Presentation on theme: "Hormonal regulation of calcium and phosphorus homeostasis."— Presentation transcript:
Hormonal regulation of calcium and phosphorus homeostasis.
Calcium Regulate neuromuscular excitability Blood coagulation Secretory processes Membrane integrity Plasma membrane transport Enzyme reactions Release of hormones and neurotransmitters Bone mineralization
Phosphorus Important role in cellular metabolism source of of energy in cellular reactions Component of phospholipids in membranes
Calcium Homeostasis James T. McCarthy & Rajiv Kumar
Hormonal Regulators Calcitonin (CT) –Lowers Ca++ in the blood –Inhibits osteoclasts Parathormone (PTH) –Increases Ca++ in the blood –Stimulates osteoclasts 1,25 Vitamin D3 –Increases Ca++ in the blood –Increase Ca++ uptake from the gut –Stimulates osteoclasts
Renal tubular reabsorption of Calcium of calcium is reabsorbed at proximal tubule and medullary loop of henle (passive transport According to physiologic needs at the DISAL tubule and adjacent cortical thick ascending limb ( where PTH, Vit D exert its effect) CCT—cortical collecting tubule; IMCD—inner medullary collecting duct or tubule; PST—proximal straight tubule.
Renal tubular reabsorption of phosphorus Most of the inorganic phosphorus in serum is ultrafilterable at the level of the glomerulus. CCT—cortical collecting tubule; IMCD—inner medullary collecting duct or tubule; PST—proximal straight tubule.
MAINTENANCE OF CALCIUM AND PHOSPHATE HOMEOSTASIS It is dependent on –Intestinal –Bone –Renal function
MAINTENANCE OF CALCIUM AND PHOSPHATE HOMEOSTASIS It is dependent on –Intestinal –Bone –Renal function Na Cl and KCL complete absorbtion at intestine but CALCIUM AND PHOSPHATE is incomplete * because of the requirement for vitamin D and formation of insoluble salts like; Calcium phosphate,calcium oxalate and magnesium phosphate at the intestinal lumen
Calcitonin Is synthesized by parafollicular cells of thyroid gland Affects the metabolism of Са and Р - Promotes the transferring of Са2+ from blood into bones - Inhibits reabsorption of Р in kidneys (decreases the content of Р in blood due to its excretion with urine)
PARATHYROID GLANDS Parathyroid hormone - protein Affects the metabolism of Са and Р - Promotes moving of Са2+ from bones into blood - Inhibits reabsorption of Р in kidneys (decreases the content of Р in blood due to its excretion with urine) - Stimulates the absorption of Ca in the intestine Дія зв’язана з вітаміном D (утворює активну форму вітаміну D в нирках)
2 Main regulators of Calcium and phosphorus: PARATHYROID HORMONEVitamin D 1.PTH ( Parathyroid hormone) 84 amino peptide Molecular mass if 9.5 kilodalton no carbohydrate or other covalently bound molecules Full biologic activity resides in the amino terminal third of the molecule PTH 1-34 has full biologic activity while region is for receptor binding Is a fat soluble steroid That is present in the diet and can be synthesized from the skin
PARATHYROID HORMONE A polypeptide secreted from the parathyroid glands in response to a decrease in the plasma concentration of ionized calcium
Parathyroid Hormone Precursor of PTH are: A.PreproPTH differs from proPTH by having additional 25 amino acid amino terminal * it is the hydrophobic end *at Rough endoplasmic reticulum
Parathyroid Hormone Precursor of PTH are: B. ProPTH differs from native hormone by having an amino terminal highly basic hexapeptide extension * it is hydrophobic end * at PTH golgi apparatus
PTH increases Ca concentration by: 1. In the presenc e of permissive amounts of vitamin D it stimulates bone resorption release of calcium phosphates 2. Enhances intestinal Calcium and phosphate absorption promotes formation of vit D 3. It augments renal calcium reabsorption
PTH Regulation of Synthesis –Biosynthesis is regulated by levels of calcium –An acute decrease of Ca results in marked increase of PTH mRNA increase of PTH synthesis –Effects is at the level of gene transciption, MRNA stability, mRNA translation –Rate of degradation of PTH is low if low calcium and high if calcium is high –1, 25 (OH)2D3 receptor complex binds with vitamin D in the promoter region of PTH gene and inhibits transcription decreases the production of PTH –PTH synthesis can be enhanced by the size and number of PTH producing chief cells in cases of prolonged hypocalcemia
Hyperfunction (Recklinghausen’s disease) - hypercalciemia - hypophosphatemia - hyperphosphaturia - osteoporosis - Accumulation of Са in tissues Hypofunction - hypocalciemia - hyperphosphatemia - hypophosphaturia - tetanus
Hyperparathyroidism: adenoma or hyperplasia or ectopic
Regulation of Metabolism and synthesis of 1,25()H)2-D3 Primary Regulators Secondary Regulators Hypocalcemia (↑) PTH(↑) Hypophosphatemia(↑) Calcitriol (↓) EstrogenAndrogensProgesteroneInsulin Growth Hormone Prolactin Thyroid Hormone
1,25 Vitamin D3 Increases Ca++ uptake from the gut –Increase transcription and translation of Ca++ transport proteins in gut epithelium Minor roll: also stimulates osteoclasts –Increase Ca++ resorption from the bone Cholesterol precursor7-dehydrocholesterol UV Vitamin D3 25 Vitamin D3 1,25 Vitamin D3 Low plasma Ca++ increase kidney enzymes
Images of Rickets Rachitic Rosary Wrist expansion: cupping and fraying of hypertrophied metaphyseal plate Rotten-stump epiphysisBone demineralization and deformity