Jan11 M1-Divalent Cations Flashcards
% body Ca in bone and % in ECF
99% in bone
0.1% in ECF
% phosphate in bone , in ICF and in ECF
85% bone, 15% ICF 1% ECF
Ca and PO4 in bone exist as ________
hydroxyapatite
2 factors in Ca homeostasis
- body Ca amount depends on balance of GI abso and kidney excretion
- distribution of Ca between bone and ECF (largely by PTH)
diff types of Ca in the body and % and which is sense by CaSR
- protein bound 40%
- ultrafilterable complexed to anions 10%
- ultrafilterable ionized Ca 50% (sensed by CaSR)
stimulus for PTH secretion
low plasma ionized Ca sensed by CaSR
3 ways PTH raises Ca levels
- Ca resorption from bone (PO4 resorption at the same time)
- increased 1-alpha hydroxylase in the kidney leading to formation of calcitriol so more GI abso of Ca
- more renal Ca reabso (acts on luminal Ca channel in DCT)
PTH effect on phosphate
resorption from bone with Ca resorption BUT promotes PO4 excretion in the kidney so overall lowers PO4 levels
primary hyperPTH def + Ca, PO4 and calcitriol levels
adenoma of one of 4 PT glands. hyperCa. hypoPO4. high calcitriol
secondary hyperPTH def + Ca, PO4 and calcitriol levels
renal failure led to hyperplasia of the 4 PT glands (bc of constant hyperPO4 and low calcitriol)
low Ca, high PO4, low calcitriol
tertiary hyperPTH def
dialysis over years led to prolonged secondary hyperPTH. PTH now released at all times
tertiary hyperPTH Ca, PO4 and calcitriol levels
Ca high, PO4 high, calcitriol low
what happens if you remove hyperPO4 and hypocalcitriol stimuli in secondary and tertiary hyperPTH
secondary: stop producing PTH
tertiary: keep producing PTH bc now autonomous
steps to produce active vit D (calcitriol)
diet or 7-dehydrocholesterol + UV light = vit D. 25-hydroxylation in liver. 1alpha hydroxylation in the kidney. get 1,25 vit D
main action of calcitriol
keep Ca and PO4 available for bone formation (and prevent hypoCa and hypoPO4)
2 stimuli to calcitriol production
high PTH
low phosphate
3 stimuli to PTH prod and which one is indirect and how
- low Ca
- high PO4 (indirect effect. no receptor for it but when high PO4, binds Ca so less Ca for the CaSRs)
- low calcitriol
calcitriol sites of action (how does it increase Ca and PO4) and which thing does PTH not do
- Ca and PO4 abso in the intestine (PTH can’t do that)
- resorption from bone (with PTH)
- reabso at distal tubule (with PTH)
2 receptors on PT gland and consequence on PTH prod
CaSR: low Ca = more PTH
calcitriol receptor: high calcitriol = less PTH prod
how hyperPO4 causes increased PTH
PO4 binds Ca so less Ca for CaSRs
if low PO4 stimulates calcitriol,
how hyperPO4 acts to inhibit it
hyperPO4 impairs 1 alpha hydroxylation
calcitonin exact site of prod + type of molecule
peptide hormone. C cells of the thyroid gland
calcitonin: stimulus for its release and what it does
high Ca.
calcitonin inhibits Ca resorption form bone (opposite of PTH)
Ca in the nephron in %
65% PCT
25% loop (TAL)
8% DCT
less 1% excrtion
Ca in PCT
passive reabsorption with favorable electrochem gradient
Ca in the loop of Henle
moves down electrochem gradient in tight junctions. favorable gradient bc lumen is positive bc K+ keeps being pumped out by ROMK even though Na-K-2Cl is pumping K in
where CaSR found other than PTH + fct
cells of TAL. if senses high Ca (in the blood), inhibits ROMK, Na-K-2Cl and impairs paracellular (tight junctions) reabso of Ca
condition where CaSR not working where + pathophgy
familial hypocalciuric hypercalcemia. CaSR not working so always reabso of Ca in TAL + need higher Ca to suppress PTH
where is Ca reabso hormonally regulated and how
in DCT. decreases Ca excretion. (PTH and calcitriol)
only part of the nephron where Na and Ca are not coupled
DCT
why can become hyperCa when on thiazides
cause volume contraction so more Na and Ca reabso ‘‘together’’ proximally
how acid base balance influences Ca levels
acidosis increases Ca excretion (bc mobilizes it from bone. bone buffers H+)
alkalosis decreases Ca excretion
common causes of hyperK
- primary hyperPTH
- excess 1,25 D prod
- excess Ca ingestion (or vit D)
- malignancy
- thiazides
- familial hypocalciuric hypercalcemia
if see lab of high Ca, low PO4 and normal Cr, what’s the likely dx
primary hyperPTH
if see lab of high Ca, Cr of 200, high PO4, normal PTH, + history of weight loss*** what’s the likely dx
malignancy involving bones
4 symptoms of hypercalcemia
- confusion, lethargy
- bone pain
- kidney stones
- poor appetite, nausea, vomiting, abdominal pain
normal response to hyperCa (4)
- less PTH
- less calcitriol (via less PTH)
- CaSR stimulation in kidney so less Ca reabso
- more calcitonin
causes of hypoCa
- hypoPT
- vit D deficiency
- low Mg (Mg important for PTH release)
- CKD (high phosphate and low calcitriol)
symptoms of hypoCa
- neuromuscular irritability
- seizures
- arrhythmias
normal response to hypoCa (3)
- more PTH
- more calcitriol (via more PTH)
- less CaSR stim in TAL so more paracellular reabso of Ca
what % of phosphate is protein bound
10%
2 factors in phosphate homeostasis and hormones acting on that
- balance of PO4 abso (GI) and excretion by kidneys (PTH)
2. distribution between ECF and ICF (PTH and calcitriol)
PO4 in PCT (% and mechanism) and what % in what parts of PCT
85% reabso in PCT (15% in more distal part of PCT/in TDL)
Na-PO4 cotransporter
3 factors regulating PO4 transport in the kidney
- plasma PO4
- PTH
- FGF-23
how plasma PO4 regulates PO4 reabso
more PO4 filtered = less Na-PO4 cotransporter activity
how PTH regulates PO4 reabso
high PO4 leads to low Ca and low calcitriol. PTH is produced and PTH reduces the Na-PO4 cotransporter activity
Ca, PO4, calcitriol and PTH in CKD
high PO4, low calcitriol, high PTH, low Ca
causes of hyperPO4 with main one
renal failure**, rhabdomyolysis or lysis after chemo, hypoPTH
normal response to hyperPO4
- more PTH (so more excretion in PCT) (direct downregulation of Na-PO4 cotransporteR)
- less calcitriol (less GI abso and bone resoprtion)
causes of hypoPO4 and main one
primary hyperPTH, Fanconi syndrome, GI loss** (typically), beta adrenergic stimulus causing ECF to ICF shift
Fanconi syndrome 2 types and def
congenital or acquired. patient has PCT dysfct (a.a, glucose, PO4, etc. waisted in urine)
normal response to hypoPO4
more calcitriol (more GI abso and bone resorption), less PTH (so more reabso).
Mg distribution in the body
60% bone
35% ICF and muscles
1% ECF
% Mg protein bound vs free
30% protein bound 70% free
renal handling of Mg (%)
30% PCT 60% TAL 5% DCT
main determinant of renal Mg excretion
plasma Mg concentration
Mg in the TAL
(same as Ca). favorable electrochem gradient bc positive lumen bc K keeps going back in lumen so Ca moves in in tight junction
in what condition can Mg bind to CaSR and how would that be useful
in hyperMg. would stop the electrochem gradient (same as in hyperCa) so Mg would stay in tubule
Mg in the distal tubule (% and mechanism: give exact channel name)
5% reabso in DCT. active transport via the TRPM6 channel. (meds can act on that)
causes of low plasma Mg
GI losses, renal losses (diuretics, diabetes, drugs that block Mg reabso in TAL or DT)
why diabetes associated with hypoMg (1/3 diabetes have it)
we don’t know
what more important condition (electrolytes) associated with hypoMg
hypoCa (bc often cause of hypoMg will also cause hypoCa)
