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

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.

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)

Increase of calcitonin

- hypocalciemia- hypophosphatemia- hyperphosphaturia

Decrease of calcitonin- hypercalciemia- hyperphosphatemia- hypophosphaturia

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 HORMONE Vitamin D1. 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• 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 resorptionrelease 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- hyperphosphate

mia- hypophosphaturia- tetanus

Hyperparathyroidism: adenoma or hyperplasia or ectopic

Hypocalcemia

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

Primary RegulatorsPrimary Regulators Secondary Secondary RegulatorsRegulators

Hypocalcemia (Hypocalcemia (↑)↑)

PTHPTH((↑)↑)

HypophosphatemiaHypophosphatemia((↑)↑)

Calcitriol (↓)Calcitriol (↓)

EstrogenEstrogen

AndrogensAndrogens

ProgesteroneProgesterone

InsulinInsulin

Growth HormoneGrowth Hormone

ProlactinProlactin

Thyroid HormoneThyroid 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 precursor 7-dehydrocholesterol

UV

Vitamin D3

25 Vitamin D3

1,25 Vitamin D3

Low plasma Ca++ increase kidney enzymes

Images of RicketsImages of Rickets

Rachitic Rosary

Wrist expansion: cupping and fraying of hypertrophied metaphyseal plate

Rotten-stump epiphysisBone demineralization and deformity