Lecture 22: Ca metabolism Flashcards
What regualtes Ca concentrations:
Ca, Vit D and PTH are responsible for Ca homeostasis
What are the main organs involved in Ca homeostasis:
Intestine
Kidneys
Bones (stores)
How is Ca found?
iCa - 50%
Protein bound - 40%
Ion-complexed - 10%
Write an overview on PTH:
- Chief cells of parathyroid gland
- Released within minutes of decreased Ca
- Main defender of the serum Ca
How does PTH act?
- Stimulates osteoclastic bone resorption
- Stimulates renal tubular reabsorption of Ca2+
- Stimulates renal 1-hydroxylation of 25(OH)D
Restores serum Ca by acting on all effector organs. Bone and kidney directly; Intestine indirectly
Insert the diagram
Slides 2-3
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What regulates PTH?
- Serum ionized Ca (most imp) (decreases PTH)
- Serum phosphate (increases PTH)
- Serum 1,25 dihydroxyvitamin D (decreases PTH)
Describe how ECF Ca is found:
45-50% ionized, bioactive
5-10% complexed with anions i.e HCO3
45-50% protein-bound, albumin and globulins
Describe how Ca can induce PTH release:
Ca binds the receptor with Mg as a cofactor to decreased PTH released from cheif cells
How does CaR regulate renal tubular Ca handling:
Ca binds CaR and decreases the absorption via:
- Paracellularly
- Na,Cl,K pumps and K efflux pumps (i.e the gradients that create the gradient for Ca paracellular transport)
Describe Vit D metabolism:
slide 10
Does calcitonin regulate serum Ca?
no
What is PTHrP?
PTH related peptide
- Important paracrine regulator of breast, skin and bone development.
- Not a physiological regulator of serum Ca BUT in excess acts same was as PTH and can cause hypercalcemia
What are the PTH-dependent causes of hypercalcemia?
Primary hyperparathyroidism
FHH/Inactivating CaSR mutations
What are the PTH-independent causes of hypercalcemia?
[High Ca and low PTH]
- Cancer
- > PTHrP
- > Lytic bone disease
- > Vit D issues - Vit D - dependent
- Sarcoidosis
- Vit D intoxication
What are the causes of hypocalcemia:
Hypoparathyroidism - Post surgical, post neck irradiation Parathyroid hormone resistance Abnormal Vit D metabolism -> Vit D deficiency, resistance -> Renal failure
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What are the important hormones in phosphate metabolism?
Vit D
PTH
Phosphotonins
What do phosphotonins do?
Regulate renal handling of phosphate
What hormone determine flux of phosphate between ICF and ECF?
High pH (Drives from ECF to ICF)
What are the important organs of phosphate metabolilsim?
Intestines (dietary)
Bone (storage)
Kidneys (Filtration and reabsorption)
What are the causes of hyperphosphatemia?
Increased input: IV phosphate, cell death
Decreased excretion: Renal failure, PTH deficiency or resistance
What are the causes of hypophosphataemia?
- Inadequate GI absorption i.e b/c Vit D deficient
- Intracellular shift
- Resp. alkalosis (Illness, pain), usually self limiting
- Prolonged intense exercise
- Refeeding malnourished patients
- renal loss
- Inc. PTH
- Inc. phosphatonins
- Alcoholism
(Sufficient impairment can alter bone metabolism)
Whats the action of phosphotonins?
Phosphatonins i.e FGF23 (derived from bone)
- > Inhibits kidney phosphate reabsoprtion
- > Inhibits Vit D and thus gut phosphate absorption
= Hypophosphatemia
What is FGF23 essential in? where does it act?
Phosphate conditions
Acts in kidneys to increase phosphate excretion and decrease renal production of 1,25 OH D…
= Phosphate loss
In the FGF23 pathway (insert slide) where can mutations occur?
- Defective luminal GI Pi transports i.e Fanconi syndrome can increase phosphate excretion in kidneys
- Ectopic FGF23 can enhance its effects i.e oncogenic osteomalacia
- Abnormal FGF23 can mean its inactivated.
- Abnormal PHEX in bones can lead to inactive FGF23
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