Vitamin D deficiency pathophysiology: Difference between revisions
Jump to navigation
Jump to search
| (8 intermediate revisions by the same user not shown) | |||
| Line 2: | Line 2: | ||
{{Vitamin D deficiency}} | {{Vitamin D deficiency}} | ||
{{CMG}}; {{AE}} | {{CMG}}; {{AE}} {{HS}} | ||
==Overview== | ==Overview== | ||
==Pathophysiology== | ==Pathophysiology== | ||
===Synthesis and Metabolism=== | ===Synthesis and Metabolism=== | ||
*The main sources of vitamin D are sunlight exposure, diet, and dietary supplements. | *The main sources of vitamin D are sunlight exposure, diet, and dietary supplements.<ref name="pmid18329892">{{cite journal| author=Holick MF| title=Vitamin D status: measurement, interpretation, and clinical application. | journal=Ann Epidemiol | year= 2009 | volume= 19 | issue= 2 | pages= 73-8 | pmid=18329892 | doi=10.1016/j.annepidem.2007.12.001 | pmc=2665033 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18329892 }} </ref> | ||
*The vitamin D synthesized in the skin is ergocalciferol or vitamin D3. The vitamin D which comes from plant sources is called D2 or cholecalciferol. | *The vitamin D synthesized in the skin is ergocalciferol or vitamin D3. The vitamin D which comes from plant sources is called D2 or cholecalciferol. | ||
*Both cholecalciferol and ergocalciferol are inactive forms of vitamin D and sequentially activated in the liver and kidney to the active form of vitamin D, which exerts the biologic effects. | *Both cholecalciferol and ergocalciferol are inactive forms of vitamin D and sequentially activated in the liver and kidney to the active form of vitamin D, which exerts the biologic effects. | ||
*Vitamin D refers to both cholecalciferol and ergocalciferol or vitamin D2 and vitamin D3. | *Vitamin D refers to both cholecalciferol and ergocalciferol or vitamin D2 and vitamin D3. | ||
'''Synthesis in the skin''' | '''Synthesis in the skin''' | ||
*The synthesis of ergocalciferol (vitamin D3) occurs in the deeper layers of epidermis namely stratum spinosum and stratum basalis by the help of a chemical reaction involving UVB radiations (wavelength, 290 - 315 nm ) from sunlight. | *The synthesis of ergocalciferol (vitamin D3) occurs in the deeper layers of epidermis namely stratum spinosum and stratum basalis by the help of a chemical reaction involving UVB radiations (wavelength, 290 - 315 nm ) from sunlight.<ref name="pmid16886050">{{cite journal| author=Holick MF| title=Resurrection of vitamin D deficiency and rickets. | journal=J Clin Invest | year= 2006 | volume= 116 | issue= 8 | pages= 2062-72 | pmid=16886050 | doi=10.1172/JCI29449 | pmc=1523417 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16886050 }} </ref> | ||
*The UVB (wavelength, 290 - 315 nm ) radiations convert 7- dehydrocholesterol to pre-vitamin D3, which isomerizes to D3. | *The UVB (wavelength, 290 - 315 nm ) radiations convert 7- dehydrocholesterol to pre-vitamin D3, which isomerizes to D3. | ||
*The formation of vitamin D3 in the skin depends on sunlight exposure, the intensity of UVB and level of melanin pigment in the skin. | *The formation of vitamin D3 in the skin depends on sunlight exposure, the intensity of UVB and level of melanin pigment in the skin. | ||
| Line 45: | Line 19: | ||
*Vitamin D synthesized in the skin and ingested from food is transported in the blood to the liver, while it is bound to vitamin D binding protein. | *Vitamin D synthesized in the skin and ingested from food is transported in the blood to the liver, while it is bound to vitamin D binding protein. | ||
'''25 - Hydroxylation in the liver''' | '''25 - Hydroxylation in the liver''' | ||
* In the liver, vitamin D undergoes hydroxylation into 25 - hydroxyvitamin D3 with the help of one or more cytochrome P450 vitamin D hydroxylases. | * In the liver, vitamin D undergoes hydroxylation into 25 - hydroxyvitamin D3 with the help of one or more cytochrome P450 vitamin D hydroxylases.<ref name="pmid18329892">{{cite journal| author=Holick MF| title=Vitamin D status: measurement, interpretation, and clinical application. | journal=Ann Epidemiol | year= 2009 | volume= 19 | issue= 2 | pages= 73-8 | pmid=18329892 | doi=10.1016/j.annepidem.2007.12.001 | pmc=2665033 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18329892 }} </ref> | ||
* The common P 450 hydroxylases involved are CYP2R1, CYP2D11, and CYP2D25. | * The common P 450 hydroxylases involved are CYP2R1, CYP2D11, and CYP2D25. | ||
* The homozygous mutation of CYP2R1 gene was found in a patient with low circulating levels of 25 - hydroxyvitamin D3 with symptoms of vitamin D3 deficiency which suggests that CYP2R1 is the main enzyme involved in vitamin D hydroxylation in the liver. | * The homozygous mutation of CYP2R1 gene was found in a patient with low circulating levels of 25 - hydroxyvitamin D3 with symptoms of vitamin D3 deficiency which suggests that CYP2R1 is the main enzyme involved in vitamin D hydroxylation in the liver. | ||
| Line 51: | Line 25: | ||
* After hydroxylation, 25 - hydroxyvitamin D3 is released into plasma where it is bound to the vitamin D binding protein and carried to the kidneys for activation. | * After hydroxylation, 25 - hydroxyvitamin D3 is released into plasma where it is bound to the vitamin D binding protein and carried to the kidneys for activation. | ||
'''1 Alpha hydroxylation in kidneys''' | '''1 Alpha hydroxylation in kidneys''' | ||
* In the proximal renal tubule of the kidney, 25 - hydroxylated vitamin D undergoes further hydroxylation into 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) or calcitriol. | * In the proximal renal tubule of the kidney, 25 - hydroxylated vitamin D undergoes further hydroxylation into 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) or calcitriol.<ref name="pmid15585789">{{cite journal |vauthors=DeLuca HF |title=Overview of general physiologic features and functions of vitamin D |journal=Am. J. Clin. Nutr. |volume=80 |issue=6 Suppl |pages=1689S–96S |year=2004 |pmid=15585789 |doi= |url=}}</ref> | ||
* The hydroxylation in the kidney is carried by 25-hydroxyvitamin D3 1-alpha-hydroxylase, which is the product of the CYP27B1 human gene. | * The hydroxylation in the kidney is carried by 25-hydroxyvitamin D3 1-alpha-hydroxylase, which is the product of the CYP27B1 human gene. | ||
* This hydroxylation is under the influence of parathyroid hormone (PTH). | * This hydroxylation is under the influence of parathyroid hormone (PTH). | ||
| Line 74: | Line 48: | ||
*[[Magnesium]] provides [[negative feedback]] on [[parathyroid hormone]]. | *[[Magnesium]] provides [[negative feedback]] on [[parathyroid hormone]]. | ||
*[[Vitamin D]] decreases the concentration of [[parathyroid hormone]]. | *[[Vitamin D]] decreases the concentration of [[parathyroid hormone]]. | ||
<br><br><br> | |||
== | <div style="text-align: center;">'''The Sequence of Events in Parathyroid, Vitamin D, and Mineral Homeostasis''' </div> | ||
<br> | |||
{{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-hydroyx vitamin D]] to the active [[1,25-dihydroy xvitamin 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}} | |||
<br><br> | |||
==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
Latest revision as of 19:18, 9 October 2017
|
Vitamin D deficiency Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Vitamin D deficiency pathophysiology On the Web |
|
American Roentgen Ray Society Images of Vitamin D deficiency pathophysiology |
|
Risk calculators and risk factors for Vitamin D deficiency pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Husnain Shaukat, M.D [2]
Overview
Pathophysiology
Synthesis and Metabolism
- The main sources of vitamin D are sunlight exposure, diet, and dietary supplements.[1]
- The vitamin D synthesized in the skin is ergocalciferol or vitamin D3. The vitamin D which comes from plant sources is called D2 or cholecalciferol.
- Both cholecalciferol and ergocalciferol are inactive forms of vitamin D and sequentially activated in the liver and kidney to the active form of vitamin D, which exerts the biologic effects.
- Vitamin D refers to both cholecalciferol and ergocalciferol or vitamin D2 and vitamin D3.
Synthesis in the skin
- The synthesis of ergocalciferol (vitamin D3) occurs in the deeper layers of epidermis namely stratum spinosum and stratum basalis by the help of a chemical reaction involving UVB radiations (wavelength, 290 - 315 nm ) from sunlight.[2]
- The UVB (wavelength, 290 - 315 nm ) radiations convert 7- dehydrocholesterol to pre-vitamin D3, which isomerizes to D3.
- The formation of vitamin D3 in the skin depends on sunlight exposure, the intensity of UVB and level of melanin pigment in the skin.
- The UVB intensity varies with season and latitude.
- The clothing and sun-screen also limit the exposure.
- Vitamin D synthesized in the skin and ingested from food is transported in the blood to the liver, while it is bound to vitamin D binding protein.
25 - Hydroxylation in the liver
- In the liver, vitamin D undergoes hydroxylation into 25 - hydroxyvitamin D3 with the help of one or more cytochrome P450 vitamin D hydroxylases.[1]
- The common P 450 hydroxylases involved are CYP2R1, CYP2D11, and CYP2D25.
- The homozygous mutation of CYP2R1 gene was found in a patient with low circulating levels of 25 - hydroxyvitamin D3 with symptoms of vitamin D3 deficiency which suggests that CYP2R1 is the main enzyme involved in vitamin D hydroxylation in the liver.
- 25 - hydroxyvitamin D3 or calcifediol is the major circulating form of vitamin D and its serum level is used to assess the individual's vitamin D status.
- After hydroxylation, 25 - hydroxyvitamin D3 is released into plasma where it is bound to the vitamin D binding protein and carried to the kidneys for activation.
1 Alpha hydroxylation in kidneys
- In the proximal renal tubule of the kidney, 25 - hydroxylated vitamin D undergoes further hydroxylation into 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) or calcitriol.[3]
- The hydroxylation in the kidney is carried by 25-hydroxyvitamin D3 1-alpha-hydroxylase, which is the product of the CYP27B1 human gene.
- This hydroxylation is under the influence of parathyroid hormone (PTH).
- 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) or calcitriol is the active form of vitamin D and responsible for most of the biologic actions of vitamin D.
Parathyroid hormone (PTH), Vitamin D and mineral homeostasis The effect of parathyroid hormone on mineral metabolism is as follows:[4][5]
- Effect of 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 inorganic phosphate metabolism:
- Increases excretion of inorganic phosphate from kidney resulting in decreased serum concentration of phosphate.
- 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 in Parathyroid, Vitamin D, and Mineral Homeostasis
| Parathyroid hormone | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Kidney | Bone | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Decreased excretion of magnesium | Increasead conversion of inactive 25-hydroyx vitamin D to the active 1,25-dihydroy xvitamin 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
References
- ↑ 1.0 1.1 Holick MF (2009). "Vitamin D status: measurement, interpretation, and clinical application". Ann Epidemiol. 19 (2): 73–8. doi:10.1016/j.annepidem.2007.12.001. PMC 2665033. PMID 18329892.
- ↑ Holick MF (2006). "Resurrection of vitamin D deficiency and rickets". J Clin Invest. 116 (8): 2062–72. doi:10.1172/JCI29449. PMC 1523417. PMID 16886050.
- ↑ DeLuca HF (2004). "Overview of general physiologic features and functions of vitamin D". Am. J. Clin. Nutr. 80 (6 Suppl): 1689S–96S. PMID 15585789.
- ↑ 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.