Which of the following is the primary mechanism by which SIADH (Syndrome of Inappropriate Antidiuretic Hormone) causes hyponatremia?

Explanation

## Pathophysiology of SIADH-Induced Hyponatremia **Key Point:** SIADH causes hyponatremia through **inappropriate ADH secretion**, which increases aquaporin-2 water channel expression in the collecting duct, leading to excessive free water reabsorption and dilutional hyponatremia. ### Mechanism of SIADH ```mermaid flowchart TD A[Inappropriate ADH secretion]:::action --> B[Increased aquaporin-2 channels<br/>in collecting duct]:::action B --> C[Enhanced free water<br/>reabsorption]:::action C --> D[Plasma volume expansion<br/>and dilution]:::action D --> E[Serum sodium ↓<br/>Serum osmolality ↓]:::outcome A --> F[Urine osmolality remains<br/>inappropriately high]:::outcome F --> G[Urine sodium often elevated<br/>due to volume expansion]:::outcome ``` ### Key Diagnostic Features of SIADH | Feature | Finding | Explanation | |---------|---------|-------------| | **Serum osmolality** | < 275 mOsm/kg | Hypotonic hyponatremia | | **Urine osmolality** | > 100 mOsm/kg (often > 200) | Inappropriately concentrated for low serum osmolality | | **Urine sodium** | Usually > 40 mEq/L | Due to volume expansion suppressing aldosterone | | **ADH level** | Elevated (inappropriately) | Normal suppression does not occur | | **Thyroid/adrenal function** | Normal | Rules out secondary causes | **High-Yield:** The hallmark of SIADH is the **paradox of concentrated urine in the setting of hypotonic plasma**. In healthy individuals, low serum osmolality suppresses ADH, leading to dilute urine; in SIADH, ADH remains elevated despite low osmolality. **Mnemonic: SIADH Causes — CHIMPANZEES** - **C**ancer (small cell lung, pancreatic, bladder) - **H**ead injury / CNS disease - **I**nfections (pneumonia, TB, meningitis) - **M**edications (SSRIs, carbamazepine, vincristine) - **P**ulmonary disease (positive pressure ventilation) - **A**cute porphyria - **N**ausea / pain / stress - **Z**oster (varicella) - **E**ndocrine (hypothyroidism, adrenal insufficiency) - **E**xcretion (renal failure — mild) - **S**urgery / trauma **Clinical Pearl:** SIADH is a diagnosis of exclusion. Before diagnosing SIADH, rule out: - Hypothyroidism - Adrenal insufficiency - Diuretic use - Volume depletion - Renal/cardiac/hepatic disease