Hormones In Calcium And Bone Metabolism Flashcards
A normal adult body contains about
1kg of Ca
70kg indiv = 1,000g Ca
1% in soft tissues and extracellular fluids
Approx. 99% is present in the skeleton as
Hydroxyapatite (Ca10(PO4)6(OH)2)
A normal diet provides how much Ca per day
20-2000mg with an ave of 1000mg Ca per day
Approx. How much is absorbed, in majority in ileum bcs of its large absorptive surface
300g
Secreted into the intestinal tract in bile, pancreatic juice and intestinal secretions so that the net absorption of Ca equals about
175mg/day
The conc of Ca in plasma ave about
9.4mg/dL
Normally varying between 9 and 10 mg/dL
This is equivalent to about 2.4mmol of Ca per liter
The Ca present in plasma is present in 3 forms:
(1) 40% (1mmol/L) of Ca is combined w the plasma CHONs = nondiffusible form thru capillary mem
(2) 10% Ca (0.2 mmol/L) diffusible thru the cap mem but is combined w other subs of the plasma and interstitial fluids (citrate and phosphate) Not ionized
(3) 50% Ca is both diffusible and ionized (1.2 mmol/L or 2.4 mEq/L) divalent
The skeleton also serves as a storage depot for phosphorus and contains about how much of the total body phosphorus?
80%
The plasma conc of total Ca (ionized and non) is about
10mg/dL
Equivalent to 5mEq/L or 2.5mmol/L
Ca is present in plasma as
A. Ionized or free (45%)
B. Complexed w HPO4^2-, HCO3- or citrate ion (10%)
C. Bound to CHON (45%)
Sum of ionized and complexes Ca constitutes the diffusible fraction (55%) of Ca
The protein-bound form constitutes the nondiffusible fraction (45%)
Regulates the serum-ionized Ca conc
PTH, Calcitonin, Vit D
Distribution (mmol/L) of Ca in normal human plasma
Total diffusible
Ionized Ca
Complexed to HCO3, Citrate etc
Total diffusible = 1.34
Ionized Ca = 1.18
Complexed to HCO3, Citrate etc = 0.16
Total nondiffusible (protein bound)
Bound to albumin
Bound to globulin
Total nondiffusible (protein bound) = 1.16 Bound to albumin = 0.92 Bound to globulin = 0.24
Total plasma Ca
2.50mmol/L
This represents the Ca pool that is not readily exchangeable and it is not available for rapid mobilization
Larger Ca pool
This represents the Ca pool that is readily exchangeable bcs it’s in physiochemical equilibrium w the ECF
The pool consists of Ca phosphate salts and provides an immediate reserve for sudden decreases in bld Ca2+
Smaller Ca pool
When the pH of ECF becomes more acidic, there is a
Relative increase in H2PO4 and decrease in HPO4-
The ave total quantity of inorganic phosphorus represented by both phosphate ions is
4mg/dL
Varying between normal limits of 3-4mg/dL in adults and 4-5mg/dL in children
Total body phosphorus is
500-800g (16.1-25.8 mol), 85-90% of wc is in the skeleton
Total plasma phosphorus is abt
12 mg/dL
with 2/3 of total in organic compounds and remaining inorganic phosphorus mostly in PO4^3-, HPO4^2- and H2PO4-
When Ca intake is high, 1,25-dihydroxycholecalciferol levels fall bcs of
Increased plasma Ca
Relationship of Ca absorption and Ca intake
Inverse
Increase absorption
Increase CHON diet in adults
Ca absorption is also decreased by subs that form
Insoluble salts w Ca (e.g phosphates and oxalates or by alkalis)
Enters the intestines via secreted GI juices and sloughed mucosal cells
An additional 250mg/day of Ca
How much of daily intake of Ca is excreted in the feces
90% (900mg/day)
Pi is absorbed in the duodenum and small intestine by
Active transport and passive diffusion
It is linearly proportionate to dietary intake
Absorption of Pi
Ingested Ca excreted in urine
10% or 100mg/day
How many percent of plasma Ca is bound to plasma proteins and not filtered by the glomerular capillaries, the rest is combine d w anions s/a phosphate (9%) or ionized (50%) and is filtered thru the glomeruli into tye renal tubules
41%
Amount of phosphorus normally entering bone is about
3mg (97 umol/kg/d), w an equal amt leaving via reabsorption
% if filtered Pi us reabsorbed
85-90%
Proximal tubule accounts for most of the reabsorption, and is inhibited by PTH
Active transport
Renal phosphate excretion is ctrlled by an overflow mechanism this is when
Phosphate conc in plasma is below the critical value of abt 1mmol/L
The rate of phosphate loss is directly proportional to the additional increase thus kidneys regulate the phosphate conc in ECF by altering rate of phosphate excretion
Above critical conc
Ca doesn’t require an active transport process bcs the conc gradient across the membrane is
larger for Ca than for any other ion
Ca conc in ICF is
10-70 mmol/L
Ca in ECF is
10^-3 mol/L (actual value is 2.5x10^-3 mol/L)
The Ca gradient from outside to inside the cell is on the order of
10,000 to 1
Ca is bound to cell surfaces and has a role in
Stabilization of membrane and intracellular adhesion
Chronic hypocalcemia or hypophosphatemia greatly decreases
Bone mineralization
Causes NS excitement and tetany
- increase neuronal mem permeability to Na, easy action potentials
Hypocalcemia
At plasma Ca conc about 50% below normal, the peripheral nerve fibers become so excitable that they begin to
Discharge spontaneously
Elicit tetanic muscle contraction
Tetany in hand
Occurs before tetany in other body parts develop
Carpopedal spasm
Occurs when bld conc of Ca falls from its normal lvl of 9.4mg/dL wc is only 35% below normal Ca conc and usually lethal at about 4mg/dL
Tetany
When lvl of Ca in body fluids rises above normal, the ND depress and reflex are sluggish
Decrease QT interval
Lack appetite
Constipation
Depressed contractility of muscle walls of GI
Depressive effects begin to appear when the blood Ca rises above
12mg/dL
Marked: 15mg/dL
Ca rises above ___ in bld, Ca phos crystals ppt
17mg/dL
Exchangeable Ca salts in bones are
Amorphous Ca phos compounds
- mainly CaHPO4
The quantity of these salts that is available for exchange is abt 0.5 to 1% of the tCa salts of the bone
Total of 5-10g Ca
Within 3-5 mins after an cute increase in Ca ion conc, the rate of PTH secretion
Decreases
Relationship of PTH and Calcitonin
Inverse
Causes rapid deposition of Ca in bones
Inc in Calcitonin
Can cause a high Ca conc to return to normal perhaps considerably more rapidly than can be achieved by the exchangeable Ca-buffering mechanism alone
Excess Ca
Ca regulation involves 3 tissues, 3 hormones and 3 cell types
3 tissues: bone, intestine, kidney
3 hormones: PTH, calcitonin, activated vit D3
3 cell types: osteoblasts, osteocytes, osteoclasts
When plasma Ca falls
PTH secretion increases
Hypercalcemic hormone
PTH
Hypocalcemic hormone
Calcitonin
A 32 AA residue polypeptide secreted by the parafollicular (C) cells of thyroid gland
Calcitonin
As plasma Ca increases
Calcitonin secretion increases
Calcitonin release is stimulated by
Pentagastrin
A secosteroid containing 27 C atoms wc makes it the largest steroid hormone
Vit D3 (cholecalciferol)
The major bld form of vit D
Prevent rickets
Calcidiol (25-hydroxyvitamin D3) 25-hydroxycholecalciferol
Another active metabolite of vit D
On a molar basis, it is 100x more potent than calcidiol
Calcitriol (1,25-dihydroxyvitamin D3) 25-dihydroxycholecalciferol
Inhibits bone resorption and increases the amount of Ca in urine
Calcitonin
Acts on one of the PTH receptors and is important in skeletal dev in the uterus
PTHrP
lower plasma Ca lvls by inhibiting osteoclast formation and activity but over long pds they cause osteoporosis by decreasing bone formation and increasing bone resorption
Glucocorticoids
They decrease bone formation by
inhibiting protein synthesis in osteoblasts
they decrease absorption of Ca and PO4^3- from the intestine and increase the renal excretion of these increases the secretion of ions
Increases Ca excretion in the U but it also increases intestinal reabsorption of Ca and this effect may be greater than the effect on excretion w a resultant positive Ca balance
GH
generated by the action of GH stimulates CHON synthesis in the bone
IGF-I
may cause hypercalcemia, hypercalciuria and sometimes osteoporosis
Thyroid hormone
prevents osteoporosis probably by direct effect on the osteoblasts
estrogen
increases bone formation and there is significant bone loss in untreated diabetes
Insulin
is found in the form of hydroxyapatite crystals
Bone Ca
The empirical chemical formula for this substance is Ca10(PO4)6(OH)2 or {(ICa3PO4)2}3
Hydroxyapatite crystals
Fluoride ion can replace the OH- group and form
fluoroapatite {(Ca3PO4)2}3 CaF2
Ca:Phos ratio in bone is
1.7:1