Calcium metabolism Flashcards
Where does calcium enter and exit body and how is it stored?
- Absorbed by GIT
- excreted in kidneys through urine and some calcium intake excreted instead of absorbed in faeces
- constant exchange of calcium between ECF and bone through bone remodelling (moves back and forth)
Where is the total body calcium stores found?
Skeleton
+ small amount in intracellular and extracellular fluid
How is calcium transported in the blood?
- most remains as free calcium
- also lots fo albumin bound and less but some globulin bound
- some anion bound also
What factors effect the proportion of each calcium transport in the blood?
- Albumin concentration (if elevated falsely high calcium can be reported and less free calcium as binds to albumin)
- PH, the lower the PH the more free calcium as hydrogen binds to albumin binding sites instead of calcium
Name some of the functions of calcium?
- Nerve and cardiac excitability
- Muscle contraction
- Cell differentiation
- Gene regulation
- Neurotransmitter release
- Enzyme and allosteric protein modulation
- Co-factor in coagulation cascade
What are the three hormones which regulate calcium?
1) Parathyroid hormone
2) Vitamin D
3) Calcitonin
What are the other two names of vitamin D
Calcitriol
1,25-dihydroxycholecalciferol (active form of Vitamin D)
What are the cells in the parathyroid which release parathyroid hormone?
Chief cells which are able to sense calcium levels and manufacture and release parathyroid hormone accordingly
What are the factors regulate the chief cells?
Release PTH when:
- Low calcium
- Low Magnesium
- High phosphate
What effect does parathyroid hormone have on bone?
Bone:
short term - calcium from bone pool moves into ECF
long term - Osteoclasts breakdown bone to release calcium
What effect does parathyroid hormone have on Kidneys?
- reabsorbs more calcium
- excretes more phosphate
- forms more active Vit D (1,25-dihydroxycholecalciferol)
What effect does parathyroid hormone have on Intestines?
Increases calcium absorption
Where is negative feedback loop in PTH secretion?
Normal calcium levels in ECF will switch off release of PTH
Why do phosphate levels decrease when calcium levels increase?
- The product of calcium and phosphate is insoluble so can precipitate in tissues
- to prevent this when there’s an increase in one body decreases other
Where can you get vitamin D?
Synthesised in skin
Diet: Dairy, oily fish, mushrooms and liver
What external factor is needed for synthesis of Vit D in the skin?
UV light needed
What reaction occurs in the skin?
7-dehydrocholesterol > cholecalciferol (Vit D3)
What is cholecalciferol converted to in the liver?
24-dehydroxycholecalciferol
which then inhibits further conversion of cholecalciferol to itself
Where is the Vit D then activated, what hormone stimulates this and what enzyme is required?
- proximal tubule kidneys
- PTH
- 1-Alpha-hydroxylase
What does Vitamin D achieve?
increased intestinal absorption of calcium which increases calcium levels in plasma
(inc plasma calcium inhibits PTH)
What two factors will affect activation of Vit K?
- PTH activates it
- Low phosphate levels will increase Vit K activation
How does Vit K increase intestinal absorption of calcium?
(acts on nuclear receptor to increase gene transcription of these and binds to Vitamin D receptor to initiate non-genomic effects)
- increase calcium binding proteins (calcitonin, transports calcium across cell)
- increases calcium stimulated ATPase (transporter protein from intestinal cell into blood)
- increase alkaline phosphatase
What condition is caused by lack of active vitamin K?
Rickets (children)
also called Osteomalacia (adults)
What are the causes of Rickets?
- Lack of dietary Vit K or sunlight
- malabsorption of fats (vit K fat soluble
- failure to form calciferol (usually due to CKD)
- mutation in 1alpha-hydroxylase
- mutation in Vit K receptor
