Calcium DSA by the learning objectives Flashcards
- Understand the synthesis and regulation of PTH secretion by the calcium sensor receptor (CaSR)
PTH is released in response to low serum Ca2+ concentrations in plasma. Normally, PTH is secreted at a low (basal) rate and when concentrations of Ca2+ fall under 10 mg/dL, PTH secretion is stimulated. It is the Ca2+-sensing receptor (CaSR) that senses extracellular calcium and controls PTH secretion.
The parathyroid cell membrane contains Ca 2+ sensing receptors that are linked, via a G protein (G q ), to phospholipase C. When the extracellular Ca 2+ concentration is increased, Ca 2+ binds to the receptor and activates phospholipase C. Activation of phospholipase C leads to increased levels of IP 3 /Ca 2+ , which inhibits PTH secretion. When extracellular Ca 2+ is decreased, there is decreased Ca 2+ binding to the receptor, which stimulates PTH secretion.
- List the four functions of PTH in calcium and phosphate homeostasis.
: 1) triggers calcium and phosphate resorption from the bone- releases ionized calcium; 2) promotes calcium resorption from the kidney; 3) promotes phosphate excretion from the kidney; 4) signals 1 alpha-hydroxylation of 25-hydroxycholecalciferol in the kidney. Overexpression or suppression of PTH will impact the above functions.
- List the functions of 1,25-dihydroxy vitamin D in calcium and phosphate homeostasis.
The major actions of 1,25-dihydroxycholecalciferol are on the intestine. There, 1,25-dihydroxycholecalciferol increases both Ca 2+ and phosphate absorption, although far more is known about its effect on Ca 2+ absorption.
. The actions of 1,25-dihydroxycholecalciferol on the kidney are parallel to its actions on the intestine—it stimulates both Ca 2+ and phosphate reabsorption.
In bone, 1,25-dihydroxycholecalciferol acts synergistically with PTH to stimulate osteoclast activity and bone resorption. This action may seem paradoxical because the overall action of 1,25-dihydroxycholecalciferol is to promote bone mineralization. However, mineralized “old” bone is resorbed to provide more Ca 2+ and phosphate to ECF so that “new” bone can be mineralized (bone remodeling).
- Understand the effect of PTH and 1,25-dihydroxyvitamin D on the bone, kidney and intestine.
At the bone, 1,25-dihydroxyvitamin D acts in synergy with PTH to stimulate resorption of both calcium and phosphate and further acts to carry out bone mineralization. In the intestine, PTH is necessary for absorption of calcium. In the kidneys, 1,25-dihydroxyvitamin D stimulates both calcium and phosphate resorption.
- Understand the mechanism of 1,25-dihydroxyvitamin D synthesis and how PTH affects this pathway. List the location where each step in the biosynthetic takes place.
2 kinds of Vitamin D: D3 (cholecalciferol-fish and meat), D2 (ergocalciferol-plants and supplements). Both D3 and vitamin D2 are converted to 25-hydroxyvitmain D in the liver by 25-hydroxylase.
In the kidney, 25-hydroxyvitamin D –> active form, 1,25-dihydroxyvitamin D by the renal tubular enzyme 1 alpha-hydroxylase.
PTH plays a role in the regulation of 1,25-dihydroxyvitamin D formation through upregulation of 1 alpha-hydroxylase. 1,25-dihydroxyvitamin D upregulates the enzyme 24-hydroxylase, which results in the formation of the inactive compound 24,25-dihydroxyvitamin D.
The production of the active metabolite, 1,25-dihydroxycholecalciferol, is regulated by changing the activity of the 1 alpha-hydroxylase enzyme . 1 alpha-Hydroxylase activity is increased by each of the following three factors: decreased plasma Ca 2+ concentration, increased circulating levels of PTH, and decreased plasma phosphate concentration.
what is the only kind of Ca that is biologically active?
free, ionized.
symptoms of hypocalcemia
Chvostek sign, or twitching of the facial muscles elicited by tapping on the facial nerve, and the Trousseau sign, which is carpopedal spasm upon inflation of a blood pressure cuff.
signs of hypercalcemia
Manifestations of hypercalcemia include constipation, polyuria, polydipsia, and neurologic signs of hyporeflexia, lethargy, coma, and death.
acidemia and alkalemia - effect on Ca
In acidemia, there is an excess of H + in blood; thus, more H + binds to albumin, leaving fewer sites for Ca 2+ to bind. In acidemia, the free ionized Ca 2+ concentration increases because less Ca 2+ is bound to albumin. In alkalemia, there is a deficit of H + in blood, and less H + will be bound to albumin, leaving more sites for Ca 2+ to bind. Thus, in alkalemia (e.g., acute respiratory alkalosis ) the free, ionized Ca 2+ concentration decreases, often accompanied by symptoms of hypocalcemia.
the role of parathyroid hormone
to regulate the concentration of Ca 2+ in ECF (i.e., plasma or serum). When the plasma Ca 2+ concentration decreases, PTH is secreted by the parathyroid glands. In turn, PTH has physiologic actions on bone, kidney, and intestine that are coordinated to increase the plasma Ca 2+ concentration back to normal.
PTH action on bone
PTH–> osteoblasts –> release signals to osteoclasts
PTH action on kidney
PTH has two actions on the kidney. (1) PTH inhibits phosphate reabsorption by inhibiting Na + -phosphate cotransport in the proximal convoluted tubule. As a result of this action, PTH causes phosphaturia, an increased excretion of phosphate in urine. The cAMP generated in cells of the proximal tubule is excreted in urine and is called nephrogenous or urinary cAMP. The phosphaturic action of PTH is critical because the phosphate that was resorbed from bone is excreted in the urine; this phosphate would have otherwise complexed Ca 2+ in ECF. Excreting phosphate in urine “allows” the plasma ionized Ca 2+ concentration to increase! (2) PTH stimulates Ca 2+ reabsorption. This second renal action of PTH is on the distal convoluted tubule and complements the increase in plasma Ca 2+ concentration that resulted from the combination of bone resorption and phosphaturia.
PTH action on small intestine
PTH does not have direct actions on the small intestine, although indirectly it stimulates intestinal Ca 2+ absorption via activation of vitamin D. PTH stimulates renal 1 alpha-hydroxylase, the enzyme that converts 25-hydroxycholecalciferol to the active form, 1,25-dihydroxycholecalciferol. In turn, 1,25-dihydroxycholecalciferol stimulates intestinal Ca 2+ absorption.
what does calcitonin do?
The major action of calcitonin is to inhibit osteoclastic bone resorption, which decreases the plasma Ca 2+ concentration.
