Describe the regulation of PTH Describe the effect of PTH on bone What is Osteocytic Osteolysis Explain the mechanism of bone resorption by PTH- RANKL/OPGL Describe the role of Osteoprotegerin (OPG) Describe the actions of PTH on kidney and intestine Describe Hyperparathyroidism and Hypoparathyroidism Describe the effect of Calcitonin on calcium homeostasis Describe Osteoporosis & Osteopetrosis

1. Calcium Homeostasis II
By
Dr. AWAIS IRSHAD

2. Learning Objectives
 Describe the regulation of PTH
 Describe the effect of PTH on bone
 What is Osteocytic Osteolysis
 Explain the mechanism of bone resorption by PTH-
RANKL/OPGL
 Describe the role of Osteoprotegerin (OPG)
 Describe the actions of PTH on kidney and intestine
 Describe Hyperparathyroidism and Hypoparathyroidism
 Describe the effect of Calcitonin on calcium homeostasis
 Describe Osteoporosis & Osteopetrosis

3. Parathyroid Hormone

4. • PTH secretion responds to small alterations in
plasma Ca2+ withinseconds
• A unique calcium-sensing receptor (CSR) within
the parathyroid cell membrane senses changes in
the extracellular fluid concentration of Ca2+.
• When Ca2+ falls, PTH is secreted
• Parathyroid glands become greatly enlarged in:
o Rickets, pregnancy and lactation
• Parathyroid glands is reduced in size
o excess quantities of calcium in the diet, increased
vitamin D in the diet, and disuse of the bones
Regulation of PTH

5. Role of PTH – To Regulate Calcium Levels
• The Parathyroid glands have only one major
function – regulate the calcium level in the body
within a very narrow range (8.5 – 10.2 mg/dL) so
that the nervous and muscular systems can
function properly

6. • Mobilizes calcium and phosphate from bone
Rapid phase:--Osteocytic Osteolysis
oExisting osteocytes stimulated (minutes to hours) to
transport calcium –calcium pump
oPTH activate calcium pump
Slow phase:--Bone resorption-RANKL/OPG
oExisting osteoclasts activated and new osteoclasts
formed (days to weeks) to digest bone and release
calcium
oStimulated indirectly by osteoblasts
Effects of PTH on Bone

7. Osteocytic Osteolysis
• Transfer of calcium from bone fluid to
extracellular fluid via activity of calcium or
osteocytic pump
• When the osteocytic pump becomes excessively
activated, the bone fluid calcium concentration
falls e lower, and calcium phosphate salts are then
released from the bone. This effect is called
osteolysis
• Does not decrease bone mass
• Removes calcium from most recently formed
crystals
• Happens quickly

8. • Within each bone unit is a minute bone fluid-
containing channel called the canaliculi
• Interior osteocytes remain connected with each
other and to surface cells,osteoblast via syncytial
cell processes, throughout the bone structure,
osteocytic membrane system
• This membrane permits transfer of calcium from
amorphous surface area of bone to bone fluid and
than to extracellular fluid by Calcium pump
Mechanism of Osteocytic Osteolysis

9. • Parathyroid hormone (PTH)
binds to receptors on osteoblasts
• Causing them to form
– receptor activator for nuclear factor κ-B
ligand (RANKL)
– release macrophage-colony stimulating
factor (M-CSF)
• RANKL binds to RANK and M-
CSF binds to its receptors on
preosteoclast cells, causing them
to differentiate into mature
osteoclasts
• The mature osteoclasts develop a
ruffled border and release
enzymes from lysosomes, as well
as acids that promote bone
resorption.
Mechanism of Bone Resorption By PTH

10. Role of Osteoprotegerin (OPG)
• Osteoblasts also produce osteoprotegerin (OPG), a
cytokine that inhibits bone resorption
• PTH & Glucocorticoids decrease production of
osteoprotegerin (OPG) and increases RANKL
• On the other hand, the hormone estrogen stimulates
OPG production
• The balance of OPG and RANKL produced
by osteoblasts plays a major role in
determining osteoclast activity and bone
resorption
• Novel drugs that mimic the action of OPG appear to
be useful for treating bone loss in postmenopausal
women and in some patients with bone cancer

11. • Increases reabsorption of calcium by
kidneys from Thick ascending loop of
Henle , DCT and Collecting ducts
– Important to prevent bone deterioration
• Decreases phosphate reabsorption from
PCT
Effects of PTH on Kidney

12. Effects of PTH on Intestine
• Increases calcium absorption
– Effect manifested via Vitamin D3
• Produces most active form of D3 in the kidney
(PCT)(1,25-dihydroxy-cholecalciferol)

13. PTH action
• The overall action of PTH is to
increase plasma Ca++ levels
• PTH acts on the bones to
mobilize Ca++ & phosphate salts
• On kidney to stimulate Ca++
reabsorption and to inhibit
reabosorptioin of phosphate
(thereby stimulating its
excretion)
• PTH also acts indirectly on
intestine by stimulating 1,25-
(OH)2-D synthesis and increases
calcium absorption

14. Primary Hyperparathyroidism
• Excess PTH secreted from
adenomatous or
hyperplastic parathyroid
tissue
• Hypercalcemia results from
combined effects of PTH-
induced bone resorption,
intestinal calcium
absorption and renal tubular
reabsorption
• Concomitant excess
production of 1,25-(OH)2-
D

15. Signs and Symptoms
 Hypercalcemia 12 –15 mg/dl
“Stones, bones, and groans
 Kidney stones:
o Excess of calcium and phosphate causing increase in the concentrations
of these substances in the urine, forming calcium phosphate stones
 Bone disease:
o Frequent fractures, large punched-out cystic areas of the bone that are
filled with osteoclasts are formed,osteitis fibrosa cystica
 GI disomfort:
o Constipation, abdominal pain, lack of appetite
 Depression of the nervous systems, muscle weakness and
decreases the QT interval of the heart
 Parathyroid Poisoning and Metastatic Calcification
o When the level of calcium rises above about 17 mg/dl in the blood,
calcium phosphate crystals are likely to precipitate throughout the body

16. Secondary Hyperparathyroidism
• High levels of PTH occur as a
compensation for hypocalcaemia
• Causes: vitamin D deficiency or chronic
renal disease

17. • PTH-deficient hypoparathyroidism
– Reduced or absent synthesis of PTH
– Often due to inadvertent removal of excessive
parathyroid tissue during thyroid or parathyroid
surgery
• PTH-ineffective hypoparathyroidism
– Synthesis of biologically inactive PTH
– Hypocalcemia occurs
– concomitant decrease in 1,25-(OH)2-D
Hypoparathyroidism

18. Clinical Features
• Tetany
• Carpopedal spasm
• Laryngeal stridor
• Troisseau’s sign
• Chvostek’s sign

19. Osteoporosis
• Results from diminished
organic bone matrix
• Osteoblastic activity in the
bone is less than normal,
the rate of bone osteoid
deposition is depressed
• Causes
• lack of physical stress
• malnutrition
• lack of vitamin C,
• postmenopausal lack of estrogen
• old age
• Cushing syndrome

20. Osteopetrosis
• Bone density increases due to defective
bone resorption
• The osteoclast activity becomes defective
• Unopposed activity of osteoblasts
• Neurological defects due to narrowing of
foramina of bones
• Haematological defects due to narrowing of
bone marrow cavity

21. Calcitonin
• Secreted by the parafollicular cells of thyroid
gland
• The major stimulus of calcitonin secretion is a
rise in plasma Ca++ levels
• Calcitonin is a physiological antagonist to PTH
with regard to Ca++ homeostasis
• Calcitonin has a weak effect on plasma calcium
concentration in adult humans
• Calcitonin has a much more potent effect of
reducing the calcium absorption in children and
in certain bone diseases, such as Paget’s disease

22. • The target cell for calcitonin osteoclast
• Calcitonin acts via increased cAMP
concentrations to inhibit osteoclast motility
and cell shape and inactivates them
• Decreases formation of new osteoclasts
• The major effect of calcitonin is rapid fall
in Ca2+ caused by inhibition of bone
resorption
• Has weak opposite to PTH effects on
kidney and intestines
Calcitonin

23. Calcium Homeostasis
• PTH and vitamin D act to increase plasma Ca++--
only calcitonin causes a decrease in plasma Ca++

24. Guyton & Hall Text Book Of Medical Physiology
Text Book Of Medical Physiology by Indu Khurana
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