Summary Summary This document provides concise, essential notes on endocrine and renal pathology, covering key diseases, their causes, clinical presentations, d
Summary Summary This document provides concise, essential notes on endocrine and renal pathology, covering key diseases, their causes, clinical presentations, diagnostic methods, and treatment approaches. It emphasizes critical differences between related conditions, such as primary versus secondary adrenal insufficiency, and outlines the pathophysiology and management of diabetes mellitus, parathyroid disorders, and renal pathologies like acute kidney injury and chronic kidney disease. The notes also touch upon lung tumours and lung transplantation, highlighting their crucial aspects for medical understanding. Key Points - Summary This document provides concise, essential notes on endocrine and renal pathology, covering key diseases, their causes, clinical presentations, diagnostic methods, and treatment approaches. - It emphasizes critical differences between related conditions, such as primary versus secondary adrenal insufficiency, and outlines the pathophysiology and management of diabetes mellitus, parathyroid disorders, and renal pathologies like acute kidney injury and chronic kidney disease. - The notes also touch upon lung tumours and lung transplantation, highlighting their crucial aspects for medical understanding. - Key Points - Adrenal Insufficiency (Addison's Disease): Inadequate cortisol ± aldosterone production due to primary (autoimmune, TB) or secondary (steroid use, pituitary issues) causes. - Primary leads to hyperpigmentation and electrolyte imbalances due to ↑ACTH, while secondary does not cause hyperpigmentation and has intact aldosterone. - - Cushing's Syndrome: Chronic excess cortisol from exogenous steroids (most common) or endogenous causes like pituitary ACTH adenoma (Cushing's disease), ectopic ACTH, or adrenal tumours. - Presents with characteristic central obesity, moon face, and metabolic disturbances. - - Hyperaldosteronism (Conn's Syndrome): Excess aldosterone leading to hypertension and hypokalaemia. Detailed Notes Key Points - Adrenal Insufficiency (Addison's Disease): Inadequate cortisol ± aldosterone production due to primary (autoimmune, TB) or secondary (steroid use, pituitary issues) causes. Primary leads to hyperpigmentation and electrolyte imbalances due to ↑ACTH, while secondary does not cause hyperpigmentation and has intact aldosterone. - Cushing's Syndrome: Chronic excess cortisol from exogenous steroids (most common) or endogenous causes like pituitary ACTH adenoma (Cushing's disease), ectopic ACTH, or adrenal tumours. Presents with characteristic central obesity, moon face, and metabolic disturbances. - Hyperaldosteronism (Conn's Syndrome): Excess aldosterone leading to hypertension and hypokalaemia. Primary (adenoma/hyperplasia) shows suppressed renin, while secondary has elevated renin. - Phaeochromocytoma: Catecholamine-secreting tumour of the adrenal medulla, causing paroxysmal hypertension, palpitations, and sweating. - Diabetes Mellitus: Type 1 (autoimmune β-cell destruction, absolute insulin deficiency) and Type 2 (insulin resistance, relative deficiency). Diagnosis via glucose levels or HbA1c. DKA (Type 1) and HHS (Type 2) are acute complications. - Parathyroid Disorders: Primary hyperparathyroidism (autonomous PTH overproduction) causes ↑Ca²⁺, ↓phosphate. Secondary (renal failure) causes compensatory ↑PTH. Hypoparathyroidism leads to ↓Ca²⁺, ↑phosphate. - Porphyrias: Enzyme defects in haem biosynthesis. Acute porphyrias are neurovisceral, while cutaneous porphyrias cause photosensitivity. Triggers are crucial. - Renal Function Evaluation: GFR is the best marker. BUN:Creatinine ratio, FENa, and urine casts are vital for diagnosing AKI and understanding intrinsic renal disease. - Acute Kidney Injury (AKI): Rapid decline in renal function (creatinine rise, ↓ urine output). Classified as prerenal (↓ perfusion), intrinsic (ATN, AIN, GN), or postrenal (obstruction). - Chronic Kidney Disease (CK D): Progressive loss of renal function (eGFR 30) strongly suggests primary hyperaldosteronism. CT scan of the adrenals is performed. Adrenal venous sampling may be needed to confirm lateralisation of the lesion. Treatment: Adrenalectomy for adenoma. Spironolactone for bilateral hyperplasia. 4. PHAEOCHROMOCYTOMA Definition: A catecholamine-secreting tumour of the adrenal medulla chromaffin cells. Rule of 10s: 10% bilateral, 10% malignant, 10% extra-adrenal, 10% familial (associated with MEN2, VHL, NF1). Clinical features (The 5 Ps): Palpitations, Perspiration, Pallor, Pain (headache), Pressure (hypertension, often paroxysmal). Diagnosis: 24-hour urinary catecholamines and metanephrines (gold standard). Plasma metanephrines are a sensitive screening test. CT or MRI of the adrenals. MIBG scan can confirm functional tissue and detect extra-adrenal lesions. Treatment: Alpha-blockade FIRST (e.g., phenoxybenzamine), followed by beta-blockade, and then surgery. Beta-blockers should never be administered first. 5. DIABETES MELLITUS Type 1: Autoimmune destruction of pancreatic β-cells, leading to absolute insulin deficiency. Typically affects young, thin individuals and is prone to Diabetic Ketoacidosis (DKA). Associated with anti-GAD and anti-islet antibodies, and HLA-DR3/DR4. Type 2: Characterised by insulin resistance and a relative deficiency in insulin secretion. Usually affects older, obese individuals with an insidious onset. Ketoacidosis is uncommon. Strong family history is common. Diagnosis: - Fasting plasma glucose ≥7.0 mmol/L - Random plasma glucose ≥11.1 mmol/L - HbA1c ≥48 mmol/mol (6.5%) - Oral Glucose Tolerance Test (OGTT) 2-hour plasma glucose ≥11.1 mmol/L DKA (Type 1): Caused by severe insulin deficiency leading to hyperglycaemia, lipolysis, ketone production, and metabolic acidosis. Common triggers include infection and missed insulin doses. Features include Kussmaul breathing, acetone breath, dehydration, elevated glucose, low pH, low bicarbonate, and elevated potassium (total body potassium is depleted and requires replacement once insulin therapy begins). Management involves IV fluids, insulin infusion, and potassium replacement. HHS (Type 2): Characterised by very high glucose levels ( 30 mmol/L), markedly elevated serum osmolality, absence of significant ketosis, and no significant acidosis. It has a high mortality rate. Management prioritises fluid resuscitation, followed cautiously by insulin. Chronic complications: - Microvascular: Nephropathy (Kimmelstiel-Wilson nodules), retinopathy, neuropathy. - Macrovascular: Ischaemic heart disease (leading cause of death), stroke, peripheral arterial disease. 6. PARATHYROID DISORDERS PTH actions: Increases renal calcium reabsorption, increases phosphate excretion, increases vitamin D activation in the kidney, leading to increased intestinal calcium absorption and increased osteoclastic bone resorption. The net effect is an increase in serum calcium. Primary Hyperparathyroidism Caused by autonomous overproduction of PTH. Most commonly due to an adenoma (85–95%), followed by hyperplasia (5–10%). Carcinoma is rare (1%). It is more common in women. Clinical features: Often referred to as "painful bones, renal stones, abdominal groans, psychic moans." However, most patients are asymptomatic and it is found incidentally on routine biochemistry. Biochemistry: Elevated serum calcium, inappropriately elevated or normal PTH, low serum phosphate, and elevated urinary calcium. Morphology: Adenoma is typically a solitary, yellow, well-circumscribed lesion composed of chief cells, with a rim of normal parathyroid tissue. Carcinoma is grey-white, invasive, and diagnosis requires evidence of invasion into surrounding structures or metastasis. Treatment: Parathyroidectomy is the definitive treatment. Medical options include cinacalcet and bisphosphonates. Secondary Hyperparathyroidism A compensatory increase in PTH in response to chronic hypocalcaemia. The most common cause is chronic renal failure. All four parathyroid glands are typically hyperplastic. Biochemistry