Vitamin D & Calcium Homeostasis (PDF)

Vitamin D 1,25-Dihydroxycholecalciferol Vitamin D3 increase both plasma Ca2+ and phosphate Synthesis depends on Ca2+ status Prolactin, Parathyroid Hormone, Oestrogens Universit y...

Vitamin D 1,25-Dihydroxycholecalciferol Vitamin D3 increase both plasma Ca2+ and phosphate Synthesis depends on Ca2+ status Prolactin, Parathyroid Hormone, Oestrogens Universit y ofGalway. ie 1,25-Dihydroxycholecalciferol Universit y ofGalway. ie Action of Vit D Intestine - Major site of action Increase Ca2+ and phosphate (indirectly) absorption Ca2+ channel in lumen is TRPV6 Vit D induces synthesis of calbindin D-28K (bind 4 Ca2+) Shuttle Ca across 2+ Universit y ofGalway. ie Action of Vit D Kidney Minor effect Reabsorption of BOTH Ca2+ and phosphate Bone Minor effect Acts with PTH to  osteoclast activity and bone resorption (old bone) Increase plasma Ca2+ and phosphate Stimulate bone (new) mineralisation due to high Ca2+ levels Universit y ofGalway. ie Calcitonin Product of parafollicular C cells of the thyroid Gland 32 aa Universit y ofGalway. ie  Calcitonin Control ↑ plasma Ca → ↑ calcitonin secretion 2+ Action short as T1/2 = 10 min - Little long term effect Acts to decrease Plasma [Ca2+] Act to inhibit osteoclast bone resorption (primary action) Decrease Ca and phosphate reabsorption in kidney 2+ No pathophysiological consequences of deficiency Possibly important in infant, pregnancy and lactation Universit y ofGalway. ie Universit y ofGalway. ie Other Hormones affecting bone turnover Oestrogen and Androgens - Decreased bone - re-absorption Cortisol - increased re-absorption of bone Thyroxine - Necessary for fetal bone development Anabolic during growth to stimulate peak bone mass acrrual Catabolic effects in adult that increase bone turnover Local factors IGF 1 - increased osteoblast proliferation TGF - increased osteoblast activity PG’s - increased bone turnover (#’s/inflammn) BMP - bone formation Universit y ofGalway. ie Hypocalcemia Total serum Calcium < 8.8 mg/dL (< 2.20 mmol/L) when plasma protein concentration normal Serum ionized Calcium concentration < 4.7 mg/dL (< 1.17 mmol/L) Hyper-reflexia, spontaneous twitching, muscle cramps Reduced threshold potential, hyperexcitability of cells Tingling and Numbness - effect on sensory nerves Muscle twitching – effect on motor neurons and muscle Trousseau (hand) and Chvostek (face) sign Universit y ofGalway. ie Trousseau’s sign Carpopedal spasms following inflation of a sphygmomanometer cuff above systolic blood pressure Occlusion of the brachial artery causes flexion of the wrist and metacarpophalangeal joints, hyper-extension of the fingers, and flexion of the thumb on the palm Hypocalcaemia induced excitability of the nerves in the arm and forearm results in spontaneous firing of nerves fire when subjected to Ischemia after inflating the cuff. Universit y ofGalway. ie Hypocalcaemia Vit D deficiency Dietary Lacking Inability to Absorb Vit D Inability to metabolise inactive Vit D - Kidney or Liver disorder Children: Rickets  Ca2+ and phosphate to mineralise bone Growth failure and skeletal deformities Adults: Osteomalacia Bending and soft weight baring bones Vit D Resistance Kidney unable to produce 1,25 hydroxycholecalciferol Congenital absence of 1α- hydroxylase or chronic renal failure Universit y ofGalway. ie Hypoparathyroidism Post thyroid/parathyroid surgery, Thyroid radioactive I 2 ablation Autoimmune and congenital less common Low PTH, hypocalcemia, hyperphosphatemia Trt with hormone replacement, oral Ca2+ and Vitamin D Pseudophypoparathyroidism Inherited autosomal dominant disorder – defective PTH receptor Universit y ofGalway. ie Hyperparathyroidism Primary hyperparathyroidism Hypercalemia ↑ bone resorption, ↑ renal Ca2+ reabsorption and ↑ intestinal reabsorption Hypophosphatemia –↓ renal phosphate reabsorption High Ca2+ excreted in urine (hypercalcemia) Ca2+ -Phosphate stones in kidney Treatment – surgical removal of parathyroid glands Secondary Hyperparathyroidism Due to hypocalemia caused by Vit D deficiency or chronic renal failure Universit y ofGalway. ie  Malignancy Associated Hypercalcaemia Parathyroid hormone (PTH) receptor family includes: PTH1 and PTH2 receptors Three Ligands PTH, PTH-related protein (PTHrP), tuberoinfundibular peptide of 39 residues (TIP39)]  Malignancy Associated Hypercalcaemia Hypercalcemia of malignancy (HCM) is the most common cause of elevated serum calcium in hospitalized patients and is found with varying frequency in patients with Universit y ofGalway. ie Osteoporosis Decrease total bone mass Long term dietary Ca or Vit D deficiency 2+ Vit C deficiency – required for collagen synthesis Immobilization, ↓ mechanical stress Menopause (↓ oestrogen) Certain drugs: anticonvlusants, glucocorticoids Universit y ofGalway. ie