Role of calcium , metabolism and its disorders

1. Dr.S.Sethupathhy.,M.D.,Ph.D.,
Professor & Head,
Dept. of Biochemistry.
RMMC, AU

2.  excitability of cell membranes
 neuromuscular transmission and muscle
contraction
 releasing of transmitters from synapses
 “second messenger”
 stimulates secretory activity of exocrine
glands and releasing of hormones
 contractility of myocardium
 blood coagulation

3. Hypocalcemia
 Muscle tetany, carpopedal spasm
 Dilatation of heart
 Increased cell membrane permeability
 Impaired blood clotting
Hypercalcemia
 Depression of nervous system, reflex
activity,
 Increased heart contractility
 Formation of calcium phosphate crystals
 Calcification, renal stones

4.  99% of skeletal calcium forms stable bone (not
exchangeable with the Ca in extracellular fluid)
 1% is in the form of releasable pool of Ca
 Balance of deposition and resorption
 Osteoblasts – bone-forming cells responsible for
bone deposition
◦ Secrete type I collagen
◦ Differentiate into osteocytes
 Osteoclasts – “bone-eating” cells that resorb the
previously formed bone

7.  Free is physiologically active
 regulated by the combined actions of
parathyroid hormone and calcitriol
 Changes in plasma [albumin] can alter
total [calcium]
 ‘adjusted/corrected [calcium]’ for any
abnormality of [albumin
 adjusted [calcium] mmol/l=
(measured [calcium] + 0.02(40 –
[albumin g/l]))

8.  Stimulation
◦ PTH
◦ 1,25 Dihydrocholecalciferol
◦ IL-1
◦ T3, T4
◦ hGH, IGF-1 (insuline-like growth factor)
◦ PGE2 (prostaglandin)
◦ TNF (tumor necrosis factor)
◦ Estrogens ?
 Inhibition
◦ Corticosteroids

9.  Stimulation
◦ PTH (not directly – through stimulation of osteoblasts)
◦ 1,25 Dihydrocholecalciferol (not directly – through
stimulation of osteoblasts)
◦ IL-6, IL-11
 Inhibition
◦ Calcitonin (directly – receptors)
◦ Estrogens (by inhibiting production of certain
cytokines)
◦ TGF-β (tranforming growth factor)
◦ PGE2(prostaglandin)

10.  Parathyroid glands
 polypeptide of 84 amino acids
 stimulus for secretion – low plasma calcium
 function – to INCREASE plasma calcium
 activation of osteoclasts – stimulates
absorption of Ca, P from bones
 decreases excretion of Ca by kidneys
 increases excretion of P by kidneys
 stimulates conversion of vitamin D to
calcitriol (vitamin D hormon) in kidneys

11.  Parafollicular cells of thyroid gland (C-cells)
 peptide of 32 amino acids
 stimulus for secretion – high plasma calcium (food
intake – gastrin, CCK, glucagon)
 function – to DECREASE plasma calcium and
phosphates
 inhibits osteolysis – decreases absorption of
Ca, P from bones
 stimulates incorporation of Ca, P to bones
 decreases absorption of Ca, P in kidneys
 decreases the effect of PTH on bones – PTH
antagonist

12. Hypovitaminosis
 RICKETS (rachitis)– children
 OSTEOMALACIA - adults ( less calcium)
◦ Osteoporosis is decrease of bone mass (matrix and
minerals)
Hypervitaminosis
 Tissue and organs calcification
 Loss of body weight
 Kidney function failure

13. Age/ sex Ca (mg)
1-3 350
4-6 450
7-10 550
11-18 M 1000
11-18 F 800
19 + 700

14.  Milk – 100 ml =120mg
 Cheese – 15gm = 110mg
 Yoghurt pot – 80gm = 160mg
 Other sources
◦ Fish
◦ Meat
◦ Bread
◦ Cereal
◦ Broccoli

15. Urine
Ca/Cr
>0.56
mmol/mm
ol
<0.56
mmol/mm
ol
Hypocalcaemic
hypercalciuria
Serum P
Low High
Vitamin D related causes
Serum 25 OH D
Serum 1,
25 (OH)2 D
VDDR
Type I
VDDR
Type II
LowNormal
Low High
Serum PTH
Low High
Vit D Deficiency
Hypo-para-
thyroidism
Pseudo-hypo-
para-thyroidism

16.  Absorption is taking place from the first and second part of
duodenum against concentration gradients
 Absorption required a carrier protein , helped by Ca-dependent
ATPase
 Increased absorption-
- calcitriol , active form of Vit-D
- PTH
- acidic pH
- Lys and Arg
 Inhibiting absorption -
- phytic acid
- oxalates
- phosphate
- Mg
caffeine
-

18. Picture quiz

19. Thank you