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
Syndrome of inappropriate antidiuretic hormone production (SIADH) is a condition in which the body develops an excess of water and a decrease the concentration of electrolytes. It may be caused by central nervous system diseases, cancers, pulmonary diseases and some drugs.
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 ofwater. Owing to it's water retaining capacity,it dilutes the blood, and decreases electrolytes especially, sodium causinghyponatremia.
Pathogenesis
Normal amounts ofADH are produced by the posteriorpituitarygland. 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 thecollecting ducts of the kidneys. HighADH level stimulates mass fusion of aquaporin-carrying storage vesicles with theplasma 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. {{#ev:youtube|https://youtu.be/MR8BABoFTP8}}
Feedback inhibition
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 dilutionalhyponatremia.
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. Congenitalnephrogenic 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 undetectableplasma arginine vasopressin hormone levels.[1]
Associated conditions
SIADH is most commonly associated with malignancies, CNS disorders, medications, pulmonary disorders.
Gross pathology
There are no gross pathology findings associated with SIADH
Microscopic pathology
There are no microscopic findings associated with SIADH
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.