Physiology of Ca-regulation hormones Flashcards
What is the most common cause of osteoporosis?
involution
What phase in bone develop has the sharpest decline?
Phase 2 in women (after menopause)
Where is 99% of the Ca? Where is the remaining 1%
Bone; .1 in extracellular, 1% intracellular
__% of Ca is free in the plasma and is regulated by hormones.
45-50%
How much Ca is anion bound? How much is protein bound?
6-9; 40-45
What is the normal range of Ca in the blood?
8.5-10.5
____ causes nervous system excitement and tetany.
Hypocalcemia
How is most of the ingested Ca eliminated?
Feces
What secretes PTH?
Chief cells
What secretes calcitonin
C cells of thyroid gland
Chemical structure of PTH
polypeptide with 84aa
Chemical structure of calcitonin
polypeptide with 32 aa
What does PTH infusion do to calcium and phosphate levels?
Increase Ca, decrease PO4
Describe how total body Ca changes in a lifetime.
Increases with bone formation- till 20ish. Then decreases
How does low Ca cause tetany? What happens with high Ca?
Low Ca causes decreased threshold for voltage gates Na channels.
High Ca- Contraction of smooth muscle is suppressed.
Describe Ca exchange between intestines and ECF
Only about 1/3 is absorbed and the rest is excreted in the feces. Ca is also secreted into the intestine, for a net absorption of 100 mg/day. Most ingested Ca is excreted in feces
Describe Ca exchange between ECF and kidneys
Kidneys have the capacity to excrete a lot of Ca by reducing resorption but usually excrete 100 mg/day.
What is bone fluid and how is it separated from ECF?
Aqueous solution that immerses bone and contains Ca and PO4. Separated by an osteocytic membrane formed by osteocytes and osteoblasts.
Describe the rapid exchanges that occur between ECF and bone fluid
PTH lowers plasma PO4, Ca permeability is increased and osteocytic pump activity increased. This allows bone salts to move into ECF
Describe the slower exchanges that occur between ECF and bone fluid
PTH slowly increases formation and activity of osteoclasts which resorb bone, thereby releasing Ca.
Where are PTH receptors in bone?
osteoblasts
How does PTH lead to osteoclast activation
PTH–> PTHR1 on osteoblasts–> express RANKL–> RANKL binds RANK on osteoclast precursor –> osteoclast gene transcription
How does osteoprotegerin lead to osteoclast inhibtion?
Released by osteoblasts. Prevents binding of RANK to RANKL.
____ decreases osteoprotegerin production. ____ stimulates it.
PTH;Estrogen
When and how does PTH cause bone formation?
Low, intermittent doses enhance proliferation and decrease apoptosis of osteoblasts.
How much Ca is filtered at the glomerulus?
50ish%… protein bound Ca can not be filtered
Where is most of the Ca reabsorbed in the kidney? Minority?
90% from proximal tubule, loop of henle, early distal tubule.
10% from late distal tubule and collecting duct
Where does PTH act at the nephron
PTH acts at the Proximal tubule to put Phosphate in Pee (4Ps)
Late distal tubule and collecting duct to increase Ca reabsorption
ECF Ca changes are sensed by ______.
GPCR on chief cells (PT)
Low calcium causes an ____ in PTH, which ___Mg and ____ PO4.
Increase in PTH
Decrease in Mg
Increase in PO4
How does PTH affect intestinal absorption of Ca
Indirectly. It is required for conversion of 25 VD to 1,25 VD which then increases Ca absorption.
What does calcitonin do to Ca and PO4?
Lowers Ca and PO4 via:
- Bone: reduce reabsorption by inhibiting osteoclast and stimulating Ca deposition
- Kidney: Inhibits reabsorption of Ca and PO4
____ protects against calcium loss during times of Ca mobilization.
calcitonin
Synthesis of VD
Skin--> liver--> kidney Skin: Pro-VD (7-dehydrocholesterol) --> cholecalciferol by UV light--> goes to liver Liver: Hydroxylated to 25 OH -VD At kidney: 25--> 1,25 OH-VD (calcitriol) Mediated by 1a hydroxylase - Increased by PTH - Decreased by Ca and FGF23
Peripheral actions of VD
Bone: resorption
Intestines: increase Ca absorption
Kidneys: increase Ca absorption
PTH: decrease synthesis of PTH
What 3 things push VD synthesis to inactive 24,25 form?
Increase serum Ca, Increase 1,25 VD, increase FGF23
What does Ca, PTH, and FGF23 do to VD synthesis towards 1,25 VD?
Ca: negative
PTH: positive
FGF23: Negative
What is the major circulating form of vitamin D?
25(OH)D
Decrease activity of 1a hydroxylase favors what?
hydroxylation to 24,25 OH-VD
T or F. It takes big Ca changes to cause changes in VD levels.
False- slight decrease in Ca below normal causes big VD increase.
What is hydroxyapatite?
complex precipitate of Ca and PO4 that is laid down in the protein osteoid matrix
[Ca]x[PO4]>solubility product=?
bone deposition
[Ca]x[PO4]<solubility product=?
bone resorption
T or F. To increase/decrease bone mineralization you need an increase/decrease in both Ca and PO4.
False. Depends on product of Ca and PO4, so only one has to go up
Phosphate lab numbers
Normal: 3-4.5
Kids normal: 4.5-6.5 due to bone growth
Approx 55% is free, 35% protein bound, 10% anion bound
Distribution of total body phosphate
85% bone, .1% extracellular, 14% intracellular
Where is phosphate excreted?
Mostly kidney but also come in feces
What does phosphate do in someone on hemodialysis
positive potassium balance, deposits in vasculature
What is the function of FGF23?
Acts at kidney to decrease the expression of Na/PO4 cotransporters, production of 1,25VD–> hypophosphatemia, reduce PTH
What conditions cause secretion of FGF23 by bone?
increased levels of PO4, 1,25VD, and PTH
