Calcium, Phosphate & Magnesium PDF

Calcium, Phosphate and Magnesium Calcium is the most abundant mineral in the human body, calcium has many functions in the body in addition to its structural role in bones and teeth, it is essential for muscle contraction, affects excitability of nerves. It is a second messenger involved in th...

Calcium, Phosphate and Magnesium Calcium is the most abundant mineral in the human body, calcium has many functions in the body in addition to its structural role in bones and teeth, it is essential for muscle contraction, affects excitability of nerves. It is a second messenger involved in the action of several hormones and is required for blood coagulation. Bone: Bone is consisted of a collagenous organic matrix (osteoid) on which a complex of inorganic hydrated calcium salts is deposited (hydroxyapatites). Bone is always biologically active. Continuous turnover (remodeling) occur with bone resorption (osteoclasts) and bone formation (osteoblasts). Bone formation requires calcium and phosphate. Alkaline phosphatase, secreted by osteablasts is essential to the process; it is acting by releasing phosphate from pyrophosphate. So in childhood the alkaline phosphatase is normally three times higher than adult. 1 Plasma calcium: Calcium present in plasma in three forms: 1. Protein bound: it is non diffusible (45%), mainly bound to albumin and lesser extent to globulin. 2. Complexed with citrate and phosphate: it is diffusible (7%). 3. Free ions (ionized) which is physiologically active and maintained by homoeostatic mechanisms (47%). It is affected by alkalosis and acidosis. In alkalosis, hydrogen ions dissociate from albumin, and 2  calcium binding to albumin increases, so there is increase in calcium complex formation and ionized calcium decreases. This may be sufficient to produce symptoms of hypocalcaemia although total calcium is normal. In acidosis, the reverse effect is observed and ionized calcium is increased. Ionized calcium is measured by ion-selective electrode. Accurate measurements require exclusion of air from the sample and tightly caped the container. Citrate, oxalate and EDTA should not be used as anticoagulant for measuring ionized calcium because they can bind to it and cause decrease in concentration. So we use heparin. Heparin 5-20 u/ml blood →  Ca+ from 15-25%. In heparinized syringe heparin is up to 100 u/ml. so we use: 1) Low heparin syringes contain 2 u/ml of heparin or 2) Calcium titrated heparin syringes. Changes in plasma albumin concentration will affect total calcium concentration independently of the ionized calcium concentration, leading to miss interpretation of results in both hypoproteinaemic and hyperproteinaemic states. So we use corrected calcium concentration in these states. If plasma albumin is < 4 g/dL corrected Ca = Ca + 0.8 (4 – serum alb.) If albumin is > 4.5 g/dL corrected Ca = Ca – 0.8 (serum alb. – 4.5) N.B.: 1 g alb in 100 ml serum bind 0.8 mg of Ca/dL. Reference Range: Alb = 3.5 – 5 g/dL = 35 – 50 g/L 3 Total Ca = 8.5 – 10.2 mg/dL = 2-2.5 mmol/L Ionized Ca+ = 4.6 – 5.3 mg/dL = 1.2 – 1.32 mmol/L Total phosphate (adult) 2.5 – 4.5 mg/dL = 0.8 – 1.5 m mol/L CHILDREN Phosphate = 4-7 mg/dl Calcium homoeostasis: Calcium concentration and inorganic phosphate in the ECF are maintained by two hormones: parathyroid hormone (PTH) and calcitriol (1.25 – dihydroxycholecalciferol). Calcitonin has a minor role in calcium homoeostasis. 4 1) PTH: It is secreted by the parathyroid glands in response to a fall in plasma (ionized) calcium and inhibited by hypercalcaemia. PTH acts on bone and kidneys, tending to increase the plasma concentration of calcium and reduce phosphate. Action of PTH: 1. Rapid release of Ca from bone.  plasma Ca+ 2.  osteoclastic resorption  plasma Ca+ 3.  calcium reabsorption  plasma Ca+ 4.  phosphate reabsorption  plasma Pi 5.  1-hydroxylation of 25-hydroxycholcalciferol  Ca and PI absorption from gut 6.  bicarbonate reabsorption → acidosis - Calcitriol inhibits PTH synthesis. 5 - PTH stimulates the formation of calcitriol. - Changes in phosphate concentration do not directly affect secretion of the hormone. Mild hypomagnesaemia stimulate PTH secretion, but severe hypomagnesaemia reduces it, as the secretion of PTH is magnesium dependent PTH is metabolized in liver and kidneys.. 6 2) Calcitriol It is derived from vitamin D after successive hydroxylation in liver (25-hydroxylation) and kidney (1  hydroxylation). Action of calcitriol: 1. In the gut, it stimulates absorption of dietary calcium and phosphate. 7 2. In bone, it promotes mineralization through the maintenance of ECF calcium and phosphate concentration (at normal conc.). 3. At high concentration, calcitriol stimulate osteocalstic bone resorption and releases Ca and Pi into ECF. 4. In the kidneys, calcitriol inhibits its own synthesis. 8  3) Calcitonin: Polypeptide hormone secreted by C-cells of thyroid gland. It is secreted when plasma calcium concentration rises and also in response to certain guts hormones. Its physiological role is uncertain; subjects who have had a total thyroidectomy do not develop a clinical syndrome due to calcitonin deficiency. Also in patients with medullary carcinoma of thyroid (tumor secrete calcitonin) calcium homeostasis is normal. Calcium and phosphate homoeostasis: I. Hypocalcaemia: 1. Hypocalcaemia stimulates the secretion of PTH and increase the production of calcitriol. 2. There is an increase in the uptake of both calcium and phosphate from the gut and also their release from bone. 3.  Phosphaturia (by PTH) and  calcium reabsorption by kidney so serum calcium  (become normal). II. Hypophosphataemia: 1. Increased secretion of calcitriol but not increase PTH secretion. 2. Any tendency of  plasma calcium by calcitriol should inhibit PTH secretion. 3. Calcium and phosphate absorption from gut is stimulated. 9  4. Calcitriol has much smaller effect on renal calcium reabsorption than PTH, so in absence of PTH, the excess Ca absorbed from the gut is excreted in urine. 5. The net outcome is restoration of phosphate concentration to normal, independently of that of calcium. Disorders of calcium, phosphate and magnesium metabolism: 1) Hypercalcaemia The common causes are: primary hyperparathyroidism due to parathyroid adenoma or hyperplasia and malignant disease, with or without metastasis to bone, including myeloma (due to secretion of calcium – mobilizing substances by tumor cells). Less common causes include sarcoidosis and over dosage with vitamin D or its derivatives. Mild hypercalcaemia is often asymptomatic, when more severe, clinical features may include bone and abdominal pain, renal calculi, polyuria, thirst and behavioral disturbances. 2) Hypocalcaemia… Causes hyper excitability of nerve and muscle, leading to muscle spasm (tetany) and in severe cases → convulsions. Causes: vitamin D deficiency and hypoparathyroidism. Vitamin D deficiency may be either dietary in origin, often increased by poor exposure to sunlight or due to malabsorption. 10 3) Hyperphosphataemia… It is associated with renal failure. It inhibits vitamin D metabolism (inhibit 1  hydroxylation to 25- hydroxycholcalcifrol in the kidney), and can cause hypocalcaemia. 4) Hypophosphataemia… Occurs with inadequate phosphate provision during intravenous feedings. It has harmful effects on many body tissues particularly blood cells and skeletal muscles (due to limiting formation of ATP). Magnesium: Is an essential cofactor for many enzymes? Its concentration in the extracellular fluid is controlled primarily through regulation of its urinary excretion. Hypomagnesaemia can cause clinical features similar to those of hypocalcaemia and indeed can cause hypocalcaemia, since the secretion of PTH is magnesium dependent.  Magnesium may occur with prolonged diarrhea and malabsorption. Hypermagnesaemia is common in renal failure, but it tolerated well by the body so increased concentration of magnesium rarely give rise to clinical disturbances. 11 12