred vision

Corticosteroids

Examples: hydrocortisone (IV), prednisone (PO), budesonide (inhaled)
Systemic corticosteroids should be given to all mod-severe asthma > improve outcomes
MOA: bind to cytoplasmic glucocorticoid receptors > change in gene transcription > down-regulates the synthesis of proinflammatory cytokines/mediators
Effects: increased B receptor responsiveness, decreased inflammation, decreased mucus secretion
Side effects: numerous! Depends on dose/duration. Examples:
- Short term: hyperglycaemia, hypokalaemia, immunosuppression, insomnia/confusion/psychosis,
- Long term: cushings, osteoporosis, skin thinning, weight gain, immunosuppression

Other potential treatment options (and MOA)

Magnesium sulphate > inhibits L type calcium channels > bronchodilation/SM relaxation
Ketamine >inhibits L type calcium channels > Bronchial smooth muscle relaxation
Aminophylline > PDEI > SM relaxation / bronchodilation
Heliox > Improves laminar airflow > may improve ventilation

Examiner comments

29% of candidates passed this question.

Answers should have included the most important aspects of the pharmacology of the most commonly used drugs e.g. class, mechanism of action, pharmacodynamics and important adverse reactions. More information on beta-agonists and corticosteroids (mainstays of management) was expected than drugs like magnesium, ketamine and other adjunctive treatments.

Online resources for this question

Question 9

Question

Compare and contrast the pharmacology of propofol and midazolam.

Example answer

Name	Midazolam	Propofol	Notes/comparisons
Class	Benzodiazepine (sedative)	Phenolic derivative (IV anaesthetic)	-
Indications	Anaesthesia, sedation, treatment of seizures, anxiolysis	Anaesthesia, sedation	-
Pharmaceutics	IV: clear solution, pH 3.5. High water solubility	White, opaque, liquid emulsion. Contains soybean oil, egg lecithin, glycerol. Poor water solubility	Midaz clear, propofol distinctive white colout
Routes of administration	IV, IM, S/C, intranasal, buccal, PO	IV
Dose	Dose depends on many pt. factors. 1-5mg premedication. 2.5-10mg seizures. Infusions.	RSI 1-2mg/kg. Infusion (4-12mg/kg/hr)
pKa	6.5	11 (almost completely unionised)	Propofol has higher pKa
Pharmacodynamics
MOA	Allosteric modulator of GABA_A receptors (ionotropic ligand gated channel) in the CNS. Binds to distinct site from GABA. Leads to Cl enters > hyperpolarisation.	Propofol binds to B subunit of GABA_A receptor > Cl enters > hyperpolarisation	Midaz binds to site distinct from GABA
Effects	CNS: sedation, amnesia, anticonvulsant effects, decreased cerebral O2 demand	CNS: depression, anti-epileptic, decreased CMRO2/CBF/ICP RESP: depression, apnoea	Both cause sedation and respiratory depression
Side effects	CVS: bradycardia, hypotension CNS: confusion, restlessness RESP: respiratory depression/ apnoea	RENAL: green urine CNS: depression, pain injection site CVS: decreased SVR > hypotension, bradycardia MET: high lipids	Both cause cardiovascular instability and respiratory depression
Pharmacokinetics
Onset	peak effect 2-3 minutes (IV)	Seconds	Propofol has faster onset / offset
Absorption	~40% oral bioavailability Absorbed well, but sig. 1st pass metabolism	IV Only (high first pass metabolism)	Propofol is IV only
Distribution	95% protein bound, very lipid soluble Vd = 1L / kg	98% protein bound VOD 2-10L/kg Readily crosses BBB	Both highly protein bound.
Metabolism	Hepatic metabolism by hydroxylation Active (1-a hydroxymidazolam) and inactive metabolites	Hepatic > inactive metabolites (glucuronides and sulphates)	Both metabolised by liver. Midaz has active metabolites
Elimination	Renal excretion T 1/2 = 4 hours	Renal excretion Bolus T1/2 - 120s.
Special points	Flumazenil - antagonist (reversal agent)	No reversal agent

Examiner comments

77% of candidates passed this question.

Highlighting important similarities and differences between the drugs scored higher marks than listing the pharmacology of each drug separately. More pharmacokinetic information was required than simply stating both drugs â€œare metabolized in the liver and excreted by the kidneyâ€.

Online resources for this question

Question 10

Question

Describe the principles of capnography, including calibration, sources of error and limitations.

Example answer

Capnography

The graphical display of expired CO₂ concentration over time
This is different to ETCO₂ (which is the CO₂ concentration at end-expiration) and capnometry (which is the measurement of CO₂ concentration)

Measurement / Principles

CO₂ concentrations (capnometry) is measured in clinical practice using infrared spectroscopy and applying the principles of the Beer-Lambert Law
- The concentration of CO₂ is measured by exploiting the differences in CO2 absorption of light in the NIR spectrum. With the degree of absorption related to concentration of substance.
Components: light emitting diode, photosensor, circuitry, microprocessor, output device
Can be monitored using 'side stream' (sampling line with sensor) or 'inline' (sensor directly inline with breathing system) methods
Calibration: capnometers are zeroed to room air

Limitations + Sources of error

Cannot distinguish Nitrous Oxide (N₂O shares similar absorption spectra to CO₂)
Not diagnostic
- Waveforms are helpful in assessment (e.g. of bronchospasm, oesophageal intubation) but not diagnostic
- Patients may have mixed disorders which lead to increased and decreased ETCO₂ which are cancelled out and appear falsely normal
Side stream monitoring have short delay in measurement and small air leak
In line monitoring devices increase dead space (more relevant in paeds)
Sensor is susceptible to blockage by secretions
Incorrect calibration
Water condensation > absorbs IR light > overestimates CO2

Examiner comments

31% of candidates passed this question.

Answers that scored well followed the structure outlined in the question and explained the principles of each component of the question.

Online resources for this question

Question 11

Question

Outline the composition of plasma (50% of marks). Describe the functions of albumin (50% of marks).

Example answer

Plasma

Cell free liquid component of blood
Constitutes ~55% of circulating blood volume
Components
- 92% water
- 7% proteins (Albumin, globulin, fibrinogen)
- ~1% other (carbohydrates, lipids, gases, hormones, electrolytes)

Proteins (~7% plasma)

60-80g/L in blood
Albumin
- Majority of plasma protein (35-45g/L)
Globulins
- Second largest component (25-35g/L)
- Subtypes
  - <math display="inline">\alpha</math>1 globulin (<math display="inline">\alpha</math>1 antitripsin, <math display="inline">\alpha</math>-lipoproteins)
  - <math display="inline">\alpha</math>2 globulin (Haptoglobin, prothrombin, <math display="inline">\alpha</math>2 macroglobulin)
  - <math display="inline">\beta</math>-globulins (CRP, transferrin)
  - <math display="inline">\gamma</math> globulins (Immunoglobulins)
Fibrinogen
- 1-5 g/L
Clotting factors

Other solutes (~1% plasma)

Carbohydrates (i.e. glucose)
Lipids (e.g. LDL, VLDL, HDL, TGs)
Gases (e.g. oxygen, carbon dioxide)
Hormones (e.g. thyroxine, cortisol, IGF-1)
Electrolytes (e.g. Na, Cl, HCO3, K, Mg, Ca)

Albumin (functions)

Osmotic pressure
- Responsible for 80% of the plasma colloid osmotic pressure
- Helps keep fluid intravascularly
Transport function
- Transports hormones (e.g. thyroxine), fatty acids, electrolytes (e.g. calcium) and drugs
Extracellular acid-base buffer
- Imidazole side chains can bind hydrogen ions and can buffer against change to pH
Anticoagulant
- Has heparin like activity. Low albumin attenuates fibrinolysis
Protein store:
- ~50-60% of plasma protein
Anti-oxidant effect
- Abundant in thio groups which readily scavenge reactive oxygen and nitrogen species
Inflammatory marker
- Negative phase protein (decreases in response to inflammation)

Examiner comments

30% of candidates passed this question.

A good answer began with a definition of plasma and then listed the components - water, albumin, globulins, fibrinogen and other proteins before mentioning the lipid content, nutrient content, wastes and electrolytes. Frequently the breakdown of the globulin component was inaccurate. A common omission was dissolved gas components. Descriptions of the calculation of oncotic pressure and GFR were not asked and hence did not attract marks.
The functions of albumin may be subdivided into: Osmotic pressure, transport function, acid-base buffer, anti-oxidant, anticoagulant effect, protein store, metabolism and 'other'.

Online resources for this question

Question 12

Question

Define pain. Outline the processes by which pain is detected in response to a peripheral noxious stimulus

Example answer

Pain

"An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage" (IASP, 2020)
Can be broadly classified by duration (e.g. acute vs chronic) or aetiology (e.g. visceral vs neuropathic)

PAIN PATHWAY

Nociceptors

Free unmyelinated nerve endings which convert noxious stimuli into action potentials (APs)
Activation
- Activated by thermal, mechanical, and chemical stimuli
- Sensitised by inflammatory mediators (e.g bradykinin, histamine, Substance P)
Leads do conformational change in nociceptor > ion channel opening > depolarisation
Relay APs from the nociceptor receptor to the dorsal horn of the spinal cord (primary afferent)
- Neuron may travel up/down the tract of Lissauer 1-2 levels prior to synapsing in the dorsal horn
Two types of nociceptor neurons
- Type A<math display="inline">\delta</math> fibres
  - Impulses from mechanical and thermal stimuli
  - Large, myelinated, fast (40m/s)
- Type C fibres
  - Impulses from thermal, mechanical and chemical stimuli
  - Small, unmyelinated, slow (2m/s)

Second order neurons (afferent)

Synapse with primary afferents in Dorsal horn
Decussates in the anterior commissure, ascends in the spinothalamic tract, synapses in the thalamus with third order neurons

Third order neuron (afferent)

Relays information from the thalamus to the cerebral cortex for central processing of pain

PAIN MODULATION

Descending inhibition
- Neurons from periaqueductal grey matter project to the spinal cord
- Noradrenaline and serotonin are main neurotransmitters
- Have inhibitory effects on the synapse of 1st/2nd order neurons
Segmental inhibition
- Initially thought to be due to gate control theory
- Now other mechanisms though to be responsible
Endogenous opioid system
- (e.g. endorphins) which can bind to opioid receptors > reduced nociception

Examiner comments

33% of candidates passed this question.

Starting with the WHO definition of pain, followed by a brief description of the nature of noxious stimuli (thermal, mechanical, chemical) then proceeding to mention the nature of the cutaneous receptors would have been a very good start to this question. Following this, a description of the various substances involved in pain (K, prostaglandins, bradykinin, serotonin, substance P) and outlining the types of nerve fibres involved in pain transmission and how they synapse in the spinal cord and cortex was expected. The presence and nature of the descending inhibitory pathways was mentioned by very few.

Online resources for this question

Question 13

Question

Describe the exocrine functions of the pancreas.

Example answer

Exocrine function of pancreas

~1L - 1.5L of exocrine pancreatic secretions are produced per day
Pancreatic (exocrine) secretions are
- Isotonic
- Alkaline (pH ~8) - Rich in HCO3
- Main cation is Na
Pancreatic secretions are important for
- Reducing acidity of contents from stomach (rich in HCO3)
- Assisting in completion of digestion (contains enzymes)

Main components of exocrine secretions

Bicarbonate
- Produced by ductal cells (up to 150mmol/L)
- Indirect process driven by Na/H exchanger in basolateral membrane
  - CO2 dissolves into ductal cell. Converted to HCO3 and H+
  - H+ is pumped back out (NA/H exchanger) to maintain gradient
  - HCO3 > facilitated diffusion into lumen
Digestive enzymes
- Produced by rough ER in acinar cells
- Stored in zymogen granules as pro-enzymes while awaiting release
- Enzymes
  - Proteases
    - Includes trypsinogen and chromotripsinogen (converted to active form by enterokinase in duodenum)
    - Hydrolyse peptide bonds between amino acids
  - Amylase
    - Secreted in active form
    - Hydrolyses glycogen, starch other carbohydrate complexes > disaccharides
  - Lipases
    - Lipase and phospholipase
    - Hydrolyses TGs to glycerol and fatty acids
  - Other enzymes
    - Elastase (breaks down eleastic tissue)
    - Ribonuclease/deoxyribonuclease (break down RNA/DNA)
Water and electrolytes

Control of exocrine secretions

Neural and hormonal control
Cephalic phase
- Thought, taste, sight, smell food > increased PSNS (vagal activity)
- Vagal (ACh mediated) efferents innervate the acinar cells
- Leads to release of pancreatic juice (~20%)
Gastric phase
- Mechanical stretch of stomach by food
- Leads to increased PSNS (Vagal activity) + Gastrin release (from G cells in stomach/duodenum)
- Leads to release of pancreatic juice (~10%)
Intestinal phase
- Acidification of duodenum (from stomach acid) > increased pancreatic exocrine secretion
- Mediated by secretin (released from S cells of duodenum) and CCK (enteroendocrine cells in duodenum)
- Major factor which leads to increased secretion of pancreatic juice.
Inhibitory factors
- Glucagon
- Somatostatin

Examiner comments

33% of candidates passed this question.

Most candidates were able to mention some pancreatic enzymes, though often in insufficient detail to attract full marks. The amount, type, pH, etc. of pancreatic secretions was often not included. Many candidates did not describe the stimuli for pancreatic secretion. Better answers described the cephalic, gastric and intestinal phases of pancreatic secretion.

Online resources for this question

Question 14

Question

Outline the classification and effects of beta-blocking drugs with examples (50% of marks). Compare and contrast the pharmacokinetics of metoprolol with esmolol (50% of marks).

Example answer

Classification of beta blockers

All beta blockers are competitive antagonists
Can be classified according to
- Receptor selectivity
  - Non selective (B1 and B2) e.g. sotalol, propranolol
  - B1 selective e.g. metoprolol, esmolol, atenolol
  - A and B effects: labetalol, carvedilol
- Membrane stabilising effects
  - Stabilising e.g. Propanolol, metoprolol, labetalol
  - Non stabilising e.g. atenolol, esmolol, bisoprolol
- Intrinsic sympathomimetic activity
  - ISA e.g. labetalol, pindolol
  - Non ISA e.g. metoprolol, sotalol, propranolol, esmolol

Effects of beta blockers

B1 antagonism
- Heart: decreased inotropy and chronotropy (decreased BP), decreased myocardial oxygen consumption + increased supply (increased diastolic time), decreased dromotropy
- Kidneys: decreased renin release > decreased RAAS activation > decreased BP
B2 antagonism
- Respiratory: bronchoconstriction
- Circulation: vasoconstriction
- Skeletal muscle: reduced glucose uptake
- Eye: decreased aqueous humour production > decrease
B3 antagonism
- Adipose tissue: reduced lipolysis

Compare/contrast metoprolol and esmolol pharmacokinetics

Name	Metoprolol	Esmolol
Pharmacokinetics
Onset	Immediate when IV	Immediate (only given IV
Absorption	95% absorption, 50% oral bioavailability (1st pass effect)	0% oral bioavailability
Distribution	VOD 5 L/kg 10% Protein bound High lipid solubility, readily crosses BBB	VOD 3L/kg 60% protein bound High lipid solubility, can cross BBB
Metabolism	- Hepatic CYP450 - Significant 1st pass metabolism. - Inactive metabolites	- Blood - Hydrolysis by RBC esterase > inactive metabolites
Elimination	Renal excretion T 1/2 approx 4 hours	Renal excretion T 1/2 10 mins

Examiner comments

47% of candidates passed this question.

Beta-blocking drugs were generally well classified. Selectivity, membrane stabilising activity and ISA should have been mentioned. Many candidates omitted or poorly answered the â€˜effectsâ€™ of beta blockers. Candidates who performed well answering the pharmacokinetics of metoprolol and esmolol provided a table of the two drugs. Superficial statements such as â€œhepatic metabolism and renal excretionâ€ attracted minimal marks. The mechanism of action of beta blockers was not requested

Online resources for this question

Question 15

Question

Define clearance and hepatic extraction ratio (30% of marks). Describe the role of the liver in drug clearance with examples (70% of marks).

Example answer

Clearance

The volume of plasma that is cleared of a drug per unit time (ml/min)
<math display="inline">Clearance = \frac {elimination \ rate}{plasma \ concentration}</math>

Hepatic Extraction Ratio (HER)

The fraction of drug entering the liver in the blood that is irreversibly removed as it is filtered through during one pass
Can be expressed by

<math display="block">ER (Hepatic) = \frac {FU \times Cl_{int} } {Q_H \; + \; FU \; \times Cl_{int}}</math>

Whereby
- FU = fraction of unbound drug in plasma (drug bound to protein cannot be cleared)
- <math display="inline">Cl_{int}</math> = intrinsic hepatic enzymatic capacity
- <math display="inline">Q_H</math> = hepatic blood flow

Hepatic clearance

The two major determinants of hepatic clearance are the HER and the hepatic blood flow

<math display="block">Clearance_{Hepatic} = Q_H \times ER_{Hepatic}</math>

Effect of hepatic blood flow changes in relation to HER
- For drugs with low ER (e.g. diazepam, warfarin) increasing Q_H leads to:
  - Minimal increase in clearance (capacity limited)
  - Decreased hepatic ER (more pronounced relatively)
- For drugs with high ER (e.g. propofol and GTN) increasing Q_H leads to:
  - Marked increase in clearance (flow limited)
  - Decreased hepatic ER (less pronounced relatively)

Role of liver in drug clearance
- Liver is heavily involved in drug metabolism
  - Phase 1 metabolic reactions
    - Involves oxidation (loss of electrons), reduction (gain of electrons) and hydrolysis (addition of H₂O molecule)
    - Driven predominately by the Cytochrome p450 system and esterases in liver
    - E.g. metabolism of Propofol, benzodiazipines, opioids, volatiles anaesthetics
    - There can be significant variability in activity of CYP enzymes which leads to variability in drug response (e.g. CYP2C19 polymorphism > variability in phenytoin and clopidogrel metabolism)

Phase 2 reactions
- Involves conjugation (increasing water solubility)
  - Typically occurs in hepatic endoplasmic reticulum
  - Includes glucuronidation (e.g. morphine), sulfation (e.g. quetiapine), acetylation (e.g. hydralazine), methylation (e.g. catecholamines)

Examiner comments

70% of candidates passed this question.

Clearance was generally well answered. It is the volume of plasma cleared of a drug per unit time, not the mass of drug cleared. An equation was helpful in identifying the relevant components of hepatic clearance.
ClHep=QH X ERHep
ERHep= FU x ClInt / QH + FU x ClInt
QH = hepatic blood flow
ERHep = hepatic extraction ratio
FU = fraction of drug unbound in plasma
ClInt = hepatic enzymatic capacity
Many candidates did not describe the effects of hepatic blood flow and intrinsic clearance on drugs with high and low hepatic extraction ratios. Some discussion of Phase I and II reactions was also expected.

Online resources for this question

Question 16

Question

Compare the structure, function and coronary circulation of the right and left ventricles

Example answer

Structure/blood supply

	Right ventricle	left ventricle
Shape	More triangular	More conical
Valves	Tricuspid (3 valve leaflets + papillary muscle) Pulmonary (3 cusps: right, left, anterior)	Mitral (2 valve leaflet + papillary muscle) Aortic (3 cusps: Right, left, posterior)
Wall thickness	Relatively thinner (2-5mm)	Relatively thicker (5-10mm)
Mass	Lighter (25g)	Heavier (100g) - due to increased afterload on LV
Position in chest	Right/anterior	Left/posterior
Arterial supply	Predominately RCA	Predominately LAD, LCx, PDA
Venous drainage	Small + anterior cardiac veins	Great and middle cardiac veins
Blood flow	Constant, maximal flow rate during systole (majority still occurs in diastole due to increase duration)	Intermittent (no flow in early systole), maximal flow rate + total flow occurs diastole

Function/Physiology

	Right ventricle	Left ventricle
Function	Receive deoxygenated blood from systemic circulation > pump to pulmonary circulation	Receive oxygenated blood from pulmonary circulation and pump to the systemic circulation
Blood flow	RA > tricuspid valve > RV > pulmonary valve > pulmonary trunk	LA > mitral valve > LV > aortic valve > aorta
C VO2	Lower	Higher
EDV	Higher	Lower
ESV	Higher	Lower
Stroke volume	Equal	Equal
Systolic pressure	Lower (~15-25mmhg)	Higher (~120mmHg)
Diastolic pressure	Lower (0-5mmhg)	Higher (5-15mmHg)
ESPVR (contractility)	Lower	Higher
EDPVR (elastance)	Lower	Higher
Ea (afterload)	Lower	Higher
Work	Lower	Higher

Examiner comments

27% of candidates passed this question.

The question sought information on the structure (anatomy), function (physiology) and vascular supply of the right and left ventricle. Good answers provided detail in each section e.g. values for ventricular pressure rather than simply stating â€œhigh- and low-pressure systemsâ€.
Many marks may be gained by a simple anatomical description & labelled PV loop for each ventricle. Many candidates focussed solely on the coronary circulation, to which only a proportion of the marks were allocated.

Online resources for this question

Question 17

Question

Explain respiratory compliance and outline the factors that affect it.

Example answer

Respiratory compliance

<math display="inline">Compliance \; = \; \frac{\Delta \;volume}{\Delta \; pressure}</math>
Compliance in the respiratory system (C_RS) is a function of lung (C_lung) and chest wall (C_CW) compliance
- <math display="inline">\frac {1}{C_{RS}}\; = \; \frac {1}{C_{Lung}} \; + \; \frac {1}{C_{CW}}</math>
- Chest wall and lung compliance are roughly equal in healthy individual
Normal compliance of the respiratory system is approximately 200mls.cmH2O
Static compliance
- Compliance of the respiratory system at a given volume when there is no flow
Dynamic compliance
- Compliance of the system when there is flow (respiration)
- Will always be less than static compliance due to airway resistance
- At a normal RR is approximately equal to static compliance
Specific compliance
- The compliance of the system divided by the FRC
- Allows comparisons between patients which are independent of lung volumes

Factors effecting compliance

Chest wall

Increased
- Collagen disorders such as Ehlers-Danlos syndrome
- Cachexia
- Rib resection
Decreased
- Obesity
- Kyphosis / scoliosis / Pectus excavatum
- Circumferential burns
- Prone positioning

Lung compliance

Increased
- Normal ageing
- Emphysema
- Upright posture
- Lung volume (highest compliance at FRC)
Decreased
- Loss of surfactant (E.g. ARDS, hyaline membrane disease)
- Loss of functional lung volume (e.g. pneumonia, lobectomy, pneumonectomy, atelectasis)
- Pulmonary venous congestion (pHTN) and interstitial oedema (APO)
- Reduced long elasticity (e.g. Pulmonary fibrosis)
- Positioning (e.g. supine positioning)

Examiner comments

51% of candidates passed this question.

Answers were generally well structured. Better answers described lung and chest wall compliance and the pressures which are used to calculate compliance. Better answers displayed an understanding of dynamic, static and specific compliance and provided a reasonably comprehensive list of the physiological factors affecting chest and lung compliance.

Online resources for this question

Question 18

Question

Compare and contrast the pharmacology of metaraminol and noradrenaline

Example answer

Name	Noradrenaline	Metaraminol
Class	Endogenous catecholamine	Synthetic non-catecholamine
Indications	Vasopressor (Hypotension/shock)	Vasopressor (hypotension/shock)
Pharmaceutics	Clear solution. 1:1000. Brown ampule (prevent light oxidation). Diluted in dextrose.	Clear solution. Typically 0.5mg/ml syringes, or 10mg/ml vials.
Routes of administration	IV only (central vein)	IV, IM
Dose	Infusion titrated to effect (generally 0 - 0.5 mcg/kg/min)	0.5mg boluses, infusion
pKA	8.85	8.79
Pharmacodynamics
MOA	Predominately Alpha 1 agonism. Some beta adrenergic receptor agonism. a1 > B1 > B2	Direct and indirect alpha-1 agonism (very weak B agonism)
Effects	CVS: peripheral vasoconstriction > increased SVR > inc. BP	CVS: peripheral vasoconstriction > increased SVR > increased BP. Also increased PVR. Reflex bradycardia.
Side effects	CVS: Hypertension, reflex bradycardia, increased afterload Extravasation > necrosis Renal, hepatic vasoconstriction > decreased blood flow	CVS: Increased afterload > worsen heart failure, bradycardia
Pharmacokinetics
Onset	Immediate	Immediate
Absorption	IV only (0% oral bioavailability)	IV (though some oral bioavailability)
Distribution	Does not cross BBB. 25% taken up in lungs.	VOD = 4L/kg 45% protein bound
Metabolism	Readily metabolised intro adrenaline by MAO and COMT	Not metabolised
Elimination	Excreted in urine as inactive metabolites (>85%). Half life ~2 mins	Minutes, renal elimination
Special points	Tachyphylaxis (slow) Effect exaggerated in patients taking MAOI (less breakdown)	Tachyphylaxis (fast( with infusion))

Examiner comments

71% of candidates passed this question.

Marks were distributed across pharmaceutics, uses, dose & administration, mechanism of action, Pharmacokinetcs and Pharmacodynamics. Common omissions were doses/rates of infusion, effects other than on heart/SVR (e.g. splanchnic, renal blood flow), indirect effect of metaraminol, receptor effect of noradrenaline other than alpha 1 and tachyphylaxis.

Online resources for this question

Question 19

Question

Describe the pharmacology of atropine.

Example answer

Name	Atropine
Class	Naturally occurring tertiary amine. Muscarinic antagonist.
Indications	Bradycardia Organophosphate poisoning Counteract muscarinic effects of anticholinesterases drying of secretions
Pharmaceutics	Clear colourless solution. 600mcg/ml. Racemic mixture with the L-isomer being active
Routes of administration	IV, IM, topical (eye)
Dose	600mcg - repeated administration can be given
Pharmacodynamics
MOA	Competitive antagonism of muscarinic anticholinergic receptors
Effects	CVS: increased HR (and CO), decreased AV conduction time RESP: bronchodilation GIT: Drying of secretions
Side effects	CNS: Hallucinations, confusion, amnesia, delirium, central anticholinergic syndrome GIT: dry mouth, delayed GIT motility CVS: may cause initial transient bradycardia when given slowly MSK: inhibits sweating
Pharmacokinetics
Onset	Seconds. Duration 2-3hours
Absorption	IV
Distribution	50% protein bound. VOD=3L/kg. Crosses blood brain barrier and placenta
Metabolism	Extensive hepatic hydrolysis into tropine and tropic acid
Elimination	Renal elimination of metabolites. T 1/2 approx 2 hours
Special points

Examiner comments

53% of candidates passed this question.

Most candidates used a good structure to compose their answer. Better candidates understood that CNS effects occur as atropine is a tertiary amine that crosses the blood brain barrier. The mechanism of action was required. Indications for use should have included bradycardia, organophosphate poisoning, drying of secretions etc. Reasonably extensive details regarding pharmacodynamics was expected, including potential toxic effects. There was limited knowledge regarding pharmacokinetics.

Online resources for this question

Question 20

Question

Compare the pharmacology of piperacillin-tazobactam and ciprofloxacin

Example answer

Name	Piperacillin-Tazobactam	Ciprofloxacin
Class	Semi-synthetic penicillin (piperacillin) B-lactamase inhibitor (tazobactam)	Fluroquinolone
Indications	Pseudomonal infection Broad spectrum antimicrobial cover of severe infections/sepsis	Effective for many infections (skin, joint, gastro, UTI, LRTI)
Pharmaceutics	Powder, reconstitutes in water/NaCl/glucose	Tablet (250-750mg) or yellowish powder for dilution.
Routes of administration	IV/IM	IV, PO
Dose	4g/0.5g 8hrly or 4g/0.5g 6hrly (pseudomonas cover) Dose reduced renal failure	250-750mg BD (PO), 200-400mg BD/TDS (IV)
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)	Bactericidal - Inhibits DNA gyrase and topoisomerase IV > inhibits DNA synthesis
Antimicrobial cover	Broad spectrum coverage of gram positive bacteria, gram negative bacteria, anaerobes. Covers pseudomonas. Doesn't cover: MRSA, VRE, ESBL, atypical	Broad spectrum (GN > GP). Effective against pseudomonas + anthrax. Effective against some atypicals (legionella, mycoplasma). No anaerobe cover.
Side effects	GIT: diarrhoea, nausea, vomiting Renal: AKI Allergy (up to 10%), rash most common, skin eruptions/SJS and anaphylaxis (<1/10,000)	MSK: tendon rupture, arthritis, myalgia CNS: peripheral neuropathy, headache GIT: nausea, vomiting, abdominal pain, dyspepsia CVS: Qtc prolongation, arrhythmias RENAL: AKI, nephritis
Pharmacokinetics
Absorption	Minimal oral absorption > IV Peak concentrations immediately after dose.	70% oral bioavailability
Distribution	Very good tissue penetration (minimal CNS without active inflammation) Low protein binding (<30%)	Low protein binding (25%). Great tissue penetration. VOD 2.5L/kg.
Metabolism	Piperacillin: not metabolised Tazobactam: metabolised to M1, an inactive metabolite	Limited hepatic metabolism (15%)
Elimination	Renal (80% unchanged) T 1/2 2 hrs	Renal excretion of metabolites. T1/2 3-5 hours.
Special points	Removed by haemodialysis	Worldwide resistance to quinolones is increasing

Examiner comments

58% of candidates passed this question.

This question was most effectively answered using a tabular format. Only a minority of candidates demonstrated a comprehensive knowledge of these level 1 drugs and very few candidates compared the two in areas which lent themselves to comparison. The spectrum of activity generally lacked detail. Few candidates mentioned that piperacillin-tazobactam had superior gram-positive cover, both have extensive gram-negative cover including Pseudomonas. Piperacillin-tazobactam is effective against anaerobes; whilst ciprofloxacin has some atypical cover against Mycoplasma.
The mechanism of action was generally well described for piperacillin; many candidates incorrectly stated the mechanism of action for ciprofloxacin, confusing the drug with a macrolide. Better answers included time- dependant and concentration-dependent killing. The concept of half-life was frequently confused with the dosing interval.
Minimal marks were awarded for â€œallergyâ€ and â€œgastrointestinal side-effectsâ€. Better candidates mentioned Liver function derangement, neutropenia, interstitial nephritis for piperacillin and tendonitis for ciprofloxacin.

2019 (2nd sitting)

Question 1

Question

Example answer

Examiner comments

Online resources for this question

Similar questions

Question 2

Question

Example answer

Examiner comments

Online resources for this question

Similar questions

Question 3

Question

Example answer

Examiner comments

Online resources for this question

Similar questions

Question 4

Question

Example answer

Examiner comments

Online resources for this question

Similar questions

Question 5

Question

Example answer

Examiner comments

Online resources for this question

Similar questions

Question 6

Question

Example answer

Examiner comments

Online resources for this question

Similar questions

Question 7

Question

Example answer

Examiner comments

Online resources for this question

Similar questions

Question 8

Question

Example answer

Examiner comments

Online resources for this question

Similar questions

Question 9

Question

Example answer

Examiner comments

Online resources for this question

Similar questions

Question 10

Question

Example answer

Examiner comments

Online resources for this question

Similar questions

Question 11

Question

Example answer

Examiner comments

Online resources for this question

Similar questions

Question 12

Question

Example answer

Examiner comments

Online resources for this question

Similar questions

Question 13

Question

Example answer

Examiner comments

Online resources for this question

Similar questions

Question 14