Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH): Pathogenesis and clinical
Malignancy
(e.g. Small cell lung cancer, head and neck cancer)
Tumor originates from neuroendocrine cells
Tumor acts as an ectopic site of ADH production
ADH binds receptors on basolateral side (facing peritubular capillary) of principal cells in nephron
ADH ↑ principal cells’ production of Aquaporin type II channels on their apical surface (side facing tubule lumen)
↑ Reabsorption of water from the collecting ducts back into circulation
↑ Blood Volume (↑ extracellular fluid volume)
Blood Na+ levels diluted
Hyponatremia
(blood Na+ <135 mEq/L) Brain injury (e.g. Stroke, encephalitis hemorrhage, trauma) ↑ hypothalamic ADH production, storage in posterior pituitary, & pituitary secretion of ADH ↑ Uncontrolled ADH secretion SIADH (Syndrome of Inappropriate Anti-Diuretic Hormone) Drugs (e.g. Cyclophosphamide, SSRIs, vincristine) Break down into active metabolites Metabolites mimic ADH activity findings Authors: Krusang Patel Yan Yu* Reviewers: Davis Maclean Brooke Fallis Juliya Hemmett* * MD at time of publication Atria and Ventricles of the heart stretch Heart secretes ↑ atrial natriuretic and B-type natriuretic peptides (ANP/BNP) Peptides promotes natriuresis (excretion of Na+ into urine) Loss of Na+ in serumàalters charge balance across neuron membranesàImproper action potential firing: ↓ Renin secretion ↓ Release of Angiotensin II & Aldosterone ↓Reabsorption of Na+ into circulation in area postrema of medulla in hypothalamus in motor neurons Extracellular fluid volume becomes hypotonic relative to intracellular fluid volume Water moves from circulation into cells Extracellular fluid volume normalizes Euvolemia Nausea Headaches Muscle Cramps ↓ Urine volume Cells, particularly neurons, swell up Cerebral edema Neurons burst and die Severe Neurocognitive Effects (confusion, mood swings, hallucinations, seizure, coma) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Dec 30, 2021 on www.thecalgaryguide.com