5 Ca/PO4 Regulation Flashcards
Why are calcium levels so tightly regulated?
Calcium is fundamentally important to ALL biologic systems
What is a normal level of blood calcium?
Total (free and bound) 8.6 to 10.6mg/dL with daily variation < 10%
How much of plasma calcium is bound?
50%
The unbound, ionized form is active (so about 5 mg/dL with daily variation <2%)
99% of Ca2+ is in …
Crystalline form found in teeth and bone (1 and 2 kg)
Of the 1%, remaining, 0.9% is contained in soft tissues and 0.1% is in the ECF (1/2 of that is free and diffusable)
What is the normal daily intake of calcium from diet?
1000mg
Of that, 800mg is excreted in feces and 200mg excreted in urine
What is the normal distribution of phosphate in the body?
85% in bone and teeth, 15% in muscle
In cells, >80% in mitochondria and remaining in cytosol
What is the normal dietary intake of phosphate?
1000mg
350mg excreted in feces, 650mg excreted in urine
If there’s a demand for phosphate, the kidney can reabsorbed a lot
Calcium and phosphate levels in the blood stream are regulated by..
Parathyroid hormone (PTH) and vitamin D
Involves the interaction of bone, intestine, and kidney (target organs for PTH)
PTH is released in response to a drop in blood calcium —> acts to normalize Ca by acting on these organs
Parathyroid glands release PTH from _________
Chief cells
Released in response to hypocalcemia (low blood Ca2+)
Effect of PTH on bone
Activates osteoclasts —> calcium and phosphate ions released to blood
Effect of PTH on Intestines
Increases calcium absorption from food
Effect of PTH on Kidneys
Promotes activation of Vitamin D (which increases calcium absorption from food)
Increases calcium reabsorption and phosphate secretion in kidney
What are the two pools of calcium in bone?
Stable pool - consists of mature mineralized bone, composed primarily of hydroxyapatite; undergoes resorption by SLOW breakdown of crystals to liberate Ca and PO4
Labile pool - consists of bone fluid, composed primarily of amorphous crystals; undergoes osteopathic osteolysis for FAST release of Ca and PO4
Which calcium pool in the bone is used for minute to minute adjustments to Calcium/phosphate levels?
Labile pool (can undergo osteolytic osteolysis)
What separates the bone itself from the plasma in the osteon canals?
Osteocytic-osteoblastic bone membrane
This is where fast exchange from labile pool occurs
Has large surface area —> large influx between bone fluid and plasma
In fast exchange from the labile pool, Ca2+ is moved into the plasma by means of …
PTH-activated Ca2+ pumps located in the osteocytic-osteoblastic membrane
In slow exchange, Ca2+ is moved from the stable pool into the plasma by means of …
PTH-induced dissolution of the bone
PTH exerts what two direct effects in the kidney
Stimulates Ca reabsorption
Inhibits PO4 reabsorption
—> Phosphaturic effect (eliminates PO4 and leads to increase in urine cAMP)
What does measuring urine cAMP tell us?
Gives you an index of PTH status. Increased PTH secretion leads to PO4 secretion (because you don’t want CaPO4 crystals) which in turn leads to an increase in urine cAMP
How does PTH effect vitamin D
Activates vitamin D by stimulating 1-alpha hydroxylase activity in kidney, which converts the inactive precursor into the active form.
Activated vitamin D targets the intestine, bone, and kidney to collectively regulate CALBINDIN synthesis, and Ca2+ and PO43- levels in the plasma
Steps in the “life cycle” of vitamin D
- Vitamin D is inactive when it enters the blood from skin or diet
- Addition of an (OH) group on carbon 25 in the liver (via 25-hydroxylase)
- Addition of an (OH) group on carbon 1 in the kidney (via 1a-hydroxylase) —> 1,25 dihydroxycholecalciferol (active form)
- Addition of an (OH) group on carbon 24 produces INACTIVE 24,25-dihydroxycholecalciferol
Actions of Vitamin D on bone
Synergizes with PTH to stimulate resorption and remodeling and to mobilize Ca and PO4
Actions of vitamin D on the kidney
Promotes calcium reabsorption from distal tubule and proximal tubular reabsorption of phosphate
Actions of vitamin D on small intestine
Increases Ca absorption by increasing expression of calbindin
Calcium diffuses into cell, binds to calbindin, and is pumped across the basolateral membrane by Ca-ATPase
