Editing Diabetes insipidus (section)

==Pathophysiology==
Electrolyte and volume [[homeostasis]] is a complex mechanism that balances the body's requirements for [[blood pressure]] and the main electrolytes [[sodium]] and [[potassium]]. In general, electrolyte regulation precedes volume regulation. When the volume is severely depleted, however, the body will retain water at the expense of deranging electrolyte levels.<ref>{{Cite journal |last=Watson |first=Fiona |last2=Austin |first2=Pauline |date=2021-10-01 |title=Physiology of human fluid balance |url=https://www.sciencedirect.com/science/article/pii/S1472029921001818 |journal=Anaesthesia & Intensive Care Medicine |language=en |volume=22 |issue=10 |pages=644–651 |doi=10.1016/j.mpaic.2021.07.010 |issn=1472-0299}}</ref>

The regulation of urine production occurs in the [[hypothalamus]], which produces [[Vasopressin|ADH]] in the [[Supraoptic nucleus|supraoptic]] and [[Paraventricular nucleus|paraventricular]] nuclei. After synthesis, the hormone is transported in neurosecretory granules down the axon of the hypothalamic neuron to the posterior lobe of the [[pituitary gland]], where it is stored for later release. In addition, the hypothalamus regulates the sensation of thirst in the [[ventromedial nucleus]] by sensing increases in serum [[osmolarity]] and relaying this information to the [[Cerebral cortex|cortex]].{{citation needed|date=April 2022}}

Neurogenic/central DI results from a lack of ADH; occasionally it can present with decreased thirst as regulation of thirst and ADH production occur in close proximity in the hypothalamus. It is encountered as a result of hypoxic encephalopathy, neurosurgery, autoimmunity or cancer, or sometimes without an underlying cause (idiopathic).{{citation needed|date=October 2021}}

The main effector organ for [[body water|fluid]] homeostasis is the [[kidney]]. ADH acts by increasing water permeability in the [[collecting ducts]] and distal convoluted tubules; specifically, it acts on proteins called [[aquaporin]]s and more specifically aquaporin 2 in the following cascade. When released, ADH binds to V2 G-protein coupled receptors within the distal convoluted tubules, increasing [[cyclic AMP]], which couples with [[protein kinase A]], stimulating translocation of the aquaporin 2 channel stored in the [[cytoplasm]] of the distal convoluted tubules and collecting ducts into the apical membrane. These transcribed channels allow water into the collecting duct cells. The increase in permeability allows for the reabsorption of water into the bloodstream, thus concentrating the urine.{{citation needed|date=September 2024}}

Nephrogenic DI results from a lack of aquaporin channels in the distal collecting duct (decreased surface expression and transcription). It is seen in [[lithium toxicity]], [[Hypercalcaemia|hypercalcemia]], [[hypokalemia]], or the release of ureteral obstruction. Therefore, a lack of ADH prevents water reabsorption and the osmolarity of the blood increases. With increased osmolarity, the osmoreceptors in the hypothalamus detect this change and stimulate thirst. With increased thirst, the person now experiences a polydipsia and polyuria cycle.{{citation needed|date=September 2024}}

Hereditary forms of diabetes insipidus account for less than 10% of the cases of diabetes insipidus seen in clinical practice.<ref>{{Cite journal |vauthors=Fujiwara TM, Bichet DG |year=2005 |title=Molecular Biology of Hereditary Diabetes Insipidus |journal=Journal of the American Society of Nephrology |volume=16 |issue=10 |pages=2836–2846 |doi=10.1681/ASN.2005040371 |pmid=16093448 |doi-access=free}}</ref>