Dr.

Farrukh Majeed
Department of Physiology
Calcium and phosphate
homeostasis
 Learning objectives
At the end of this lecture student should be able to:
• Discuss calcium and phosphate regulation in the
extracellular fluid and plasma
• Describe the role of bones in regulation of
extracellular calcium and phosphate
 Case scenario
• A 35-year-old lady mother of 6 kids presented to medicine
OPD with complains of severe back pain, generalized
weakness, lethargy, frequent muscle cramps.
• Her blood analysis revealed
– Hb% 6 gm/dl (12-14 gm/dl)
– Calcium 6 ng (8.6–10.5 mg/dL)
– PO4 2mg/dl (2.8 to 4.5 mg/dL)

Which one of the above blood analysis is mainly responsible for her
symptoms, justify your answer?
What other pathophysiological disturbance you might expect in this
patient?
Ca distribution
Overview of calcium exchange
 Calcium Balance
Intake = output
• Negative calcium balance:
– Output > intake
– Pregnancy, lactation
– Neg Ca 2+ balance leads to osteoporosis
• Positive calcium balance:
– Intake > output
– Occurs during growth Calcium is essential,
we can’t synthesize it
PO4 distribution
Why Ca Homeostasis is important?
1. Neuromuscular
excitability.
• influence of Ca on membrane
permeability to Na.
• A fall in free Ca results in over
excitability of nerves and muscles A
decrease in free Ca increases Na
permeability easily excitable  go
into spasm Tetany If severe
enough, spastic contraction of the
respiratory muscles results in death by
asphyxiation.
• Rise in free Ca depresses neuromuscular
excitability. Hypercalcemia causes cardiac
arrhythmias and generalized depression of
neuromuscular excitability.
Hypocalcemia: sign
2. Excitation–contraction coupling in cardiac and
smooth muscle.
• Entry of ECF Ca into cardiac, smooth muscle cells,
in response to an action potential, triggers the
contractile mechanism.
• Calcium is also
necessary for
excitation–
contraction
coupling in skeletal
muscle fibers, but
in this case the Ca
is released from
intracellular stores.
3. Stimulus–secretion coupling.
• entry of Ca into secretory cells,
increased permeability to Ca
stimulation release of the
secretory product by exocytosis.
– neurotransmitters by nerve cells
– secretion of hydrophilic
hormones by endocrine cells.
4. Excitation–secretion coupling.
• In pancreatic beta cells, Ca entry from the ECF
in response to membrane depolarization leads
to insulin secretion
5. Maintenance of tight junctions between cells.
• Calcium forms part of the intercellular cement
that holds particular cells tightly together.
6. Clotting of blood.
7. Intracellular Ca functions
• second messenger in many cells
• involved in cell motility and cilia action.
• Ca in bone and teeth is essential for the
structural and functional integrity of these
tissues.
Calcium Homeostasis
 Bone and Its Relation to Extracellular
Calcium and Phosphate
• bone contains 30 % matrix and 70 %
salts
• Organic Matrix of Bone.
– 90 to 95 per cent collagen fibers 
powerful tensile strength.
– homogeneous gelatinous medium called
ground substance proteoglycans,
especially chondroitin sulfate and
hyaluronic acid  they help to control
the deposition of calcium salts.
Bone Salts.
• The crystalline salts deposited in the organic
matrix of bone are composed principally of
calcium and phosphate.
• crystalline salt, known as hydroxyapatite
– Ca10 (PO4)6(OH)2
Bone cells types
 Mechanism of Bone Calcification
• Osteoblasts secretes  collagen
molecules (called collagen monomers) and
ground substance (mainly proteoglycans).
• The collagen monomers polymerize
rapidly to form collagen fibers becomes
osteoid, a cartilage-like material
• some osteoblasts become entrapped in
the osteoid and become inactive 
osteocytes.
• Within a few days calcium salts begin to
precipitate on the surfaces of the collagen
fibers hydroxyapatite crystals.
Mechanism of Bone Calcification
Why Hydroxyapatite does not precipitate in extracellular fluid despite supersaturation of calcium and
phosphate ions
 Bone resorption (removal)
• The osteoclasts resorb bone in their vicinity.
• The large, multinucleated osteoclasts attach
to the organic matrix and form a “ruffled
membrane” that increases its surface area in
contact with the bone.
• osteoclast actively secretes hydrochloric
acid  dissolves the Ca3(PO4)2 crystals and
break down organic matrix.
• After it has created a cavity, an osteoclast
moves on to an adjacent site to burrow
another hole.
Bone resorption (removal)
Repair of fracture
Summary
 Reading material
• Guyton 13th edition, chapter 80 page no, 1001-
1007.
• Sherwood 9th edition, page no 701- 712