Hormonal regulation of calcium and phosphorus homeostasis
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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.

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Hormonal regulation of calcium and phosphorus homeostasis

Hormonal regulation of calcium and phosphorus homeostasis.


Calcium

Calcium

  • Regulate neuromuscular excitability

  • Blood coagulation

  • Secretory processes

  • Membrane integrity

  • Plasma membrane transport

  • Enzyme reactions

  • Release of hormones and neurotransmitters

  • Bone mineralization


Phosphorus

Phosphorus

Important role in cellular metabolism

source of of energy in cellular reactions

Component of phospholipids in membranes


Calcium homeostasis

Calcium Homeostasis

James T. McCarthy & Rajiv Kumar


Hormonal regulators

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

Renal tubular reabsorption of Calcium

80-85 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

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

MAINTENANCE OF CALCIUM AND PHOSPHATE HOMEOSTASIS

  • It is dependent on

    • Intestinal

    • Bone

    • Renal function


Maintenance of calcium and phosphate homeostasis1

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


Hormonal regulation of calcium and phosphorus homeostasis

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)


Hormonal regulation of calcium and phosphorus homeostasis

  • Increase of calcitonin

  • hypocalciemia

  • hypophosphatemia

  • hyperphosphaturia

  • Decrease of calcitonin

  • - hypercalciemia

  • hyperphosphatemia

  • hypophosphaturia


Hormonal regulation of calcium and phosphorus homeostasis

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

Vitamin D

2 Main regulators of Calcium and phosphorus:

PARATHYROID HORMONE

  • 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 25-34 is for receptor binding

  • Is a fat soluble steroid

  • That is present in the diet and can be synthesized from the skin


Parathyroid hormone

PARATHYROID HORMONE

A polypeptide secreted from the parathyroid glands in response to a decrease in the plasma concentration of ionized calcium


Parathyroid hormone1

Parathyroid Hormone

Precursor of PTH are:

  • PreproPTH differs from proPTH by having additional 25 amino acid amino terminal

    * it is the hydrophobic

    end

  • *at Rough endoplasmic reticulum


Parathyroid hormone2

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

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


Hormonal regulation of calcium and phosphorus homeostasis

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


Hormonal regulation of calcium and phosphorus homeostasis

  • Hypofunction

  • hypocalciemia

  • hyperphosphatemia

  • hypophosphaturia

  • tetanus

  • Hyperfunction(Recklinghausen’s disease)

  • hypercalciemia

  • hypophosphatemia

  • hyperphosphaturia

  • osteoporosis

  • Accumulation of Са in tissues


Hyperparathyroidism adenoma or hyperplasia or ectopic

Hyperparathyroidism: adenoma or hyperplasia or ectopic


Hypocalcemia

Hypocalcemia


Hormonal regulation of calcium and phosphorus homeostasis

Vitamin D

Metabolism


Regulation of metabolism and synthesis of 1 25 h 2 d3

Regulation of Metabolism and synthesis of 1,25()H)2-D3


1 25 vitamin d3

UV

Cholesterol precursor

7-dehydrocholesterol

Vitamin D3

25 Vitamin D3

1,25 Vitamin D3

Low plasma Ca++ increase kidney enzymes

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


Hormonal regulation of calcium and phosphorus homeostasis

Images of Rickets

Wrist expansion: cupping and fraying of hypertrophied metaphyseal plate

Rachitic Rosary

Bone demineralization and deformity

Rotten-stump epiphysis


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