46. Schwartz-Bartter syndrome (SIADH) and diabetes insipidus - etiology, pathogenesis, clinical manifestations.

Schwartz - Bartter syndrome (SIADH) and diabetes insipidus – etiology, pathogenesis, and clinical manifestations.

Schwartz- Bartter syndrome (SIADH)

Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH).

Excessive release of ADH (vasopressin) → water retention → hyponatremia.

Etiology

Ectopic ADH production:

• Small cell lung carcinoma (most common cause).

CNS disorders:

• Stroke, trauma, infections (meningitis, encephalitis), tumors.

Pulmonary diseases:

• Pneumonia, tuberculosis.

Drugs:

• SSRIs, carbamazepine, cyclophosphamide.

Pathogenesis

1. Excess ADH → increased water reabsorption in renal collecting ducts (via aquaporin-2 channels).
2. Increased total body water → dilutional hyponatremia (low plasma sodium).
3. Increased extracellular fluid volume → but usually no significant edema (because sodium excretion increases to counteract volume).

Clinical manifestations

Due to hyponatremia:

• Mild: nausea, headache.
• Moderate: confusion, lethargy, muscle cramps.
• Severe: seizures, coma.

Volume status: euvolemic (no obvious signs of fluid overload or depletion).

Diabetes Insipidus (DI)

Definition 2

Condition caused by deficiency of ADH (central DI) or renal insensitivity to ADH (nephrogenic DI) → inability to concentrate urine → polyuria and polydipsia.

Etiology

Central (neurogenic) DI

Damage to hypothalamus or posterior pituitary.

• Trauma, surgery.
• Tumors (craniopharyngioma, metastases).
• Infections.
• Idiopathic.

Nephrogenic DI

Kidneys unresponsive to ADH.

Causes:

• Genetic mutations (AVPR2 gene).
• Chronic lithium use.
• Hypercalcemia.
• Hypokalemia.
• Chronic kidney disease.

Pathogenesis

1. Lack of ADH (central) or resistance to ADH (nephrogenic).
2. Decreased aquaporin-2 expression in renal collecting ducts.
3. Decreased water reabsorption → large volume of dilute urine.
4. Increased plasma osmolality → intense thirst (polydipsia).

Clinical manifestations

Polyuria: excretion of large volumes of dilute urine (3–20 L/ day).

Polydipsia: excessive thirst and water intake.

Dehydration signs:

• Dry mucous membranes.
• Hypotension, tachycardia (if water intake insufficient).

Hypernatremia (if unable to compensate by drinking enough water).