Ca Homeostasis Flashcards
IC use of Ca I E M H
Plasma Ca use N M C M S F
IC signal transduction
Enzyme action
Muscle contraction (excitation/contraction coupling)
Hormone/NT release (exocytosis)
Nerve/muscle excitability (nerve most important) Membrane perm Coagultion of blood Maintain TJ Synaptic transmission Fxn integrity of bones/teeth
Fraction of Ca hormonally regulated
99% of total Ca is located in
IF Ca conc
Plasma (% as Ca++)
% protein bound
% unionized
% in IC fluid
Plasma free/ionized
Bone (CaPhos salts/hydroxyappetite)
<1, Ca
50
40
10
<1, Ca++ and protein bound
Free Ca in plasma
Normal value
Tightly _____ over long term
Continuous exchange w
9-10 mg
regulated
gut, kidney, bone
GI tract
Ca and PO4 ions are ___ via AT/diffusion
Only ____ is hormonally regulated
___ of ingested Ca absorbed
Majority is -____
If gastric empties too fast (gastrectomy)
Major determinant of net Ca uptake
affected by _____ to inc Ca in
absorbed in SI
AT
1/3
excreted in feces
less Ca is absorbed
Ca absorbtion
VD3, GI tract
Kidney
Filters _____ from plasma
Rate of excretion =
usually 99% of filtered Ca is
regulation of Ca occurs in
PTH helps to
Free Ca ions
rate of absorption from gut
reabsorbed (most in PT)
distal nephron (major site of regulation)
inc Ca reabsorption
Bone
Stable Ca pool
slow exchange w
regulated by
releases ____ to plasma
Labile Ca pool
rapid exchange from
bone remodeling
Osteoblasts (form) and osteoclasts (resorption)
Ca and PO4
readily available pool in bone fluid
Labile Ca pool
Osteocytes
Canaliculi
Osteocytic osteolysis
OC transfers ____ from ___ to ____
Mechanical stress inc, later
absence of ____ inhibits OB
Embedded OC
contain bone fluid & free Ca
Ca ions, bone fluid to plasma
flow of BF, osteocytic activation of bone remodeling
stress
Bone remodeling stage 1
PTH and 1,25 OH VD stimulate ______ to release
OB express receptors for
Mature OC express ___ receptors for RNKL released by
also express
OB cytokines activate
activation of OB
OB, MCSF, RANKL, IL1/IL6/TNFA
PTH, VD3
RANK, OB
calcitonin
OC recruitment, differentiation, activation
Boen remodeling stage 2
activated, mature OC secrete
____ to dissolve bone crystals, releasing
____ to break down exposed matrix
occurs for
H+, Ca and PO4
enzymes
2-4 wks
Bone remodeling stage 3/4
OB with reversal signal secrete _____, to suppress OC _____
synthesize ____, such as hydroxyproline and osteocalcin
Regulate
Complete bone formation takes
OPG, formatiom and activation
alkaline phosphatase, matrix proteins
mineralization
2-4 mnths
Regulation of OC osteolysis
_____ stimulate OC to inc _____ and transfer to circulation via
Inc _____ inc _____, which inc ______, ultimately inc
Dec ______ inc _______, dec ______
PTH/VD, Ca uptake, canaliculi
shear stress, fluid flow, OC RANKL release, OC activation
mechanical stress, inc osteocytic sclerostin release, dec OB function
Serum phosphate levels during the day
Most of ingested phosphate is
Primary site of phosphate homeostasis/regulation
Hormones that regulate Ca hoeostasis
P A C G and I G T
vary widely
absorbed in GI tract
renal phosphate reabsorption
PTH Active VD3 (1,25OH VD3) Calcitonin GH and IGF1 GC TH
PTH prevents
secreted by
primary targets
fxn
acts via
Regulation
dec plasma free Ca
Inhibited by
this occurs via
hypoCa
Chief cells of 4 PT glands
bone (OB and OC), kidney
inc plasma Ca, dec plasma PO4
cAMP
inc PTH
inc plasma free Ca via NF
membrane Ca sensing receptor (CaSR)
Maximum response of PTH in bone requires
VD3 synth in
Final step in
1, 25OH VD3 aka
VD3
skin, liver, kidney
kidney
calcitriol
PTH actions
Bone (requires VD3)
Inc ____ and ____, resulting in inc _____
Kidney
_____ Ca reab
____ PO4 reab
____ calcitriol syn
Intestine
bone resorp and OC osteolysis, serum Ca/PO4
Inc
Dec (prevents CaPO4 in ST)
inc
no direct action
Active VD3 actions
Intestine
Bone
Acts via
inc Ca absorp by inc calbindin synth
permissive to PTH
nuclear receptor VDR
Calcitriol synth control point
Renal 24 hydroxylase activation results in formation of
24 hydroxylase activated by high
kidney- PTH activates 1-hydroxylase to form VD3
24,25 OHD3
1,25OH VD3
Plasma Ca levels are
inc/dec causes ____ in plasma PTH
very controlled
large change
Pubertal growth spurt inc rate of
stimulated by ___ in F, ____ in males
mediated by ____ in both
High levels of __ causes epiphyseal closure
E2 throghout life
activates ____ and dec ____
postmenopasual ____ in E2, leading to
long bone growth
inc plasma E2, inc plasma T (eventually E2)
estrogen receptors
E2
protects bone
OB, cytokine
drop, bone loss/osteo
In men, T leads to
decreases w
Calcitonin secreted by, fxn
Regulated by ____ to inc ___
Inhibits _____ which express
Plasma Ca can be regulated after _____ or with Calcitonin excess
Uses- tx of hyperCa with
Severe
Marker for
inc bone strength
age
C cells (parafollicular), lower Ca
Inc plasma Ca, calcitonin
OC, calcitonin receptors
thyroidectomy
excessive OC activity (Paget)
Osteo
medullary thyroid ca
TH and bone turnover
High levels can cause
GC essential for
High levels cause
____ intestinal Ca absorp
____ renal Ca reabs
Inhibits
Excess GC can cause
Inc GH/IGF1 at puberty
inc
Osteo (HyperT)
normal Ca balance
hypoCa
dec
Dec
bone formation
osteo (cushing, high GC)
pubertal growth spurt
Inc age ___ bone mass, inc
due to
2 phases of bone loss in
Phase 1 is
phase 2 is , also in
Estrogen loss contributes to bone loss in
dec, fractures
dec sex steroids
women, 1 in men
rapid, @ menopause
slower, men
elderly M/F
Other causes of bone loss
Low ____ in YA
Peak bone mass at
____ GH/IGF1
____ TH or
_____ due to high glucose activating
Inad metabolism of ___, ususally in
M, M, A
Lack of
S, A
Drugs such as G, A (inc rate of VD3 conversion to inactive form)
peak bone mass, end puberty
dec inc, GC T1DM VD3 to active form Liver/kidney dz
Malabsorp, malnutr, anorexia
exercise
smoking, alcohol
GC, anticonvulsants
HypoC
Primary_______, lab values
such as
P______, lab values
due to
____ def, labs
etiologies
Insufficient ______
Inad enzyme conversion to
inc rate of metabolism to, to treat
____ receptor defect
HypoPTH, low PTH/Ca, inc PO4
lost PT gland fxn
pseudohypoPTH, inc PTH/PO4, dec Ca
PTH receptor defect
Calcitriol, Inc PTH, low Ca/PO4
sun, intake, mal
active form (kidney/liver/1-OHase dz)
inactive form, epilepsy
HypoCa causes
Renal faulure
____ PO4 excretion
____ PO4
_____1-OHase activity
______
dec inc dec dec VD3, Ca
HypoCa sx
O/R inc N due to low Ca H, t, C, T S D T- death dye to
osteomalacia (weak bones), ricketts NM activity Hyperactive reflexes, tingling, Chvosteks, Trousseas Seizures Dec myocardial act Tetany- asphyx due to laryngospasm
HyperCa causes
H, labs
Due to
Excessive ingestion of
labs
M, labs
due to tumors secreting
B
P____ to cross react w pth receptors and
HyperPTH, inc PTH/Ca, low PO4
tumor PT gland, ectopic tumor w PTH sec
Ca,VD3
dec PTH, high Ca/PO4
malignancy, low PTH/PO4, high Ca
bone mobilizing substance
PTHrP, activating them
Sx of HyperCa
M, F, L Neuropsych do w P- Ca inc gastrin leading to Calcified C
muscle weakness, fatigue, lethargy depression, EEG changes, mem/pers problems Peptic ulcers, GA secretion calcified soft tissues cardiac arrest
