Diabetes insipidus pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
The posterior pituitary consists of paraventricular and the supra-optic nuclei that synthesizes oxytocin and arginine vasopressin respectively. In Central DI, there is an absence of vasopressin which is responsive to the exogenous administration of desmopressin. On the contrary, in nephrogenic DI, solute excretion and all filtration functions of the kidney are normal but urine is hypotonic and there is a characteristic resistance to the antidiuretic effects of both endogenous and exogenous administration of vasopressin. More than 55 different genetic mutations resulting in a defective prohormone and a deficiency of AVP have been identified in familial central diabetes. Many conditions have been associated with the development of diabetes insipidus such as Wolfram syndrome also known as DIDMOAD, Langerhans cell histiocytosis (LCH), sickle cell disease, amyloidosis etc.
Pathogenesis
Central Diabetes insipidus
The posterior pituitary consists of paraventricular and the supra-optic nuclei that synthesizes oxytocin and arginine vasopressin respectively. The axons of these hormones project to the neurohypophysis where the hormones are secreted into the blood stream to allow maximum antidiuresis for 5–10 days. The maintenance of water balance in healthy humans is achieved principally by three interrelated determinants:
AVP acts on the kidney, where it increases urine osmolality. It binds to the V2-receptors in the basolateral membrane of the renal collecting tube and activates the Gs-adenyl cyclase system, increasing intracellular levels of cyclic 3′,5′-adenosine monophosphate (cAMP) activating protein kinase A, which in turn phosphorylates preformed AQP2 water channels localized in intracellular vesicles.[1]
Nephrogenic diabetes insipidus
In nephrogenic DI, solute excretion and all filtration functions of the kidney are normal but urine is hypotonic and there is a characteristic resistance to the antidiuretic effects of endogenous vasopressin. Abnormalities in the medullary osmotic gradient directed by antidiuretic hormone (ADH) or arginine vasopressin (AVP) and inhibition of the action of ADH on the renal tubules are both thought to be mechanisms of development of nephrogenic DI. The lack of response to ADH is due to the inhibition of adenylate cyclase and resultant decreased formation of cAMP. cAMP serves as a second messenger to protein kinase A and the fusion of aquaporin storage vesicles to the luminal cell wall, which in turn allows the collecting ducts to become permeable and reabsorb water.
Psychogenic diabetes insipidus
This disorder is also known as factitious diabetes insipidus, a condition whereby due to some psychological disordera patient drinks excessive amount of water thereby decreasing the plasma osmolarity and suppressing the release of ADH. This leads to polyuria. The presence of a psychoneurotic disorder, the absence of a preference for iced fluids, and prompt antidiuresis in response to the administration of hypertonic saline, nicotine, or water deprivation will usually establish the diagnosis.
Genetics
- More than 55 different genetic mutations resulting in a defective prohormone and a deficiency of AVP have been identified in familial central diabetes.[2][3]
- Majority have an autosomal dominant form of inheritance
Associated Conditions
- Langerhans cell histiocytosis (LCH)
- Wolfram syndrome also known as DIDMOAD
- Sickle cell disease
- Amyloidosis
- Obstructive uropathy
- Electrolyte disorders (e.g.,hypokalemia and hypercalcemia)
- Pregnancy
- Conditions induced by a drug (e.g., lithium, demeclocycline, amphotericin B and vincristine)
- Lithium is the most common cause of drug-induced nephrogenic DI
Gross Pathology
There are no gross pathology findings associated with diabetes insipidus.
Microscopic Pathology
There are no microscopic findings associated with diabetes insipidus.
References
- ↑ Agre P (2004). "Nobel Lecture. Aquaporin water channels". Biosci Rep. 24 (3): 127–63. PMID 16209125.
- ↑ Christensen, Jane H.; Rittig, Søren (2006). "Familial Neurohypophyseal Diabetes Insipidus—An Update". Seminars in Nephrology. 26 (3): 209–223. doi:10.1016/j.semnephrol.2006.03.003. ISSN 0270-9295.
- ↑ Ghirardello, S.; Garrè, M.-L.; Rossi, A.; Maghnie, M. (2007). "The Diagnosis of Children with Central Diabetes Insipidus". Journal of Pediatric Endocrinology and Metabolism. 20 (3). doi:10.1515/JPEM.2007.20.3.359. ISSN 2191-0251.