ChemPath: Calcium Metabolism Flashcards
Review calcium metabolism and homeostasis, recognising the importance of a fixed calcium level on nerve and muscle function. Common calcium disorders Hypercalcaemia Hypocalcaemia Common metabolic bone disorders Osteporosis Osteomalacia / Rickets Pagets To understand the effects of vitamin D and PTH Renal stones
What percent of calcium in the body is stored in bones?
99%
What percent of calcium is stored in serum?
1%
What are the three forms of serum Calcium?
- Free (“ionised”) ~50% - biologically active
- Protein-bound ~40% - albumin
- Complexed ~10% - citrate / phosphate
What is the normal range of total calcium serum?
2.2 - 2.6 mmol/L
How is corrected Calcium calculated?
serum calcium + 0.02 * (40 – serum albumin in g/L)
adjust calcium levels to account for very high/low albumin in blood
determine if there actually is high/low ionised Ca2+
Why is control of serum calcium levels so important?
Calcium levels important in muscle depolarisation and thus in the control of nerve and muscle
Chronic low Ca2+ –> loss of Ca2+ from bone to maintain circulatory Ca2+
If you have a low albumin, the bound calcium will be ____, but the free calcium will be _____. Thus the corrected calcium tells you that the problem is with the _____ and that the ionised calcium will also be ______.
If you have a low albumin, the bound calcium will be low, but the free calcium will be normal. Thus the corrected calcium tells you that the problem is with the albumin and that the ionised calcium will also be normal.
- Free (“ionised”) ~50% - biologically active
- Protein-bound ~40% - al
How are circulating calcium levels maintained?
Plasma concentration of calcium must be maintained despite calcium and vitamin D deficiency.
Chronic calcium deficiency thus results in loss of calcium from bone in order to maintain circulating calcium.
Describe briefly calcium homeostasis in response to decreased Calcium?
Hypocalcaemia is detected by parathyroid gland.
Parathyroid gland releases PTH.
PTH “obtains” Calcium from 3 sources: Bone (resorption)
Kidney (resorption and renal 1 alpha hydroxylase activation)
Gut (absorption due to increased vitamin D production)
2 main hormones in Ca2+ homestasis
PTH
Vitamin D
What are the main roles of PTH?
- Stimulate osteoclasts to release Ca from bone
- Stimulate renal Ca resorption
- Stimulates 1,25 (OH)2 Vit D synthesis (1alpha-hydroxylation)
- Stimulates renal phosphate wasting (Phosphate trashing hormone)
What enzyme does PTH activate in the kidney?
1alpha-hydroxylase
Describe Vitamin D synthesis.
- 7-dehydrocholesterol is converted into cholecalciferol (D3) by UV light.
- Cholecalciferol (D3) is converted into 25-hydroxycholecalciferol (25-OH D3) by 25-hydroxylase in the liver.
- 25-hydoxycholecalciferol (25-OH D3) is converted by 1,25-dihydroxycholecalciferol (1,25-(OH)2 D3) by 1alpha-hydroxylase in the kidney.
- 1,25(OH)2 D3 is the physiologically active form of Vitamin D
What inactive form is Vit D stored in the body as?
25-hydroxycholecalciferol
this is what is measure in Vitamin D blood test
What is the physiologically active form of Vit D?
1,25-dihydroxycholecalciferol
Which of these is a plant product?
A. Ergocalciferol (D2)
B. Cholecalciferol (D3)
A. Ergocalciferol (D2)
can take either as a supplement –> 1st pass metbaolism in liver
What percent of any absorbed Vit D is hydroxylated at the 25 position in the liver?
100%
What enzyme in the liver hydroxylases Vit D at the 25 position?
25-hydroxylase
What is the rate limiting step in Vit D activation?
1-alpha hydroxylase in the kidney. This enzyme is activated by PTH only when calcium is needed.
Where may 1-alpha hydroxylase sometimes be expressed pathologically?
Rarely, it can be expressed in lung cells of sarcoid tissue.
With sarcoidosis, there are macrophages in the lung that may express this enzyme in a non-regulated fashion. This may cause hypercalcaemia but only during the summer time when Vit D levels are increased.
