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Lecture Notes (Chapt 80) Parathyroid Hormone, Calcitonin, Calcium and Phosphate
Metabolism and Vitamin D

Objective 80.1 Contrast the dietary origins, intestinal absorption, and excretion characteristics
of calcium and phosphate.

Absorption and Excretion of Calcium and Phosphate

 Calcium
 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.
 Diffusi
ble
throug
h
membr
ane.
 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.

 Phosphate

 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.
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(2) In the form of H2PO4, 0.26 mmol/litre.

 When pH of the extracellular fluid is more acidic, concentration of HPO 4 

decreases with relative increase of H2PO4.

 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.
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Objective 80.2 Identify the vitamin D compounds, the sequence of events leading to the
formation of an active form of vitamin D3, and its regulatory role in calcium absorption.

Role of Vitamin D in Calcium and Phosphate absorption

Vitamin D
 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 as follows.

 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,
 Ca ion concentration return to its normal level.

 Minor effect:
- Calcium ion itself directly has slight effect on preventing the conversion.

Objective 80.3 Identify the effect of vitamin D forms of calcium and inorganic phosphate in extracellular
fluids

 Vitamin D effect on calcium

 1, 25-dihydroxycholecalciferol promotes absorption of calcium by intestinal tract by
 Increasing the formation of calcium-binding protein in intestinal epithelial cells 
promotes 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 absorption.

 Vitamin D effect on phosphate

 Enhance absorption of phosphate in gastrointestine which might resulted from the increased
absorption of Ca that acts as a transport mediator to increase phosphate transport.

Objective 80.4 Identify the major consequences of altered states of calcium and phosphate concentrations of
the body fluids.

Non-Bone Effects of Calcium and Phosphate Concentration in Body Fluids

 Hypocalcemia ( low Ca ion concentration in extracellular fluid ) causes:

 Increase of membrane permeability to Na ions,  easy initiation of membrane action
potential.
 When Ca ion concentration is 50% below normal the 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.
 Change of phosphate concentration in extracellular fluid ( from far below to 2 - 3 times
above normal ) has no significant immediate effect on body.
Objective 80.5 Identify the organic and inorganic components of bone, and their function
significance in states of tension and compression.

Bones

 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.
Objective 80.6 Identify the mechanisms, functional significance, and characteristics of bone
remodelling.
Bone Remodelling

 Bone is continuously being deposited by osteoblasts and being absorbed by osteoclasts.

 The rates of bone deposition and absorption are equal, so that the total bone mass remains
constant.
 Bone absorption and deposition
 Osteoclast is a 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 ( 0.2-1
mm 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.

 Significance of bone remodelling

 The new bone replaces the old bone mass that is relatively brittle and weak so that
the normal toughness of bone can be maintained.

 Because the bone deposition rate is proportional to the compressional stress on

bones. It can adjust bone strength according to the degree of bone stress ( heavy
load cause bone thickening ).

 The compressional stress can produce a "piezoelectric effect", that is, it

develops a negative electrical potential in the compressed area and a
positive potential elsewhere in the bone.  This causes a small
amount of electric current flowing in bone,  Promotes osteoblastic
activity at the negative end of the current flow,  Increases the
deposition at compression sites.

 It reshapes the bone according to stress pattern to obtain better support of

 mechanical load.

 Fracture of a bone maximally activates osteoblasts  immediate great increase of

new osteoblasts from osteoprogenitor cells  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 in the blood can be an indicator of the rate of bone deposition
because when the osteoblasts are depositing bone matrix they secrete large amount of
alkaline phosphatase that diffuses into blood.

Objective 80.7 Identify parathyroid hormone and its effect on bone, the kidneys, the intestinal
epithelial, and extracellular fluid concentrations of calcium and phosphate.

Parathyroid Hormone

 Parathyroid gland

 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 ) by kidney.

 Increase excretion of phosphate in the urine because 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 as follows.

(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.
 The osteocytic membrane system separates the bone from extracellular fluid.
 The bone fluid exists between the osteocytic membrane and bone and the
osteocytic membrane pumps Ca ions from the bone fluid into extracellular fluid,
 decrease the Ca concentration in the bone fluid,  absorption of Ca
from bone.

 The cell membrane of osteoblasts and osteocytes have receptor proteins for
binding parathyroid hormone,  parathyroid hormone activates calcium
pump ( increase Ca permeability of osteocytic membrane ),  causes
removal of calcium phosphate salt from bone.

(2) Slow phase of bone absorption and calcium phosphate release

 Slow absorption for several days to weeks.

 Parathyroid hormone activates osteoclasts through the activated osteoblasts and

osteocytes and promotes the formation of new osteoclasts in a slow developing
process ( weeks to months ).

 The Ca absorption of osteoclasts, in turn, stimulates osteoblasts to correct

weakened bones  cause both osteoblastic and osteoclastic activities.
Objective 80.8 Identify the effects of parathyroid hormone on bone deposition and reabsorption.

 Effect on calcium and phosphate concentration in extracellular fluid

 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 ( even though the phosphate

absorptions from bone and intestine are increased ) , this is caused by excessive
phosphate excretion in urine.

Objective 80.9 Identify the regulatory mechanisms for parathyroid secretion.

Regulation of Parathyroid Secretion

 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.

Objective 80.10 Identify calcitonin, its target actions, its regulatory mechanisms, and its
functional significance.

Calcitonin

 A type of hormone ( large polypeptide with MW 3400, chain of 32 amino acids ).

 Secreted from C cell in thyroid gland ( not parathyroid glands ) in human being.
 Effects are opposite to those of parathyroid hormone.
 Reduce blood Ca ion concentration by
 Short term effect:
- Decrease absorption of osteoclasts.
 Long term effect:
- Decrease the production of new osteoclasts,  in turn, depress the
formation of osteoblasts,  reduce both osteoclastic and osteoblastic
activities.

 The 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, because
 the 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.

Regulation of Calcitonin Secretion

 Increase of blood calcium concentration ( 10% ) causes increase of secretion rate of

calcitonin ( twice or more ).

 The calcitonin is the second hormonal feed-back mechanism for controlling blood Ca ion
concentration.

Difference Between Calcitonin and Parathyroid Feedback System

(1) Calcitonin mechanism operates more rapidly. Time for reaching to peak activity:
For calcitonin: in < 1 hour.
For parathyroid hormone: in > 3 to 4 hours.

(2) Calcitonin mechanism acts weakly and as a short-term regulator of Ca ion concentration
but parathyroid hormone is more potent and acts over prolonged period of time.
Objective 80.11 Identify the relative roles of the buffer system of exchangeable salts of bone,
hormonal control, and intestinal and renal control in the regulation of the calcium ion
concentration of the body fluids.

Overall Control of Calcium Ion Concentration

 The calcium absorption and loss from body fluid can be as much as 0.3g/hour (comparing
with the total Ca ions in extracellular fluid being 1 g ). This could cause serious
hypercalcemia or hypocalcemia.

 There is a first line of defense to prevent this from occurring even before the parathyroid
and calcitonin hormone feedback system acts.

 Buffer system of exchangeable salts of bone ( first line of defense )

 Exchangeable calcium

 0.4 - 1.0% of total bone calcium are exchangeable 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 of calcium concentration in extracellular fluid above normal will
cause immediate deposition of exchangeable calcium ions into the bone so that
the Ca ion concentration in extracellular fluid can return to normal.

 When the extracellular calcium concentration is too low then the exchangeable
calcium can release into the extracellular fluid.

 Hormone control of calcium concentration ( second line of defense )

 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.

 Bone 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.