1. Hormonal regulation of calcium and phosphorus homeostasis.

2. Calcium Regulate neuromuscular excitability Blood coagulation
Secretory processes
Membrane integrity
Plasma membrane transport
Enzyme reactions
Release of hormones and neurotransmitters
Bone mineralization

4. Phosphorus Important role in cellular metabolism
source of of energy in cellular reactions
Component of phospholipids in membranes

5. James T. McCarthy & Rajiv Kumar
Calcium Homeostasis
James T. McCarthy & Rajiv Kumar

6. Hormonal Regulators Calcitonin (CT) Parathormone (PTH) 1,25 Vitamin D3
Lowers Ca++ in the blood
Inhibits osteoclasts
Parathormone (PTH)
Increases Ca++ in the blood
Stimulates osteoclasts
1,25 Vitamin D3
Increase 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 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.

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 on
Intestinal
Bone
Renal function

13. 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

14. 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) 14

15. Increase of calcitonin hypocalciemia hypophosphatemia
hyperphosphaturia
Decrease of calcitonin
- hypercalciemia
hyperphosphatemia
hypophosphaturia 15

16. 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) 16

18. 2 Main regulators of Calcium and phosphorus:
PARATHYROID HORMONE
Vitamin D
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

19. PARATHYROID HORMONE
A 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 hydrophobic
end
*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 resorptionrelease of calcium phosphates
2. Enhances intestinal Calcium and phosphate absorption promotes formation of vit D
3. It augments renal calcium reabsorption

23. 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

24. Hyperfunction (Recklinghausen’s disease)
Hypofunction
hypocalciemia
hyperphosphatemia
hypophosphaturia
tetanus
Hyperfunction (Recklinghausen’s disease)
hypercalciemia
hypophosphatemia
hyperphosphaturia
osteoporosis
Accumulation of Са in tissues 24

25. Hyperparathyroidism: adenoma or hyperplasia or ectopic

26. Hypocalcemia

27. Vitamin D
Metabolism

28. Regulation of Metabolism and synthesis of 1,25()H)2-D3
Primary Regulators
Secondary Regulators
Hypocalcemia (↑)
PTH(↑)
Hypophosphatemia(↑)
Calcitriol (↓)
Estrogen
Androgens
Progesterone
Insulin
Growth Hormone
Prolactin
Thyroid Hormone

29. 1,25 Vitamin D3 UV 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 UV
Cholesterol precursor
7-dehydrocholesterol
Vitamin D3
25 Vitamin D3
1,25 Vitamin D3
-made in the liver, the skin, the liver, and the kidney
Liver: cholesterol precursor transformed to 7-dehydrocholesterol
Skin: UV transforms 7-dehydrocholesterol to Vit D3
Liver: Enzyme transforms Vit D3 to 25-OH-Vit D3
Kidney: 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 D3
Low plasma Ca++ increase kidney enzymes

30. Images of Rickets
Wrist expansion: cupping and fraying of hypertrophied metaphyseal plate
Rachitic Rosary
Bone demineralization and deformity
Rotten-stump epiphysis