Biochemistry of Calcium metabolism covering the source, factors effecting absorption, normal level of calcium, regulation of the calcium, hypercalcemia, hypocalcemia, disorders related to calcium and bone markers.
Useful for students of MBBS, BDS, BSc, MSc, MLT, Physiotherapy (BPT), Nursing etc.
2. A naturally occurring, homogeneous
inorganic solid substance having a definite
chemical composition and characteristic
crystalline structure, color, and hardness.
Dr
Anurag
Yadav
3. FUNCTIONS
Medium for cell activity – muscle & nerve cell
excitability, permeability of cell membrane.
Involved in maintenance of body fluid
They are structural elements in body – bone &
teeth
Minerals are part of physiological compounds ---
Iron of Hb, Iodine of Thyroxine
Cofactors of enzymes ---
Dr
Anurag
Yadav
4. Cu- ceruloplasmin, tyrosinse
Zn –DNA RNA Polymerase, Alc DH
Iron – Cyt oxidase, catalase, peroxidase
Mg –hexoKinase
Se – Glu peroxidase
Mo – xanthine oxidase
Ni – urease
Dr
Anurag
Yadav
10. Increased absorption
Vit D – synthesis of Calbindin
PTH – activate Vit D
Acidity
Amino acids – arginine and lysine
Inhibit absorption
Phytic acid - cereals
Oxalates – leafy vegetables
Malabsorption syndrome
High phosphates = calcium-
phosphate
Chronic renal failure, Coeliac disease
Dr
Anurag
Yadav
11. FUNCTIONS OF CALCIUM
Intracellular Calcium
Muscle contraction
Initiated by binding of calcium to Troponine
Release of hormones, neurotransmitter
Influx of calcium from extracellular space into
the neurons causes release of neurotransmitter
into synaptic cleft by exocytosis
Action of enzymes
Calcium ions stabilize the active conformation
of the enzyme
Cell division
Involved in Mitosis
Dr
Anurag
Yadav
12. Extracellular Calcium
Maintenance of intracellular calcium
Calcium in bone acts as reservoir helps to
maintain extracellular fluid calcium
concentration
Bone mineralization
99% is deposited as Hydroxyapatite crystal
Blood coagulation
Inactive prothrombin to active thrombin
Membrane excitability
Ca++ ions activate Na channels decreased Ca
decreased Na channel activity – Tetany
Membrane potential
Dr
Anurag
Yadav
13. Calcium levels
9-11mg/dL
3 forms
Free/ Ionic/Unbound calcium
50% ---- 5mg/dL metabolically active
Bound
40% ---- 4mg/dL bound to albumin
Complexed calcium
10% complexed with anions
Bicarbonate, Phosphate, Citrate
Dr
Anurag
Yadav
14. Regulation of Calcium levels
3 organs
Bone
Kidney
Intestine
3 Hormones
Parathyroid
Vit D
Calcitonin
Dr
Anurag
Yadav
15. 3 processes
Absorption of Calcium from the
intestine – Vit D
Reabsorption of Calcium from the
Kidney – PTH & Vit D
Demineralization of the bone --- PTH
Dr
Anurag
Yadav
16. 1) Vitamin D
Active form – 1, 25 dihydroxy
cholecalciferol / Calcitriol
In Intestine
Absorption of Calcium from intestine
Dr
Anurag
Yadav
17. In BONE
Calcitriol stimulates osteoblasts
Osteoblasts secrete Alkaline phosphatase
Local concentration of phosphates is
increased
When ionic product of Calcium &
Phosphorus increases MINERALIZATION
takes place
In RENAL TUBULES
Increases the reabsorption of Calcium &
Phosphorus
Dr
Anurag
Yadav
18. 2) Parathyroid hormone PTH
Secreted by parathyroid glands
PTH secretion is controled by negative
feed back by the ionized calcium in the
serum
Acts via cAMP
Dr
Anurag
Yadav
19. PTH action on bones
Demineralization
Induces phosphatases in osteoclasts
Osteoclasts release lactate in the
surroundin– solubilizes calcium
Increases secretion of Collagenase from
osteoclast --- loss of matrix
Dr
Anurag
Yadav
20. PTH action on Kidney
Decrease renal excretion of calcium by
increasing the reabsorption
Increased renal excretion of Phosphates
PTH action on Intestine
Increases Calcium absorption via Vit D
by activating Vit D
Stimulates 1 hydroxylation in the
Kidney
Dr
Anurag
Yadav
22. 3) Calcitonin
Secreted by thyroid parafollicular cells
Decrease Calcium levels
Inhibits resorption of bone
Decreases activity of osteoclasts &
increases activity of osteoblasts
Increases Excretion of Ca &
Phosphorus
Dr
Anurag
Yadav
24. 4) Phosphorus
Reciprocal relationship
Ionic product of calcium & phosphorus is
kept constant --- 40
Renal failure phosphorus excretion
decreased --- increase in phosphorus & Ca
level decreased
5) Children
Upper limit
Ionic product 50
Dr
Anurag
Yadav
25. 6) Serum proteins
Hypoalbuminemia – decreased total
calcium
0.8mg of Ca reduced per gm/dL decrease
in albumin
Metabolically active form normal
7) Alkalosis & Acidosis
Alkalosis favours binding of Ca to
proteins --- decrease in ionic Ca
Acidosis favours ionization
Dr
Anurag
Yadav
34. Hypocalcemia can be treated by
Oral calcium with vitamin D supplementation
Underlying cause should be treated.
Tetany needs IV calcium (usually 10 mL 10% calcium
gluconate over 10 minutes, followed by slow IV
infusion. IV calcium should be given only very slowly.
Dr
Anurag
Yadav
36. OSTEOPOROSIS
After the age of 40–45, calcium absorption is
reduced and calcium excretion is increased
there is a net negative balance for calcium. This
is reflected in demineralization.
After the age of 60, osteoporosis is seen.
reduced bone strength and an increased risk of
Fractures is seen in patients.
Decreased absorption of vitamin D and reduced
levels of androgens/estrogens in old age are the
causative factors.
Dr
Anurag
Yadav
37. Osteopetrosis
It is otherwise called marble bone disease. There is
increased bone density.
It is due to mutation in gene encoding carbonic
anhydrase type II.
The deficiency of the enzyme in osteoclasts leads to
inability of bone resorption.
Paget’s Disease
Localized disease of bone characterized by
osteoclastic bone resorption followed by disordered
replacement of bone. It is common in people above
40 and may affect one or several bones. Familial
incidence is also reported.
Bone markers are useful in monitoring response to
treatment using bisphosphonates.
Dr
Anurag
Yadav
38. Renal Osteodystrophy
Secondary hyperparathyroidism as a
consequence of persistent hypocalcemia causes
high turnover bone disease, osteitis fibrosa.
Osteomalacia may result (low bone turnover) due
to defective synthesis of 1,25 DHCC
Dr
Anurag
Yadav
39. MARKERS OF BONE DISEASE
Metabolic bone diseases result from an imbalance
between bone resorption and bone formation.
Osteopenia is more common than excess bone
formation.
Dr
Anurag
Yadav
40. GENERAL MARKERS OF BONE DISEASE
Serum Calcium,
Serum Inorganic Phosphorus,
Serum Magnesium And
Urinary Excretion Of Calcium And Phosphorus,
Total Alkaline Phosphatase And Total Acid
Phosphatase Levels.
These are the routine tests of bone metabolism.
Vitamin D nutrition should be determined by
measuring serum 25-hydroxy vitamin D.
PTH measurement would be required if serum
calcium is abnormal.
Dr
Anurag
Yadav
41. Markers of bone resorption Markers of bone formation
Telopeptide
•Serum carboxy terminal
telopeptide of type I collagen
•N-telopeptide of type I collagen
Serum bone specific isoenzyme of
alkaline phosphatase (sBAP)
Pyridinium cross links derived
from collagen
Serum osteocalcin (s-OC)
Tartrate resistant acid
phosphatase (TRAP)
Serum midportion of osteocalcin
(sm-OC)
Urinary hydroxyproline excretion Procollagen type 1 peptidase
Serum intact osteocalcin (s-OC)
Serum amino-terminal propeptide
of type I collagen (PINP)
Dr
Anurag
Yadav
42. Dr Anurag Yadav
MBBS, MD
Assistant Professor
Department of Biochemistry
Instagram page –biochem365
Email: dranurag.y.m@gmail.com