Practice 13 structured short- and long-answer medical questions on Endocrine & Renal Pathology. Review model answers for exam revision.
Answer: This document provides comprehensive notes on endocrine and renal pathology, covering a range of diseases affecting the adrenal glands, pancreas, parathyroid glands, and kidneys. It details the definitions, causes, clinical presentations, diagnostic methods, morphological features, and treatment strategies for conditions such as adrenal insufficiency, Cushing's syndrome, hyperaldosteronism, phaeochromocytoma, and various types of diabetes mellitus. Additionally, it delves into parathyroid disorders, porphyrias, renal function evaluation, acute and chronic kidney injury, and renal calculi. The document also includes information on lung tumours, their paraneoplastic syndromes, and lung transplantation, highlighting key features and management approaches for each. ## Key Points - **Adrenal Insufficiency (Addison's Disease):** Inadequate cortisol and potentially aldosterone production, with primary causes including autoimmune disease and TB, and secondary causes often linked to prolonged steroid use. Diagnosis involves an ACTH stimulation test, and treatment requires hormone replacement. - **Cushing's Syndrome:** Chronic excess cortisol, categorized by exogenous steroid use (most common) or endogenous causes like pituitary adenomas (Cushing's disease) or ectopic ACTH production. Clinical features include central obesity and hypertension. - **Hyperaldosteronism (Conn's Syndrome):** Excess aldosterone leading to hypertension and hypokalaemia, often caused by adrenal adenomas or hyperplasia. The aldosterone:renin ratio is a key diagnostic marker. - **Phaeochromocytoma:** A catecholamine-secreting tumour of the adrenal medulla, characterized by the "5 Ps" (palpitations, perspiration, pallor, pain, pressure). Diagnosis relies on elevated urinary catecholamines and metanephrines, with alpha-blockade preceding surgical removal. - **Diabetes Mellitus:** Types 1 (autoimmune beta-cell destruction) and 2 (insulin resistance and beta-cell exhaustion) have distinct mechanisms, onset, and clinical features. Diagnosis is based on glucose levels and HbA1c, with management focused on glycemic control and preventing complications. - **Parathyroid Disorders:** PTH regulates calcium and phosphate. Primary hyperparathyroidism involves autonomous PTH secretion, often from an adenoma, leading to hypercalcaemia. Secondary hyperparathyroidism results from chronic hypocalcaemia, commonly due to renal failure. - **Porphyrias:** Enzyme defects in haem biosynthesis leading to toxic accumulation. Acute porphyrias cause neurological symptoms, while cutaneous porphyrias manifest with photosensitivity. - **Renal Function Evaluation:** GFR is the primary marker of kidney function, assessed via eGFR. Urine studies, including casts and crystals, aid in diagnosing specific renal pathologies. - **Acute Kidney Injury (AKI):** A rapid decline in kidney function, classified as prerenal, intrinsic renal damage (ATN, AIN, GN), or postrenal obstruction. - **Chronic Kidney Disease (CKD):** Persistent kidney damage or reduced GFR for over three months, most commonly caused by diabetic and hypertensive nephropathy. Complications include anaemia, secondary hyperparathyroidism, and cardiovascular disease. - **Renal Calculi:** Kidney stones formed from calcium oxalate, uric acid, struvite, or cystine, presenting with severe colic and haematuria. Treatment varies based on stone type and size. - **Lung Tumours:** Adenocarcinoma, squamous cell carcinoma, and small cell carcinoma are the main types, strongly associated with smoking. Paraneoplastic syndromes and local effects are common. - **Lung Transplantation:** A treatment for end-stage lung disease, with early complications including infections and later complications like acute rejection and chronic bronchiolitis obliterans. ## Detailed Notes ### 1. ADRENAL INSUFFICIENCY (ADDISON'S DISEASE) **Definition:** Inadequate cortisol ± aldosterone production. **Primary causes:** Autoimmune (#1 in developed world), TB (#1 in developing world), Waterhouse-Friderichsen syndrome, metastases, fungal infections. **Secondary causes:** Prolonged steroid use (#1 overall), pituitary tumours, Sheehan's syndrome. | Feature | Primary | Secondary | |---|---|---| | ACTH | ↑ High | ↓ Low | | Aldosterone | ↓ Low | Normal | | Hyperpigmentation | Yes | No | | Hyperkalaemia | Yes | No | | Cause | Adrenal destroyed | Pituitary/hypothalamus fails | **Clinical:** Fatigue, weight loss, postural hypotension, salt craving, nausea, hypoglycaemia, hyperpigmentation (primary only). **Diagnosis:** Short ACTH stimulation test (gold standard), ↑ACTH (primary), ↓ACTH (secondary), hyponatraemia, hyperkalaemia, anti-21-hydroxylase antibodies. **Morphology:** - Autoimmune → small atrophic glands, lymphocytic infiltration, cortical fibrosis - TB → enlarged, caseating granulomas, Langhans giant cells - Waterhouse-Friderichsen → bilateral haemorrhagic necrosis, DIC **Treatment:** Hydrocortisone + fludrocortisone (primary only). Stress dose during illness/surgery. Patient education — emergency injection, MedicAlert bracelet. ### CASE 8.1
Answer: **Q: What is the diagnosis and explain the findings.** **A:** Primary autoimmune adrenal insufficiency (Addison's disease). - Hyperpigmentation → ↑ACTH stimulates melanocytes (POMC precursor shared with MSH) - Postural hypotension → aldosterone deficiency → Na⁺ loss → volume depletion - Hyponatraemia + hyperkalaemia → aldosterone deficiency - Hypoglycaemia → cortisol deficiency → impaired gluconeogenesis - Failed ACTH stimulation test → adrenal cortex destroyed, cannot respond - ACTH 500 ng/L (10× normal) → no feedback suppression from cortisol - Positive anti-adrenal antibodies → confirms autoimmune cause ### 2. CUSHING'S SYNDROME **Definition:** Chronic excess cortisol — exogenous or endogenous. | Cause | ACTH | Adrenal Appearance | |---|---|---| | Exogenous steroids (#1) | ↓ Suppressed | Bilateral atrophy | | Cushing's Disease (pituitary adenoma) | ↑↑ High | Bilateral hyperplasia | | Ectopic ACTH (small cell lung, carcinoid) | ↑↑↑ Very high | Bilateral hyperplasia | | Adrenal adenoma | ↓ Suppressed | Unilateral nodule | | Adrenal carcinoma | ↓ Suppressed | Large necrotic mass | **Clinical:** Central obesity, moon face, buffalo hump, wide purple striae, proximal muscle weakness, hypertension, hyperglycaemia, osteoporosis, hirsutism, amenorrhoea, easy bruising, depression. ** Ectopic ACTH:** Rapid onset, severe hypokalaemic alkalosis, hyperpigmentation — no classic cushingoid features (tumour grows too fast). **Diagnosis:** - Confirm hypercortisolism: 24h urinary free cortisol, 1mg dexamethasone suppression test (cortisol not suppressed = abnormal) - Find cause: plasma ACTH (↑ = ACTH-dependent; ↓ = adrenal) - Localise: pituitary MRI, CT adrenals, high-dose (8mg) dexamethasone suppression test **Morphology:** - Pituitary adenoma → small basophilic corticotroph adenoma, ACTH immunostain positive - Adrenal adenoma → yellow, well-circumscribed, uniform clear cells, thin capsule - Adrenal carcinoma → large, irregular, necrotic, pleomorphic cells, vascular invasion **Treatment:** Transsphenoidal surgery (pituitary), adrenalectomy (adrenal), treat primary tumour (ectopic). Medical: ketoconazole, metyrapone, mifepristone. ### 3. HYPERALDOSTERONISM (CONN'S SYNDROME) **Definition:** Excess aldosterone → hypertension + hypokalaemia. | Feature | Primary (Conn's) | Secondary | |---|---|---| | Cause | Adrenal adenoma/hyperplasia | Renal artery stenosis, CCF, cirrhosis | | Renin | ↓ Suppressed | ↑ Elevated | | Aldosterone | ↑↑ | ↑ | | Aldosterone:Renin ratio | >30 (diagnostic) | Normal/low | **Clinical:** Resistant hypertension, hypokalaemia (weakness, cramps, polyuria), metabolic alkalosis. No oedema. **Diagnosis:** Aldosterone:Renin ratio >30, CT adrenals, adrenal venous sampling (gold standard for lateralisation). **Treatment:** Unilateral adenoma → laparoscopic adrenalectomy. Bilateral hyperplasia → spironolactone. ### CASE 8.4
Answer: **Q: Diagnosis and explain findings.** **A:** Primary hyperaldosteronism (Conn's syndrome). - Aldosterone:Renin ratio 155 (markedly elevated >30) → autonomous aldosterone production - Hypokalaemia → aldosterone drives K⁺ excretion in collecting duct - Hypertension → Na⁺ retention → volume expansion - Low renin → high aldosterone suppresses renin via negative feedback - Next step: CT adrenals → adrenal venous sampling to confirm lateralisation → adrenalectomy if adenoma confirmed ### 4. PHAEOCHROMOCYTOMA **Definition:** Catecholamine-secreting tumour of adrenal medulla chromaffin cells. **Rule of 10s:** 10% bilateral, 10% malignant, 10% extra-adrenal, 10% familial (MEN2, VHL, NF1). **Clinical (5 Ps):** Palpitations, Perspiration, Pallor, Pain (headache), Pressure (hypertension — paroxysmal). **Diagnosis:** 24h urinary catecholamines + metanephrines (gold standard). Plasma metanephrines (sensitive screening). CT/MRI adrenals. MIBG scan (confirms functional tissue, detects extra-adrenal disease). **Treatment:** Alpha-blockade FIRST (phenoxybenzamine) → then beta-blockade → then surgery. Never beta-block first — causes unopposed alpha → hypertensive crisis. ### CASE 8.6
Answer: **Q: Diagnosis, explain findings, management.** **A:** Left adrenal phaeochromocytoma. - Symptoms mimic hyperthyroidism → TFTs done to exclude it → normal - Urine adrenaline 10× elevated → adrenaline produced almost exclusively by adrenal medulla (requires PNMT enzyme induced by local cortisol) → confirms adrenal origin - Normal noradrenaline → noradrenaline comes from both adrenal medulla and sympathetic nerve terminals → extra-adrenal paraganglioma secretes mainly noradrenaline, not adrenaline - MIBG scan → taken up by chromaffin tissue → confirms functional catecholamine-secreting mass + excludes extra-adrenal disease - Management: phenoxybenzamine (alpha-block) for 10–14 days → add beta-blockade → laparoscopic left adrenalectomy → lifelong follow-up ### 5. DIABETES MELLITUS | Feature | Type 1 | Type 2 | |---|---|---| | Mechanism | Autoimmune β-cell destruction | Insulin resistance + β-cell exhaustion | | Age | Usually <30 | Usually >40 | | Build | Thin | Obese | | Onset | Acute | Insidious | | Ketoacidosis | Yes | Rare | | Autoantibodies | Anti-GAD, anti-islet, anti-insulin | Absent | | HLA | DR3, DR4 | None | | C-peptide | Low/absent | Normal/high initially | **Diagnosis:** Fasting glucose ≥7.0 / Random ≥11.1 / HbA1c ≥48 mmol/mol / OGTT 2h ≥11.1 mmol/L. **HbA1c:** Reflects 2–3 month average glucose. Falsely low in haemolytic anaemia, haemoglobinopathies. Unreliable in pregnancy. ### DKA vs HHS | Feature | DKA | HHS | |---|---|---| | DM type | Type 1 | Type 2 | | Glucose | >11 mmol/L | >30 mmol/L (often >50) | | Ketones | Yes — significant | Absent/minimal | | pH | <7.3 | Normal | | Osmolality | Mildly elevated | >320 mOsm/kg | | Onset | Hours–days | Days–weeks | | Mortality | ~1% | ~15% | | Treatment | Fluids + insulin + K⁺ | Fluids first, cautious insulin | ** Potassium in DKA:** Serum K⁺ appears high initially (acidosis + no insulin drives K⁺ out of cells). Total body K⁺ depleted (lost in urine). When insulin given → K⁺ shifts into cells → fatal hypokalaemia if not replaced. **DKA Management:** IV 0.9% NaCl → fixed rate insulin infusion → K⁺ replacement (once K⁺ <5.5, urine output present) → monitor hourly glucose, 2-hourly electrolytes → treat precipitant. **Chronic Complications:** - Microvascular: nephropathy (Kimmelstiel-Wilson nodules — pathognomonic), retinopathy, neuropathy - Macrovascular: IHD (#1 cause of death in DM), stroke, peripheral arterial disease ### CASE 11.2
Answer: **Q: Diagnosis and explain findings.** **A:** Diabetic Ketoacidosis (DKA) — new presentation Type 1 DM. - Kussmaul breathing → respiratory compensation for metabolic acidosis — blowing off CO₂ (PCO₂ 2.0 kPa = very low) - Acetone breath → ketone bodies (acetone volatile) - pH 7.05, bicarbonate 5 → severe metabolic acidosis from ketoacids - Glucose 32 → insulin deficiency → uncontrolled gluconeogenesis + glycogenolysis - K⁺ 5.8 (high) → acidosis + insulin deficiency drives K⁺ out of cells. Total body K⁺ actually depleted — must replace when insulin started - Na⁺ 130 (low) → osmotic diuresis + water drawn into ECF by hyperglycaemia - ↑ Urea + creatinine → prerenal AKI from dehydration (osmotic diuresis) ### CASE 11.5 Young T1DM male. Collapsed during 10-mile run. Disoriented, incoherent. Glucose 1.6 mmol/L. Given 25g IV glucose → rapid recovery. Had injected normal insulin dose + eaten normal breakfast before run. **Q: What happened and what advice should he receive?** **A:** Exercise-induced hypoglycaemia. - Strenuous prolonged exercise → ↑ muscle glucose uptake + ↑ insulin sensitivity → glucose fell to 1.6 mmol/L - Normal insulin dose + normal breakfast calculated for sedentary activity → insufficient carbohydrates for exercise demands - Rapid recovery with IV glucose → pure neuroglycopenia (brain glucose-dependent), no structural damage - Advice: reduce insulin dose on exercise days OR take extra carbohydrates before/during prolonged exercise, carry fast-acting glucose always, exercise with informed companion, consider CGM, wear MedicAlert bracelet ### CASE 11.1 Young T1DM male. Feels well. Doesn't check glucose (dislikes finger-prick). Glucose 2h post-breakfast: 18 mmol/L. HbA1c: 48 mmol/mol (6.5% — near normal). **Q: How do you explain the discrepancy?** **A:** Normal HbA1c with grossly elevated postprandial glucose = significant glucose variability. Recurrent hypoglycaemic episodes are lowering the average, masking hyperglycaemic spikes — giving a falsely reassuring HbA1c. This is dangerous — patient experiencing both extremes. HbA1c alone is insufficient in T1DM. Regular SMBG or continuous glucose monitoring (CGM) essential for safe management. ### 6. PARATHYROID DISORDERS **PTH actions:** ↑ renal Ca²⁺ reabsorption, ↑ phosphate excretion, ↑ Vitamin D activation → ↑ GI Ca²⁺ absorption, ↑ osteoclastic bone resorption → net effect: ↑ Ca²⁺. ### Calcium Disorders — Quick Reference | Condition | Ca²⁺ | PTH | Phosphate | |---|---|---|---| | Primary hyperparathyroidism | ↑ | ↑ | ↓ | | Secondary hyperparathyroidism | ↓ | ↑↑ | ↑ (renal failure) | | Tertiary hyperparathyroidism | ↑ | ↑↑ | ↑ | | Hypoparathyroidism | ↓ | ↓ | ↑ | | Pseudohypoparathyroidism | ↓ | ↑↑ | ↑ | | Malignancy hypercalcaemia | ↑ | ↓ | Variable | | Vitamin D deficiency | ↓ | ↑ | ↓ | ### Primary Hyperparathyroidism Autonomous PTH. Adenoma (85–95%), hyperplasia (5–10%), carcinoma (1%). More common in women, peak 50s–60s. **Clinical:** Painful bones, renal stones, abdominal groans, psychic moans. Most found incidentally as asymptomatic hypercalcaemia. **Biochemistry:** ↑Ca²⁺, ↑PTH (inappropriately elevated for Ca²⁺ level), ↓phosphate, ↑urinary Ca²⁺. **Distinguish from malignancy:** Malignancy → PTH ↓ low + PTHrP ↑ elevated. Primary HPT → PTH ↑ elevated + PTHrP normal. **Morphology:** - Adenoma → solitary yellow nodule, chief cells, rim of compressed normal tissue at edge, other glands shrunken - Carcinoma → grey-white, invasive — diagnosis requires invasion or metastasis (not cytology alone) **Molecular:** Cyclin D1 (CCND1) rearrangement (10–20%), MEN1 mutation (30–35%), CDC73 mutation (70% of carcinomas). **Treatment:** Parathyroidectomy. Medical (if inoperable): cinacalcet, bisphosphonates, hydration. ### Secondary Hyperparathyroidism Compensatory ↑PTH from chronic hypocalcaemia. #1 cause = chronic renal failure. All 4 glands hyperplastic. Treat: Vitamin D supplementation, phosphate binders, dietary phosphate restriction. **Calciphylaxis:** Vascular calcification → ischaemic skin necrosis — serious complication of secondary HPT. ### Tertiary Hyperparathyroidism Prolonged secondary HPT → autonomous PTH secretion even after hypocalcaemia corrected (e.g. post-renal transplant). ↑Ca²⁺ + ↑↑PTH. Needs parathyroidectomy. ### Hypoparathyroidism ↓PTH → hypocalcaemia + hyperphosphataemia. **Causes:** Post-surgical (#1), autoimmune APS-1 (AIRE mutation — candidiasis + hypoparathyroidism + adrenal insufficiency), DiGeorge (22q11 deletion — absent parathyroids + thymic aplasia + cardiac defects), hypomagnesaemia. **Clinical:** Tetany — circumoral tingling, carpopedal spasm, laryngospasm, generalised seizures. Chvostek's sign (tap facial nerve → facial twitch). Trousseau's sign (BP cuff → carpal spasm — most specific). Prolonged QT on ECG, cataracts, basal ganglia calcification, parkinsonism, dental abnormalities, papilloedema. **Treatment:** Acute → IV calcium gluconate. Chronic → oral calcium + calcitriol. ### Pseudohypoparathyroidism End-organ PTH resistance (Gsα mutation). PTH ↑↑, Ca²⁺ ↓, phosphate ↑ — same biochemistry as hypoparathyroidism but PTH is HIGH not low. Albright's hereditary osteodystrophy: short stature, short 4th metacarpal, obesity, round face, intellectual disability. ### 7. PORPHYRIAS **Definition:** Enzyme defects in haem biosynthesis → toxic accumulation of ALA, PBG, porphyrins. | Feature | Acute Porphyrias | Cutaneous Porphyrias | |---|---|---| | Symptoms | Abdominal pain, neuropathy, autonomic, psychiatric | Photosensitivity, blistering, scarring | | Urine | Dark red-brown (darkens on standing) | Variable | | Key test | Urinary PBG (↑ during attack) | Plasma porphyrins (↑) | | Examples | AIP, Variegate, HCP | PCT, CEP, EPP | **Triggers:** Barbiturates, sulfonamides, anti-epileptics, alcohol, oestrogens (OCP), fasting, stress, infection. **Pathogenesis:** Enzyme defect → substrate accumulates → haem deficiency → derepresses ALA synthase (rate-limiting enzyme) → worsens accumulation → neurotoxicity (ALA/PBG) or photosensitivity (porphyrins + UV → ROS → skin damage). **Management:** Avoid triggers. Acute attack → IV haem arginate + high carbohydrate loading (suppresses ALA synthase) + analgesia. Cutaneous PCT → phlebotomy + sun avoidance. ### 8. RENAL FUNCTION EVALUATION **GFR:** Best overall marker. eGFR via CKD-EPI formula. Cystatin C — not affected by muscle mass, useful in extremes of weight. **BUN:Creatinine ratio:** >20:1 = prerenal. ~10:1 = intrinsic renal disease. **Proteinuria:** Normal <30 mg/day. Microalbuminuria 30–300 mg/day (early CKD/DM). Macroalbuminuria >300 mg/day. Nephrotic >3.5g/day. **FENa = (urine Na × plasma Cr) / (plasma Na × urine Cr) × 100** - <1% = prerenal (kidneys avidly reabsorbing Na⁺) - >2% = intrinsic renal damage (tubules cannot reabsorb Na⁺) ### Must-Know Urine Casts | Cast | Significance | |---|---| | Hyaline | Normal / dehydration | | RBC casts | Glomerulonephritis | | WBC casts | Pyelonephritis / AIN | | Muddy brown granular casts | ATN | | Fatty casts / oval fat bodies | Nephrotic syndrome | | Broad waxy casts | CKD (chronic tubular atrophy) | ### Must-Know Urine Crystals | Crystal | Shape | Stone Type | |---|---|---| | Calcium oxalate | Envelope / dumbbell | Most common stone | | Uric acid | Rhomboid / needle | Gout, tumour lysis | | Struvite | Coffin-lid | UTI (Proteus, Klebsiella) | | Cystine | Hexagonal | Cystinuria | ### 9. ACUTE KIDNEY INJURY (AKI) **Definition (KDIGO):** Creatinine ↑ ≥26.5 μmol/L in 48h OR ≥1.5× baseline in 7 days OR urine output <0.5 mL/kg/hr for >6h. | Parameter | Prerenal | ATN | AIN | GN | |---|---|---|---|---| | FENa | <1% | >2% | >2% | Variable | | Urine Na⁺ | <20 mmol/L | >40 mmol/L | >40 | Variable | | Specific gravity | >1.020 | ~1.010 | ~1.010 | Variable | | Casts | Hyaline | Muddy brown | WBC + eosinophils | RBC casts | | Response to fluids | Rapid | Slow | Slow | No | **Prerenal causes:** Hypovolaemia, heart failure, sepsis, NSAIDs (afferent arteriole constriction), ACEi/ARBs (efferent arteriole dilation). **ATN causes:** Prolonged ischaemia, aminoglycosides, contrast media, myoglobin (rhabdomyolysis), haemoglobin. **AIN:** Drug hypersensitivity (NSAIDs, penicillins, sulfonamides). Classic triad: fever + rash + eosinophilia. WBC casts + eosinophils in urine. **Postrenal:** BPH, stones, malignancy → hydronephrosis on USS. **Complications:** Hyperkalaemia (most dangerous — arrhythmias), metabolic acidosis, fluid overload, pulmonary oedema, uraemia. ### 10. CHRONIC KIDNEY DISEASE (CKD) **Definition:** eGFR <60 mL/min/1.73m² OR kidney damage markers for ≥3 months. ### CKD Staging | Stage | eGFR | Description | |---|---|---| | G1 | ≥90 | Normal/high with damage markers | | G2 | 60–89 | Mildly decreased | | G3a | 45–59 | Mild-moderately decreased | | G3b | 30–44 | Moderately-severely decreased | | G4 | 15–29 | Severely decreased | | G5 | <15 | Kidney failure — dialysis/transplant | **Causes:** Diabetic nephropathy (#1), hypertensive nephropathy (#2), chronic GN (IgA, lupus, membranous), PKD, chronic pyelonephritis, obstructive uropathy. **Pathophysiology:** Nephron loss → surviving nephrons hyperfiltrate → ↑ intraglomerular pressure → glomerulosclerosis → more nephron loss → vicious cycle → tubulointerstitial fibrosis. **Complications:** - Anaemia → ↓EPO production - Secondary HPT → ↓Vit D → ↓Ca²⁺ → ↑PTH → renal osteodystrophy - Hyperkalaemia, metabolic acidosis, hyperphosphataemia - Hypertension → LVH → accelerated atherosclerosis - Uraemia → nausea, pruritus, pericarditis, encephalopathy, platelet dysfunction - Calciphylaxis (in advanced CKD) **Imaging:** Small shrunken kidneys <9cm. Exception: DM and PKD → enlarged kidneys. **Treatment:** ACEi/ARBs (BP + proteinuria), glucose control, phosphate binders, calcitriol, EPO + iron, dietary K⁺/phosphate restriction. ESRD → dialysis or transplant. ### 11. RENAL CALCULI ### Stone Types | Stone | Frequency | Urine pH | X-ray | Crystal | Associations | |---|---|---|---|---|---| | Calcium oxalate | 70–80% | Acidic/neutral | Radiopaque | Envelope | Hypercalciuria, hyperoxaluria | | Uric acid | 5–10% | Acidic <5.5 | Radiolucent | Rhomboid | Gout, tumour lysis | | Struvite | 10–15% | Alkaline >7.5 | Radiopaque (staghorn) | Coffin-lid | UTI — Proteus, Klebsiella | | Cystine | 1% | Acidic | Faintly opaque | Hexagonal | Cystinuria (AR) | **Clinical:** Loin-to-groin colic, haematuria, nausea, vomiting. Fever + stone = infected obstructed system = **urological emergency.** **Imaging:** CT KUB (gold standard — all stones). USS (pregnancy/children — detects hydronephrosis). X-ray KUB (radiopaque only). **Management:** NSAIDs (analgesia), tamsulosin (medical expulsion <10mm), ureteroscopy + laser, ESWL (<2cm), PCNL (staghorn). Prevention: high fluid intake (>2.5L/day), treat underlying metabolic cause. ### 12. LUNG TUMOURS **Lung cancer = #1 cause of cancer death worldwide.** 90–95% carcinomas. Risk factors: smoking (#1, 80%), asbestos, radon, ionising radiation. ### Lung Cancer Types — Summary | Type | % | Location | Smoking | Key Histology | Markers | Treatment | |---|---|---|---|---|---|---| | Adenocarcinoma | 50% | Peripheral | Less so | Glandular, lepidic growth, mucin | TTF-1, napsin A | Surgery + TKIs (EGFR/ALK) | | Squamous cell | 20% | Central | Strongly | Keratinisation, squamous pearls, intercellular bridges | p40, p63 | Surgery (early) | | Small cell | 15% | Central/peripheral | Always | Small cells, salt-pepper chromatin, nuclear moulding, Azzopardi effect | CD56, synaptophysin, chromogranin | Chemo ± radiotherapy | | Large cell | 2% | Variable | Yes | Exclusion — large cells, prominent nucleoli | None | Surgery if early | **Precursor lesions (adenocarcinoma):** AAH → AIS (lepidic, no invasion, <3cm, excellent prognosis) → microinvasive → invasive. **Precursor lesions (squamous cell):** Squamous metaplasia → dysplasia → CIS → invasive (detectable on sputum cytology before X-ray changes). ### Paraneoplastic Syndromes | Syndrome | Tumour | Mechanism | |---|---|---| | SIADH → hyponatraemia | Small cell | Ectopic ADH | | Cushing's syndrome | Small cell | Ectopic ACTH | | Lambert-Eaton syndrome | Small cell | Anti-VGCC antibodies → proximal weakness (improves with repeated movement — unlike MG) | | Hypercalcaemia | Squamous cell | PTHrP secretion | | Hypertrophic osteoarthropathy + clubbing | Adenocarcinoma, squamous | Periosteal new bone formation | | Cerebellar degeneration | Small cell | Anti-Hu, anti-Yo antibodies | ### Local Effects of Lung Cancer - **SVC obstruction** → facial/arm swelling, distended neck veins - **Pancoast tumour** (apex) → Horner's syndrome (ptosis, miosis, anhidrosis) + brachial plexus pain - **Recurrent laryngeal nerve** → hoarseness - **Phrenic nerve** → diaphragm paralysis - **Oesophagus** → dysphagia - **Pericardium** → pericarditis, effusion, tamponade ### Metastatic Tumours to Lung Lung = most common site of metastases. Pattern: multiple peripheral cannonball lesions. Common primaries: breast, colon, kidney, melanoma, sarcoma. ### 13. LUNG TRANSPLANTATION **Indications:** End-stage COPD, IPF, cystic fibrosis, pulmonary arterial hypertension. Bilateral transplant → better survival but scarce donors. | Complication | Timing | Features | Histology | Treatment | |---|---|---|---|---| | Bacterial infection | Early (first weeks) | Fever, infiltrates | — | Antibiotics | | CMV pneumonia | 3–12 months | Fever, dyspnoea | Viral inclusions | Ganciclovir | | Fungal (Aspergillus, Candida) | 3–12 months | Variable | Hyphae | Antifungals | | **Acute rejection** | Weeks–months | Fever, dyspnoea, infiltrates (mimics infection) | Lymphocytic infiltrates around vessels + airways | Immunosuppression ↑ | | **Chronic rejection** | >3–5 years (≥50%) | Progressive irreversible ↓ lung function | **Bronchiolitis obliterans** — fibrotic small airway occlusion | Cannot be reversed | ** Bronchiolitis obliterans:** Patchy → hard to diagnose on transbronchial biopsy. Irreversible. Leading cause of late mortality. Median post-transplant survival: **6 years.** **Other:** EBV-associated B-cell lymphoma may arise within the lung allograft. ## Practice Questions
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