Parathyroid Gland & Calcium Metabolism

1. Parathyroid Gland & Calcium Metabolism George Liapakis, PhD

2. Calcium in our body About 99% calcium in our body is in crystalline form within bones and teeth. Remaining 1% calcium in our body 0.1% extracellular fluid 0.9% within cells 0.05% NOT FREE 0.05% FREE COMPLEXED WITH PO43- ANIONS BOUND TO PLASMA PROTEINS Calcium can readily pass from plasma into tissues

3. 0.05% FREE CALCIUM Biologically active Blood clotting Secretion of neurotransmitters and hormones Control of neuromuscular excitability The most profound and immediate impact of even minor deviations from normal free calcium levels is the effect on neuromuscular excitability. Fall of free calcium levels (hypocalcemia) Over-excitability of nerves and muscles that discharge and contract “spontaneously” Severe contraction of respiratory muscles causes asphyxiation and death. Rise of free calcium levels (hypercalcemia) It causes cardiac arrhythmias and generalized depression of neuromuscular excitability.

4. The profound effects of small deviations of calcium on neuromuscular excitability suggest that the plasma concentration of calcium must be regulated with extraordinary precision. Hormonal control of calcium intake from food (intestine) and secretion (kidneys) Hormonal control of calcium exchange between the extracellular fluid and the bone PARATHYROID HORMONE (PTH) Parathyroid is a peptide It raises free plasma Ca2+ levels by acting on bone, kidneys and intestine.

5. Parathyroid hormone is secreted by the parathyroid glands. Parathyroid glands are four glands with the size of a rice grain, which are located on the back surface of the thyroid gland, one in each corner.

6. Actions of parathyroid hormone INTESTINE BONE KIDNEYS 1 Vitamin D 3 2

7. INTESTINE • PTH indirectly increases the absorption of both Ca2+ and PO43-from the intestine by activating vitamin D. • Vitamin D directly increases intestinal absorption of Ca2+ and PO4 3- from intestine. • Only a small fraction of calcium we get from food is absorbed. Most of it leaves our body in the feces. Vitamin D

8. Vitamin D • It can be produced in the skin from a precursor related to cholesterol, which is next released into the blood. • This happens only when the skin is exposed to sunlight.

9. Vitamin D • Everything that blocks sunlight to reach skin (wearing clothes, staying home) does not allow the skin to produce sufficient amounts of vitamin D. • Vitamin D must be obtained from food, such as milk, eggs, cheese, fish.

10. Vitamin D • When vitamin D enters the blood from either the skin or the digestive tract is biologically inactive. • Vitamin D is activated by 2 biochemical reactions. First reaction It takes place in the liver • Second reaction • It takes place in kidneys. • The kidney enzymes that activate vitamin D are stimulated by parathyroid hormone

11. BONE • Calcium is found in the organic extracellular matrix of bones, as Ca3(PO4)2crystals. • Constant construction by osteoblasts and demolition of bone by osteoclasts results in its constant remodeling • Usually, throughout most of adult life, the rates of bone formation and demolition are about equal, so total bone mass remains constant.

12. BONE If calcium (Ca2+) plasma levels fall and there is no dietary intake of calcium, then PTH withdraws Ca2+from bone in order to maintain constant its plasma levels PTH promotes the movement of Ca2+into the plasma from the Ca2+-rich bone fluid, which is located in an extensive network of small canals in the bone

13. No dietary intake of calcium for a long period of time PTH inhibits osteoblasts and stimulates osteoclasts, thus promoting the dissolution of bone and the transfer of both Ca2+and PO43–from bone into the plasma. Elevated levels of plasma PO43– are undesirable, because they react with the free calcium just released from bone, and form again Ca3(PO4)2 crystals, which return to bone. The body must get rid of the excess of plasma PO43–. How? Action of PTH on kidneys

14. KIDNEYS • PTH decreases the reabsorption of PO43–by the renal tubules, thus increasing urinary PO43– excretion. • PTH helps kidneys to reabsorb more of the filtered Ca2+, thus increasing plasma Ca2+ levels • PTH activates Vitamin D in kidneys Vitamin D

15. CONCLUSION

16. Regulation of PTH PTH secretion increases when plasma Ca2+ falls and decreases when plasma Ca2+rises. Calcitonin lowers plasma Ca2+ levels.

17. Calcitonin Calcitonin is produced by the thyroid gland (C cells, between thyroid follicles). OPPOSITE EFFECTS OF PTH

18. Disorders in Ca2+ metabolism • PTH Hypersecretion • PTH Hyposecretion • Vitamin D Deficiency

19. PTH Hyper-secretion • Hyperparathyroidism (Hypersecreting tumor in parathyroid gland) • Depressed neural and muscle activity , muscle weakness • Neurologic disorders, decreased alertness, poor memory • Cardiac disturbances • Bones are more fragile • Kidney stones

20. PTH Hypo-secretion • Hypoparathyroid (Rare situation) • Increased neuromuscular excitability, manifested as muscle cramps and twitches (spasms in respiratory muscles) , sensations of pins and needles. • Complete lack of parathyroid hormone can cause death (PTH is essential for life).

21. Vitamin D Deficiency • Impaired intestinal absorption of Ca2+. Release of PTH, which moves Ca2+ from bones to plasma • Formation of soft and deformed bones. • This condition is known as rickets in children and osteomalaciain adults.

22. SUMMARY Distribution of calcium in our body 0.05% free calcium is biologically active. Control of neuromuscular excitability Parathyroid hormone (PTH) raises free plasma Ca2+ levels by acting on bone, kidneys and intestine. PTH is secreted by the parathyroid glands Intestine: PTH indirectly increases the absorption of both Ca2+ and PO43- from the intestine by activating vitamin D Activation of vitamin D Vitamin D in skin and foods

23. SUMMARY Bone: PTH promotes the movement of Ca2+ into the plasma from the Ca2+-rich bone fluid Kidneys: PTH decreases the reabsorption of PO43– and increases the reabsorption of more of the filtered Ca2+ Regulation of PTH Calcitonin Disorders in Ca2+metabolism

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