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Department of Physiology

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Presentation on theme: "Department of Physiology"— Presentation transcript:

1 Department of Physiology
Parathyroid Hormone, Calcitonin, Calcium and Phosphate Metabolism, Vitamin D and Bone Prof. Dr. Bayram Yılmaz Faculty of Medicine Department of Physiology YEDİTEPE UNIVERSITY

2 Skeleton * Bone tissue

3 Regulation of calcium and phosphate levels in the extracellular fluid and plasma
Extracellular fluid calcium concentration normally is regulated very precisely. Normal plasma value is about 9.4 mg/dl Hypercalcemia, progressive depression of the nervous system Hypocalcemia, increased excitability of the nervous system Only about 0.1% of total body calcium is found in the extracellular fluid, about 1 % in the cells and the rest is stored in the bones

4 Calcium in the Plasma and Interstitial Fluid
The calcium in the plasma is present in three forms: About 41% of the calcium is combined with the plasma proteins and in this form is indiffusible thorugh the capillary membrane About 9% of the calcium is diffusible through the capillary membrane but is combined with anionic substances of the plasma and interstitial fluid (such as citrate and phosphate) The remaining 50% of the calcium in the plasma is both diffusible and ionized

5 Calcium in the Plasma and Interstitial Fluid

6 Inorganic phosphate in the extracellular fluids
About 85% of the body phosphate is found in the bones; % in the cells and less than 1% in the extracellular fluid Inorganic phosphate in the plasma is mainly in two forms: HPO4- H2PO4- The average total quantity of inorganic phosphorus for both ions is about 4 mg/dl

7 Non-bone physiologic effects of altered calcium and phosphate concentrations in the body fluids
Changing the level of phosphate in the extracellular fluid from far below normal or two or three times normal does not cause major immediate effects on the body In contrast, even a slight increase or decrease of calcium ion in the extracellular fluid can cause extreme immediate physiologic effects. Hypocalcemia causes nervous system excitement and tetany. Increased permeability of neurons to sodium ions Hypercalcemia depresses nervous system and muscle activity. These effects become marked as the calcium level rises above 15 mg/dl

8 Absorption and Excretion of Calcium and Phosphate
Intestinal absorption and fecal excretion of calcium and phosphate Renal excretion of calcium and phosphate Approximately 10% (100 mg/day) of the ingested calcium is excreted in urine Normally, the renal tubules reabsorb 99% of the filtered calcium, and only 100 mg/day is excreted in urine Renal phosphate excretion is controlled by an over-flow mechanism, when phosphate level is below 1 mmol/lt, all phosphate in the glomerular filtrate is reabsorbed…

9 Absorption and Excretion of Calcium and Phosphate

10 Bone and its relation to extracellular calcium and phosphate
Organic matrix of the bone: 90-95% collagen fibers, and the remaining is homogenous gelatinous medium called ground substance The ground substance is composed of extracellular fluid plus proteoglycans, especially chondroitin sulfate and hyaluronic acid Bone salts: The crystalline salts deposited in the organic matrix of the bone are composed principally of calcium and phosphate. Hydroxyapatite = collagen + Ca(PO4)2 + OH + bicarbonate Metals, radioactive and toxic substances can also be deposited in the bone

11 Precipitation and absorption of calcium and phosphate in bone
Concentrations of calcium and phosphate in extracellular fluid are greater than those required to cause precipitation of hydroxyapatite Role of inhibitors: pyrophosphate Mechanism of bone calcification: The initial stage in bone production is secretion of collagen molecules and the ground substance (mainly proteoglycans) by the osteoblasts Formation of osteoid… Importance of amorphous salts that are not converted in hydroxyapatite: fall in extracellular calcium and reabsorption of amorphous compounds Precipitation of calcium in nonosseous tissues under abnormal conditions: formation of arteriosclerosis, precipitation in blood clots.

12 Calcium exchange between bone and extracellular fluid
Importance of exchangeable calcium; a rapid buffering mechanism Deposition of bone by the osteoblasts Absorption of bone – function of the osteoclasts Bone deposition and absorption are normally in equlibrium Value of continual bone remodeling Control of the rate of bone deposition by bone “stress” Repair of a fracture activates osteoblasts

13 skeleton is not only important for locomotion, but protects the soft parts of the body like the brain, produces blood cells in the bone marrow of certain bones and is needed, with the muscles, to give the body shape and support. Some bone is built up in layers between or beneath specialized tissue layers. That tissue is typically tough and not too unlike canvas in thickness and toughness. The plates of the skull are made wholly from bone layered between two such membranes. The shafts of long bones get thicker by deposition of bone beneath an encircling tube of similar tissue. Bone gets strength from two things. 1) What it is made from (kind of bone), and 2) How it is shaped and organized.

14 A coronal section of bone tissue

15 RANK: Osteoclast procursor cells produce a surface receptor protein
RANK Ligand Ostaoblasts produce osteoprotegerin which interferes with RANKL

16 Vitamin D Vitamin D has a potent effect to increase calcium absorption from the intestinal tract Vitamin D itself is not the active substance It must first be converted through a succession of reactions in the liver and kidneys to the final active product; 1,25-dihydroxycholecalciferol Cholecalciferol (Vitamin D3) is formed in the skin: UV and 7-dehydroxycholesterol Cholecalciferol that we ingest in food Vitamin D is lipid soluble and can be stored in fat tissue

17 Synthesis and Functions of 1,25-dihydroxycholecalciferol

18 Calcium ion concentration controls the formation of 1,25-dihydroxycholecalciferol
Formation of 1,25-dihydroxycholecalciferol is controlled inversely proportional to plasma levels of calcium When plasma calcium levels rise, parathyroid hormone secretion is inhibited, conversion of 25-hidroxycalciferol to 1,25-dihydroxycholecalciferol is prevented Instead, Vitamin D is converted to an inactive form, 24,25-dihydroxycholecalciferol

19 Calcium ion concentration controls the formation of 1,25-dihydroxycholecalciferol

20 Synthesis and Functions of 1,25-dihydroxycholecalciferol

21 Actions of Vitamin D Hormonal effect of vitamin D to promote intestinal calcium absorption It does this by increasing formation of a calcium-binding protein in the intestinal epithelial cells Vitamin D promotes phosphate absorption by the intestines Vitamin D decreases renal calcium and phosphate excretion Effect of Vitamin D on bone and its relation to parathyroid hormone activity Vitamin D in smaller quantities promotes bone calcification, whereas in extreme quantities causes bone absorption In the absence of Vit D, bone resoptive action of PTH is greatly reduced

Physiologic anatomy of the parathyroid glands The chief cells in the parathyroid glands secrete PTH Chemistry of parathyroid hormone: protein

23 Parathyroid Glands

24 Parathyroid Glands

25 Parathyroid Glands and Histology

26 Effect of PTH on calcium and phosphate concentrations in the extracellular fluid
PTH increases plasma calcium concentrations 1- It increases calcium and phosphate absorption in the bone 2- With the fast action of PTH, it decreases renal excretion of calcium Rapid phase of calcium and phosphate absorption: Osteolysis Slow phase of bone absorption and calcium phosphate release: Activation of the osteoclasts Osteoclasts do not themselves have membrane receptors for PTH

27 PTH decreases calcium excretion and increases phosphate excretion by the kidneys
PTH causes rapid loss of phosphate in urine, by decreasing its tubular reabsorption In contrast, PTH increases tubular reabsorption of calcium The increased calcium absorption occurs mainly in the late distal tubule and collecting tubules PTH increases intestinal absorption of calcium and phosphate Role of Vitamin D

28 Control of PTH Secretion by Calcium
PTH secretion is controlled by plasma concentrations of calcium Increased activity of parathyroid glands in pregnancy and lactation Conditions that increase plasma calcium levels above normal cause decreased activity and reduced size of the parathyroid glands

29 CALCITONIN Calcitonin is a peptide hormone secreted by parafollicular (C type) cells in the thyroid gland High plasma calcium concentrations increase calcitonin release In turn, calcitonin reduces plasma calcium concentrations 1- The immediate effect is to decrease the absorptive activities of the osteoclasts and possibly the osteolytic effect of the osteolytic membrane 2- The second and more prolonged effect of calcitonin is to decrease the formation of new osteoclasts Calcitonin has a weak effect on plasma calcium concentration in the adult human

30 Control of calcium concentrations in the extracellular fluid
1- The first line of defense: Fuffer function of exchangable calcium in the bone 2- The second line of defense: Hormonal control

31 Regulation of PTH Secretion

32 HYPOPARATHYROIDISM When the parathyroid glands do not secrete sufficient PTH, osteocytic reabsorption of exchangable calcium decreases and the osteoclasts become almost totally inactive Hypoparathyroidism causes hypocalcemia In its treatment, Vitamin D and calcium are administered Hypoparathyroidism is usually not treated with PTH administration

The cause of primary hyperparathyroidism is usually a tumor of one of the parathyroid glands Bone disease in hyperparathyroidism: In severe hyperparathyroidism, increased osteoclastic reabsorption far exceeds osteoblastic deposition And the bone may be eaten away entirely In addition to absorption of the old bones, osteoblastic activity to form new bone also increases When osteoblasts become active, they secrete large quantities of alkaline phosphatase Effects of hypercalcemia Parathyroid poisoning and metastatic calcification CaHPO4 crystals become deposited in the alveoli of the lungs, kidneys, thyroid gland, arteries and stomach Formation of kidney stones in hyperparathyroidism

In secondary hyperparathyroidism, high levels of PTH occur as a compensation for hypocalcemia rather than a primary tumor of the parathyroid gland It can be caused by Vit D deficiency or failure to form active Vit D in chronic renal disease Rickets – Vitamin D deficiency Mainly occurs in children It results from calcium or phosphate deficiency in the extracellular fluid Usually caused by vitamin D deficiency

Rickets: Plasma concentration of calcium and phosphate decrease in Rickets: The plasma calcium concentration is rickets is only slightly depressed, but the level of phosphate is greatly decreased Rickets weakens bones Tetany in rickets Treatment of rickets: Supplying adequate calcium and phosphate in the diet Administering large amount of Vit D

36 Rickets Deficiency of Vit D in childhood Lack of sun exposure
Deficiency in diet Decreased plasma calcium Increased PTH secretion Increased bone resorption O or X legs

Osteomalacia (adult rickets) Adults seldom have a dietary deficiency of vit D or calcium Serious deficiency of vit D or calcium occasionally occur as a result of steatorrhea (failure to absorb fat) Osteomalacia caused by renal rickets:

38 OSTEOPOROSIS Osteoporosis: decreased bone matrix Osteoporosis is the most common of all bone diseases in adults. Most common causes are: 1- Inactivity (lack of physical stress) 2- Malnutrition, lack of protein in diet 3- Deficiency of Vit C (reduced osteoblastic activity) 4- In older ages, markedly decreased growth hormone and other factors 5- Cushing Syndrome 6- Reduced secretion of estrogen in menopause


40 Estrogen and Osteoporosis
Role of cytokines in the bone tissue Bone resorption increasing effect Estrogen - IL-1, IL-6, TGF-b and TNF-a + Bone resorption


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