Master essential chemical pathology concepts for Year 5 ENT students. This Semester 1 guide covers key diagnostic tests, disease mechanisms, and their clinical
CHEMICAL PATHOLOGY SEM 1 First 4 given in class --- SECTION A: CASE-BASED SHORT ANSWER QUESTIONS (40 Marks Total) QUESTION 1: SIADH / Hyponatremia (10 marks) An elderly male smoker is admitted with acute confusion. Examination reveals digital clubbing and a right-sided pleural effusion. Laboratory results show: - Serum sodium: 118 mmol/L - Serum osmolality: 236 mOsm/kg - Urine osmolality: 350 mOsm/kg - Urine sodium: 50 mmol/L - Urea and creatinine: normal Chest radiograph shows a right lower-zone mass suggestive of carcinoma. a) What is the most likely cause of his hyponatremia? (2 marks) b) State two biochemical features characteristic of SIADH. (2 marks) c) Explain why the urine osmolality is high despite hyponatremia. (2 marks) d) Name the lung tumour most commonly associated with SIADH. (2 marks) e) State one major risk of rapid correction of hyponatremia. (2 marks) --- ANSWER 1: a) Most likely cause: (2 marks) Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) secondary to ectopic ADH production by lung carcinoma (paraneoplastic syndrome). b) Two biochemical features of SIADH: (2 marks) - Hyponatremia with low serum osmolality ( 100 mOsm/kg, usually 300 mOsm/kg) - Elevated urine sodium ( 40 mmol/L) despite hyponatremia, indicating continued sodium excretion due to volume expansion c) Explanation of high urine osmolality: (2 marks) In SIADH, there is excessive and inappropriate secretion of ADH despite low serum osmolality. ADH acts on the collecting ducts of the kidney to increase water reabsorption, leading to concentrated urine. Normally, low serum osmolality should suppress ADH, resulting in dilute urine, but in SIADH this feedback mechanism is overridden. d) Lung tumour most commonly associated with SIADH: (2 marks) Small Cell Lung Carcinoma (SCLC) - accounts for approximately 75-80% of cases of ectopic ADH production. SCLC is of neuroendocrine origin and can synthesize and secrete ADH autonomously. e) Major risk of rapid correction: (2 marks) Osmotic Demyelination Syndrome (ODS) , formerly called Central Pontine Myelinolysis. Rapid correction ( 10-12 mmol/L in 24 hours) causes acute osmotic stress on brain cells that have adapted to chronic hyponatremia, leading to irreversible brainstem damage with quadriplegia, pseudobulbar palsy, and altered consciousness. --- QUESTION 2: Thiazide + Laxative Abuse (Hypokalemic Metabolic Alkalosis) (10 marks) A 67-year-old woman presents with profound muscle weakness. She has a long history of laxative use and was recently started on a thiazide diuretic. Investigations show severe hypokalemia and metabolic alkalosis. a) What is the most likely biochemical abnormality? (2 marks) b) Briefly explain how thiazide diuretics cause hypokalemia. (2 marks) c) Explain how chronic laxative abuse produces metabolic alkalosis. (3 marks) d) Mention one common ECG change seen in hypokalemia. (2 marks) e) State the first-line management for severe hypokalemia. (1 mark) --- ANSWER 2: a) Most likely biochemical abnormality: (2 marks) Hypokalemic metabolic alkalosis with hypochloremia - combined effect of thiazide diuretic and chronic laxative abuse leading to severe potassium and chloride depletion. b) Mechanism of thiazide-induced hypokalemia: (2 marks) Thiazide diuretics inhibit the Na-Cl cotransporter in the distal convoluted tubule, causing: - Increased sodium delivery to the collecting duct - Enhanced sodium reabsorption via epithelial sodium channels (ENaC) - Increased potassium secretion in exchange for sodium (via ROMK channels) - Net result: urinary potassium loss and hypokalemia c) Mechanism of laxative-induced metabolic alkalosis: (3 marks) Chronic laxative abuse causes: - Gastrointestinal bicarbonate loss initially - laxatives cause diarrhea with loss of bicarbonate-rich fluid from the colon - Volume depletion - chronic diarrhea leads to extracellular fluid loss - Contraction alkalosis - volume depletion stimulates aldosterone secretion, which:Increases renal hydrogen ion excretion (via H+-ATPase in collecting duct) - Increases bicarbonate reabsorption in proximal tubule - Enhances potassium loss, worsening hypokalemia - Hypokalemia perpetuates alkalosis - low potassium causes intracellular shift of hydrogen ions and increased renal acid excretion d) Common ECG changes in hypokalemia: (2 marks) U waves (prominent U waves after T waves, best seen in V2-V3) Other changes include: ST depression, T wave flattening/inversion, prolonged QT interval, increased P wave amplitude e) First-line management: (1 mark) Intravenous potassium chloride replacement - KCl infusion (rate usually 10-20 mmol/hour via peripheral line, or faster via central line in severe cases), with continuous cardiac monitoring. --- QUESTION 3: Shock + Acute Abdomen (Severe Metabolic Acidosis) (10 marks) A 60-year-old man presents with severe abdominal pain for 24 hours. He is shocked, has a rigid distended abdomen, and absent femoral pulses. Arterial blood gases show: - pH: 7.05 - PaCO₂: 26.3 mmHg - PaO₂: 90 mmHg - HCO₃⁻: 7 mmol/L a) Identify the acid–base disturbance present. (2 marks) b) Explain the biochemical mechanism producing this metabolic acidosis. (3 marks) c) Why is the PaCO₂ low in this patient? (2 marks) d) What is the most likely underlying diagnosis? (2 marks) e) State two causes of markedly elevated lactate in acute abdomen. (1 mark) --- ANSWER 3: a) Acid-base disturbance: (2 marks) Severe metabolic acidosis with appropriate respiratory compensation (partially compensated metabolic acidosis with high anion gap) b) Biochemical mechanism: (3 marks) The severe metabolic acidosis results from: - Lactic acidosis - absent femoral pulses indicate vascular insufficiency (likely acute mesenteric ischemia or ruptured abdominal aortic aneurysm) - Anaerobic metabolism - tissue hypoperfusion forces cells to undergo anaerobic glycolysis, producing lactate instead of CO₂ and water - High anion gap - accumulation of lactate (unmeasured anion) increases the anion gap - Shock state - inadequate tissue oxygen delivery leads to cellular hypoxia and multi-organ dysfunction with acid accumulation c) Explanation of low PaCO₂: (2 marks) Respiratory compensation (Kussmaul breathing) - the low pH stimulates peripheral and central chemoreceptors, triggering hyperventilation to blow off CO₂ and partially correct the pH. The expected compensatory PaCO₂ can be calculated using Winter's formula: Expected PaCO₂ = 1.5 × HCO₃⁻ + 8 (±2) = 1.5 × 7 + 8 = 18.5 mmHg (±2). The measured PaCO₂ of 26.3 mmHg indicates appropriate compensation. d) Most likely underlying diagnosis: (2 marks) Acute mesenteric ischemia (due to superior mesenteric artery occlusion/thrombosis) Evidence supporting this: - Absent femoral pulses (peripheral vascular disease) - Severe abdominal pain out of proportion to examination - Rigid distended abdomen (bowel necrosis/perforation) - Severe lactic acidosis (bowel infarction) - Shock state Alternative diagnosis: Ruptured abdominal aortic aneurysm with bowel ischemia e) Two causes of elevated lactate in acute abdomen: (1 mark) - Bowel ischemia/infarction - mesenteric vascular occlusion - Septic shock - bowel perforation with peritonitis/sepsis --- QUESTION 4: Head Injury (Respiratory Alkalosis) (10 marks) A young woman is admitted unconscious following head trauma. CT scan reveals extensive cerebral contusions. She is hyperventilating at 38 breaths per minute. Arterial blood gas shows: - PaCO₂: 29 mmHg - HCO₃⁻: 19 mmol/L a) What acid–base disorder is present? (2 marks) b) Explain the mechanism of respiratory alkalosis in head injury. (3 marks) c) Why is the bicarbonate level slightly reduced after 3 days? (2 marks) d) State one effect of respiratory alkalosis on cerebral blood flow. (2 marks) e) Which area of the brain regulates the respiratory drive? (1 mark) --- ANSWER 4: a) Acid-base disorder: (2 marks) Acute respiratory alkalosis with partial metabolic compensation (or respiratory alkalosis with compensatory metabolic acidosis if