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USC BISC 307L - Ca Balance and Reproduction
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BISC 307L 2nd Edition Lecture 20 Current LectureCalcium in the BodyRoles:As Ca2+: ~ 1%• Intracellular signal for enzymes, contraction, exocytosis, etc.• Necessary for adhesion at tight junctions• Cofactor for blood coagulation• Affects neuronal excitability (hypocalcemia ® hyperexcitability) (side note: hypercalcemia leads to hypoexcitability.)All those functions of Ca2+ really only amount to 1% of the calcium in the body. Most of the rest of it is in bones. Not as free Ca2+ ions, but as a type of Ca2+ phosphate called hydroxyapatite, which forms the mineral portion of bones. As calcium phosphate (hydroxyapatite): ~ 99%• forms the mineral portion of bonesSo calcium exists in the body not only as the most importantstructural component of bone, but as a storage pool whereexcess Ca2+ can be deposited or liberated to maintain thereservoir of Ca2+ in the body at appropriate levels. Hormones that Regulate Body CalciumThe hormones that regulate plasma Ca2+ come from 2 mainplaces – the thyroid and the parathyroid . Pictured to the rightis a thyroid gland, seen from the back. Calcitonin is synthesizedby the C cells in between the thyroid follicles. And embeddedwithin the thyroid gland are the PT glands(pink nodules). There are 3 main hormones that regulate plasma Ca2+: 1. Parathyroid hormone released from the PT glands,embedded in the posterior surface of the thyroidgland(pink nodules). PT hormone is essential for life – itraises plasma calcium. 2. The second hormone has 3 names – calcitriol, vitaminD3, or 1,25 dihydroxy-cholecalciferol. It is a steroidhormone made from vitamin D. Vitamin D can be made in the skin or can be taken in through diet. 3. The liver cells take that circulating vitamin D and change it into an intermediate, which isprocessed in the kidney. PTH will stimulate the conversion of the intermediate into calcitriol, which also raises plasma calcium. 4. Calcitonin – secreted by C cells in the thyroid gland(in between the thyroid follicles in the thyroidgland)Ca 2+ Balance:The small intestine isthe only source ofdietary Ca2+, and is thesource of new Ca2+being added to thebody (new Ca2+ comesfrom absorptionacross the wall of theSI). Dietary Ca2+ in the SIhas two fates: stayand be passed ontothe larger intestine to be excreted out in feces, or be absorbed into the ECF. The ECF is the box in the middle, and it shows the normal level of free Ca2+ concentration. And the circle at the bottom is the intracellular fluid in cells where the free calcium is much less (a thousandth or lower relative to the ECF) – we’ve talked about how active transport creates a strong inward gradient for Ca to enter cells(active transport pumps it out). Bone is a very important reservoir of Ca2+ - Ca2+ can be taken from the ECF and deposited into the bones – shown in the upper left corner of the diagram above. Ca2+ deposited in the bone causes new bone formation, and the cells that do that are called osteoblasts. Ca2+ can also be released from bones, by osteoclasts, which break or resorb the bone and liberate Ca2+. On the right is the kidney, and Ca2+, being a small ion, is freely filtered into the tubular fluid of the kidney where it passes along the kidney tubule. That Ca2+ in the kidney tubule can be reabsorbed back into the blood or left to pass out with the urine. These hormones achieve Ca2+ balance by acting on the rates of different processes:The first hormone we are looking at is PTH – it raises plasma Ca2+ in 3 ways: 1. Strongly stimulates bone reabsorption of calcium. PTH on top of the arrow pointing from bone to EF indicates that it stimulates the activity of osteoclasts in breaking down bone and liberating Ca2+. 2. PTH on the right arrow, pointing from kidney to ECF, stimulates reabsorption of Ca2+ from the kidney tubule back into the blood and ECF. Ca2+ has two effects on ion transport across the kidney tubule wall – it stimulates Ca2+ reabsorption back into the blood, and stimulates phosphate excretion. This is important because if Ca2+ and phosphate concentration were to go up simultaneously, than insoluble calcium-phosphate salts would form and precipitate out of the blood, forming Ca2+ deposits in the tissue, which would have negative consequences. 3. The third effect is indirect – PTH(on the arrow pointing from SI to ECF) stimulates the synthesis of calcitriol, which raises plasma calcium. So PTH also indirectly raises plasma calcium.The second hormone we are looking at is calcitriol, whose main effect is to stimulate Ca2+ absorption from the small intestine up at the top. So the PTH in parenthesis enhances that action by stimulating calcitriol synthesis. That’s the main effect of calcitriol – bringing new Ca2+ into the body. Another effect is to stimulate bone resorption like PTH does (shown on left). Another anterior pituitary hormone we are looking at is Prolactin, which also raises plasma Ca2+.Its main functions are centered around the production of milk in mammary glands. Here, Prolactin also stimulates Ca2+ reabsorption from the digestive tract, which important in lactating women because this ensures that the Ca2+ necessary for the milk from lactation comes out of ECF, not out of bone. Lastly, we have calcitonin – it lowers plasma Ca2+. It does this mainly by counteracting the effectsof PTH. If PTH stimulates bone resorption, calcitonin stimulates bone deposition. If PTH stimulates Ca2+ reabsorption in the kidney, calcitonin inhibits it. So calcitonin lowers Ca2+ levels by depositing it into the bone, or allowing it to pass out through the urine. In adults, calcitonin doesn’t’t play much of a role in Ca2+ maintenance in body. But in children and lactating women, it is important. In children, where bones are growing rapidly, stimulation of osteoblast activity by calcitonin is important for growth. And in lactating women and during pregnancy, there is extra demand for Ca2+ in the body (for adding to the milk, and for the fetus, respectively). Calcitonin secretion is relatively high in pregnant and lactating women – it stimulates bone growth to protect the mother’s bones from weakening from osteoporosis. But calcitonin does not actually lower plasma calcium levels – it is important for these levels to be maintained at normal. This is achieved because there is a simultaneous increase in secretion of calcitriol and prolactin, which raise plasma Ca2+.So you have no net effect on plasma Ca2+ concentration, but you have a


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USC BISC 307L - Ca Balance and Reproduction

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