Calcium metabolism

Mushtaq’s biochemistry vol. 2 chap. 6

Lippincott’s biochemistry chap .29
 Learning outcomes
Explain dietary sources, metabolism and
biochemical functions of calcium and
phosphate
Discuss regulation of calcium metabolism in
bone metabolism and role of parathyroid and
calcitriol in it
Interpret hyper and hypocalcemic conditions
on basis of sign/symptoms and clinical data
 Distribution of Calcium
 Calcium is the most abundant macro mineral in the human
body.
 The average adult body contains in total approximately 1.0kg
 99% of calcium is in the skeleton in the form of calcium
phosphate or carbonate salts(component of hydroxylapatite)
 Normal serum calcium level is 8.5 to 10.5 mg/dL(1.4 mmol/L,
0.03% of total calcium)
 The concentration of calcium ions in the intracellular fluid
( ER, mitochondria) is 10,000 times lower than in the plasma
i.e. at <0.0002 mmol/L, compared with 1.4 mmol/L in the
plasma.
 Dietary sources
Milk & milk products
Egg yolk
Green leafy vegetables
Hard drinking water
Betel leaves( paan )
 Distribution of Calcium
Approximately 10mmol(0.5 to 1%) of calcium is
exchanged between bone and the ECF over a
period of twenty-four hours.
This exchange process is regulated primarily by
the
i. Parathyroid hormone(PTH)
ii. Vitamin D
iii. Calcitonin
 Plasma Calcium
It occurs in two forms:
1. Non diffusible: This fraction of calcium is in firm
combination with negatively charged plasma proteins.
It is approx. 3.4-4.4 mg/dl
2. Diffusible:
i)Ionized calcium: This is physiologically active form
of calcium. Its level is 5.45-6.23mg/dl
ii) Complexed calcium: Its is in complex with plasma
anions such as citrate and phosphate. Its level 0.6mg/dl
Three Forms of Circulating Ca2+
Biochemical Functions of Calcium
1. Bone & tooth development:
Calcium acts structurally as supporting material in bones as calcium
phosphate.
2. Clotting of blood: Several of the clotting factors in the blood
plasma are functionless in the absence of calcium ions.
3. Excitability of nerves
4. Activator of certain enzymes
5. Contraction of muscles: In skeletal and heart muscle calcium
ions, released from the sarcoplasmic reticulum binds to the troponin
C present on the actin-containing thin filaments of the myofibrils.
6.Calcium binds to a variety of proteins like calmodulin,
phospholipase A2 , calbindin and protein kinase C
Biochemical Functions of Calcium
7. Initiates contraction in vascular & smooth muscles
8. Essential for maintaining integrity of capillary wall
9. Involved in exocytosis and endocytosis
10. Voltage regulated calcium channels
11. Action of hormone:
This can therefore serve as a very effective intracellular signal
(or "second messenger) in a variety of circumstances, including
i. The release of hormone e.g. insulin from the beta cells in
the pancreatic islets
ii. The release of neurotransmitters (e.g. acetylcholine from pre-
synaptic terminals of nerves)
 Absorption of calcium
Calcium is reabsorbed in inorganic form.
95% of absorption occurs in proximal part of small
intestine by an active transport mechanism stimulated
by active vitamin D.
Remaining 5% of absorption occurs in the distal
segments of the small intestine involving passive
transport
Total absorption is approximately 100mg /day.
Absorption of calcium
Factors increasing calcium absorption
1. Vitamin D
2. Parathyroid hormone
3. Bile salts
4. Proteins in diet
5. Intestinal pH acidic pH
6. Calcium deficiency
7. Idiopathic hypercalcemia
8. Intake of calcium deficient diet
Factors decreasing calcium absorption
1. Old age
2. Glucocorticoids
3. Intestinal diseases
4. Calcium/phosphate ratio in the food
phosphates
5. Presence of free fatty acids
6. Presence of anions
Phytic acid (inositol hexaphosphate) in cereals
binds calcium in the intestinal lumen, preventing
its absorption.
Other minerals, including zinc, are also chelated
by phytate.
This is mainly a problem among people who
consume large amounts of unleavened whole-
wheat products; yeast contains an enzyme,
phytase, that dephosphorylates phytate, so
rendering it inactive.
Factors influencing calcium absorption
 Vitamin D

Vitamin D acts to increase blood concentrations of

calcium.
It is generated through the activity of parathyroid
hormone within the kidney.
Far and away the most important effect of vitamin D
is to facilitate absorption of calcium from the small
intestine.
In concert with parathyroid hormone, vitamin D also
enhances fluxes of calcium out of bone.
 Vitamin D
Synthesis of the intracellular
calcium binding protein,
calbindin, required for
calcium absorption, is
induced by vitamin D, which
also affects the permeability
of the mucosal cells to
calcium.
 Parathyroid hormone preserves blood
calcium by four major effects:
1. Stimulates production of the
biologically-active form of
vitamin D within the kidney.
2. Facilitates mobilization of
calcium and phosphate from
bone.
3. To prevent detrimental
increases in phosphate,
parathyroid hormone also has
a potent effect on the kidney
to eliminate phosphate
(phosphaturic effect).
4. Maximizes tubular
reabsorption of calcium
within the kidney. This
activity results in minimal
losses of calcium in urine.
 Calcitonin
It is a peptide hormone produced by parafollicular
cell of thyroid gland.
It lowers the plasma level of calcium by
antagonizing the PTH
It is secreted in response to hypercalcemia and has
at least two effects:
1. Suppression of renal tubular reabsorbtion of
calcium. In other words, calcitonin enhances
excretion of calcium into urine.
2. Inhibition of bone resorption, which would
minimize fluxes of calcium from bone into
blood.
Inverse relationship b/w plasma calcium &
inorganic phosphates: the product of plasma
calcium and inorganic phosphorus is constant
at 30-40 mg/dL in adults and 40-50 mg/dL in
children.
Plasma protein level: each gram of negatively
charged plasma proteins bind 0.84mg of
calcium. Thus hypoproteinemia will result in
decrease level of bound calcium
Blood Calcium Regulation
Hormonal regulation of calcium
 Calcium Deprivation Calcium Loading

Parathyroid Secretion stimulated Secretion inhibited

Hormone
Vitamin D Production stimulated Synthesis suppressed
by increased due to low parathyroid
parathyroid hormone hormone secretion
secretion

Calcitonin Very low level Secretion stimulated

secretion high blood calcium
 CALCIUM BALANCE
It is the difference
between the
quantity of calcium
ingested & lost
from the body over
a certain period of
time
 CALCIUM BALANCE
Positive calcium Negative calcium balance
Balance 1. Rickets & osteomalacia,
1. Growth, 2. Sprue,
2. Pregnancy, 3. Starvation,
3. Hyperpituarism, 4. Hyperparathyroidism,
4. Calcium Intake 5. Hyperthyroidism,
6. Decreased calcium intake,
7. Deficiency of sex hormones
in old age
 Related Pathology
Hypocalcemia and hypercalcemia are both
serious medical disorders.
Renal osteodystrophy is a consequence
of chronic renal failure related to the
calcium metabolism.
Osteoporosis and osteomalacia have been
linked to calcium metabolism disorders.
 Causes of Hypercalcemia
1.Excessive intake of calcium
2. Hypervitaminosis D
3. Hyperparathyroidism
4. Miscellaneous causes like Paget’s disease ,
thiazide diuretics, hypophosphatemia.
 Milk-alkali syndrome is characterized by a triad of elevated
calcium levels, metabolic alkalosis, and acute kidney injury that
commonly occurs due to the combined intake of large amounts
of calcium and absorbable alkali.
 Zollinger ellison syndrome ;a condition in which a gastrin-
secreting tumour or hyperplasia of the islet cells in the pancreas
causes overproduction of gastric acid, resulting in recurrent
peptic ulcers.
 Hungry bone syndrome is a state of profound hypocalcemia that
can persist for prolonged periods, most notably after
parathyroidectomy and thyroidectomy. The hypocalcemic state
can be challenging to control and requires varying doses of
supplementation to avoid untoward morbidity for patients.
 https://youtu.be/0Y_3ExChTdA
 UQs
What is normal serum calcium level? Give mechanism
by which vitamin D regulates it.
Give the biochemical regulators through which body
regulates calcium balance
How is calcium content of body maintained?
Give biochemical functions of the following calcium.