Dr.

Farrukh Majeed
Department of Physiology
Vitamin D & Calcitonin
 Learning objectives
At the end of this lecture student should be able
to:
• Describe activation and function of vitamin D
• Discuss regulation and function of Calcitonin
hormone
• Understand Pathophysiology of vitamin D and
bone disease
 Case scenario: slow growth
A 6-year old boy has slow growth and an unusual
gait. He has bowed legs, thick wrists, and dental
caries. His weight (12 kg) and height (72.5 cm). His
diet consists predominantly of home made food 5
times daily. The mother's antenatal, delivery, and
post-natal history are unremarkable.
Labs:
• elevated total alkaline phosphatase
• elevated parathyroid hormone level.
• The 25-hydroxyvitamin D level is decreased
• Plain x-rays of the patient's knees and wrists
shows -metaphyseal cupping and flaring,
epiphyseal irregularities, and widening of the
physeal plates.
Approach to this Child??
diet and degree of sunlight exposure should be
noted.
A detailed dietary history should include specifics of
vitamin D and calcium intake.
A family history of : short stature • orthopedic
abnormalities, • poor dentition, alopecia, • inherited
rickets.
 Vit D: Vitamin or Hormone?
• Vitamin D hormone because the skin
(specifically, the keratinocytes)  produce it from a
cholesterol exposure to sunlight released into
the blood  act at a distant target site, the
intestine.
• Vit D Vitamin it was originally discovered and
isolated from a dietary source.
Activation
of
Vitamin D

Regulation of
Vit D
Vit D receptors
Vit D in: Calcium and phosphate homeostasis

vitamin D  regulates Ca2+ and PO by action at the

three major targets; intestine, bone, kidney.
– stimulates the intestinal absorption of Ca2+
and PO
– stimulates the transport of Ca2+ and PO
from the bone fluid compartment to the ECF
compartment.
– facilitates the renal reabsorption of Ca2+ and
PO
 VitD and intestinal absorption of Ca2+ & PO

• Vit D regulates the

synthesis of two classes
of calcium-binding
proteins (calbindins)
found in mammalian
intestine and kidney.
– An intestinal protein
(calbindin-D9k) binds two
calcium ions per
molecule.
• Direct absorption of PO4
 VitD and Renal absorption of Ca2+ & PO

• Vit D  Distal
tubules
– A renal protein
(calbindin-D28k)
binds five to six
calcium ions per
molecule.
• Directly absorbs
PO4
 Vit D action on bone
• Vitamin D  smaller quantities promotes
bone calcification by increase calcium and
phosphate absorption from the intestines.
• administration of extreme quantities of
vitamin D  absorption of bone
• In the absence of vitamin D, the effect of
PTH in causing bone absorption greatly
reduced.
Vit D:Other effects
 Calcitonin

• Calcitonin, a peptide
hormone secreted by the
parafollicular cells, or C
cells of Thyroid glands
• Calcitonin is a 32-amino
acid peptide with a
molecular weight of about
3400
Regulation
of
Calcitonin
by
↑Calcium
 Calcitonin ↓Ca
Experimentally injecting calcitonin  decreases blood
calcium ion concentration within minutes in two ways.
• The immediate effect 
– decrease the absorptive activities of the osteoclasts
– decrease osteolytic effect of the osteocytic membrane
– stimulate deposition of calcium in the exchangeable bone calcium
salts.
• Prolonged effect 
– decrease the formation of new osteoclasts
– decreased numbers of osteoblasts
– the net result is reduced osteoclastic and osteoblastic activity
 Calcitonin Weak Effect on Ca
Weak effect of calcitonin on plasma calcium in adults is twofold.
• First, any initial reduction of the calcium ion concentration
caused by calcitonin  stimulation of PTH secretion, which
almost overrides the calcitonin effect.
• Second, in the adult, the daily rates of absorption and
deposition of calcium are small, and even after the rate of
absorption is slowed by calcitonin, this still has only a small
effect on plasma calcium ion concentration.
The effect of calcitonin in children is much greater:
– because bone remodeling occurs rapidly in children
– absorption and deposition of calcium as great as 5 grams or more
per day—equal to 5 to 10 times the total calcium in all the
extracellular fluid.
• Also, in certain bone diseases, such as Paget’s disease, in
which osteoclastic activity is greatly accelerated, calcitonin
has a much more potent effect of reducing the calcium
absorption
 Calcitonin: kidney &intestines
• Calcitonin also has minor effects on calcium
handling in the kidney tubules and the
intestines. Again, the effects are opposite
those of PTH, but they appear to be of such
little import that they are seldom considered.
PTH Hypo secretion
Pathophysiology:
– ↓PTH  osteocytic reabsorption of exchangeable
calcium decreases and the osteoclasts become almost
totally inactive. calcium reabsorption from the bones
↓  ↓calcium in the body fluids.
– because calcium and phosphates are not being absorbed
from the bone  the bone usually remains strong.
Treatment:
– PTH (expensive)
– Vitamin D with Ca
Types
 PTH Hyper secretion
• Hyperparathyroidism,
– The affected individual can be asymptomatic
– “bones, stones, and abdominal groans.”
consequences:
• Hypercalcemia reduces the excitability of muscle and nervous tissue, muscle
weakness and neurologic disorders, including decreased alertness, poor memory,
and depression. Cardiac disturbances may also occur.
• Excessive mobilization of Ca and PO4 from skeletal stores thinning of bone, 
skeletal deformities, fractures.
• An increased incidence of Ca-containing kidney stones  excess quantity of Ca
being filtered through the kidneys may precipitate and form stones may impair
renal function. extreme pain. Because of these potential
• can cause peptic ulcers, nausea, and constipation
Vit D Deficiency causes
 Vit D Deficiency: consequence:

•  impaired intestinal absorption of Ca. PTH maintains the

plasma Ca level at the expense of the bones.  the bone
matrix is not properly mineralized because Ca salts are not
available for deposition The demineralized bones become
soft and deformed, bowing under the pressures of weight
bearing, especially in children.
• This condition is known as
– rickets in children and
– osteomalacia in adults
Rickets-features
 Vit D Toxicity
• Hypervitaminosis D results from the excessive
consumption of vitamin D supplements,
• Not from the consumption of usual diets or
from unlimited exposure to sunshine.
• Vitamin D toxicity is due primarily to the
hypercalcaemia caused by the increased
intestinal absorption of calcium, together with
increased resorption of bone.
Osteoporosis—Decreased Bone Matrix
 Reading material
• Guyton 11th edition, chapter 79 page no, 978-
994
• Sherwood 9th edition, page no: 701- 712