Sakurai 2016

2020B 01: 72% of candidates passed this question.
This question details an aspect of cardiac physiology which is well described in multiple texts. Comprehensive answers included both a detailed description of each action potential and a comparison highlighting and explaining any pertinent differences. The question lends itself to well-drawn, appropriately labelled diagrams and further explanations expressed in a tabular form. Better answers included a comparison table with points of comparison such as the relevant RMP, threshold value, overshoot value, duration, conduction velocity, automaticity, ion movements for each phase (including the direction of movement) providing a useful structure to the table. Incorrect numbering of the phases (0 – 4) and incorrect values for essential information (such as resting membrane potential) detracted from some responses.

Functional residual capacity

• Volume of air in lungs at the end of normal tidal expiration
• Occurs at equilibrium point between the recoil of chest/diaphragm and lungs to collapse inwards
• Sum of residual volume and expiratory reserve volume
• Normal FRC 30ml/kg (approx 2.2l in 70kg male)

Function of FRC

• Oxygen reservoir
  • Normally 270mls O2 → can be expanded to 1.8l if breathing FiO2 100%
• PaO2 buffer
  • Ensures no fluctuation in PaO2 between inspiration and expiration
• Prevents atelectasis
  • Normally FRC above closing capacity
  • Decreases V/Q mismatch
• Minimizes work of breathing
  • Minimizes airway collapse → resistance decreased
  • Minimizes alveolar atelectasis → decreased work required to re-inflate alveoli
• Lung kept at most compliant segment of compliance curve
• Decreases pulmonary vascular resistance
  • Extra-alveolar and alveolar capillaries kept open
  • Minimizes hypoxic vasoconstriction

Factors Affecting FRC

Sakurai / Gladwin / JC 2020

2020B 02: 79% of candidates passed this question.
This question was in two parts with the percentage of marks allocated an indication of the relevant time or detail expected per part. The second part of the question also contained two distinct headings which should have been used in the answer. As an outline question, dot points with a brief explanation of each point were expected. Most candidates drew diagrams, few of which added value. For a diagram to add value it should be accurate, have labelled axes, a scale with numerical values and units. As a general rule, diagrams should also be explained and help to illustrate or relate to a written point.
For factors affecting FRC, to score full marks, it should be clearly stated if the factor causes an increase or decrease in FRC. This topic is well covered in the recommended respiratory texts.

2020B 03: 69% of candidates passed this question.
Hydrocortisone is a level 1 drug in the syllabus. Most answers were well structured, many used key headings. In general, detailed information specific to hydrocortisone was lacking. Answers that focused on the mechanism of action, pharmacodynamic effects and pharmacokinetics effects which were detailed and accurate scored well. It was expected that significant detail be included in the sections with relevance to clinical practice for example, the mechanism of action and pharmacodynamic effects including the side effect profile. An indication/appreciation of the timelines of such was also represented in the marking template.

Fat

Carbohydrate

Protein

Gladwin 2016

2020B 04: 54% of candidates passed this question.
This question relates to basic hepatic physiology and is well described in the recommended texts.
The mark allocation and division of time was indicated in the question. Better answers used the categorisation in the question as an answer structure. Many candidates gave a good description of beta oxidation, the formation of Acetyl Co A and ketone synthesis. A description of the synthesis of cholesterol, phospholipids, lipoproteins and fatty acid synthesis from proteins and carbohydrates mainly using glycogen, glucose and lactate also received marks. Candidates seem to have a better understanding of fat and glucose metabolism than protein metabolism. Higher scoring candidates appreciated the anabolic and catabolic processes of each component.

Anatomy of SNS

• Posterior hypothalamus is the main site of sympathetic nervous outflow
• Receives input from cardiovascular centres of medulla and pons
• Sympathetic innervation from Sympathetic trunks
• Paired bundle of sympathetic neurons run lateral from vertebral bodies from T1 to L2
• Consists of two neurons in series
  • Short Pre-ganglionic neuron → Sympathetic ganglion → Long Post-ganglionic neuron

Origin

• Origin: Preganglionic fibres originate in the grey matter of the spinal cord lateral horn
• Nerve Fibres and Pathway: Leave the spinal cord through ventral roots (with spinal nerves)
  • Leave spinal nerves, travel as white rami communicantes (short myelinated B fibres)
  • Meet with the ganglia of the sympathetic trunk
    • Synapse with post-ganglionic neurons
• Neurotransmitter: Preganglionic neurotransmitter is acetylcholine
• Receptor: nicotinic receptors

Sympathetic trunk:

4 parts

• Cervical part
  • Head
  • Neck
  • Thorax
• Thoracic part (T1-T5)
  • Aortic plexus
  • Pulmonary plexus
  • Cardiac plexus
  • Thoracic splanchnic nerves
• Lumbar sympathetic ganglia
  • Coeliac plexus
• Pelvic part
  • Hypogastric plexus
  • Pelvic plexus

Post-ganglionic

• Nerve Fibres and Pathway: Post-ganglionic neurons leave the ganglia as grey rami communicantes
  • Long unmyelinated C fibres
  • Rejoin the spinal nerves to travel to target organs
• Neurotransmitter: Postganglionic neurotransmitter is noradrenaline
  • (acetylcholine in muscles, sweat glands and hair follicles)
• Receptor: Adrenergic alpha and beta receptors on target organs/vessels

Exception is adrenal medullary outflow:

• Modified post-ganglionic cells release adrenaline into circulation
• Innervated directly by pre-ganglion sympathetic fibres

Effects of SNS

Mooney / JC 2020

2020B 05: 51% of candidates passed this question.
Most candidates had a suitable structure to their answers, those without a clear organisation of thought tended to gain fewer marks. In many cases incorrect information or limited detail, particularly around the anatomical organisation prevented higher marks.

JC 2019

Click to Open CICMWrecks Pharmacopeia Table: Hypoglycaemic Agents

2020B 06: 37% of candidates passed this question.
High scoring answers most often started with a strong and logical structure and focused on the requested categories of information. Many candidates gave good answers across the wide range of drugs. Several candidates could have scored more highly by giving more correct information on biguanides and sulphonylureas,

Guo 2021

2020B 07: 22% of candidates passed this question.
This question is ideally suited to a tabular format, where candidates are expected to highlight the significant similarities and differences as well as why a certain monitor may be chosen in preference to another rather than compile two lists written next to each other. To score well in this question, a statement of what could be measured (ICP: global vs local), a description of the measurement principles, along with other measurement related information like calibration and sources of error was required. Also sought was information regarding anatomical placement (e.g., lateral ventricle for EVD) and method of placement. Furthermore, a comparison with each other (e.g., higher infection/bleeding risk with EVD, greater risk of trauma due to size and insertion, expertise to insert, cost, therapeutic benefit, risk of blocking) was required for completion. Candidates who structured these elements into advantages and disadvantages were generally able to elucidate this information and score better.

Afferent

• In response to chemical, mechanical or noxious stimuli in larynx, trachea, carina or bronchi
• Signal transduced via internal laryngeal nerve (vagus nerve)

Central processor

• Medullary respiratory centre
  • No single “cough centre” isolated

Efferent

Co-ordinated action of inspiratory muscles, pharyngeal muscles, and expiratory muscles

1. Inspiratory phase
   • Inhalation of a volume of air sufficient for cough generation (phrenic nerve and intercostal nerves)
2. Compressive phase
   • Closure of the glottis (recurrent laryngeal nerve)
   • Activation of expiratory muscle against closed glottis
   • Generation of transient increase in pressure of 300mmHg in thorax arterial blood and CSF
3. Expulsive phase
   • Opening of glottis due to posterio-cricoarytenoid muscle activation
   • High velocity flow generated in bronchi, trachea and larynx
     • “Choke point” – high velocity flow causes turbulant flow → increased shear stress between gas and airway lining → drag and expulsion of irritant

Intrinsic muscles of the larynx

• Cricothyroid
  • Upper lip of cricoid cartilage → Inferior aspect of thyroid cartilage
  • Innervated by superior laryngeal nerve
  • Tenses vocal cords – elevates vocal tone
• Thyroarytenoid
  • Anterior inner surface of thyroid à arytenoid cartilage
  • Innervated by inferior laryngeal nerve
  • Relaxes vocal cords – depresses vocal tone
• Posterior cricoarytenoid
  • Posterior aspect of cricoid cartilage → arytenoid cartilage
  • Innervated by inferior laryngeal nerve
  • Abducts vocal cords
• Lateral cricoarytenoid
  • Lateral aspect of cricoid cartilage → arytenoid cartilage
  • Innervated by inferior laryngeal nerve
  • Adducts vocal cords
• Transverse and Oblique arytenoids
  • Spans the arytenoid cartilages
  • Innervated by the inferior laryngeal nerve
  • Adducts vocal cords

Sakurai 2016

2020B 08: 62% of candidates passed this question.
Overall, this question was reasonably well answered. Those that performed well had suitably detailed knowledge and structured their responses which generally included a definition and purpose of the reflex as well as the identification and a description of the afferent, integrator/controller, and efferent limbs of the reflex. This structure allowed a logical platform for the elucidation of the detail required in the answer, including types of stimulus, receptors, nerves (for both limbs of the reflex) and the muscles used in the phasic response to be clearly articulated

MACRONUTRIENTS

CHNOPS (carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulphur)

Provide bulk energy

• Carbohydrates: compounds made up of types of sugar.
  • monosaccharides (such as glucose and fructose)
  • disaccharides (such as sucrose and lactose)
  • oligosaccharides
  • polysaccharides (such as starch, glycogen, and cellulose).
• Proteins: are organic compounds that consist of amino acids joined by peptide bonds.
  • Essential (cannot be manufactured in the body: phenylalanine, valine, threonine, tryptophan, methionine, leucine, isoleucine, lysine, and histidine) and non-essential
• Fats: glycerin molecule with three fatty acids attached.
  • Essential (alpha-linolenic acid (ω-3) and linoleic acid (ω -6)) and non-essential
  • Saturated and Unsaturated

MICRONUTRIENTS

Support metabolism

• Dietary minerals:  exogenous chemical elements indispensable for life
• Vitamins: organic molecules essential for an organism that are not classified as amino acids or fatty acids. They commonly function as enzymatic cofactors, metabolic regulators, or antioxidants.

Suggested daily nutritional requirements in humans

Please include common sources of specific nutrients – This is best done based on individual candidate’s method of presentation

JC 2020

2020B 09: 40% of candidates passed this question.
This topic is well covered in the recommended physiology textbooks. Many answers unfortunately simply listed the various components without providing sufficient detail; outline questions require some context around the key points as opposed to just a list. Most candidates had a good estimate for the basal energy requirements of a resting adult. Good candidates were able to outline the g/kg daily protein requirements and the distribution of remaining energy intake between carbohydrates and lipids and included how this may change during periods of stress. They also stated the energy derived per gram of each of those food groups. Few candidates mentioned the need to include essential amino acids. Similarly, with fat intake, few candidates mentioned the need for essential fatty acids. A definition of “vitamin” would have received credit. Most candidates were able to classify vitamins as water soluble or fat soluble. Most candidates mentioned trace elements (with an abbreviated list) and mentioned bone minerals. A daily intake requirement for Na and K was expected, though not for bone minerals or trace elements.

2020B 10: 63% of candidates passed this question.
This was a level 1 pharmacology question, and it represents core knowledge. The mechanism of action of suxamethonium and the interactions at the neuromuscular junction as well as pharmaceutics were areas that often required further detail. Few candidates mentioned the effects of suxamethonium on the autonomic nervous system. Another common omission related to the factors that reduce plasma cholinesterase activity beyond genetic deficiency (such as liver disease, renal failure, thyrotoxicosis). Pleasingly, there was generally a good understanding of role, dosing, side effect profile, pharmacokinetics and of special situations and limitations of use pertinent to this drug.

Definition:

Exercise = Strenuous physical activity where there is increased metabolic activity leading to increased requirement for energy and oxygen  

CVS changes to accommodate and compensate for such increase in metabolism

Normal parameters at rest:

Changes to CVS parameters:

Redistribution of blood flow

• Increased muscle activity -> increased o2 demand 
• Regional vasodilation
  • Increased local concentration of metabolites ie Co2, lactate, K+
  • Vasoactive mediator released by endothelium ie NO, ATP 
  • Sympathetic stimulation -> B2 adrenoceptor activation 
• Overall: decrease in vascular resistance to muscles -> increased blood flow 
• Corresponding vasoconstriction of viscera and skin

Increase in cardiac output

• Cardiac output can increase up to 0L/min
• Due to both increase in HR and SV and decreased afterload
• With increasing workload HR increases but SV decreases due to dec diastolic time

Guo 2021

2020B 11: 22% of candidates passed this question.
This is an applied physiology question. Better answers categorised the changes in some manner and included a measure of the degree of change as applicable (e.g., what increases, what decreases and what may stay the same). The question was to describe the changes so that the detail behind the mechanisms enabling these changes to occur was expected (e.g., neurohumoral, local factors). Marks were also awarded for any regional variation that occurs.

Physiology of Albumin

Pharmacology of Albumin

CICMWrecks Table – Albumin (Click to Open)

Guo / JC 2021

2020B 12: 19% of candidates passed this question.
The question required an equal treatment of the physiology and pharmacology of albumin. The physiology discussion needed to include synthesis, factors affecting synthesis, distribution in the body (including the proportion divided between the plasma and interstitial space), functions, breakdown, and elimination half-life. Discussion of the pharmacology should have included available preparations (4% and 20% Albumin) and pharmaceutics, distribution, elimination (both the protein and crystalloid components), mechanism of action to expand the plasma compartment, longevity in the plasma compartment, indications, and adverse effects. Oedema, circulatory overload, immunological reactions, and relative contraindication in brain injury were important to mention. There was some confusion regarding the infectious risks of albumin. An outline of the manufacturing process from donated plasma and pasteurisation was expected.

Anatomy

• Thin walled arteries and veins, contains little smooth muscle  → easily distorted by lung expansion
• Pulmonary arteries (deoxygenated blood) -> pulmonary capillaries (gas exchange) → pulmonary veins (oxygenated blood)

• Pulmonary capillaries are exposed to alveolar pressure and not supported by solid tissue → prone to collapse
• Contains 10% of circulating blood volume – 500mls

Physiology

• General:
  • Low pressure 25/8 MPAP 15mmHg
  • Low resistance 20-120 dynes.sec.cm-5
  • Flow: total of cardiac output 5L/min
• Pulmonary blood volume
  • ~500mls of blood – blood reservoir
  • Varies over course of the respiratory and cardiac cycle and in response to gravity
  • Varies in response to changes in intrathoracic pressure
• Pulmonary blood pressure
  • Normal PA systolic pressure = 18-25 mmHg
  • Normal PA diastolic pressure = 8-15 mmHg
  • Normal mean pulmonary arterial pressure = 9-16 mmHg
  • Capillary pressure is 8-10 mmHg
  • Venous pressure 6-12 mmHg
• Resistance
  • The resistance in the pulmonary circulation can be calculated as follows:
  • PVR = 80 × (mPAP- PAOP)/CO
  • The normal value for PVR is 100-200 dynes/sec/cm-5
  • Approximately 1/10th of systemic circulation
• Regulation of blood flow/resistance
  • West zones
    • In zone 1, PA > Pa > Pv No flow of blood
    • In zone 2, Pa > PA > Pv Resistance to flow is determined by alveolar pressure (Starling resistor effect)
    • In zone 3, Pa > Pv > PA Resistance to flow is determined by venous pressure Venous pooling causes increased distension of pulmonary capillaries
    • In zone 4 Low lung volume causes narrowing of extra-alveolar vessels
  • Hypoxia – pulmonary hypoxic vasoconstriction
  • Lung volumes

• Regional distribution
  • Distension of partially collapsed capillaries 
  • Recruitment of completely collapsed capillaries
  • Local mediators: NO, prostacycline
• Function
  • Gas exchange
  • Filtration of clots and debris
  • Immunological – pulmonary macrophages, IgA production
  • Metabolic – metabolism of drugs, removal of proteases
  • Endocrine – source of ACE

Guo 2021

2020B 13: 25% of candidates passed this question.
The examiners consider that an understanding of the pulmonary circulation is core area of the syllabus. In general, the anatomy section was better answered than the physiological features. As well as a description of the gross anatomy of the pulmonary circulation tracking it from the pulmonary valve to the left atrium, some mention of the microscopic anatomy was required (e.g., that the pulmonary arteries are thin walled with little smooth muscle).
For the second part of the question, a breadth of knowledge was required. Candidates were expected to address the following physiological features of the pulmonary circulation: volume, pressure, resistance, regulation and regional distribution and function. Marks were apportioned to each section, so it was important to write something on each section. Focussing on one section in detail (e.g., a very detailed description of West’s Zones) usually came at the expense of missing one or more of the other sections, most commonly the functions of the pulmonary circulation. Indeed, candidates that scored well provided information on each section and for the functions of the pulmonary circulation mentioned more than gas exchange.

Cartilages

• Unpaired
  • Thyroid cartilage – Level of C4~5
  • Cricoid cartilage
  • Epiglottis
• Paired
  • Arytenoid
  • Cuneiform
  • Corniculate

Muscles

• Intrinsic
  • Cricothyroid
    • Originates in cricoid cartilage and inserts into thyroid
    • Tenses vocal cords and elevates voice
  • Thyroarytenoid
    • Originates in thyroid cartilage and inserts into arytenoid cartilage
    • Relaxes vocal cords and depresses voice
  • Posterior cricoarytenoid
    • Abducts the vocal cords
  • Lateral cricoarytenoid
    • Adducts the vocal cords
  • Oblique and transverse arytenoids
    • Adducts the vocal cords
• Extrinsic
  • Strap muscles

Innervation

Sensory

• Internal branch of superior laryngeal nerve

Motor

• Cricothyroid – External branch of the superior laryngeal nerve
• All other intrinsic muscles – Recurrent laryngeal nerve

Blood supply

• Superior laryngean artery (branch of external carotid)
• Inferior laryngeal artery (branch of thyrocervical trunk from subclavian artery)

Associations

• The thyroid glands lie inferolateral to the larynx (lateral to the cricoid, the isthmus is inferior to the cricoid)
• The oesophagus, anterior longitudinal ligament, cervical vertebrae lies posterior to the larynx
• The brachiocephalic trunk may arch superiorly close to the cricothyroid membrane in an anatomical variant

Sakurai 2016

2020B 14: 40% of candidates passed this question.

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

2020B 15: 41% of candidates passed this question.
The objective of this question was that candidates relay a detailed knowledge of both drugs with respect to their individual pharmacology highlighting the important clinical aspects of each drug (e.g., mechanism of action, metabolism, duration of effect). Then an integration of this knowledge was in the contrast section where the better candidates highlighted features of the drug that would influence when or why one may use it with respect to the second agent. Tabular answers of the pharmacology of each drug without any integration or comparison scored less well. A detailed knowledge of both agents was expected to score well.

Volume and composition of gastric juice:

• 2-2.5 L/day of gastric juice is produced
• It contains:
  • H2O and electrolytes (> 99.5%)
    • Gastric juice is slightly hyperosmotic (325 mOsm/L) with ↑ H+ (150-170 mmol/L), ↑ Cl- (190 mmol/L), and ↑ K+ (10 mmol/L), but ↓ Na+ (2-4 mmol/L) → cf. plasma
    • It is also more acidic (pH 1-1.5) → due to ↑ H+ content
  • Solid material (< 0.5%)
    • Digestive enzymes – Pepsin, Gastric lipase, Gastric amylase
    • Mucous in alkaline fluid (HCO3 – -rich)
    • Intrinsic factor

Gastric Acid Secretion:

Parietal cells contain an H⁺-K⁺ ATPase (exchange) pump – GPCR – cAMP dependent

• This pump is activated in response to increased levels of intracellular Ca²⁺ from stimulation by:
  • ACh
  • Histamine (H₂)
  • Gastrin
• Inhibited by:
  • Low gastric pH
  • Somatostatin

Process:

• H⁺ is produced by action of carbonic anhydrase on CO₂ and water, with ‘waste’ HCO₃^– removed from the cell in exchange for Cl^–.
  • Respiratory quotient of the stomach may become negative due to consumption of CO₂
• HCO3^– :
  • transported out of the basolateral membrane in exchange for chloride.
  • Outflow into blood results in a slight elevation of blood pH known as the “alkaline tide”. This process serves to maintain intracellular pH in the parietal cell.
• Chloride and potassium ions are transported into the lumen of the cannaliculus by conductance channels, and such is necessary for secretion of acid.
• Hydrogen ion is pumped out of the cell, into the lumen, in exchange for potassium through the action of the proton pump; potassium is thus effectively recycled.

Regulation of gastric juice secretion:

• Cephalic phase → 50% of gastric juice secretions
  • Initiated by thought, sight, taste and smell of food
  • Mediated via vagal (ACh) outflow
• Gastric phase → ~ 50% of gastric juice secretions (prolonged secretion at a slower rate)
  • Initiated by entry of food into stomach
  • Mediated by – (i) Local and vago-vagal reflexes → due to distension of body (of stomach), and (ii) Gastrin release from G-cells → due to antral distension
• Intestinal phase → < 1% gastric juice secretion
  • Initiated by chyme entering duodenum
  • Mediated by enterogastric neural (ANS/ENS) and hormonal (CCK, VIP, GIP, Etc.) reflexes

JC 2019

2020B 16: 26% of candidates passed this question.
The is question was divided into two sections offering equal marks. The first section required a description of the generation and transport of both H+ and Cl into the stomach lumen by the parietal cell. The contributions of basolateral and luminal ion channels, the role of carbonic anhydrase and accurate description of the net flux was expected for full marks. The second section required comments on the roles of neural and endocrine regulation. Increased acid secretion via acetylcholine (via muscarinic M3), histamine (via H2) and gastrin were expected as was reduced secretion via secretin and somatostatin. Better responses were able to combine and integrate these into cephalic, gastric, and intestinal phases. The nature and function of other gastric secretions and the role of pharmacologic agents was not asked for and therefore not awarded any marks.

2020B 17: 24% of candidates passed this question.
Nitric Oxide (NO) is an inorganic colourless and odourless gas presented in cylinders containing 100/800 ppm of NO and nitrogen. Many candidates mentioned oxygen instead of nitrogen. The exposure of NO to oxygen is minimized to reduce formation of nitrogen dioxide and free radicals. Hence it is administered in inspiratory limb close to the endotracheal tube. Many candidates did not mention the contraindications/caution for NO use. Candidates generally did well in mentioning the impact on improving V/Q mismatch by promoting vasodilatation only in the ventilated alveoli and reducing RV afterload. Many candidates did not mention the extra cardio-respiratory effects. The expected adverse effects of NO were nitrogen dioxide related pulmonary toxicity, methemoglobinemia and rebound pulmonary hypertension on abrupt cessation. Pharmacokinetics of NO carried a significant proportion of marks. It was expected that the answers would involve mention of location of delivery of NO in inspiratory limb and reason behind it, the high lipid solubility and diffusion, the dose (5-20ppm), very short half-life of < 5 seconds and combination with oxyhemoglobin to produce methaemoglobin and nitrate. The main metabolite is nitrate which is excreted in urine.

Afterload

• Load against which the muscle exerts its contractile force (Guyton)
• It is represented by the gradient of the line connecting the end-diastolic volume, to the end-systolic point
• pressure which the ventricle has to contract against (Power & Kam)

Determinants of Afterload

Modified Laplace Equation

• where
  • T represents afterload
  • P represents aortic pressure
    • Therefore, afterload increases as aortic (or pulmonary arterial) pressure increases
  • R represents ventricular radius
    • Afterload increases as ventricular radius increases
  • H represents ventricular thickness
    • Afterload decreases as the thickness of the ventricular wall increases (hypertrophy secondary to chronic hypertension and cardiac remodelling)

Modified Hagen-Poiseuille Equation

• Afterload is affected by resistance to cardiac output
  • Afterload increased by reduced radius of systemic vasculature
  • Afterload increased by increasing viscosity of blood

Resistance in parallel

• Afterload is affected by addition, or loss of large capillary networks in parallel
  • Systemic vascular resistance is increased significantly by loss of placenta, with parallel vascular networks
  • Pulmonary vascular resistance is decreased significantly by inflation of lung, causing creation of vast capillary network in parallel

Factors affecting Right Ventricular Afterload

• Pulmonary vascular resistance increases afterload
  • Hypoxic vasoconstriction increases PVR
  • Lung volumes
    • Pulmonary vascular resistance minimal at FRC
• Increased pulmonary artery pressure increases RV afterload
  • Left heart failure
  • Critical mitral stenosis, mitral regurgitation
  • Pulmonary emboli
• Right ventricular outflow tract obstruction increases afterload
  • Pulmonary stenosis
  • Saddle pulmonary embolism
• Right ventricular dilation
  • Susceptible due to thin RV wall
  • Acute PE
    • RV spiral of death
      • Increased intraventricular pressure decreases blood flow à ischaemia à decreased contractility à further increase in ventricular volume

Factors affecting Left Ventricular afterload

systemic vascular resistance, aortic impedance and ventricular radius

According to La Place Equation

• Aortic pressure
  • Afterload increases as aortic pressure increases (increases with hypertension)
• Ventricular radius
  • Afterload increases as ventricular radius increases (increases with ventricular dilation)
• Ventricular wall thickness
  • Afterload decreases and ventricular wall thickness increases (decreases with ventricular hypertrophy)

Determinants of aortic pressure indirectly affect afterload

• Aortic compliance
  • Afterload decreases with increased compliance
• Arterial blood volume
  • Given set compliance, afterload will increase with arterial volume
• From Modifed Poisuille-Hagen Equation
  • Radius of aorta
    • Autonomic vasomotor tone
    • Increased intrathoracic pressure
    • Physical compression
  • Viscosity of blood
• From equation MAP = CO / SVR
  • Tissue flow autoregulation
    • Myogenic
    • Metabolic

Other

• Left ventricular outflow tract obstruction
  • Aortic stenosis
  • HOCM
  • Coarctation of aorta

Sakurai 2016

2020B 18: 53% of candidates passed this question.
Afterload can be defined as factors resisting ventricular ejection and contributing to myocardial wall stress during systole. Most answers utilised the law of Laplace to expand upon factors affecting ventricular wall tension. Systemic vascular resistance was commonly mentioned, but less frequently defined. Aortic and left ventricular outflow tract impedance were commonly referred to. Effects of preload and neurohumoral stimuli were less well outlined. Description of factors affecting right ventricular afterload and depictions of left ventricular pressure volume loops earned no extra marks unless directly referenced to the question.

Non-volatile acid

” An acid produced from sources other than carbon dioxide, which cannot be excreted in the lungs. “

• e.g. lactate, sulphate, phosphate and ketone bodies
• 70-100mmol non-volatile acid produced per day
• 4000-5000mmol HCO₃^– filtered by glomerulus per day
• Renal acid-base is largely determined by handling of bicarbonate ions
  • 80% of filtered bicarbonate resorbed in proximal tubule
  • 20% resorbed in distal tubule and collecting duct
  • Urinary Buffers (Dibasic Phosphate and ammonia) play a role

Bicarbonate Resorption

Proximal tubule

In the tubular cell:

• H⁺ leaves the tubular cell through the apical membrane via
  • H⁺/Na⁺ antiporter (secondary active transport via Na⁺/K⁺ ATPase on basolateral membrane)
• The HCO₃^– re-enters the circulation via the Na/HCO₃^– symporter
• H⁺ combines with HCO₃^– in tubule to form H₂CO₃
• H₂CO₃ switches back to CO₂ and H₂O, CO₂ is resorbed to turn back into the tubular cell to generate more HCO₃ for resorption

More bicarbonate resorbed when:

• Higher filtered HCO₃^–
• Higher PaCO₂
• Lower luminal flow rate
• Angiotensin 2

Distal convoluted tubule and collecting duct

• Similar mechanism with regards to resorption of HCO₃^– via secretion of H⁺
• Difference is that H⁺ is transported across the apical membrane via an H⁺ ATPase (active transport)

Role of Buffers

• The maximum urinary pH is 4.5
• To eliminate more protons, they must be buffered in the tubular fluid
• H⁺ is bound preferentially to buffers only in the presence of low tubular HCO₃^–
• Buffering, and so elimination of H⁺ without its conjugate HCO₃^–, requires resorption of HCO₃^– in the proximal convoluted tubule

Phosphate (HPO₄^2-):

• Becomes concentrated in tubules
• pKa = 6.8, so operates effectively as a buffer at tubular pH

Ammonia

• Glutamine broken down in tubular epithelia cells to two NH₄⁺ and two HCO₃^–
  • Comes from hepatic amino acid metabolism
• The new HCO₃^– is transported back to the circulation via the Na/HCO₃^– symporter to re-enter the circulation
• NH₄⁺ becomes ion trapped in the tubular fluid
• Proximal tubular fluid is not acidic enough to keep NH₄⁺ in the tubule
• It is resorbed in the ascending limb, moves through the medulla to re-enter the collecting duct
• Here urine has a low pH, and so NH₄⁺ can be eliminated with its proton attached

Mooney 2016

2020B 19: 51% of candidates passed this question.
This question required candidates to understand the renal response to an acid load. It was expected that candidates would answer with regard to recycling of bicarbonate in the proximal tubule, excretion of titratable acid via the phosphate buffer system and generation of ammonium and its role in acid secretion. Many candidates had a good understanding of the bicarbonate system but used this to explain the secretion of new acid.

2020B 20: 49% of candidates passed this question.
This was a straightforward pharmacology question relating to a relatively common and archetypal intensive care medication. The structure of the question was well handled by most of the candidates; easily falling into the classic pharmaceutics, pharmacokinetic and pharmacodynamics framework. Many candidates had a superficial knowledge of the presentation and formulation of the drug, aside from its light sensitivity. Better answers detailed the drug according to the above-mentioned framework but also accurately highlighted specific points relevant to the ICU practise such as the metabolic handling of sodium nitroprusside and relating this to the consequences of the various metabolic products.