Calcium and Phosphorous Metabolism - Basok Flashcards
How is calcium found in the serum? What are the properties of each form?
Total serum calcium = ionized + complexed + protein bound (8-10.2mg/dl)
Ionized calcium is biologically active (4-4.9mg/dl)
40% of calcium is bound to proteins, 45% ionized, 15% as citrate, SO4, and PO4
Increase of albumin of 1gr/dl - increase
calcium by 0.8 mg/dl
Decrease of albumin of 1gr/dl - decrease
calcium by 0.8 mg/dl
A pH change of 0.1 changes protein bound calcium by 0.12mg/dl (up or down correspondingly)
Decreases with increased serum phosphorous
How is phosphorous found in the serum?
Organic and inorganic
Organic is bound to proteins (as phospholipid and phosphate esters)
Inorganic H2PO4- to HPO4= ratio 1:4 (20% and 80%)
Normal serum concentration
2.5-4.0 mg/dl
Children 4.0-6.0 mg/dl –reflects
skeletal growth
Decreases during hyperventilation, refeeding and alkalosis
What are the actions of PTH and what does it react to?
Increases osteoclast activity and decrease osteoblast activity, stimulates bone resorption with release of calcium phosphate
Stimulates formation of 1,25(OH)D3 in the kidney proximal tubule by stimulating alpha-1-hydroxylase
Phosphaturia: inhibits Na-PiII (sodium phosphate cotransporter) in the proximal tubule-net decrease in serum Phosphate
Stimulates Ca reabsorption in the distal tubule
Acts through 1,25 cholecalciferol (calcitriol/Vit D) to increase Ca2+ and phosphate absorption from the intestines
Secreted in response to a decrease in plasma Ca2+, high PO4 or low calcitriol
Decreased with a Ca2+ infusion and increased with phosphorous infusion
Suppressed secretion from vitamin D
How is calcium excreted by the kidneys?
How is this changed by furosemide?
What receptor plays a role?
50-70% of filered Ca is reabsorbed passively in
the proximal nephron (together with Mg between cells)
30-40% paracellular reabsorbtion in thick medullary ascending loop. Blocked by furosemide because neutralizes positive charge by blocking Na-K-ATPase-causes calciuria (used to treat hypercalcemia of malignancy but not before volume depletion)
and lumen positive voltage drive the
force for Ca reabsorbtion
10% active Ca reabsorbtion in the distal
tube through calcium channel ( TRPV5)-active transport
and carrier protein calbindin-D28k and
then extruded through basolateral
membrane-increased with thiazides to prevent stone formation
Receptor:
Expressed in the parathyroid glands and the kidney
Variations in the serum calcium are sensed with change in PTH secretion
Expressed on the basolateral membrane of the thick
ascending limb of loop of Henle
Hypercalcemia activates Ca sensing receptor and reduces calcium and sodium transport in the loop of Henle
How is hypercalcemia connected with fluid volume in the body?
Hypercalcemia = volume depleted
Found in multiple myeloma and hypercalcemia of malignancy, etc.
Viscious cycle: causes smooth muscle contraction–>vasoconstriction, vomiting (increasing volume contraction), nephrogenic diabetes insipidus (increasing water loss by the kidney) increased calcium reabsorption stimulates receptor mediated calciuria and sodium excretion causing more volume depletion.
If furosemide given before saline, will increase jeopardize volume status further. First correct volume then give furosemide.
Types of hyperparathyroidism and description
Primary:
Defect in gland
“stones (in bladder), moans (altered mental status), groans (constipation) and bones (resorption)”
Equilibrium hypercalcemia (longterm), hypophosphatemia, high PTH level. No surgery unless symptoms dire.
Secondary:
Depleted vitamin D or calcium secondary to renal failure
“Trade-off theory:” increase PTH to maintian P normal
Autonomous-clonality of hyperplastic PT gland-neoplastic transformation. Leads to bone diseases with new set point for Ca and vit D.
Tertiary:
Caused after kidney transplant because of maladapted parathyroid gland. Recommended parathyroidectomy before renal graft.
Production of Vitamin D (calcitriol)
Absorbed through the skin. First converted in the liver to 25-hydroxy-D3 and then activated in the kidney through alpha-1 hydroxylase to 1,25(OH)D3-calcitriol
Proximal tubular cells are the major site of
calcitriol production
Calcitriol may be produced by
keratinocytes, bone cells, endothelial cells
and monocytes - macrophage
Granulomatous disease can oversynthesize vitamin D (like in sarcoidosis)
Renal Bone Diseases caused by secondary hyperparathyroidism
- Osteitis fibrosa cystica -subperiostal bone resorption in the middle phalanges of hands, distal ends of clavicles, proximal ends of tibia (Hyperparathyroid bone disease) with rapid bone turnover. Multiple cysts with woven bone, serious skeletal deformities and fractures. Acidosis turns alkalosis.
- Adynamic bone disease-most common, 60% of dialysis patients
- Osteomalacia - aluminium bone disease
Very low bone turnover
with suppression of
PTH level by high level of
calcitrio
