Parathyroid hormone , Calcitonin ,Calcium , and Phosphate Metabolism, VitaminD

OUT LINES ■Overview of calcium and phosphate regulation in the extracellular fluid and . plasma ■ Non- Bone physiologic effects of altered calcium and phosphate concentrations in the body fluids . ■ Absorption and excretion of calcium and phosphate . ■ Bone and its relation to extracellular calcium and phosphate .

CALCIUM AND PHOSPHATE METABOLISM ■ functions of calcium: 1- contraction of skeletal , cardiac and smooth muscles. 2- blood clotting 3- transmission of nerve impulses . ■ Normal Ca level 9.4 mg /dl or 2.4 mmol / L . ■ Hypercalcemia → cause depression of nervous system ■ Hypocalcemia → cause excitation of nervous system . Calcium and phosphate concentration is determined by the interplay of : 1- calcium and phosphate absorption from the GI tract 2- renal excretion of calcium 3- bone uptake and release of calcium

■ 0. 1 % of the total body Ca is in extracellular fluid ■ 0.1 % of the total body Ca is in extracellular fluid . ■ 1% is in the cells , and the rest is stored in bones. ■ The bones serve as large reservoirs , releasing Ca when extracellular fluid concentration decreases and storing excess Ca . ■ about 85% of the body’s phosphate is stored in bones, 14-15 % is in the cells, and less than 1% is in the extracellular fluid.

50% of calcium in the plasma is both diffusible and ionized. ■ Calcium in the plasma is present in three forms : - 41% combined with the plasma proteins and this form is non diffusible through the capillary membrane , and it is not ionized. - 9% is combined with anionic substances of the plasma and interstitial fluids ( citrate ,phosphate ) , and this form is diffusible through the capillary membrane , and it is not ionized. 50% of calcium in the plasma is both diffusible and ionized. - the ionic form is the form that is important for most functions of calcium in the body. ■

Inorganic phosphate in the extracellular fluid ■ Inorganic phosphate in the plasma is mainly in two forms : HPO- and H²PO-  mmol/L s about 1.05 The concentration of HPO- And H²PO-  is about 0.26 mmol/L . ■ When the PH of extracellular fluid becomes more acidic there is a relative increase in H2PO-  and a decrease in HPO- , and the opposite occurs when the extracellular fluids becomes Alkaline .

■ The average total quantity of inorganic phosphorus represented by both phosphate ions is about 4 mg/dl . In adult 3-4 mg/dl and in children 4-5 mg/dl.

■ Changing in Ca level ↑↓cause extreme immediate physiologic effects ,While changing in Ph level ↓or ↑2-3 times doesn't cause major immediate effect on the body . ■ Chronic hypocalcemia or hypophosphatemia greatly decreases bone mineralization .

■ Hypocalcemia . at plasma Ca ion concentration about 50% below normal → the peripheral nerve fibers become more excitable → ( ↑neuronal membrane permeability to Na ions) → easy initiation of action potentials . ■ Tetany in the hand(carpopedel spasm), usually occurs at lower concentration of calcium of about 6 mg/dl.Tetany of all part of the body, usually occurs after hand teteny. - lethal levels are about 4 mg/dl.

Hypercalcemia causes: 1- depressed nervous system and muscle activity Hypercalcemia causes: 1- depressed nervous system and muscle activity. 2- decreased the QT interval of the heart. 3- lack of appetite and constipation. 4- depressed contractility of the GI tract. - above12 mg/dl →depressed central nervous - above 15 mg/dl marked depressive effect above 17 mg/dl, precipitation of Calcium phoshate crystals throughout the body.

Absorption and excretion of calcium and phosphate ■ Intestinal absorption and fecal excretion of Calcium and phosphate. the usual rates of intake is about 1000 mg/ day each for Ca ,and Ph . - Calcium ions are poorly absorbed from the intetines. Vit. D promotes calcium absorption by the intestines, and about 35% of the ingested calcium is absorbed, and the remaining is excreted in the feces, and additional 250 mg/day of calcium enters the intestines via secreted GI juices. Thus, 900mg of daily intake of Ca is excreted in the feces .

■ Phosphate absorption from intestine easily occurs, except for the portion of phosphate that is secreted in the feces in combination with nonabsorbed calcium, and most of the absorbed phosphate is excreted in the urine. ■ about 10% of the ingested calcium is excreted in the urine. ■ PTH increases calcium reabsorption in the distal tubules. ■PTH increases phosphate excretion by the kidnyes ■ Renal phosphate excretion is controlled by an over flow mechanism.

Ca exchange between bone and extracellular fluid ■ The bone contains a type of exchangeable Ca that is always in equilibrium with the Ca ions in the extracellular fluid . ■ The importance of exchangeable calcium is that it provides a rapid buffering mechanism to keep the calcium ion concentration in the extracellular fluids from rising to high levels or falling to very low levels. ■ most of the exchangeable calcium is in the bone, its normal concentration about 0.4 to 1% of the total bone calcium .

Vitamin D ■ Vitamin D increases Ca absorption from the GI tract and bone deposition, ■Steps of formation and activation of vitamin D: D3(cholecalciferol) is formed in the skin by ultraviolet rays from the sun → D3 (cholecalciferol) is converted to 25- hydroxycholecalciferol in the liver. ■ conversion of 25-hydroxy. Into 1,25- dihydroxycholecalciferol occurs in the kidneys under the control of PTH. ■ calcium ion concentration controls the formation of 1,25-Dihydroxycholecalceferl.

Actions of vitamin D 1- active form of vitamin D promotes intestinal calcium absorption. 2- it promotes absorption of phosphate by the intestines . 3- it decreases renal calcium and phosphate excretion. 4- active vit. D in smaller quantities promotes bone calcification. 5- in high concentration causes absorption of bone.

Parathyroid glands - there are four parathyroid glands in humans, they are located immediated behand the thyroid gland, and each is about 6 mm long,3 mm wide, and 2 mm thick PTH. Controls the plasma concentration of calcium and phosphate by; 1- regulating intestinal reabsoption, 2- renal excretion, 3- and exchange of these ions between the extracellular fluid and bone. - removal of half the parathyroid glands usually causes no major physiologic abnormalities. - PTH. Is a polypeptide hormone containing 84 amino acids, with MW of 9500, and is secreted by the chief cells.

Effects of parathyroid hormone 1- increases calcium and phosphate absorption from the bone, 2- decreases the excretion of calcium by the kidneys, 3- increases renal phosphate excretion, 4- increases phosphate absorption from the bone, 5- increases intestinal absorption of calcium and phosphate, by active form of vitamin D. Cyclic adenosine monophosphate mediates the effects of parathyroid hormone. Control of PTH secretion by plasma calcium ion concentration

Calcitonin hormone Is a peptide hormone secreted by the C cells of the thyroid gland. Decreases plasma calcium concentration Increased plasma calcium concentration stimulates calcitonin secretion