Hypoparathyroidism pathophysiology: Difference between revisions
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{{Hypoparathyroidism}} | {{Hypoparathyroidism}} | ||
{{CMG}}; {{AE | {{CMG}}; {{AE}} | ||
==Overview== | ==Overview== | ||
The exact pathogenesis of [disease name] is not fully understood. | The exact pathogenesis of [disease name] is not fully understood. | ||
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==Pathophysiology== | ==Pathophysiology== | ||
===Parathyroid, Vitamin D, and mineral homeostasis=== | |||
The effect of [[parathyroid hormone]] on [[mineral]] [[metabolism]] is as follows:<ref name="pmid14184232">{{cite journal |vauthors=HARRISON MT |title=INTERRELATIONSHIPS OF VITAMIN D AND PARATHYROID HORMONE IN CALCIUM HOMEOSTASIS |journal=Postgrad Med J |volume=40 |issue= |pages=497–505 |year=1964 |pmid=14184232 |pmc=2482768 |doi= |url=}}</ref><ref>{{cite book | last = Nussey | first = Stephen | title = Endocrinology : an integrated approach | publisher = Bios NCBI | location = Oxford, UK Bethesda, Md | year = 2001 | isbn = 1-85996-252-1 }}</ref> | |||
*Effect of [[parathyroid hormone]] on [[inorganic phosphate]] [[metabolism]]: | |||
**Increases [[excretion]] of [[Phosphate|inorganic phosphate]] from [[kidney]] resulting in decreased serum concentration of [[phosphate]]. | |||
*Effect on [[parathyroid hormone]] on [[calcium]] [[metabolism]]: | |||
**Direct effect: | |||
***Increased [[resorption]] of [[Bone (disambiguation)|bones]]. | |||
***Decreases [[excretion]] from [[kidney]]. | |||
**Indirect effect: | |||
***Increases conversion of inactive [[25-hydroxy vitamin D]] to the active [[1,25-dihydroxy vitamin D]] which increases absorption of [[calcium]] from [[gut]]. Decreased phosphate concentration also increases this conversion process. [[Vitamin D]] shows synergism with [[parathyroid hormone]] action on [[bone]]. | |||
***Decreased serum [[inorganic phosphate]] concentration prevents [[Precipitation (chemistry)|precipitation]] of [[calcium phosphate]] in [[Bone (disambiguation)|bones]]. | |||
**Both these direct and indirect mechanism results in an increased serum [[calcium]] concentration. | |||
*Effect of [[parathyroid hormone]] on [[magnesium]] concentration: | |||
**Decreases [[excretion]] of [[magnesium]] resulting in increased serum [[magnesium]] concentretion. | |||
Effect of [[Mineral|minerals]] and [[vitamin D]] on [[parathyroid hormone]]: | |||
*Decrease in serum [[calcium]] concentration stimulates [[parathyroid hormone]]. | |||
*[[Calcium]] provides [[negative feedback]] on [[parathyroid hormone]]. | |||
*[[Magnesium]] provides [[negative feedback]] on [[parathyroid hormone]]. | |||
*[[Vitamin D]] decreases the concentration of [[parathyroid hormone]]. | |||
The sequence of events is shown in the algorithm below: | |||
{{familytree/start |}} | |||
{{familytree | | | | | | | | | | | | A01 |A01='''Parathyroid hormone'''}} | |||
{{familytree | | | | | | | |,|-|-|-|-|^|-|-|-|-|-|-|-|-|-|-|-|-|-|-|.|}} | |||
{{familytree | | | | | | | B01 | | | | | | | | | | | | | | | | | | B02 | | |B01=Kidney|B02=Bone}} | |||
{{familytree | |,|-|-|-|-|-|+|-|-|-|-|v|-|-|-|-|-|-|.| | | | | | | |!| }} | |||
{{familytree | C01 | | | | C02 | | | C03 | | | | | C04 | | | | | | C05 |C01=Decreased excretion of magnesium|C02=Increasead conversion of inactive 25-hydroyxvitamin D to the active 1,25-dihydroyxvitamin D|C03=Increase excretion of inorganic phosphate|C04=Decrease excretion of calcium|C05=Increased resorption of bone}} | |||
{{familytree | |!| | | | | |!| | | | |!| | | | | | |!| | | | | | | |!| |}} | |||
{{familytree | D01 | | | | D02 | | | D03 | | | | | |`|-|-|-|-|.| | |!|D01=Increased serum concentration of magnesium|D02=Increased absorption of calcium from gut|D03=Decreased serum concentration of inorganic phosphate}} | |||
{{familytree | | | | | | | |!| | | | |!| | | | | | | | | | | |!| | |!|}} | |||
{{familytree | | | | | | | |!| | | | |`|-|-| E01 |-|-|-|-|.| |!| | |!| E01=Prevents precipitation of calcium phosphate in bones}} | |||
{{familytree | | | | | | | |!| | | | | | | | | | | | | | |!| |!| | |!| | | | | |}} | |||
{{familytree | | | | | | | |`|-|-|-|-|-|-|-|-|-|-|-|-|-|-| F01 |-|-|'| | |F01=Increased serum concentration of calcium}} | |||
{{familytree/end}} | |||
===Calcium-sensing receptors=== | |||
*[[Calcium]]-sensing [[Receptor (biochemistry)|receptors]] are present on [[Parathyroid gland|parathyroid glands]]. They are a type of 7-transmembrane receptors in [[G-protein coupled receptors]] superfamily of receptors.<ref name="pmid8255296">{{cite journal| author=Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O et al.| title=Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. | journal=Nature | year= 1993 | volume= 366 | issue= 6455 | pages= 575-80 | pmid=8255296 | doi=10.1038/366575a0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8255296 }} </ref> | |||
*[[Calcium]]-sensing [[Receptor (biochemistry)|receptors]] sense change in [[extracellular]] concentration of ionized [[calcium]].<ref name="pmid7791841">{{cite journal| author=Brown EM, Pollak M, Seidman CE, Seidman JG, Chou YH, Riccardi D et al.| title=Calcium-ion-sensing cell-surface receptors. | journal=N Engl J Med | year= 1995 | volume= 333 | issue= 4 | pages= 234-40 | pmid=7791841 | doi=10.1056/NEJM199507273330407 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7791841 }} </ref> | |||
*[[Calcium]]-sensing [[Receptor (biochemistry)|receptor]] [[Gene expression|expression]] in reduced in primary hyperparathyroidism ([[parathyroid adenoma]]) and secondary hyperparathyroidism.<ref name="pmid8995751">{{cite journal| author=Gogusev J, Duchambon P, Hory B, Giovannini M, Goureau Y, Sarfati E et al.| title=Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism. | journal=Kidney Int | year= 1997 | volume= 51 | issue= 1 | pages= 328-36 | pmid=8995751 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8995751 }} </ref> | |||
*This reduced [[expression]] of receptor causes an increases in [[calcium]] sensing set point.<ref name="pmid8636374">{{cite journal| author=Kifor O, Moore FD, Wang P, Goldstein M, Vassilev P, Kifor I et al.| title=Reduced immunostaining for the extracellular Ca2+-sensing receptor in primary and uremic secondary hyperparathyroidism. | journal=J Clin Endocrinol Metab | year= 1996 | volume= 81 | issue= 4 | pages= 1598-606 | pmid=8636374 | doi=10.1210/jcem.81.4.8636374 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8636374 }} </ref> | |||
*This in turn leads to increase in [[secretion]] of [[parathyroid hormone]] in presence on normal serum concentration of extracellular ionized [[calcium]]. | |||
===Pathogenesis=== | ===Pathogenesis=== |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
The exact pathogenesis of [disease name] is not fully understood.
OR
It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
OR
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
OR
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
OR
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
OR
The progression to [disease name] usually involves the [molecular pathway].
OR
The pathophysiology of [disease/malignancy] depends on the histological subtype.
Pathophysiology
Parathyroid, Vitamin D, and mineral homeostasis
The effect of parathyroid hormone on mineral metabolism is as follows:[1][2]
- Effect of parathyroid hormone on inorganic phosphate metabolism:
- Increases excretion of inorganic phosphate from kidney resulting in decreased serum concentration of phosphate.
- Effect on parathyroid hormone on calcium metabolism:
- Direct effect:
- Increased resorption of bones.
- Decreases excretion from kidney.
- Indirect effect:
- Increases conversion of inactive 25-hydroxy vitamin D to the active 1,25-dihydroxy vitamin D which increases absorption of calcium from gut. Decreased phosphate concentration also increases this conversion process. Vitamin D shows synergism with parathyroid hormone action on bone.
- Decreased serum inorganic phosphate concentration prevents precipitation of calcium phosphate in bones.
- Both these direct and indirect mechanism results in an increased serum calcium concentration.
- Direct effect:
- Effect of parathyroid hormone on magnesium concentration:
Effect of minerals and vitamin D on parathyroid hormone:
- Decrease in serum calcium concentration stimulates parathyroid hormone.
- Calcium provides negative feedback on parathyroid hormone.
- Magnesium provides negative feedback on parathyroid hormone.
- Vitamin D decreases the concentration of parathyroid hormone.
The sequence of events is shown in the algorithm below:
Parathyroid hormone | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Kidney | Bone | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Decreased excretion of magnesium | Increasead conversion of inactive 25-hydroyxvitamin D to the active 1,25-dihydroyxvitamin D | Increase excretion of inorganic phosphate | Decrease excretion of calcium | Increased resorption of bone | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Increased serum concentration of magnesium | Increased absorption of calcium from gut | Decreased serum concentration of inorganic phosphate | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Prevents precipitation of calcium phosphate in bones | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Increased serum concentration of calcium | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Calcium-sensing receptors
- Calcium-sensing receptors are present on parathyroid glands. They are a type of 7-transmembrane receptors in G-protein coupled receptors superfamily of receptors.[3]
- Calcium-sensing receptors sense change in extracellular concentration of ionized calcium.[4]
- Calcium-sensing receptor expression in reduced in primary hyperparathyroidism (parathyroid adenoma) and secondary hyperparathyroidism.[5]
- This reduced expression of receptor causes an increases in calcium sensing set point.[6]
- This in turn leads to increase in secretion of parathyroid hormone in presence on normal serum concentration of extracellular ionized calcium.
Pathogenesis
- The exact pathogenesis of [disease name] is not fully understood.
OR
- It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
- [Pathogen name] is usually transmitted via the [transmission route] route to the human host.
- Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
- [Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
- The progression to [disease name] usually involves the [molecular pathway].
- The pathophysiology of [disease/malignancy] depends on the histological subtype.
Genetics
- [Disease name] is transmitted in [mode of genetic transmission] pattern.
- Genes involved in the pathogenesis of [disease name] include [gene1], [gene2], and [gene3].
- The development of [disease name] is the result of multiple genetic mutations.
Associated Conditions
Gross Pathology
- On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
Microscopic Pathology
- On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
References
- ↑ HARRISON MT (1964). "INTERRELATIONSHIPS OF VITAMIN D AND PARATHYROID HORMONE IN CALCIUM HOMEOSTASIS". Postgrad Med J. 40: 497–505. PMC 2482768. PMID 14184232.
- ↑ Nussey, Stephen (2001). Endocrinology : an integrated approach. Oxford, UK Bethesda, Md: Bios NCBI. ISBN 1-85996-252-1.
- ↑ Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O; et al. (1993). "Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid". Nature. 366 (6455): 575–80. doi:10.1038/366575a0. PMID 8255296.
- ↑ Brown EM, Pollak M, Seidman CE, Seidman JG, Chou YH, Riccardi D; et al. (1995). "Calcium-ion-sensing cell-surface receptors". N Engl J Med. 333 (4): 234–40. doi:10.1056/NEJM199507273330407. PMID 7791841.
- ↑ Gogusev J, Duchambon P, Hory B, Giovannini M, Goureau Y, Sarfati E; et al. (1997). "Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism". Kidney Int. 51 (1): 328–36. PMID 8995751.
- ↑ Kifor O, Moore FD, Wang P, Goldstein M, Vassilev P, Kifor I; et al. (1996). "Reduced immunostaining for the extracellular Ca2+-sensing receptor in primary and uremic secondary hyperparathyroidism". J Clin Endocrinol Metab. 81 (4): 1598–606. doi:10.1210/jcem.81.4.8636374. PMID 8636374.