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CNSLF Path - Ca Metabolism & Disorders of Ca Balance (i) (PTH…
CNSLF Path - Ca Metabolism & Disorders of Ca Balance (i)
Intro
99% of Ca in bone - active storage-reservoir
dietary intake - 1/2 leaves body in faeces
most ca thats filtered kidneys gets reabsorbed, 1% in urine
Ca levels affected by endocrine system: PTH + calcitriol
Role of GIT in Ca balance
ca absorption is incomplete due to 2 factors
1/ activated vit D required for intestinal ca absorption
2) insoluble salts (ca phosphate, ca oxalate) not absorbed
normal adult...
ingests 1000mg (1g) of ca per day
absorbs 400-500mg
loses 300mg into stool via digestive secretions
thus net absorption is only 100-200mg
in stead state, this quantity of ca is excreted in urine
Role of bone in Ca balance
main reservoir
most ca exists in bone as hydroxyapatite
involved in maintaining a normal plasma ionised ca conc
this process depends on the activity of blasts + clasts, which are regulated by many hormones + proteins - PTH (mobilises Ca) + calcitriol (active vit D)
Role of renal system in Ca balance
only ionised Ca (unbound, affect hormone levels, active, influences firing state of tissues) filter by glom
97-99% of filtered Ca reabsorbed in nephron
70% reabsorbed passively in the proximal tubule
20% reabsorbed passively in the TALH (thin ascending LOH)
15% reabsorbed actively in distal nephron
responsible for the physiological ca regulation as well as the dysregulation observed in many disease states
Different forms of Ca in plasma
only a small % of total body Ca in plasma
40% bound to albumin
15% complexed with citrate, sulfate or phosphate
45% ionised (free - under hormonal control)
Ca balance mediated by PTH + calcitriol
lab reports total (free + bound) Ca
caution in hypoalbuminaemia, acid-based disorders, CKD
Ca corr (serum Ca corrected for albumin, in mmol/L) = 0.02* (40 - pt's albumin) + serum ca
PTH
84 AA polypeptide produced by chief cells
ionised Ca sensed by CaSR on parathyroid cells
secreted in response to a fall in iCa (hypocalcaemia)
"phosphate trashing hormone" - increases renal PO4 excretion
Net effect: increased Ca, decreased PO4
increased GI absorption
PTH promotes renal formation of calcitriol via upreg of 1-alpha hydroxylase enzyme activity
calcitriol enhances intestinal ca + phosphate absorption
increased bone resorption
activates bone resorption by binding to PTH Rs on clasts
results in increased clast no's + activity
increased renal resorption
PTH causes a rapid increase in Ca reabsorption in the distal nephron
PTH also promotes renal formation of calcitriol (i.e. vit D activation) via upreg of 1-alpha hydroxylase enzyme activity
increased PO4 excretion
responds rapidly as a fall in CA can cause an arrhythmia
drives Ca out of bone reservoir + into bloodstream
Calcitriol (1, 25 OH Vit D)
active form of vit D (precursor in sunlight + diet - has other effects unrelated to Ca balance, e.g. immune system)
has mineral effects
enzymatic activation in liver + kidneys
increased production by PTH (1-alpha hydroxylase upreg)
net effect: increased Ca, increased PO4
enhances apical intestinal Ca absorption by increasing expression of TRPV6 channels
increases bone ca please by biding to blasts + cytes + by increasing pyrophosphate levels, a mineralisation inhibitor
increases renal reabsorption of Ca in DCT + collecting duct by increasing expression of TRPV5 channels + calbindin-D28k