Syndrome of inappropriate antidiuretic hormone pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vindhya BellamKonda, M.B.B.S [2]
Overview
Pathophysiology
The normal function of ADH on the kidneys is to control the amount of water reabsorbed by kidney nephrons. ADH acts in the distal portion of the renal tubule (Distal Convoluted Tubule) as well as on the collecting duct and causes the retention of water. Owing to it's water retaining capacity,it dilutes the blood, and decreases electrolytes especially, sodium causing hyponatremia.
Developmentally, mammalian organisms have evolved in times of water scarcity and ADH is secreted to prevent water loss in the kidneys. When water is ingested, it is taken up into the circulation and results in a dilution of the plasma. This dilution, otherwise described as a reduction in plasma osmolality is detected by osmoreceptors in the hypothalamus of the brain and these then switch off the release of ADH. The decreasing concentration of ADH effectively inhibits the aquaporins in the collecting ducts and distal convoluted tubules in the nephrons of the kidney. Hence, less water is reabsorbed, thereby increasing urine output, decreasing urine osmolality, and increasing (normalization of) blood osmolality.
In general, the plasma Na+ concentration is the primary osmotic determinant of AVP release. In SIADH, there is non physiological secretion of AVP. There is enhanced water reabsorption, leading to dilutional hyponatremia.
- Pathogenesis: Normal amounts of ADH are produced by the posterior pituitary gland. In SIADH ,ADH level rises above the normal value. Aquaporins are localized on storage vesicles in the cytoplasm of the epithelial cells which make up the collecting ducts of the kidneys. High ADH level stimulates mass fusion of aquaporin-carrying storage vesicles with the plasma membrane. High aquaporin density facilitates high diffusion of water across the plasma membrane. Excess water is reabsorbed from the nephrons and is returned to the blood.
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Genetics
Clinical picture of SIADH may result from genetic disorders that result in antidiuresis. A mutation affecting the gene for the renal V2 receptor, which some investigators have named nephrogenic syndrome of inappropriate antidiuresis, has been found to cause clinically significant hyponatremia. Congenital nephrogenic diabetes insipidus is characterized by a resistance of the renal collecting duct to the action of the arginine vasopressin hormone responsible for the inability of the kidney to concentrate urine. The X-linked form is due to inactivating mutations of the vasopressin 2 receptor gene leading to a loss of function of the mutated receptors. Conversely, the nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is linked to a constitutive activation of the V(2)-receptor due to activating mutations with clinical and biological features of inappropriate antidiuresis but with low or undetectable plasma arginine vasopressin hormone levels.[1]
Associated conditions
SIADH is most commonly associated with malignancies, CNS disorders, medications, pulmonary disorders.
Gross pathology
Microscopic pathology
References
- ↑ Pillai BP, Unnikrishnan AG, Pavithran PV (2011). "Syndrome of inappropriate antidiuretic hormone secretion: Revisiting a classical endocrine disorder". Indian J Endocrinol Metab. 15 Suppl 3: S208–15. doi:10.4103/2230-8210.84870. PMC 3183532. PMID 22029026.