Hormonal Control of Calcium & Phosphate Metabolism & the Physiology of Bone PDF

First Part Role of Calcium 1. Intracellular messenger 2. Extracellular functions (e.g.; blood clotting) Control of body calcium conc. is vital System that maintain Ca+2 hemostasis: 1. PTH: Secreted from parathyroid gland. Mobilize Ca+2 from bone and increase urinary phosphate excretion 2....

First Part Role of Calcium 1. Intracellular messenger 2. Extracellular functions (e.g.; blood clotting) Control of body calcium conc. is vital System that maintain Ca+2 hemostasis: 1. PTH: Secreted from parathyroid gland. Mobilize Ca+2 from bone and increase urinary phosphate excretion 2. 1,25-(OH)2D3 (steroid hormone): Derived formed from vitamin D3 and activated successively by liver then by kidney. Increase Ca+2 absorption from intestine 3. Calcitonin: secreted from thyroid gland. Inhibit bone reapportion (decrease body Ca+2 conc.). This hormone has minor role. These 3 hormones operate to maintain constant Ca+2 level in body fluids MCQ: The control of body calcium concentrations is vitally important. Which of the following is correct in controlling body calcium concentration? A. PTH increase urinary calcium excretion B. 1,25-(OH)2D3 decrease GI absorption of calcium C. Calcitonin decrease urinary excretion of calcium D. PTH increase calcium mobilization from bone E. All options are corrects Role of phosphate 1. Inclusion in ATP 2. Biological buffer 3. Modifying proteins (e.g.; activation of enzymes) Systems that regulate Ca+2 hemostasis also regulate phosphate in a reciprocal manner Calcium metabolism  Total body Calcium = 1,100g (99% in bone & 1% out of bone)  Plasma conc. = 10mg/dL  5.36mg/dL is ionized (diffusible)  4.64mg/dL is bound to plasma proteins (nondiffusible) MCQ: Calcium is an essential intracellular signaling molecule and also plays a variety of extracellular functions. Which of the followings is incorrect about calcium distribution? A. The total body content is about 1,100g B. 99% of total body calcium is in the bone C. About 5.36mg/dL of plasma calcium is diffusible D. Free calcium is inversely proportionate to plasma protein conc. E. Citrate calcium is a nondiffusible form of calcium Role of free calcium (ionized) 1. Second messenger 2. Blood coagulation 3. Muscle contraction 4. Nerve function Hypocalcemic  Means: a decrease in extracellular Ca+2 level  Effect: Net excitatory effects on nerve and muscle cells Hypocalcemic tetany  Characterized by: extensive skeletal muscle spasm (especially the extremities and larynx (sever occlusive laryngospasm & fatal asphyxia)  Note: Fatal tetany occurs before compromising the clotting reactions Free Ca+2 vs plasma proteins  The relation is inverse  As plasma proteins increase, free Ca+2 is decrease  As plasma protein ionized (at high pH), free Ca+2 is decrease (more binding cause low ionized levels)  Hyperventilation in patients (decrease blood CO2 level) cause blood pH to increase (respiratory alkalosis), thus symptoms of hypocalcemic tetany appear even if the blood calcium is high MCQ: A decrease in extracellular Ca2+ exerts an net excitatory effects on nerve and muscles cells in vivo. Which of the followings is correct about hypocalcemic tetany? A. Develop when blood pH is drop toward acidic ranges. B. Accompany by compromised clotting reaction. C. Can occurs during hypervitaminosis D D. It can be caused by hypoparathyroidism E. Characterized by flaccid muscle paralysis Bone calcium 1. Readily exchangeable – reservoir (small pool) 2. Slowly exchangeable - stable (large pool) Systems that affect bone calcium  That regulate plasma Ca+2: by altering absorption (1,25- (OH)2D3) & excretion (PTH) - ~ 500mmol/day absorbed and excreted  That involve bone remodeling: by activation of bone resorption (osteoclast activation) or bone deposition (osteoblast activation)  About 7.5mmol/dL Ca+2 is exchanged between plasma and bone  The transport (exchange) process is regulated by 1,25- (OH)2D3. As Ca+2 uptake (hence plasma Ca+2) is increased, 1,25-(OH)2D3 levels fall. Renal excretion  Ca+2 is filtered from plasma  98-99% of the filtrated Ca+2 is reabsorbed 60% in PCT 40% in ascending LH and DCT  Distal tubular reabsorption is regulated by PTH Role of phosphorus. It is present in: 1. ATP 2. cAMP & DAG 3. DNA & RNA 4. Many proteins Phosphorylation and dephosphorylation: are involved in the regulation of cell signaling and function Body phosphorous  Total body content: 500-800g  Bone amount: 85-90% in the bone & 10-15% out of the bone  Plasma conc.: 12mg/dL (2/3 is organic & 1/3 is inorganic “PO4 3- , HPO4 2-, H2PO4 – ”  Exchange rate: Amount entering bone 3mg/kg/day with equal amount leaving via reabsorption from bone Renal excretion  Pi is filtered from plasma  85-90% of the filtrated is reabsorbed largely in PCT via NaPi- IIa and NaPi-IIc  NaPi-Iia is powerfully inhibited by PTH by internalization and degradation and thus reduce renal reabsorption of Pi.