4 Phosphorus Important role in cellular metabolism source of of energy in cellular reactionsComponent of phospholipids in membranes
5 James T. McCarthy & Rajiv Kumar Calcium HomeostasisJames T. McCarthy & Rajiv Kumar
6 Hormonal Regulators Calcitonin (CT) Parathormone (PTH) 1,25 Vitamin D3 Lowers Ca++ in the bloodInhibits osteoclastsParathormone (PTH)Increases Ca++ in the bloodStimulates osteoclasts1,25 Vitamin D3Increase Ca++ uptake from the gut
10 Renal tubular reabsorption of Calcium 80-85 of calcium is reabsorbed at proximal tubule and medullary loop of henle (passive transportAccording to physiologic needsat 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.
11 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.
12 MAINTENANCE OF CALCIUM AND PHOSPHATE HOMEOSTASIS It is dependent onIntestinalBoneRenal function
13 MAINTENANCE OF CALCIUM AND PHOSPHATE HOMEOSTASIS It is dependent onIntestinalBoneRenal functionNa 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
14 Calcitonin Is synthesized by parafollicular cells of thyroid gland Affects the metabolism of Са and РPromotes the transferring of Са2+ from blood into bonesInhibits reabsorption of Р in kidneys (decreases the content of Р in blood due to its excretion with urine)14
15 Increase of calcitonin hypocalciemia hypophosphatemia hyperphosphaturiaDecrease of calcitonin- hypercalciemiahyperphosphatemiahypophosphaturia15
16 PARATHYROID GLANDS Parathyroid hormone - protein Affects the metabolism of Са and РPromotes moving of Са2+ from bones into bloodInhibits 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 intestineДія зв’язана з вітаміном D (утворює активну форму вітаміну D в нирках)16
18 2 Main regulators of Calcium and phosphorus: PARATHYROID HORMONEVitamin DPTH ( Parathyroid hormone)84 amino peptideMolecular mass if 9.5 kilodaltonno carbohydrate or other covalently bound moleculesFull biologic activity resides in the amino terminal third of the moleculePTH 1-34 has full biologic activity while region is for receptor bindingIs a fat soluble steroidThat is present in the diet and can be synthesized from the skin
19 PARATHYROID HORMONEA polypeptide secreted from the parathyroid glands in response to a decrease in the plasma concentration of ionized calcium
20 Parathyroid Hormone Precursor of PTH are: PreproPTH differs from proPTH by having additional 25 amino acid amino terminal* it is the hydrophobicend*at Rough endoplasmic reticulum
21 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
22 PTH increases Ca concentration by: 1. In the presenc e of permissive amounts of vitamin D it stimulates bone resorptionrelease of calcium phosphates2. Enhances intestinal Calcium and phosphate absorption promotes formation of vit D3. It augments renal calcium reabsorption
23 PTH Regulation of Synthesis Biosynthesis is regulated by levels of calciumAn acute decrease of Ca results in marked increase of PTH mRNA increase of PTH synthesisEffects is at the level of gene transciption, MRNA stability, mRNA translationRate of degradation of PTH is low if low calcium and high if calcium is high1, 25 (OH)2D3 receptor complex binds with vitamin D in the promoter region of PTH gene and inhibits transcription decreases the production of PTHPTH synthesis can be enhanced by the size and number of PTH producing chief cells in cases of prolonged hypocalcemia
24 Hyperfunction (Recklinghausen’s disease) HypofunctionhypocalciemiahyperphosphatemiahypophosphaturiatetanusHyperfunction (Recklinghausen’s disease)hypercalciemiahypophosphatemiahyperphosphaturiaosteoporosisAccumulation of Са in tissues24
25 Hyperparathyroidism: adenoma or hyperplasia or ectopic
28 Regulation of Metabolism and synthesis of 1,25()H)2-D3 Primary RegulatorsSecondary RegulatorsHypocalcemia (↑)PTH(↑)Hypophosphatemia(↑)Calcitriol (↓)EstrogenAndrogensProgesteroneInsulinGrowth HormoneProlactinThyroid Hormone
29 1,25 Vitamin D3 UV Increases Ca++ uptake from the gut Increase transcription and translation of Ca++ transport proteins in gut epitheliumMinor roll: also stimulates osteoclastsIncrease Ca++ resorption from the boneUVCholesterol precursor7-dehydrocholesterolVitamin D325 Vitamin D31,25 Vitamin D3-made in the liver, the skin, the liver, and the kidneyLiver: cholesterol precursor transformed to 7-dehydrocholesterolSkin: UV transforms 7-dehydrocholesterol to Vit D3Liver: Enzyme transforms Vit D3 to 25-OH-Vit D3Kidney: Enzyme transforms 25-Vit D3 to 1,25 Vit D3-lack of melanin pigment in Northen Europeans was thought to account for the lower light level: let more UV across the skin to ensure high enough levels of Vit. D3-increases Ca++ uptake from the gut-made from cholesterol…….acts like a steroid…..what kind of receptors? How would they act? (they increase transcription and translation of Ca++ transport proteins in the epithelial cells of the gut)-minor roll: also acts to stimulate osteoclasts, (which would do what?) increasing Ca++ resorption from the bone-control of secretion:-low Ca++ levels causes increase of PTH, which increases enzymes in the kidney (more enzyme, more 1,25 Vit. D3)1,25 Vitamin D3Low plasma Ca++ increase kidney enzymes
30 Images of RicketsWrist expansion: cupping and fraying of hypertrophied metaphyseal plateRachitic RosaryBone demineralization and deformityRotten-stump epiphysis
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