L11 – The Physiology of Calcium and Phosphate Metabolism Flashcards
(39 cards)
Describe the storage and transport forms of calcium?
Storage = 99% in bones
Transport:
- Free ionized form - active (50%)
- Protein-bound form (40%)
- Complexed with anions (10%) e.g., phosphates, HCO3-, citrate
Describe the storage and transport forms of phosphate?
Storage = 85% in bones, complexed with Ca as hydroxyapatite or calcium phosphate
Extra-skeletal tissues (14%): phosophoproteins, phosopholipids, nuclei acids
Circulation (1%):
- Free ionized form (60%) as H2PO4- or HPO42-
- Protein-bound form (10%)
- Complexed with cations (30%)
Compare the rate of mobilization between hydroxyapatite and calcium phosphate?
Hydroxyapatite = stable pool = require Oct and Ob to process, takes time to mobilize
CaPO4 = exchangeable pool = Rapid absorption and mobilization, non-crystalline
Both calcium and phosphate levels are age and sex specific. True or False?
False
Calcium = highly age and sex specific
Phosphate = age specific (only infant vs adult, not by year)
Variation in extracellular Ca elicits a larger response than variation in Phosphate. T or F?
True
Ca needs more tight control
Intake amount, absorption and excretion of Ca? which organs involved
Adults: 1000 mg/day = 1g/day
GIT absorption (inefficient) + Kidney reabsorption (99%)
Feces (majority) + urine excretion
Organs for absorption and excretion of PO4?
absorbed by the alimentary tract
90% plasma PO4 freely filtered, 80% reabsorbed in PCT
Phosphate level determined by renal phosphate excretion rate:
What determines the rate of PO4 excretion?
GFR vs reabsorption in PCT by Na/PO4 symporters (transport maximum)
Which hormones regulate Ca and PO4 levels?
calcitonin, active vitamin D, and parathyroid hormone
List some functions of Ca?
Bone and teeth
Cell signaling (IP3-Ca2+ pathways)
Neural transmission
Muscle contraction (e.g. heartbeat)
Blood coagulation (e.g. factor IV, IX and X)
List some functions of PO4?
- Protein, RNA, DNA > growth, maintenance, repair
- Energy metabolism, ATP production
- Chemical buffer to neutralize acids
arterial supply of parathyroid glands?
Inferior thyroid artery
Mechanism of PTH control in Chief cells under high serum Ca levels?
Chief cells:
- calcium sensing receptor (CaSR = Gαq protein-coupled receptor) activated during high serum Ca >> Activate phospholipase A2 >> arachidonic acid cascade >> increase PTH degradation >>suppresses PTH release
Mechanism of PTH control in Chief cells under low serum Ca levels?
Low serum Ca
> relax calcium sensing receptor
remove inhibitory signal
Release PTH from secretory vesicles
*Increase CaSR stimulation also increases calcitonin release from parafollicular cells**
How does PO4 level influence the PTH control in Chief cells?
High serum PO4 = low serum Ca
High PO4 inhibits Phospholipase A2 and arachidonic acid cascade» decrease PTH degradation
Works synergistic with Ca to increase PTH release
How does Vitamin D influence PTH secretion in Chief cells?
Vit D decreases stability of mRNA of PTH»_space; less PTH translated»_space; decrease PTH release
Describe the intracellular mechanism of low PTH on the Osteoblasts?
Low PTH:
activates Gαq*
> > PLC»_space; stimulates IP3 /Ca2+ pathways (intracellular Ca2+ release)
> > osteoblast proliferation***, synergistic with Bone formation mediated by Calcitonin
Describe the intracellular mechanism of High PTH on Osteoblasts?
High [PTH] (= low [Ca2+])»_space; activates Gαs*: activates adenylyl cyclase»_space; stimulates cAMP/PKA pathway»_space; transcription factor activation:
1) Produces + release receptor-activated nuclear kappa B ligand (RANKL): bind to RANK on OsteoCLAST precursors = Osteoclastogenesis = increase bone resorption and Ca, PO4 release
2) Inhibit Osteoprotegerin (OPG) from Ob, remove inhibition on RANKL = increase Oct maturation
Effects of High PTH on kidneys?
In PCT:
- expression of 1α- hydroxylase»_space; increase formation of 1,25-dihydroxy-vitamin D (calcitriol)»_space; act on intestines for Ca and PO4 absorption
- Stimulate PLC/PKC and cAMP/PKA pathways:
i) Phosphorylate NHERF, cause internal degradation of Na/PO4 cotransporter NPT2a»_space; Increase PO4 excretion
ii) PLC/PKC pathway degrade NPT2a mRNA»_space; reduce expression
Describe the sequence of VitD metabolism?
Skin/ diet = Vit D
Liver: convert to 25-hydroxyvitamin D (inactive)
Circulate to kidney: convert to active 1,25-dihydroxyvitamin D by 1a- hydroxylase
Describe the effect of Calcitriol from kidneys on Intestines?
Increase Ca absorption by increasing expression of:
- apical membrane calcium channel TRPV6 = import Ca
- calcium binding protein ‘calbindin-D9k’ = traffick Ca
- Basolateral Ca2+-ATPase (PMCA1b) = export Ca to blood
- apical membrane Na+/PO42− cotransporter, NPT2b = increase Phosphate absorption
Describe the effects of Calcitriol on bone cells during low Ca?
Bind to vit D receptor:
1) Increases expression of RANKL, hence osteoclast formation and action
2) Inhibit bone mineralization: increase expression of pyrophosphate (PPi) and osteopontin (OPN)
»> Inhibits formation of hydroxyapatite
» inhibits bone matrix mineralization
Compare the effects of Vit D in vivo and as a drug?
Drug = Vit D Increase BMD by increase bone mineralization
In vivo = Vit D decrease BMD by increasing osteoclastic bone resorption
Describe the effects of Calcitriol on DCT in kidneys ?
Increase renal Ca absorption: enter by TRPV5
a. Increases expression of the basolateral Ca2+-ATPase (PMCA1b)
b. Increases expression of intracellular calcium binding protein - calbindin-D28k
