Parathyroid Hormone, Calcitonin, Calcium and

Chapter 80
▪ At the end of this lecture, you should be able to:

▪ Know the cells of origin for parathyroid hormone, its biosynthesis, and mechanism
of transport within the blood.
▪ List the target organs and cell types for parathyroid hormone and describe its
effects on each.
▪ Describe the functions of the osteoblasts and the osteoclasts in bone remodeling
and the factors that regulate their activities.
▪ Describe the regulation of parathyroid hormone secretion and the role of the
calcium-sensing receptor.
▪ Understand the causes and consequences of a) over-secretion, and b) under-
secretion of parathyroid hormone.
▪ Identify the sources of vitamin D and diagram the biosynthetic pathway and the
organs involved in modifying it.
▪ Identify the target organs and cellular mechanisms of action for vitamin D.
▪ Describe the negative feedback relationship between the parathyroid hormone
and the biologically active form of vitamin D.
▪ Describe the consequences of vitamin D deficiency and vitamin D excess.
▪ List the cell of origin and target organs or cell types for calcitonin and the stimuli
that can promote its secretion.
▪ Describe the actions of calcitonin and identify which (if any) are physiologically
important.
▪ Absorbed poorly from intestine, ( 1mg/day ), absorption can be promoted
by vitamin D.
▪ Normal calcium concentration in plasma is about 2.4 mmol/litre and is
present in
Three forms:
(1) Bind with plasma proteins
•40%, •Non-diffusible through capillary membrane.
(2) Bind with citrate and phosphate
•10%, •Diffusible through capillary membrane.
(3) In the form of free Ca ions
•50%, ionized. •
Diffusible through membrane. •
The most important Ca
form for body functions.
▪ Daily intake is excreted

•in feces ( 90% ),
•in urine (10%), can be reabsorbed by tubules if the blood calcium
concentration is low.
▪ Absorbed easily from intestine into blood ( 1mg/day ).
‹Inorganic phosphate is present in plasma in two forms:
(1) In the form of HPO4--, 1.05 mmol/litre.
(2) In the form of H2PO4-, 0.26 mmol/litre.
‹When pH of the extracellular fluid is more acidic, concentration of HPO4--

decreases with relative increase of H2PO4_x0010_.
▪ Excreted in urine, excretion rate is regulated by phosphate concentration in
plasma and affected by parathyroid hormone.
•
If phosphate concentration is below critical value ( 1mmol/litre )
▪ all phosphates are absorbed; no loss into urine.
•
If above critical value
▪ excretion in urine is proportional to the increase of phosphate
concentration.
▪ Vitamin D3 ( Cholecalciferol ) is one of vitamin D family,
▪ ‹Obtained from daily intake of food; or
▪ ‹Formed in skin from 7-dehydrocholesterol by ultraviolet rays from the
sun.
▪ ‹Inactive substance that does not cause effects.
▪ Vitamin D3 must be firstly converted to active substance →
1, 25-Dihydroxycholecalciferol in liver and kidney
▪ ‹Cholecalciferol is converted to 25-hydroxycholecalciferol in the liver,
▪ The concentration of 25-hydroxycholecalciferol in the plasma remains almost constant
and is regulated by the concentration of 25-hydroxycholecalciferol itself through a
negative feedback mechanism (inhibitory).
The negative feedback mechanism:

▪ Prevents excessive action of vitamin D.
▪ Conserves vitamin D stored in liver for future use ( for months ).
▪ 25-hydroxycholecalciferol is converted to 1, 25-dihydroxycholecalciferol
in kidney.
▪ The conversion requires parathyroid hormone
▪ The formation of 1, 25-dihydroxycholecalciferol is inversely affected by
the calcium concentration in plasma.
Principal effect:
▪ When the Ca concentration in blood is too high ( above 9-10 mg/dl )
▪ Suppress secretion of parathyroid hormone
▪ Suppress formation of 1,25-dihydroxycholecalciferol ( the 25-
hydroxycholecalciferol is converted to 24,25-dihydroxycholecalciferol
that has no vitamin effect ),
▪ Decrease Ca absorption from intestine, bones and renal tubules
▪ Result: Ca ion concentration return to its normal level
Minor effect:
▪ Calcium ion itself directly has slight effect on preventing the conversion.
▪ 1, 25-dihydroxycholecalciferol promotes absorption of calcium by
intestinal tract thru:
▪ Increasing the formation of calcium-binding protein in intestinal
epithelial cells
▪ promoting the transport of calcium through cell membrane by
facilitated diffusion
▪ Promoting the formation of calcium stimulated ATPase (enzyme) in
the border of the epithelial cells and alkaline phosphatase in the
epithelial cells
▪ ‹Vitamin D in smaller quantities promotes bone calcification ( the
mechanism is unknown ) but extreme quantities of vitamin D
cause bone resorption.
▪ Enhance absorption of phosphate in gastrointestine
▪ might resulted from the increased absorption of Ca that acts as a transport
mediator to increase phosphate transport.
▪ Hypocalcemia ( low Ca ion concentration in
extracellular fluid ) causes:
▪ Increase of membrane permeability to Na ions -->
easy initiation of membrane action potential.
▪ If Ca is 50% below normal:
▪ nerve fibers become very excitable and elicit
spontaneous nerve impulses to the peripheral
skeletal muscles --> cause tetanic muscle
contraction ( tetany ).
▪ Hypercalcemia ( excessive Ca ion concentration in extracellular fluid ) causes:
▪ Depress of nervous system.
▪ Reflex of CNS becomes sluggish.
▪ Decreases QT interval of the heart.
▪ Constipation.
▪ Lack of appetite.
▪ ˆChange of phosphate concentration in extracellular fluid ( from far below to 2 - 3

times above normal ) has no significant immediate effect on body
▪ Bone is composed of
▪ (1) Organic matrix (30%) composed of
▪ ‹Collagen fibers (90%), - give tensile strength.
▪ ‹Ground substance, - including extracellular
fluid, chondroitin and hyaluronic acid
▪ (2) Inorganic salt crystals composed of

▪ ‹Calcium and phosphate ( hydroxyapatite )
Ca10 (PO4)6 (OH)2 ( principal component),
give compressional strength.
▪ ‹Other salts: magnesium, sodium, potassium
and carbonate ions
▪ The osteoblasts secrete collagen monomers and ground substance
(proteoglycan) -> the collagen monomers polymerize to form collagen
fibers -> the resultant tissue becomes osteoid -> osteoblasts become
entrapped in the osteoid ( called osteocytes or bone cell ) -> the calcium
salt deposited on the surface of the collagen fibers to become
hydroxyapatite.
▪ Collagen fibers and bone salts are bond together to provide a bony
structure to give both great tensile and compressional strength.
▪ Bone is continuously being deposited by osteoblasts and being absorbed
by osteoclasts.
▪ rates of bone deposition and absorption are equal

▪ the total bone mass remains constant
▪ Osteoclast :
▪ large phagocytic cell in bone marrow
▪ When osteoclasts developed it sends out villus-like projections toward
the bone to form a ruffled border adjacent to the bone.
▪ The villus secretes two types of substances:
(1) Proteolytic enzymes ( released from lysosomes of osteoclast ) to
digest and dissolve organic matrix.
(2) Citric acid and lactic acid ( released from mitochondria ) to
dissolve bone salts.
▪ In this way the osteoclasts eat away at the bone to form a tunnel ( 0.2-1mm
in diameter and few milimeter long ) for 3 weeks., then osteoclasts
disappear.
▪ Osteoblasts replace the osteoclasts
→ new bone mass begins to develop
and to be deposited on the inner
surface of the cavity to form layers of
concentric circles for several months
until the tunnel is filled.
▪ Each new area of bone deposited is
called osteon
▪ When the bone mass begins to
encroach on the blood vessels the
deposition of new bone stops
▪ Fracture of a bone maximally activates osteoblasts:
▪ immediate great increase of new osteoblasts from osteoprogenitor cells Î
large bulge of osteoblastic tissue and new organic bone matrix develop
between the two broken ends of the bone (callus) --> deposition of
calcium salt.
▪ The alkaline phosphatase
▪ indicator of the rate of bone deposition
▪ osteoblasts are depositing bone matrix they secrete large amount of alkaline
phosphatase
▪ 4 glands located behind thyroid gland
▪ ( each upper poles and lower poles of
thyroid gland )
▪ Composed of:
▪ Chief cells - Secrete parathyroid
hormone.
▪ Oxyphil cells- Function is unknown and
absent in many animals and young
human beings.
Steps of synthesis of parathyroid hormone:
▪ Synthesized on ribosomes to preprohormone ( polypeptide, chain

of 110 amino acids ) →
▪ cleaved to prohormone ( 90 amino acids )→
▪ Parathyroid hormone ( 84 amino acids, MW 9500 ) by endoplasmic
reticulum and Golgi apparatus → packaged in vesicles in the
cytoplasm of cells
Effect on calcium and phosphate excretion by kidney
▪ ‹Decrease the excretion of calcium in the urine by increasing the tubular
reabsorption of calcium ( as well as magnesium, hydrogen )
▪ ‹Increase excretion of phosphate in the urine

▪ parathyroid hormone reduces the tubular reabsorption of phosphate ions ( as
well as Na, K, and amino acids )
Effect on calcium and phosphate absorption from bones
▪ Increase the absorption of Ca and phosphate in two phases:
▪ (1) Rapid phase of calcium and phosphate absorption ( Osteolysis )

▪ Begins in minutes and increases progressively for several hours.
▪ ‹Parathyroid hormone causes absorption of bone salt from two areas in the
bone:
▪ in the vicinity of existing osteocytes ( bone cell )
▪ in the vicinity of osteoblasts along bone surface
▪ (2) Slow phase of bone absorption and calcium phosphate release
▪ ‹several days to weeks
▪ ‹activates osteoclasts through the activated osteoblasts and osteocytes and
promotes the formation of new osteoclasts in a slow developing process ( weeks
to months ).
▪ ‹Ca absorption of osteoclasts --> stimulates osteoblasts to correct weakened
bones --> cause both osteoblastic and osteoclastic activities
▪ Increase of blood calcium concentration caused by
▪ Increasing the absorption of calcium from bone
▪ Decreasing the excretion of Ca ions in urine and increasing reabsorption of Ca
by kidney,
▪ Increasing vitamin D formation for promoting absorption of Ca by intestine
▪ Decrease of blood phosphate concentration caused by

▪ excessive phosphate excretion in urine
▪ Secretion is regulated by Ca ion concentration in the extracellular
fluid.
▪ Slight decrease of Ca concentration causes increase of secretion rate of
parathyroid hormone.
▪ Parathyroid gland will be enlarged if
▪ decrease of Ca concentration persists
▪ in pregnancy or lactation ( Ca is used for milk production ).
▪ Increase of Ca concentration above normal causes decreased
activity and size of parathyroid glands
▪ A type of hormone
▪ large polypeptide with MW 3400
▪ chain of 32 amino acids
▪ Secreted from C cell in thyroid gland ( not parathyroid glands )
▪ Effects are opposite to those of parathyroid hormone
▪ Reduce blood Ca ion concentration by
▪ Short term effect:

▪ Decrease absorption of osteoclasts.
▪ Long term effect:

formation of
▪ Decrease the production of new osteoclasts --> idepress the
osteoblasts --> reduce both osteoclastic and osteoblastic activities.
▪ effect on blood calcium is short ( lasts only a few hours or days ).
▪ Has only a weak effect on blood Ca concentration in adult human being
▪ initial reduction of Ca concentration resulted from by calcitonin will cause
powerful stimulation of secretion of parathyroid hormone,
▪ in adults, the daily absorption and deposition rate of Ca are small and has
small effect on blood Ca concentration
▪ Increase of blood calcium concentration ( 10% ) --> increase of secretion
rate of calcitonin ( twice or more )
▪ calcitonin - second hormonal feed-back mechanism for controlling blood

Ca ion concentration
▪ Calcitonin mechanism:
▪ For calcitonin: in < 1 hour.
▪ acts weakly and as a short-term regulator of Ca ion concentration
▪ PTH mechanism:
▪ For parathyroid hormone: in > 3 to 4 hours.
▪ more potent and acts over prolonged period of time
▪•
The calcium absorption and loss from body fluid can be as much as 0.3g/hour
(total Ca ions in ECF being 1 g )
▪ could cause serious hypercalcemia or hypocalcemia.
▪ first line of defense--> prevent this from occurring even before the parathyroid
and calcitonin hormone feedback system acts
▪ Exchangeable calcium
▪ 0.4 - 1.0% of total bone calcium
▪ Deposited in the bone in the form of readily mobilizable calcium phosphate
salts (CaHPO4)
▪ ‹The important role is to maintain the Ca ion concentration in the
extracellular fluid in relatively equilibrium level ( Buffer function ) as
follows.
▪ Slight increase --> immediate deposition of exchangeable calcium ions
into the bone
▪ ECF calcium concentration is too low--> exchangeable calcium can
release into the extracellular fluid.
▪ ‹Parathyroid hormone and calcitonin system:
▪ act as second line of defense ( in 3 - 5 minutes after the increase of Ca ion
concentration in extracellular fluid ).
▪ ‹In prolonged excess or deficiency of Ca concentration the parathyroid
hormone plays an important role in maintaining a normal blood Ca ion
concentration through Ca absorption from bone or deposition to the
bone.
▪ ˆBone is a large buffer-reservoir of calcium for one year or more.
▪ When the bone reservoir runs out of calcium the parathyroid hormone and vitamin
D control calcium absorption from intestine and kidney ->
▪ cause reduced excretion of calcium in feces and urine.
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
▪ Treatment:
▪ Vitamin D and calcium administration
▪ *Hypoparathyroidism is usually not treated with PTH administration
PRIMARY HYPERPARATHYROIDISM
▪ usually a tumor of one of the parathyroid glands
▪ Bone disease in hyperparathyroidism:

▪ increased osteoclastic reabsorption far exceeds osteoblastic deposition
▪ bone may be eaten away entirely
PRIMARY HYPERPARATHYROIDISM
▪ 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
SECONDARY HYPERPARATHYROIDISM
▪ high levels of PTH occur as a compensation for hypocalcemia rather than a

primary tumor of the parathyroid gland
▪ Causes:
▪ Vit D deficiency
▪ failure to form active Vit D in chronic renal disease

▪ Vitamin D deficiency
▪ Mainly occurs in children
▪ It results from calcium or phosphate

deficiency in the extracellular
fluid
▪ decrease plasma concentration of calcium and phosphate
▪ 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
SECONDARY HYPERPARATHYROIDISM
▪ 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

OSTEOPOROSIS
▪ decreased bone matrix
▪ 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

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Chapter 80

▪ At the end of this lecture, you should be able to:

▪ Daily intake is excreted

‹When pH of the extracellular fluid is more acidic, concentration of HPO4--

The negative feedback mechanism:

▪ ˆChange of phosphate concentration in extracellular fluid ( from far below to 2 - 3

▪ (2) Inorganic salt crystals composed of

▪ rates of bone deposition and absorption are equal

▪ Synthesized on ribosomes to preprohormone ( polypeptide, chain

▪ ‹Increase excretion of phosphate in the urine

▪ (1) Rapid phase of calcium and phosphate absorption ( Osteolysis )

▪ Decrease of blood phosphate concentration caused by

▪ Short term effect:

▪ Long term effect:

▪ calcitonin - second hormonal feed-back mechanism for controlling blood

▪ When the parathyroid glands do not secrete sufficient PTH:

▪ usually a tumor of one of the parathyroid glands

▪ Bone disease in hyperparathyroidism:

▪ In addition to absorption of the old bones, osteoblastic activity to form new

▪ high levels of PTH occur as a compensation for hypocalcemia rather than a

▪ failure to form active Vit D in chronic renal disease

▪ Mainly occurs in children

▪ It results from calcium or phosphate

▪ 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

▪ Osteomalacia caused by renal rickets

▪ most common of all bone diseases in adults.

▪ Most common causes are:

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