Calcium Homeostasis & Calcium Balance PDF

Calcium Homeostasis & Calcium Balance Objectives Describe the importance of calcium hemostasis physiological actions of parathyroid H , calcitonin H and vitamin D Effect of altered (hypo and hyper) secretion of these hormones secretion. Calcium: In adult human body...

Calcium Homeostasis & Calcium Balance Objectives Describe the importance of calcium hemostasis physiological actions of parathyroid H , calcitonin H and vitamin D Effect of altered (hypo and hyper) secretion of these hormones secretion. Calcium: In adult human body, 1.5% of body weight is Ca. 99% of Ca is in the bones 98% - 99% of the filtered Ca++ in kidney is reabsorbed, 60% of reabsorption occurs in the proximal tubule and less in ascending loop of Henley and distal tubules The plasma Ca++ is about 9-10.5 mg/dL, and it is in three forms:  50% as ionized calcium (Ca2+), which is free diffusible  10% non-ionized or complexed with organic ions such as citrate and phosphate,  40% protein-bound calcium, mainly to albumin, it is non-diffusible through capillary membranes  Functions and health benefit of calcium Muscle contraction and nerve excitability. Neurotransmitter and hormonal release. Enzyme function. Blood coagulation. maintain healthy bone and strong teeth. Membrane integrity and permeability.  Phosphorus: About 90% of which is found in skeleton. Plasma phosphates is about 2.48–4.34 mg/dL, Pi is absorbed in duodenum and small intestine by active transport and passive diffusion. Absorption is linearly correlated with dietary intake. 1, 25 Dihydroxycholecalciferol increases Pi absorption. Pi is filtered in glomeruli, 85% - 90% is reabsorbed by proximal tubules and the active transport is powerfully inhibited by PTH. Bone structure and physiology: Bone is a special form of connective tissue made up of microscopic crystals of phosphates and calcium within a matrix of collagen. The cells that are concerned primarily with bone formation and resorption are osteoblasts and osteoclasts, both derived from bone marrow. Bone growth: Specialized areas at the end of each long bone (epiphysis) are separated from the shaft by a plate of actively proliferating cartilage, epiphyseal plate. The bone increases in length as this plate lays down new bone at the end of the shaft. Bone remodeling is mainly a local process carried out in small areas by populations of cells called bone-remodeling units. First osteoclasts resorb bone forming a tunnel of few millimeters in length, and then osteoblasts lay down new bone in the same area in successive layers of concentric circles (Larnellae). The benefit of remodeling is to adjust the shape and strength of bone in response to stress (bone thickened when subjected to heavy load and resorbed in long bed rest).  Parathormone Parathormone: PTH is a peptide hormone produced by the chief cells of the parathyroid glands. Synthesis:Derived from preproparathyroid hormone in the parathyroid glands. Regulation: Secretion stimulated by low blood calcium levels. Inhibited by high blood calcium levels (negative feedback).  Mechanism of Action Bone:Stimulates osteoclast activity, increasing bone resorption and calcium release. Kidneys: – Increases calcium reabsorption in renal tubules. – Promotes phosphate excretion. – Stimulates conversion of vitamin D to its active form (calcitriol). Intestines: – Enhances intestinal absorption of calcium indirectly via calcitriol. Regulation  Clinical applications: Hyperparathyroidism: 1. Primary Hyperparathyroidism: Usually increased PTH level in functioning parathyroid tumor is characterized by Hypercalcemia, hypophosphatemia, demineralization of bone (increase bone resorption), hypercalcuria, increase urinary phosphate excretion, and calcium containing renal stones. 2. Secondary Hyperparathyroidism: In disease of kidney and in rickets, chronic low Ca++ level exert a feedback stimulation on PTH. Chronic renal failure: It is characterized by decreased glomerular filtration rate which leads to:  Decreased filtration of phosphate, phosphate retention, and increased serum phosphate concentration.  Increased serum phosphate complexes Ca++ and leads to decreased ionized Ca++ concentration.  Decreased production of active vitamin D3 by the diseased renal tissues also contributes to the decreased ionized Ca++ concentration.  Decreased Ca++ concentration causes secondary hyperparathyroidism Hypoparathyroidism: PTH is essential for life. After parathyroidectomy, steady decline in plasma Ca++ level causes hyper-excitability of excitable tissues followed by hypocalcaemia tetany. The condition can occur after thyroid surgery  Vitamin D A fat-soluble vitamin that functions as a hormone. 2 Forms: Vitamin D2 (ergocalciferol): From dietary sources and supplements. Vitamin D3 (cholecalciferol): Synthesized in the skin upon exposure to sunlight. Synthesis and Activation Synthesis: – Skin: 7-dehydrocholesterol converts to cholecalcifrol via UVB radiation. Activation Process: – Liver: Converts vitamin D to 25-hydroxy cholecalcifrol D(calcidiol). – Kidney: Converts calcidiol to 1,25-dihydroxy cholecalcifrol (calcitriol, the active form). Clinical Significance Deficiency: Causes: Inadequate sunlight exposure, poor dietary intake, malabsorption. Consequences: Rickets in children, osteomalacia in adults, increased fracture risk. Excess: Can lead to hypercalcemia and associated complications. Calcitonin (Calcium lowering hormone): Protein hormone produced by the parafollicular cells (C cells) of the thyroid gland. Regulation: Secreted in response to hypercalcemia. Inhibitory feedback by low calcium levels. When Ca++ level increase, calcitonin secretion is increased (calcitonin level is proportional to calcium level) and vice versa. Mechanism of Action Calcitonin receptors are mainly found in bones and kidneys. The net results of the calcitonin are decreased Ca++ and phosphate plasma levels through the following mechanisms: 1. Direct (immediate) effect by inhibiting the activity of osteoclasts (inhibit bone resorption). 2. Indirect (prolonged) effect by reducing the formation of new osteoclasts. 3. Increases Ca++ and phosphate excretion in urine. Clinical Significance Hypercalcitoninemia: Can occur in thyroid carcinoma. Monitoring: Levels may be assessed in specific clinical contexts, such as thyroid tumors. Calcitonin Therapy: Used in conditions like osteoporosis disease to help manage bone density. Hypocalcaemia: A decrease of plasma calcium (free and bound forms). 1. It can cause muscle tetany (occurs at a blood Ca level of about 6 mg/dl) and subsequently increases motor nerves excitability leading to carpopedal and laryngeal spasm. 2. It can cause prolongation of ST-segment and prolonged QT- interval in ECG. Hypercalcemia: An increase of plasma calcium (free and bound forms). It is associated with depressed nervous system activity, sluggish reflex activity, shortened QT-interval in ECG, enhanced myocardial contractility, constipation and reduced appetite, and predispose to renal stone formation. Clinical applications: Bone Disease: 1. Rickets and Osteomalacia: Due to deficiency of calcium concentration per unit bone matrix in new bone occurs due to: Inadequate vitamin D intake. Abnormalities in vitamin D receptors. Inadequate exposure to sunlight. Abnormal 1-α hydroxylase. It causes bone weakness broadening of ends of ulna and radius, growth retardation in children, abnormal skull sutures and in adults causes easy fractures especially in hip joint. 2. Osteoporosis: Matrix and minerals are both lost with loss of bone mass and strength with increased incidence of fractures. Involutional (primary) osteoporosis occurs in advancing age and menopause as estrogen has direct stimulating effect on osteoblasts (estrogen receptors are present on osteoblasts). Other causes of osteoporosis are:  Lack of physical activity.  Malnutrition and Vit. C deficiency (necessary for osteoblast activity).  Excess glucocorticoids.