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Parathyroid & Ca physiology

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Physiology 3120
Tom Stavraky

Human Physiology Wednesday, March 3, 2010 “Endocrine VI” Parathyroid Physiology & Calcium Metabolism • Regulation of Ca mostly by parathyroid hormone (PTH); more tightly regulated than any other ion in the body • Processes requiring calcium  Signal transduction (secretory vesicle release, transcriptional activation [coactivator])  Maintenance of membrane potential  Muscle contraction  Enzyme cofactor (troponin C, calcium-calmodulin) • Human skeleton  Important for. . .  Support & protection  Locomotion  Hematopoiesis (formation of blood cells)  Calcium regulation • Calcium distribution  1% of Ca is non-skeletal (blood, in ionized, protein-bound, or complexed forms); only about half of this non-skeletal Ca is “free” and diffusible  99% of Ca found in bone (calcium phosphate; accounts for 50% of skeletal weight) • 3 organs involved in Ca balance 1. Intestine (about 1000mg)  Site for Ca absorption from diet  Apical surface = faces gut lumen; basolateral surface = faces circulation  Contain Ca transporters that open up in presence of gut Ca, allowing Ca into cells; carried across cytoplasm to basolateral membrane, where a Ca ATPase pumps it into bloodstream; maintains gradient across cell  Some excreted in feces (~800mg); can be from (I) unabsorbed Ca, and (II) normal gut secretion of fluids and enzymes (many enzymes require Ca) 2. Kidney  Some excreted in urine  Most (98%) is reabsorbed, 25-30% of that occurs in distal tubule (here, it is an active process that is saturable and regulated by PTH) • Ca reabsorbed passively in Loop of Henle, but actively in distal tubule  Reabsorption occurs through channel TRPV5 • Production and activity of it can be stimulated • Have binding proteins (calbindin) to carry Ca across cell; there is a Na/Ca exchanger on basolateral membrane and a Ca ATPase that pumps it into bloodstream • All these actions stimulated by PH; its receptors are on the basolateral surface 3. Bone  Large daily movement of Ca both into and out of  In the long, narrow shaft of a long bone, the marrow is primarily involved in Ca production  Two types of bone • Compact bone  protection • Spongy/trabecular bone  inner scaffold to support and give flexibility to outer layer; also highly metabolically active; involved in providing Ca  Bone turnover/remodelling • ~15-18% of trabecular bone is remodelling at any given time (so the scaffold renews itself every 6 years) • Types of cells o Large multi-nucleated  osteoclast; breaks down existing bone protein matrix  Formed by fusion of mononuclear cells  Fuse onto bone surface (very tight seal) using integrins  Has many microvilli  Highly secretory (H ions, TRAP to break down protein components of bone), and absorptive o Small mononuclear cell  osteoblast; responsible for laying down new bone matrix  Formed from cells of mesenchymal lineage  After mature osteoblasts recede, minerals get deposited in bone o Osteocytes  buried osteoblasts that develop a lot of cytoplasmic processes; communication & distribution system  Sense stress fractures, which is one reason we undergo remodelling at all  Mechanosensory; detect shear forces (from stress), and undergo apoptosis; when signals from these cells are absent, remodelling is initiated  Surrounding ECF is the source of “fast-release” Ca
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