Parathyroid Hormone, Calcitonin, Vitamin D.docx

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1. Parathyroid Hormone, Calcitonin, Vitamin D,
Calcium and Phosphate Metabolism and Bone.
Calcium homeostasis
Functions of calcium:
- Formation of bone & teeth
- Contraction of muscles
- Intracellular second messenger
- Transmission of nerve impulses
- Blood clotting

2. Regulation of calcium
Total body calcium in adults = 1kg
99% in bone
1% in soft tissues & plasma
- Some calcium in bone is exchangeable with plasma
- The level of calcium in plasma = 2.5 mmol/L
Present in three forms:
50% is ionized
41% is combined with plasma proteins
9% is combined with anionic substances (citrate & bicarbonate)

- Calcium level in the plasma is affected by:
Total amount of proteins
Other electrolytes
pH

3. - Dietary sources of calcium include milk, milk products, other
animal products
- About 30-80% of ingested calcium is absorbed in duodenum and
Ileum:
- Passive diffusion
- Actively (regulated by vitamin D)

Factors that decrease calcium absorption:
- Phosphate, oxalate
- High intestinal pH

4. - Calcium is excreted mainly in stool and some in urine.
- In kidney:
99% of filtered calcium is reabsorbed in:
- PCT (60%)
- Loop of Henle
- DCT (is controlled by the parathyroid hormone)

5. Phosphate
- Total phosphate in adults is about 0.5-0.8 kg
90% is found in the skeleton.
- Concentration in the plasma = 12 mg/dL.
- ⅔ is organic phosphorus
- ⅓ is inorganic.
- Phosphorus is found in the following compounds:
- ATP
- cAMP
- 2,3 DPG
- Phosphoproteins
- phospholipids

6. - Phosphate is absorbed in the duodenum by:
- Simple diffusion
- Stimulated by vitamin D
- In the kidney
- About 90% of filtered phosphate is reabsorbed mainly in the PCT.
- This decreased by PTH

7. Bone
- Is a type of connective tissue consisting of bone cells and matrix
- The matrix consists of:
Organic substances (collagen, especially type 1)
Inorganic substances (salts of calcium and phosphate)
- The bone cells
Are many types; two of these types participate in calcium
homeostasis:
- Osteoblasts
- Osteoclasts

8. Osteoblasts
- Cauuse bone mineralizaion
- Transfer of calcium from the plasma to the bone matrix.
- Activated by many hormones including:
vitamin D, GH, thyroid hormones, estrogens & androgens
Osteoclasts
- Are derived from monocytes
- Responsible for bone resorption
- They break down collagen and release calcium from bone to the
plasma
- Stimulated by PTH and vitamin D
- Inhibited by calcitonin

9. Functions of bone
- Protection of vital organs
- Movement and support
provides attachments for muscles
and functions with the tendons, ligaments and joints to move the body
- Production of blood cells
- Detoxification
stores some heavy metals to remove them from the blood
- Participation in hearing

10. Diseases of bone
Osteoporosis
Loss of bone matrix
- It develops when the rate of bone resorption exceeds the rate of
formation
- Causes:
- Hyperparathyroidism
- post-menopausal period (decreased estrogen)

- Resulting in increased possibility of fractures.

11. Rickets and osteomalacia
- Rickets is softening and weakening of bones in children due to
failure of bone mineralization.
- Causes:
- severe and prolonged vitamin D deficiency
- low Ca in diet
Resulting in hypocalcemia

- Leading to deformities in the legs, ribs, wrists and skull.

Osteomalacia
Is a similar condition in adults.

12. Regulation of calcium
Many hormones participate in calcium homeostasis
- Parathyroid hormone
- Vitamin D
- Calcitonin

13. parathyroid glands
- These are four small glands.
- They lie in the posterior surface of
the thyroid gland
- Each one is weighing about 20-50 mg.
- Release parathyroid hormone (PTH)

parathyroid hormone (PTH)
- is polypeptide 84 amino acids.
- Half life is about 10 min.

14. Effects of PTH:
Regulation of calcium & phosphate level in plasma:
- Increases calcium level
- Decreases phosphate
It acts on:
Bone:
- Stimulates osteoclasts to
increase bone resorption
and release calcium.

15. Kidney:
- Stimulates calcium reabsorption (in the DCTs & CDs)
- Decreases phosphate reabsorption (in the PCTs)
- Activates vitamin D (by activating the enzyme 1-α hydroxylase to
add (OH) on carbon number 1)
Intestine:(indirectly)
- Increases calcium absorption (by activating vitamin D).

16. Summary of effects of parathyroid hormone:

17. Control of the PTH:
increased by:
- Hypocalcemia
- Hypomagnesemia
- Hyperphosphatemia (lowers plasma calcium and inhibits vit D3)
- Stimulation of β2 receptors

It is decreased by:
- Hypercalcemia (-ve feedback)
- Hypermagnesemia
- Increased 1,25 dihydroxy-cholecalciferol

18. Hypoparathyroidism:
Decreased production of PTH due to:
- Damage to the parathyroid glands by a tumor or auto-antibodies
- Surgical removal.
Features:
- Hypocalcemia
- Convulsions
- Neuro-muscular hyperexcitability (Tetany)

19. Tetany:
Neuromuscular hyper-excitability caused by hypocalcemia.
Characterized by:
- Numbness in the fingers, toes and lips.
- Muscle cramps
- Carpopedal spasm
- Risk of death due to laryngeal spasm.

20. Vitamin D3:
Vitamin D:
 Is fat soluble vitamin.
 Sources:
- Ingested with food.
- Synthesized in the skin by the action of sunlight from
cholesterol
 It is activated in the liver to form 25-hydroxycholecalciferol
and then in the kidney (in the PCT cells) to form
1, 25-dihydroxycholecalciferol (1, 25 (OH)2 D3 (Calcitriol).
(Cholecalciferol).

 Activation in the kidney is catalyzed by the enzyme 1 α hydroxylase.
 Vitamin D3 is the major circulating form in the body.

22. Effects of vitamin D3:
Regulation of calcium & phosphate level in plasma.
Act on:
- Intestine:
To increases calcium and phosphate absorption.
- Kidney:
To increases calcium and phosphate reabsorption.
- Bone:
Stimulates osteoblasts for bone calcification (bone formation).

23. Control of vitamin D3:
Increased by:
- Hypocalcemia
- Hypophosphatemia
- PTH, growth hormone, prolactin and calcitonin
(all increase the activity of 1α-hydroxylase).
- Estrogens (increase the binding protein).
Inhibited by:
- Hypercalcemia.
(the kidneys form the inactive compound 24,25 (OH)2 D3 )
- Hyperphosphatemia.
- 1,25 (OH)2D3
- Exerts -ve feedback it inhibits the enzyme 1α-hydroxylase.
- Stimulate formation of 24,25 (OH)2D3
- Inhibit PTH production.

24. Vitamin D deficiency:
o In children: Rickets
- It is characterized by:
hypocalcemia and failure of bone
mineralization
- Resulting in weakness & bowing of bones.

o In adults: Osteomalacia
Characterized by weak and easily
fractured bones.

25. Calcitonin:
Characteristics:
- Polypeptide hormone 32 amino acid
- produced by parafollicular cells of the thyroid gland (C cells)
- Its half life is less than 10 minutes in humans.
Actions:
- Lower calcium level in the blood (hypocalcemic hormone)
- Inhibits bone resorption by inhibiting osteoclasts
- Increases calcium excretion in urine
Control:
It is stimulated by:
- Hypercalcemia (when plasma calcium level reach 9.5 mg/dL)
- hormones (gastrin, CCK, secretin, glucagon)
- β adrenergic agonists