Diabetes insipidus pathophysiology: Difference between revisions
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{{Diabetes insipidus}} | {{Diabetes insipidus}} | ||
{{CMG}} | {{CMG}}; {{AE}} {{DAMI}} | ||
==Overview== | ==Overview== | ||
The [[posterior pituitary]] consists of the [[Paraventricular nucleus of hypothalamus|paraventricular]] and [[Supraoptic nucleus|supraoptic nuclei]], which synthesize [[oxytocin]] and [[arginine vasopressin|arginine vasopressin,]] respectively. In cases of [[Central diabetes insipidus|central DI]], there is an absence of [[vasopressin]], which is responsive to the exogenous administration of [[desmopressin]]. On the contrary, in cases of [[Nephrogenic diabetes insipidus|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 [[ADH]] have been identified in familial [[Central diabetes insipidus|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|sickle cell disease]], [[amyloidosis]], and several others. | |||
==Pathogenesis== | ==Pathogenesis== | ||
The posterior pituitary consists of paraventricular and | ===Central Diabetes Insipidus=== | ||
The maintenance of water balance in healthy humans is achieved principally by three interrelated determinants: | The [[posterior pituitary]] consists of the [[Paraventricular nucleus|paraventricular]] and [[Supraoptic nucleus|supraoptic]] nuclei that synthesize [[oxytocin]] and [[arginine vasopressin]], respectively. The [[axons]] of these [[hormones]] project to the [[neurohypophysis]], where the [[hormones]] are secreted into the [[blood stream|bloodstream]] to allow for maximum anti-diuresis over the course of 5–10 days. The maintenance of water balance in healthy humans is achieved principally by three interrelated determinants: | ||
*Thirst | *[[Thirst]] | ||
*AVP | *[[ADH|AVP]] | ||
*Kidney function | *[[Kidney]] function | ||
[[ADH]] acts on the [[kidney]], where it increases [[urine osmolality]]. It binds to the [[V2 receptor|V2 receptors]] in the [[basolateral membrane]] of the [[Collecting duct system|renal collecting tube]] and activates the [[Adenyl cyclases|Gs-adenyl cyclase]] system, increasing intracellular levels of [[Cyclic adenosine monophosphate|cyclic 3′,5′-adenosine monophosphate]] ([[Cyclic adenosine monophosphate|cAMP]]) and thus activating [[protein kinase A]], which in turn phosphorylates preformed [[Aquaporin 2|AQP2 water channels]] localized in intracellular [[vesicles]].<ref name="pmid16209125">{{cite journal| author=Agre P| title=Nobel Lecture. Aquaporin water channels. | journal=Biosci Rep | year= 2004 | volume= 24 | issue= 3 | pages= 127-63 | pmid=16209125 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16209125 }} </ref> | |||
===Nephrogenic Diabetes Insipidus=== | |||
In cases of [[Nephrogenic diabetes insipidus|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 by which [[Nephrogenic diabetes insipidus|nephrogenic DI]] develops. The lack of response to [[ADH]] is due to the inhibition of [[adenylate cyclase]] and the resultant decreased formation of [[Cyclic adenosine monophosphate|cAMP]]. [[cAMP]] serves as a second messenger to [[Protein kinase A|protein kinase A]] and facilitates the fusion of [[aquaporin]] storage vesicles to the [[luminal]] cell wall, which in turn allows the [[Collecting duct system|collecting ducts]] to become [[permeable]] and reabsorb water. | |||
===Psychogenic Diabetes Insipidus=== | |||
This [[Disorder (medicine)|disorder]] is also known as [[Factitious disorder|factitious]] diabetes insipidus, a condition whereby, due to some [[psychological]] [[Disorder (medicine)|disorder]], a patient drinks an 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 [[Antidiuretic effect|antidiuresis]] in response to the administration of [[Hypertonic|hypertonic saline,]] [[nicotine]], or water deprivation will usually establish the [[diagnosis]]. | |||
===Gestational Diabetes Insipidus=== | |||
This disorder is classically identified during [[pregnancy]] in a woman of childbearing age. Gestational diabetes insipidus (DI) is a very rare [[complication]] of pregnancy. Undiagnosed and untreated cases may lead to serious complications in both the mother and the fetus. Gestational DI results when an [[enzyme]] made by the [[placenta]] destroys [[ADH]] in the mother. The [[placenta]] is the system of [[blood vessels]] and other tissues that develops with the [[fetus]]. The [[placenta]] allows for the exchange of [[nutrients]] and waste products between mother and [[fetus]]. Most cases of gestational DI can be treated with [[desmopressin]]. In rare cases, however, an abnormality in the thirst mechanism causes gestational DI, and [[desmopressin]] should not be used.<ref name="pmid26707038">{{cite journal| author=Ejmocka-Ambroziak A, Grzechocińska B, Jastrzebska H, Kochman M, Cyganek A, Wielgoś M et al.| title=Gestational diabetes insipidus. Case Report. | journal=Neuro Endocrinol Lett | year= 2015 | volume= 36 | issue= 5 | pages= 410-3 | pmid=26707038 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26707038 }} </ref> | |||
==Genetics== | ==Genetics== | ||
More than 55 different [[genetic mutations]] resulting in a defective [[prohormone]] and a deficiency of [[AVP]] have been implicated in the development of familial [[Central diabetes insipidus|central diabetes]].<ref name="ChristensenRittig2006">{{cite journal|last1=Christensen|first1=Jane H.|last2=Rittig|first2=Søren|title=Familial Neurohypophyseal Diabetes Insipidus—An Update|journal=Seminars in Nephrology|volume=26|issue=3|year=2006|pages=209–223|issn=02709295|doi=10.1016/j.semnephrol.2006.03.003}}</ref> The majority of relevant [[genetic mutations]] have an [[autosomal dominant]] form of inheritance.<ref name="GhirardelloGarrè2007">{{cite journal|last1=Ghirardello|first1=S.|last2=Garrè|first2=M.-L.|last3=Rossi|first3=A.|last4=Maghnie|first4=M.|title=The Diagnosis of Children with Central Diabetes Insipidus|journal=Journal of Pediatric Endocrinology and Metabolism|volume=20|issue=3|year=2007|issn=2191-0251|doi=10.1515/JPEM.2007.20.3.359}}</ref> | |||
==Associated Conditions== | ==Associated Conditions== | ||
Conditions associated with DI include: | |||
*[[Langerhans cell histiocytosis]] (LCH) | |||
*[[Wolfram syndrome]], also known as DIDMOAD ([[diabetes insipidus]], [[Diabetes mellitus|diabetes mellitus,]] [[Optic atrophy|optic atrophy,]] and [[deafness]]) | |||
*[[Sickle-cell disease|Sickle cell disease]] | |||
*[[Amyloidosis]] | |||
*[[Obstructive uropathy]] | |||
*[[Electrolyte disturbance|Electrolyte disturbances]] (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 diabetes insipidus|nephrogenic DI]] | |||
==Gross Pathology== | ==Gross Pathology== | ||
There are no gross pathology findings associated with diabetes insipidus. | |||
==Microscopic Pathology== | ==Microscopic Pathology== | ||
There are no microscopic findings associated with diabetes insipidus. | |||
There are | |||
==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}} | ||
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[[Category:Endocrinology]] | [[Category:Endocrinology]] | ||
[[Category:Nephrology]] | [[Category:Nephrology]] | ||
Latest revision as of 19:49, 26 October 2017
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]
Overview
The posterior pituitary consists of the paraventricular and supraoptic nuclei, which synthesize oxytocin and arginine vasopressin, respectively. In cases of central DI, there is an absence of vasopressin, which is responsive to the exogenous administration of desmopressin. On the contrary, in cases of 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 ADH 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, and several others.
Pathogenesis
Central Diabetes Insipidus
The posterior pituitary consists of the paraventricular and supraoptic nuclei that synthesize oxytocin and arginine vasopressin, respectively. The axons of these hormones project to the neurohypophysis, where the hormones are secreted into the bloodstream to allow for maximum anti-diuresis over the course of 5–10 days. The maintenance of water balance in healthy humans is achieved principally by three interrelated determinants:
ADH 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) and thus activating protein kinase A, which in turn phosphorylates preformed AQP2 water channels localized in intracellular vesicles.[1]
Nephrogenic Diabetes Insipidus
In cases of 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 by which nephrogenic DI develops. The lack of response to ADH is due to the inhibition of adenylate cyclase and the resultant decreased formation of cAMP. cAMP serves as a second messenger to protein kinase A and facilitates 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 disorder, a patient drinks an 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.
Gestational Diabetes Insipidus
This disorder is classically identified during pregnancy in a woman of childbearing age. Gestational diabetes insipidus (DI) is a very rare complication of pregnancy. Undiagnosed and untreated cases may lead to serious complications in both the mother and the fetus. Gestational DI results when an enzyme made by the placenta destroys ADH in the mother. The placenta is the system of blood vessels and other tissues that develops with the fetus. The placenta allows for the exchange of nutrients and waste products between mother and fetus. Most cases of gestational DI can be treated with desmopressin. In rare cases, however, an abnormality in the thirst mechanism causes gestational DI, and desmopressin should not be used.[2]
Genetics
More than 55 different genetic mutations resulting in a defective prohormone and a deficiency of AVP have been implicated in the development of familial central diabetes.[3] The majority of relevant genetic mutations have an autosomal dominant form of inheritance.[4]
Associated Conditions
Conditions associated with DI include:
- Langerhans cell histiocytosis (LCH)
- Wolfram syndrome, also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness)
- Sickle cell disease
- Amyloidosis
- Obstructive uropathy
- Electrolyte disturbances (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.
- ↑ Ejmocka-Ambroziak A, Grzechocińska B, Jastrzebska H, Kochman M, Cyganek A, Wielgoś M; et al. (2015). "Gestational diabetes insipidus. Case Report". Neuro Endocrinol Lett. 36 (5): 410–3. PMID 26707038.
- ↑ 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.