Calcium & Phosphate Metabolism, Parathyroid Hormone Biochemistry Unit 14 PDF

CALCIUM & PHOSPHATE METABOLISM, PARATHYROID HORMONE BBM1233 MEDICAL BIOCHEMISTRY 2  Learning Objectives At the end of this lecture, the student will be able to: Describe the role of calcium and the factors that enhance or limit its absorption Explain the roles of calci...

CALCIUM & PHOSPHATE METABOLISM, PARATHYROID HORMONE BBM1233 MEDICAL BIOCHEMISTRY 2  Learning Objectives At the end of this lecture, the student will be able to: Describe the role of calcium and the factors that enhance or limit its absorption Explain the roles of calcitonin, parathyroid hormone and calcitriol in blood calcium regulation Outline the causes, symptoms of hypocalcemia and hypercalcemia Describe the functions of phosphate in the body  CALCIUM Most abundant mineral in the human body Average adult body: approx. 1000 g of which: 99% is found in the skeleton (bones and teeth) 1% in extracellular fluid (ECF) Functions: Transmission of nerve impulses Formation of teeth & bone Muscle contraction Blood coagulation Activation of enzymes Secretion of hormone  Food sources: milk, dairy products, cereals, fish, egg, cabbage Daily requirement: Adult: 500 mg/day Children: 1200 mg/day Pregnancy & lactation: 1500 mg/day Elderly: 1500 mg/day  Absorption of Calcium Absorption is taking place from the first and second part of duodenum Two mechanisms have been proposed for the absorption of calcium by gut mucosa: Active transport process, involving energy and calcium pump Simple diffusions  Normal concentration of plasma calcium: 9-11 mg/dL Calcium is present in plasma in THREE forms: About 4 mg/dl is bound to proteins (albumin) About 5 mg/dl is in the ionized form About 1 mg/dl is complexed with bicarbonate, citrate or phosphate The ionized form is the only form that is physiologically active About 30% of dietary calcium is absorbed (must be in a soluble and ionized form) Factors Affecting Calcium Absorption Factors acting on mucosal cells Vitamin D (calcitriol) Vitamin D induces the formation of a carrier protein (Calbindin) that is important for the transfer of calcium across the intestinal mucosal epithelium Parathyroid hormone It increases calcium transport from the intestinal cells by enhancing 1α hydroxylase activity Factors affecting the availability of calcium in the gut pH of the intestine Calcium salts are soluble in acid solutions so acidity increases calcium absorption Amount of carbohydrates in diet Lactose promote calcium absorption by creating the acidity in the gut as they favors the growth of acid producing bacteria Amount of protein in diet Amino acids (lysine & arginine) increase calcium absorption  Phytic acid Present in oatmeal and cereals. They are considered anti- calcifying factor as they combine with calcium in the diet thus forming insoluble salts of calcium Oxalates They are present in some leafy vegetables, which cause formation of insoluble calcium oxalates Phosphate High phosphate content will cause precipitation as calcium phosphate (the optimum ratio is about 1:1 or 1:2) Malabsorption syndromes Fatty acid is not absorbed, causing formation of insoluble calcium salt of fatty acid Excretion of Calcium Calcium leaves the body mainly in urine and feces, but also in other body tissues and fluids, such as sweat The renal threshold for calcium in blood is 10 mg/dL. Calcium starts getting excreted in urine when this level is reached  Homeostasis of Calcium Plasma calcium concentration is controlled by THREE (3) hormones: 1. Parathyroid hormone (PTH) 2. Calcitriol 3. Calcitonin  Parathyroid Hormone (PTH) PTH secretion is stimulated in response to decreased in the concentration of plasma ionized calcium Exert its action at: Bone: acts on bone to cause rapid release of calcium and increased osteoclastic resorption Kidneys: increase calcium reabsorption/decrease renal calcium excretion Intestine: stimulates production of calcitriol, which acts to increase absorption of calcium from intestine Osteoclast is a type of bone cells that removes bone tissue by removing its mineralized matrix and breaking up the organic bone. This process is known as bone resorption  Calcitriol Active form of vitamin D Calcitriol increases blood calcium level by: Increase absorption of dietary calcium from the intestinal Increase renal tubular reabsorption of calcium Increases osteoclast activity causing bone demineralization  Calcitonin Secreted by parafollicular cells of thyroid gland  Hypercalcemia Serum calcium level > 11 mg/dL  Hypocalcemia Serum calcium level < 8.8 mg/dL  Symptoms of hypocalcemia: Muscle cramps Paresthesia, especially in fingers Neuromuscular irritability, muscle twitching Tetany ( intermittent muscular spasm) Seizures Bradycardia Rickets Osteoporosis  Phosphorus An adult body contains about 1 kg phosphate and it is found in every cell of the body Daily requirement: 500 mg/day  Food sources: milk, dairy products, cereal, nuts Phosphate is present in serum in THREE forms: Free ions (40%) Complex form with cations such as Ca2+, Mg2+,Na+, K+ (50%) Bound to protein (10%)  Functions of Phosphate Formation of bone and teeth Production of high energy phosphate. compounds, such as ATP, CTP, GTP, creatine phosphate Synthesis of nucleoside co-enzymes, such as NAD and NADP DNA and RNA synthesis, where phosphodiester linkages form the backbone of the structure Formation of phosphate esters, such as glucose-6-phosphate, phospholipids Activation of enzymes by phosphorylation Phosphate buffer system in blood. The ratio of Na2HPO4: NaH2PO4 in blood is 4:1. This maintains the pH of blood at 7.4  Absorption of Phosphate Occurs in jejunum Calcitriol promotes phosphate uptake along with calcium Acidity favors uptake while phytate decreases phosphate uptake by intestinal cells  The renal threshold is 2 mg/dL The reabsorption of phosphate by renal tubules is inhibited by PTH Hyperphosphatemia Hypophosphatemia