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Shock is a state of inadequate oxygen delivery to tissues relative to demand, leading to cellular hypoxia and organ dysfunction. Types - Hypovolaemic: loss of volume (haemorrhage, dehydration, burns); low preload; cold, clammy skin, tachycardia, low central venous pressure. - Cardiogenic: pump failure (myocardial infarction, arrhythmia, valve disease); raised filling pressures, pulmonary oedema. - Obstructive: mechanical obstruction (pulmonary embolism, tension pneumothorax, cardiac tamponade). - Distributive: vasodilation (septic, anaphylactic, neurogenic); warm peripheries in early sepsis, low systemic vascular resistance. Stages: compensated (baroreflex, sympathetic activation, renin-angiotensin, vasopressin; blood pressure maintained), decompensated (falling pressure, lactic acidosis, oliguria, confusion) and irreversible (multi-organ failure).

Signs: hypotension (systolic below 90 mmHg), tachycardia, tachypnoea, altered mental state, oliguria, raised lactate. Management: oxygen, intravenous access, monitoring, and treatment of the cause. Hypovolaemic: fluids and blood products, stop the bleeding. Cardiogenic: inotropes, revascularisation, mechanical support; avoid excess fluid. Obstructive: relieve the obstruction (drainage, thrombolysis). Septic: early antibiotics, source control, fluids and noradrenaline (vasopressor). Anaphylactic: intramuscular adrenaline.

1. List the four types of shock with an example of each. 2. Which compensatory mechanisms operate in early shock? 3. What is the first-line drug in anaphylactic shock? 4. Which type of shock has warm peripheries?

1. Hypovolaemic (haemorrhage), cardiogenic (myocardial infarction), obstructive (pulmonary embolism), distributive (sepsis). 2. Baroreflex-mediated sympathetic activation, renin-angiotensin-aldosterone system and vasopressin. 3. Intramuscular adrenaline. 4. Distributive shock (early septic shock).

Definition (KDIGO): rise in serum creatinine of at least 0.3 mg/dL within 48 hours, or 1.5 times baseline within 7 days, or urine output below 0.5 mL/kg/h for 6 hours. - Prerenal (reduced perfusion; commonest): hypovolaemia, heart failure, sepsis, drugs (NSAIDs, ACE inhibitors, diuretics). Reversible if perfusion is restored; urinary sodium low. - Intrinsic: acute tubular necrosis (ischaemia, nephrotoxins such as contrast, aminoglycosides), acute interstitial nephritis, glomerulonephritis, vasculitis. - Postrenal: obstruction (prostatic hypertrophy, stones, tumours). Management: identify and treat the cause, restore volume, stop nephrotoxic drugs, relieve obstruction, treat hyperkalaemia, acidosis and fluid overload; dialysis for refractory complications.

Nephrotic syndrome: proteinuria above 3.5 g/day, hypoalbuminaemia, oedema and hyperlipidaemia; causes minimal change disease (children), focal segmental glomerulosclerosis, membranous nephropathy and diabetic nephropathy. Complications: infection, thrombosis. Nephritic syndrome: haematuria with red cell casts, hypertension, oliguria and mild proteinuria; causes post-streptococcal glomerulonephritis, IgA nephropathy, lupus nephritis and rapidly progressive (crescentic) glomerulonephritis such as anti-GBM disease and ANCA vasculitis.

Stages G1-G5 by eGFR (above 90, 60-89, 45-59, 30-44, 15-29, below 15 mL/min/1.73 m2) and albuminuria categories. Main causes: diabetes and hypertension. Complications: hypertension, anaemia (low erythropoietin), mineral and bone disease (low calcitriol, hyperphosphataemia, secondary hyperparathyroidism), metabolic acidosis, hyperkalaemia, fluid overload and accelerated cardiovascular disease. Management: control of blood pressure and glucose, ACE inhibitors or ARBs and SGLT2 inhibitors, treating complications, and renal replacement (dialysis or transplantation) in kidney failure.

1. Define AKI. 2. Give causes of prerenal, intrinsic and postrenal AKI. 3. Compare nephritic and nephrotic syndrome. 4. Which conditions most often cause CKD?

1. Rise of creatinine by at least 0.3 mg/dL in 48 hours, or 1.5 times baseline in 7 days, or oliguria. 2. Prerenal: hypovolaemia; intrinsic: acute tubular necrosis; postrenal: prostatic obstruction. 3. Nephrotic: heavy proteinuria, low albumin, oedema. Nephritic: haematuria, hypertension, oliguria. 4. Diabetes and hypertension.

Atherosclerotic plaque rupture or erosion exposes thrombogenic material and produces a platelet-fibrin thrombus. Complete occlusion gives ST-elevation myocardial infarction (STEMI, transmural necrosis; treat with primary PCI or thrombolysis); partial or transient occlusion gives non-ST-elevation MI (troponin rise) or unstable angina (no troponin rise). Symptoms: chest pressure radiating to the arm or jaw, dyspnoea, sweating. Diagnosis: ECG and serial troponin. Treatment: aspirin plus P2Y12 inhibitor, anticoagulation, beta-blocker, statin, ACE inhibitor and revascularisation. Complications: arrhythmias, heart failure, papillary muscle rupture, ventricular septal rupture, free wall rupture and pericarditis.

Types: reduced ejection fraction (systolic dysfunction; ischaemia, dilated cardiomyopathy) and preserved ejection fraction (diastolic dysfunction; hypertension, ageing). Mechanisms: reduced output activates the sympathetic system and the RAAS, giving fluid retention and remodelling that worsen failure. Symptoms: dyspnoea, orthopnoea, fatigue, oedema; signs: raised jugular venous pressure, crackles, third heart sound. Treatment: ACE inhibitor or ARNI, beta-blocker, mineralocorticoid antagonist, SGLT2 inhibitor, diuretics for congestion.

Cardiomyopathies: dilated (impaired systolic function), hypertrophic (asymmetric septal hypertrophy, outflow obstruction, risk of sudden death in young athletes) and restrictive (amyloidosis). Valve disease: stenosis (pressure overload; aortic stenosis causes angina, syncope and heart failure) and regurgitation (volume overload). Rheumatic disease and degeneration are the main causes. Atrial fibrillation: irregular rhythm without P waves, risk of embolic stroke; management: rate or rhythm control and anticoagulation according to the CHA2DS2-VASc score.

Obstructive disease (asthma, COPD, bronchiectasis): reduced FEV1/FVC, air trapping, increased residual volume; airflow limitation, wheeze. Restrictive disease (interstitial lung disease, fibrosis, chest wall disease, neuromuscular disease): reduced lung volumes with a normal or high FEV1/FVC, reduced compliance and diffusing capacity.

Type 1 (hypoxaemic): PaO2 below 60 mmHg with normal or low PaCO2; causes V/Q mismatch, shunt or diffusion impairment (pneumonia, pulmonary oedema, embolism, ARDS). Type 2 (hypercapnic): PaCO2 above 50 mmHg from alveolar hypoventilation (COPD exacerbation, neuromuscular disease, sedatives). Treatment: oxygen (controlled in type 2), treat the cause, non-invasive or invasive ventilation.

1. Distinguish STEMI from NSTEMI. 2. List the therapies that improve prognosis in reduced-EF heart failure. 3. What is the spirometric pattern of restrictive disease? 4. Define type 2 respiratory failure.

1. STEMI: complete occlusion with ST elevation, transmural necrosis. NSTEMI: partial occlusion with troponin rise but no ST elevation. 2. ACE inhibitor or ARNI, beta-blocker, mineralocorticoid antagonist, SGLT2 inhibitor. 3. Reduced volumes with normal or increased FEV1/FVC. 4. PaCO2 above 50 mmHg due to hypoventilation, with hypoxaemia.

Causes of liver injury: viral hepatitis (A, B, C, E), alcohol, metabolic-associated steatotic liver disease, autoimmune and drug-induced injury. Persistent injury activates stellate cells, causing fibrosis and finally cirrhosis with nodular regeneration. Complications of cirrhosis: portal hypertension (varices, ascites, splenomegaly), hepatic encephalopathy (ammonia), hepatorenal syndrome, coagulopathy, spontaneous bacterial peritonitis and hepatocellular carcinoma. Liver function tests: transaminases (hepatocellular injury), alkaline phosphatase and gamma-GT (cholestasis), bilirubin, albumin and INR (synthetic function). Cholestasis: impaired bile flow (intra- or extrahepatic): jaundice, pruritus, pale stools, raised alkaline phosphatase.

Acute pancreatitis: commonest causes gallstones and alcohol; also hypertriglyceridaemia, drugs and ERCP. Pathogenesis: intracellular trypsinogen activation, autodigestion and inflammation. Diagnosis: severe epigastric pain radiating to the back, lipase or amylase above three times normal, imaging. Complications: necrosis, pseudocyst, systemic inflammatory response and organ failure. Treatment: fluids, analgesia, early feeding, treat the cause. Chronic pancreatitis: fibrosis, exocrine insufficiency (steatorrhoea) and diabetes.

Ulcerative colitis: continuous mucosal inflammation from the rectum proximally; bloody diarrhoea. Crohn disease: transmural, patchy inflammation anywhere from mouth to anus, terminal ileum commonly; abdominal pain, diarrhoea, fistulae, strictures and perianal disease. Extraintestinal manifestations: arthritis, uveitis, erythema nodosum, primary sclerosing cholangitis. Pathogenesis: genetic susceptibility, microbiota and immune dysregulation. Treatment: aminosalicylates, corticosteroids, immunomodulators, biologics, surgery.

1. Name the complications of cirrhosis. 2. What are the commonest causes of acute pancreatitis? 3. Compare Crohn disease and ulcerative colitis. 4. Which enzymes indicate cholestasis?

1. Portal hypertension with varices and ascites, encephalopathy, hepatorenal syndrome, coagulopathy, infections and hepatocellular carcinoma. 2. Gallstones and alcohol. 3. UC: continuous mucosal disease starting in the rectum. Crohn: transmural, patchy, anywhere in the gut, with fistulae and strictures. 4. Alkaline phosphatase and gamma-glutamyl transferase.

Type 1: autoimmune destruction of beta cells, absolute insulin deficiency, ketoacidosis. Type 2: insulin resistance with relative insulin deficiency, associated with obesity. Diagnosis: fasting glucose 126 mg/dL or more, HbA1c 6.5 percent or more, 2-hour OGTT glucose 200 mg/dL or more. Acute complications: diabetic ketoacidosis, hyperosmolar hyperglycaemic state, hypoglycaemia. Chronic complications: microvascular (retinopathy, nephropathy, neuropathy) and macrovascular (coronary, cerebrovascular and peripheral artery disease, diabetic foot). Mechanisms: advanced glycation end products, polyol pathway, oxidative stress.

Hyperthyroidism (suppressed TSH, raised free T4/T3): Graves disease (TSH receptor stimulating antibodies; goitre, orbitopathy), toxic nodular goitre, thyroiditis. Signs: weight loss, tachycardia, tremor, heat intolerance. Hypothyroidism (raised TSH, low T4): Hashimoto thyroiditis (anti-TPO antibodies), iodine deficiency; fatigue, weight gain, cold intolerance, bradycardia. Nodules: assessed by ultrasound and fine needle aspiration for cancer.

Cushing syndrome (excess cortisol; iatrogenic steroids, pituitary adenoma, adrenal tumour): central obesity, striae, hypertension, diabetes, osteoporosis. Primary aldosteronism: hypertension with hypokalaemia. Phaeochromocytoma: paroxysmal hypertension, headache, palpitations and sweating; catecholamine-secreting tumour. Adrenal insufficiency (Addison disease): fatigue, hypotension, hyponatraemia, hyperkalaemia, pigmentation; adrenal crisis needs hydrocortisone.

Calcium homeostasis: PTH, vitamin D and calcitonin. Hypercalcaemia: primary hyperparathyroidism and malignancy (stones, bones, groans and psychic moans). Hypocalcaemia: hypoparathyroidism and vitamin D deficiency (tetany). Osteoporosis: reduced bone mass and microarchitecture with fragility fractures; risk factors: age, menopause, steroids, low body weight, smoking. Diagnosis: DXA T-score of minus 2.5 or lower. Treatment: calcium and vitamin D, bisphosphonates, denosumab, teriparatide. Gout: monosodium urate crystals; acute monoarthritis (first metatarsophalangeal joint) treated with NSAIDs or colchicine; urate-lowering with allopurinol. Pseudogout: calcium pyrophosphate crystals.

1. Give the diagnostic criteria for diabetes. 2. Compare Graves disease and Hashimoto thyroiditis. 3. Name three features of Cushing syndrome. 4. What T-score defines osteoporosis? 5. Which drug is used for long-term urate lowering?

1. Fasting glucose 126 mg/dL or more, HbA1c 6.5 percent or more, or 2-hour OGTT glucose 200 mg/dL or more. 2. Graves: stimulating TSH-receptor antibodies, hyperthyroidism. Hashimoto: anti-TPO autoimmunity, hypothyroidism. 3. Central obesity, striae, hypertension, diabetes, osteoporosis, proximal weakness. 4. Minus 2.5 or lower. 5. Allopurinol.