Calcium and Parathyroid Hormone
Hyperparathyroidism
Excessive production of PTH is usually due to the presence of a tumor, Vitamin D deficiency
Low serum calcium effect on homeostasis
Low serum Ca2+ increases parathyroid hormone (PTH) and 1,25-(OH)2D, which then enhance Ca2+ uptake from the gut and bone demineralization and inhibit its excretion.
Hypocalcemia
a significant decrease in serum Ca2+, results in loss of normal neuromuscular stimulation
Biochemical Hallmarks of Hypoparathyroidism
1 Decreased plasma ionized calcium and elevated phosphate levels. 2 Symptoms include neuromuscular irritability, which causes muscle cramps and tetany in mild cases. 3 Severe, acute hypocalcemia results in tetanic paralysis of the respiratory muscles, laryngospasm, severe convulsions and death.
PTH Increases Plasma Calcium in Three Ways
1) PTH increases the rate of dissolution of bone, including both organic and inorganic phases. 2) PTH reduces the renal clearance or excretion of calcium. 3) PTH increases the efficiency of calcium absorption from the intestine by promoting the conversion of 25-dihydroxycholecalciferol to 1,25-dihydroxycholecalciferol (active form of Vitamin D)
Three effector sites for regulation of extracellular Calcium
1. Bone 2. GI tract 3. Kidney
Biochemical Hallmarks of Hyperparathyroidism:
1. Elevated serum ionized calcium and PTH and depressed phosphate levels. 2. Extensive bone resorption. 3. Renal effects, including kidney stones, frequent urinary tract infections, and, in severe cases, decreased renal function.
Regulation of blood calcium is achieved by 3 hormones:
1. Parathyroid hormone 2. vitamin D metabolite 1,25-dihydroxycholecalciferol 3. calcitonin
2 hormones that are required for calcium absorption in kidney
1. Vitamin D 2. Parathyroid hormone
Which hormone controls phosphate excretion in the kidneys?
Parathyroid hormone
High serum calcium effect on homeostasis
High serum Ca2+ decreases PTH. Low PTH allows 25- (OH)-D to → 24,25-(OH)2D, which is inactive. Excess Ca2+ is deposited in bone or excreted (stimulated by calcitonin, CT).
Hypoparathyroidism
Insufficient PTH is produced, usually due to accidental removal or damage to the parathyroid glands during neck surgery or to autoimmune destruction of the glands.
Osteoclast activity (calcium release from bon) promoted by:
PTH Vitamin D
Hormone that promotes calcium reabsorption (back into plasma) and phosphate excretion from the kidney
Parathyroid hormone
Mechanism of activation of CaMK by Ca2+ and calmodulin
Upon binding Ca2+, CaM undergoes a change in its conformation which exposes a hydrophobic domain. This domain can interact with a wide variety of CaM-binding proteins (a kinase in this example) because of the conformational flexibility provided by the central helix of CaM.
Effect of decreased PTH on GI tract, kidneys and bone
When PTH is decreased there is net movement of calcium and phosphate into bone, urinary calcium is raised, and GI tract absorption of calcium is reduced.
Blood calcium and phosphate is stored in
bone
Osteoclast activity inhibited by
calcitonin
Reason for reciprocal relationship of calcium and phosphate
decrease in phosphate ion concentration reduces the likelihood that calcium will precipitate with phosphate at unwanted sites in the body, an effect that does occur in the blood, muscle, tendons and elsewhere when both the calcium and phosphate concentrations rise too high at the same time
Hypercalcemia
increase in serum Ca2+ - leads to muscle weakness and coma. There may also be calcification in the kidneys (stone formation) or in the cornea of the eye
blood calcium is excreted by
kidneys or bile and intestines
PTH is secreted from parathyroid gland in response to
low plasma calcium levels
Calcitonin
lowers serum calcium and phosphate primarily by inhibiting bone resorption and increasing renal excretion
Plasma Ca2+ and phosphate therefore exhibit a __________ relationship
reciprocal; when phosphate is diminished, Ca2+ elevated, and vice versa.
Function of IP2
stimulates the release of Ca2+ from the endoplasmic reticulum (ER)