Master Physiology
for PMDC NLE Step 1

What the PMDC NLE Step 1 Tests in Physiology

PMDC NLE Step 1 Physiology tests the ability to apply homeostatic mechanisms and organ system physiology to clinical scenarios. Candidates must interpret arterial blood gas values (e.g., pH <7.35 for acidaemia, PaCO2 >45 mmHg for respiratory acidosis), calculate anion gap (normal 8–12 mEq/L), and identify compensatory responses. Renal physiology questions focus on GFR estimation (CKD-EPI formula), tubular function (e.g., SGLT2 inhibitors in diabetes), and acid-base handling. Cardiovascular physiology emphasises Frank-Starling mechanism, pressure-volume loops, and autonomic effects (e.g., baroreceptor reflex in haemorrhage). Respiratory physiology includes spirometry interpretation (FEV1/FVC <0.7 for obstruction), shunt vs. dead space, and oxygen dissociation curve shifts (right shift by 2,3-BPG, acidosis). Neurophysiology covers action potential propagation, synaptic transmission, and autonomic nervous system divisions. Endocrine physiology tests feedback loops (e.g., thyroid axis in Graves’ disease), insulin-glucose dynamics, and adrenal insufficiency (hyponatraemia, hyperkalaemia).

High-Yield Concepts

• Acid-Base Disorders: Winter’s Formula: For metabolic acidosis, expected respiratory compensation is PaCO2 = (1.5 × HCO3) + 8 ± 2. If measured PaCO2 is higher, suspect additional respiratory acidosis; if lower, respiratory alkalosis. In diabetic ketoacidosis, anion gap >12 mEq/L with ketonaemia; first-line treatment is IV 0.9% saline and insulin infusion (0.1 U/kg/hr).
• Renal: Tubular Transport Maximum (Tm): Glucose Tm is ~375 mg/min; when exceeded (e.g., in uncontrolled diabetes), glycosuria occurs. SGLT2 inhibitors (e.g., empagliflozin) lower renal threshold, used in type 2 diabetes with eGFR >30 mL/min/1.73m². For phosphate, Tm is regulated by PTH and FGF23; hypophosphataemia in oncogenic osteomalacia.
• Cardiovascular: Baroreceptor Reflex in Haemorrhage: Acute blood loss reduces arterial pressure, activating carotid sinus baroreceptors. Response: increased sympathetic outflow (tachycardia, vasoconstriction) and decreased vagal tone. Compensatory mechanisms maintain MAP until ~30% blood loss; then decompensatory bradycardia (vasovagal syncope) may occur.
• Respiratory: Spirometry in Obstructive vs. Restrictive: Obstructive pattern: FEV1/FVC <0.7 (e.g., COPD, asthma). Restrictive: FEV1/FVC normal or increased but TLC <80% predicted (e.g., pulmonary fibrosis). DLCO reduced in emphysema and fibrosis; normal in asthma. For acute asthma exacerbation, first-line: inhaled short-acting beta-agonist (salbutamol) and systemic corticosteroids.
• Endocrine: Thyroid Axis Feedback: Primary hypothyroidism: high TSH, low free T4. Secondary: low TSH, low free T4 (pituitary lesion). In Graves’ disease, TSH low, free T4 high, with positive TSH receptor antibodies. First-line treatment: carbimazole or propylthiouracil (in pregnancy first trimester).
• Neurophysiology: Resting Membrane Potential & Action Potential: Resting membrane potential ~ -70 mV, maintained by Na+/K+ ATPase (3 Na+ out, 2 K+ in). Depolarisation to threshold (~ -55 mV) opens voltage-gated Na+ channels (rapid upstroke). Absolute refractory period: Na+ channels inactivated; relative: some K+ channels open. Local anaesthetics (e.g., lidocaine) block Na+ channels, used for infiltration anaesthesia.
• Gastrointestinal: Gastric Acid Secretion: Parietal cells secrete HCl via H+/K+ ATPase (proton pump). Stimulated by histamine (H2 receptors), gastrin, and acetylcholine. Inhibited by somatostatin and prostaglandins. Proton pump inhibitors (omeprazole 20 mg daily) are first-line for peptic ulcer disease and GERD. H. pylori eradication: triple therapy (clarithromycin, amoxicillin, PPI).
• Haematology: Oxygen Dissociation Curve: Right shift (decreased affinity): increased 2,3-BPG, acidosis, hyperthermia, increased CO2 (Bohr effect). Left shift (increased affinity): alkalosis, hypothermia, decreased 2,3-BPG, carbon monoxide (CO) poisoning. In CO poisoning, PaO2 normal but SaO2 falsely low; treatment: 100% O2 or hyperbaric oxygen.

Common Traps in Physiology Questions

• Confusing respiratory acidosis compensation (renal retention of HCO3) with metabolic alkalosis; remember compensation never fully normalises pH.
• Assuming that a high anion gap always indicates metabolic acidosis; it can be seen in alkalosis with volume contraction (e.g., vomiting) due to increased unmeasured anions.
• Thinking that the Frank-Starling mechanism applies in heart failure with reduced ejection fraction; it is blunted due to decreased contractility and increased afterload.
• Mixing up the effects of PTH on renal phosphate handling (increases excretion) vs. vitamin D (increases absorption); PTH also increases calcium reabsorption in distal tubule.
• Forgetting that the baroreceptor reflex responds to rate of change, not just absolute pressure; chronic hypertension resets the set point.
• Believing that a left shift on the oxygen dissociation curve improves tissue oxygen delivery; it actually impairs unloading at tissues.

How to Revise Physiology for the PMDC NLE Step 1

Prioritise acid-base disorders (especially mixed), renal tubular function, and autonomic reflexes. Questions often present a clinical vignette (e.g., a patient with vomiting, hypotension, or dyspnoea) and ask for the underlying physiological derangement or compensatory mechanism. Practise interpreting ABGs, spirometry, and lab values (e.g., electrolytes, GFR). Focus on how physiology explains drug actions (e.g., loop diuretics inhibit Na-K-2Cl cotransporter in thick ascending limb). Use flowcharts for feedback loops (endocrine, baroreceptor). Review common pitfalls: compensatory vs. primary disorders, and the difference between shunt and dead space. Do not memorise isolated values; apply them in context.

Practise it: MedLumen has 50 Physiology questions for the PMDC NLE Step 1, each with a full explanation and references.