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Layout: Introduction Biosynthesis and regulation Transport Mechanism of action Metabolism Metabolic Actions Abnormalities associated with calcitriol - Hypovitamenosis D - Hypervitamenosis D
Introduction: Calcitriol also called 1,25-dihydroxycholecalciferol, active form of vitamin D with three alcohol groups It increases the level of calcium (Ca2+) in the blood
Biosynthesis and its regulation: Produced in the cells of the proximal tubule of the nephron By the action of 25-hydroxyvitamin D3 1-alpha-hydroxylase The activity of the enzyme is stimulated by - PTH. - Prolactin - Decreased levels of serum phosphate
Transport: Vitamin D-binding protein belongs to the albumin family 458 amino acids Coded by 1690 nucleotides on chromosome 4 Found in -plasma, -cerebrospinal fluid -on the surface of many cell types It binds to vitamin D and its plasma metabolites and transports them to target tissues
Mechanism of action:
Metabolism: Half life - approx. 5-8 hours. This enzyme plays a role in calcium homeostasis and of calcitriol 24-hydroxylase calcitriol Calcitric acid
Intestinal Ca+2 absorption: Increases the absorption of Ca Increases the production of Calmodulin (CaBP).
On bones: Type 1 Collagen osteoclastin Osteoblasts Osteoclast absorption of Cain bones
Action on kidneys A major action of calcitriol is to regulate renal 25-hydroxyvitamin D,-1-hydroxylase It has been shown that calcitriol brings about a suppression of this enzyme Thus it helps to regulate the formation of calcitriol by negative feedback inhibition.
On skeletal and cardiac muscles the rate of Ca uptake by sarcoplasmic reticulum of skeletal muscles skeletal muscle mass Can cause the calcification of cardiac muscle Lead to myocardial failure
On cancer cells: Cancerous cells have receptors for calcitriol Calcitriol represses the cell proliferation So it along with its analogs can be use for treating the cancer
On skin: melanin synthesis. preventing the skin penetration of sunlight. 7-dehydrocholesterol is not converted to pre-vitamin D Feedback regulation.
Endocrine functions: Parathyroid Gland: Inhibits the proliferation of parathyroid cells Inhibits the parathyroid genes form transcription Thus can be used to treat hyper-parathyroidism. Pituitary gland Increases prolactin synthesis and secretion from pituitary cells.
Pancreas: vitamin D deficiency inhibited insulin secretion from the pancreas, whereas vitamin D repletion improved insulin secretion
Disorders related to calcitriol: Vitamin D deficiency: Type I: Type II: Body is unable to utilize vitamin D due to defect in the receptor of calcitriol. hydroxylase 25,OH –D3 calcitriol
Diseases related to vitamin D deficiency Rickets - Softening of bones in children potentially leading to fractures and deformity in bones
The predominant cause is a vitamin Ddeficiency
Sign & symptoms: Bone pain or tenderness dental problems muscle weakness Growth disturbance Hypocalcemia Tetany
Treatment and prevention: Increase dietary intake of calcium, phosphates and vitamin D. Exposure to sunlight cod liver oil
Osteomalacia Osteomalacia is the softening of the bones due to defective bone mineralization Signs and Symptoms Weak bones Bone pain Muscle weakness Hypocalcemia Compressed vertebrae Fractures Bone softening Bending of bones Pain
Treatment Oral administration of vitamin D. Osteomalaciadue to malabsorption may require treatment by injection of significant amounts of vitamin D.
Hypervitaminosis D Is tolerable But deleterious in extreme large dosage 500-1000 times than normal Effects: Immediate effects: Anorexia Thirst Lassitude(fatigue) Constipation Polyuria Nausea Vomiting Diarrhoea
Delayed effects: persistent hypercalcemia and hyperphospatemia may result Urinary lithasis Metastatic calcification Effecting
References Research paper by U Sipmson & Ronald www.wikipedia.com
Acknowlegdements Allah Almighty Parents Prof. Dr. Khawaja Muhammad Fayyaz Dr. ShafqatNazir Dr. JamshedIqbal. Mam Jawaria Mam Uummaya
Friends HaroonGull UsmanBaig. Musa Khan Ali Aasil Talha Tariq Mudassir Butt MaazBarlas AtifRana AbubakrDastgir AtharSaleem GulamMurtaza Sahib