Calcium absorption, Calcium excretion, biochemical functions of calcium, calcium homeostasis

1. Calcium metabolism
Seminar presentation
PRESENTED BY
Somya Jain
PG 1st year
RCDS & RC,Bhopal

2. Contents
1. Introduction
2. Sources of calcium
3. Body distribution of calcium
4. Calcium absorption
5. Excretion of calcium
6. Biochemical functions of calcium
7. Calcium homeostasis
8. Clinical importance
9. Conclusion
2

3. Introduction
• Nutrients are the nutritious components
in foods that an organism utilizes to
survive and grow.
• Classified as –
3
1. Macronutrients 2. Micronutrients
a. Carbohydrates
b. Fats
c. Protein
d. Water
a. Vitamins
b. Minerals
Biochemistry by U Satyanarayana & U. Chakrapani 3rd edition

4. What are Minerals???
• Inorganic elements that constitute only a
small proportion of the body wt.
• Perform several vital functions absolutely
essential for the existence of organism.
• Wide variation in their body wt.
distribution.
4
Biochemistry by U Satyanarayana & U. Chakrapani 3rd edition

5. Classification of Minerals
5
• Constitute 60-80% body’s
inorganic material
• Reqd. in amt. > 100mg/day
Principal
elements /
Macro
minerals
• Present in small amount
• Reqd. in amt. <100mg/day
Trace
elements /
Micro
minerals
Biochemistry by U Satyanarayana & U. Chakrapani 3rd edition

6. Principal Elements
• Constituents of bone and teeth
Calcium, Phosphorus, Magnesium
• Maintenance of acid base balance & osmotic
control of water metabolism
Sodium, Potassium, Chloride
• Constituent of A.A’s like cysteine & methionine
• Thiamine , biotin , lipoic acid , CoA
Sulfur
6
Biochemistry by U Satyanarayana & U. Chakrapani 3rd edition

7. Trace Elements
Fe, Cu, I,
Mn, Zn, Mo,
Co, F, Se,
Cu
Ni , V , Cd ,
Ba
Al , Pb , Hg,
B, Ag, Bi
7
ESSENTIAL
POSSIBLY
ESSENTIAL
NONESSENTIAL
Biochemistry by U Satyanarayana & U. Chakrapani 3rd edition

8. Sources of Calcium
• Most abundant among the minerals in body.
8
Dietary
• Best sources – Milk , yogurt , cheese
• Good sources – beans, leafy vegetables,
cauliflower, egg yolk , nuts , figs
Dietary
supple-
ments
• Calcium carbonate
• Calcium citrate
Available
drugs in
market
• Gromin - As a vitamin and mineral supplement in
growing children.
• Minigadine - For prophylaxis of trace
element deficiency in children, anorexia, nutritional growth
failure, retarded mental development.
http://ods.od.nih.gov/factsheets/Calcium-HealthProfessional/- national institute
of health office of dietary supplements ; cimsasia.com

9. Recommended dietary allowances
for calcium (FNB)
Age Male Female Pregnant Lactating
0-6 months 200mg 200 mg
7-12 months 260mg 260mg
1-3 years 700mg 700mg
4-8 years 1000mg 1000mg
9-13 years 1300 mg 1300mg
14-18 years 1300mg 1300mg 1300mg 1300mg
19-50 years 1000mg 1000 mg 1000mg 1000 mg
51-70 years 1000 mg 1200 mg
71+ years 1200 mg 1200 mg
9
Recommended Dietary Allowance (RDA): average daily level of intake sufficient
to meet the nutrient requirements of nearly all (97%–98%) healthy individuals
http://ods.od.nih.gov/factsheets/Calcium-HealthProfessional/- national institute of health office of dietary supplements

10. Distribution of Calcium
• Body of a young adult human contains
abt. 1100 gms (27.5 mol) of calcium.
• 99% of Ca is in skeleton.
10
Guyton textbook of medical physiology – 11th edition

11. Overview of Ca in ECF
• Normal value of ECF = 9.4mg/dl (2.4mmol Ca/lt)
• ECF conc. – regulated very precisely.
• An important feature of extracellular calcium
regulation is that only about 0.1 % of the total body
calcium is in the ECF, about 1 % is in the cells, and
the rest is stored in bones.
• Therefore, the bones can serve as large reservoirs,
releasing calcium when ECF concentration
decreases and storing excess calcium.
11
Guyton textbook of medical physiology – 11th edition

12. Overview of Ca in plasma & ICF
12
Guyton textbook of medical physiology – 11th edition

13. Absorption of Calcium
• Abt. 40% of avg. daily dietary intake
of Ca is absorbed from the gut.
• Mainly from the duodenum & first half
of the jejunum.
• Absorption occurs against electrical &
conc. gradients.
Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition
13

14. Mechanism of absorption
• 2 mechanisms have been proposed-
1. Simple diffusion
2. An “active” transport process involving
energy & Ca²⁺ pump.
 Both the processes require 1,25
dihydroxycholecalciferol & also Ca²⁺
dependent ATPase.
14
Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

15. Factors affecting absorption
1. pH of intestinal milieu –
 Acidic pH – favors absorption – soluble Ca
salts formed .
 Alkaline medium – lowers absorption –
formation of insoluble tricalcium
phosphate.
15
Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

16. 2. Composition of diet –
16
Favors absorption
• High protein diet
• Sugars & organic
acids
• Vit. D
• Ca:P – not more than
2:1 and less than
1:2.
Lowers absorption
• Fatty acids
• Phytic acid
• Oxalates
• Fibers
• Minerals like P , Mg &
Fe.
Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

17. 3. State of health of indivual & aging –
 Healthy adult : absorbs 40% of dietary
Ca.
 >60 yrs : gradual decline in intestinal
absorption.
4. Hormonal –
 Parathhormone – favors absorption
 Calcitonin & glucocorticoids – lowers
absorption.
17
Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

18. Distribution of Calcium
Serum
• 9-11mg/100ml
CSF
• 4.5-5mg/100ml
Muscle
• 70 mg/ 100gm
Nerve
• 15 mg/
100gm
Fundamentals of biochem – Dr. A.C.Deb 7th edition
18

19. Excretion of Calcium
• Excreted in urine, bile & digestive secretions.
• Unabsorbed Ca – excreted as fecal calcium.
• 70-90% of Ca eliminated from body – excreted in
feces.
• Small amt. – excreted into intestines after
absorption.
• Daily loss of Ca in sweat is abt.- 15%
19
Fundamentals of biochem – Dr. A.C.Deb 7th edition

20. • Renal threshold for serum Ca – 10mg/dl
Ingestion of excess proteins
Increases acidity
Increased Ca excretion in urine
 Excretion of Ca into feces- increased in
Vit.D deficiency.
20
Biochemistry by U Satyanarayana & U. Chakrapani 3rd edition

21. 21
Overview of calcium exchange between different tissue compartments in a
person ingesting 1000 mg of calcium per day.
Guyton textbook of medical physiology – 11th edition

22. Biochemical functions of Calcium
1. Calcification of bones & teeth –
 Formation of hydroxyapatite & physical
strength of skeletal tissue.
 Continuous process.
 Bones in dynamic state acts as a reservoir
of Ca.
22
Biochemistry by U Satyanarayana & U. Chakrapani 3rd edition

23. 2. Muscle contraction
3. Nerve transmission
4.Blood coagulation
5. Membrane integrity & permeability
6. Enzyme activation
7.Calmodulin activated action of Ca²⁺
23
Biochemistry by U Satyanarayana & U. Chakrapani 3rd edition

24. 8. Intracellular messenger
9. Hormonal release
10. Secretory process
11. Contact inhibition
12. Myocardial action
13. Neurotransmitter release
14. Role in mitotic division
24
Biochemistry by U Satyanarayana & U. Chakrapani 3rd edition

25. Calcium Homeostasis
• Blood Ca is tightly regulated by –
1. Principle organ systems –
a. Intestine
b. Bone
c. Kidney
2. Hormones –
a. Parathyroid hormone
b. Vit. D
c. Calcitonin
25
Guyton textbook of medical physiology – 11th edition

26. CALCIUM HOMEOSTASIS
DIETARY CALCIUM
INTESTINAL ABSORPTION
DIETARY HABITS,
SUPPLEMENTS
BLOOD CALCIUM
BONE
KIDNEYS
URINE & FAECES
THE ONLY “IN”
THE PRINCIPLE “OUT”
Balance should exists between “IN” & “OUT” factors
Guyton textbook of medical physiology – 11th edition

27. Hormonal Control of Calcium
Metabolism
• Hormones involved –
1. 1,25 dihydrocholecalciferol
2. Parathyroid hormone
3. Calcitonin
4. Parathyroid hormone related protein
5. Miscellaneous hormones –
a. Glucocorticoids
b. Growth hormone
c. Estrogen
d. Thyroid hormone
e. Insulin 27
Guyton textbook of medical physiology – 11th edition

28. VITAMIN D
28
• Sources of Vit.D –
• Synthesized by the body on its own.
• Dietary sources – milk & multiple
vitamins.
Guyton textbook of medical physiology – 11th edition

29. SYNTHESIS
SKIN LIVER KIDNEY
7-DEHYDROCHOLESTEROL
VITAMIN D3
VITAMIN D3
25(OH)VITAMIN D
UV rays
25-HYDROXYLASE
25(OH)VITAMIN D
1,25(OH)2 VITAMIN D
(ACTIVE METABOLITE)
1a-HYDROXYLASE
Best screening test
for Vit.D adequacy
Mediates tissue specific
Vit.D responses
Guyton textbook of medical physiology – 11th edition

30. Mechanism of action
• 1,25 dihydroxycholecalciferol (steroid
compound)
• Acts via steroid receptor superfamily
• Exposes the DNA binding domain &
result in increased transcription of
some mRNA’s
30
Guyton textbook of medical physiology – 11th edition

31. Actions of Vitamin D
1. “Hormonal” Effect of Vitamin D to
Promote Intestinal Calcium
Absorption
• 1,25-Dihydroxycholecalciferol itself
functions as a type of “hormone” to
promote intestinal absorption of
calcium.
31
Guyton textbook of medical physiology – 11th edition

32. • It does this principally by –
Increasing, over a period of about 2 days,
formation of a calcium-binding protein in
the intestinal epithelial cells. (brush
border)
Calcium then moves through the
basolateral membrane of the cell by
facilitated diffusion into cell cytoplasm.
32
Guyton textbook of medical physiology – 11th edition

33. • Rate of calcium absorption is directly
proportional to the quantity of this
calcium-binding protein.
• Protein remains in the cells for
several weeks after the Vit.D has
been removed from the body, thus
causing a prolonged effect on
calcium absorption.
33
Guyton textbook of medical physiology – 11th edition

34. • Other effects of Vit.D that might play
a role in promoting calcium
absorption are the formation of -
(1)a calcium-stimulated ATPase in the
brush border of the epithelial cells
(2) an alkaline phosphatase in the
epithelial cells.
34

35. 35
Guyton textbook of medical physiology – 11th edition

36. 2. Promotes Phosphate Absorption by
the Intestines.
3. Decreases Renal Calcium and
Phosphate Excretion
• Vitamin D also increases calcium and
phosphate absorption by the epithelial
cells of the renal tubules.
• Thus, decrease excretion of these
substances in the urine.
36
Guyton textbook of medical physiology – 11th edition

37. 4. Effect of Vitamin D on Bone and Its
Relation to Parathyroid Hormone
Activity
• extreme quantities of vitamin D causes
absorption of bone.
• In absence of Vit.D, the effect of PTH in
causing bone absorption is greatly
reduced or even prevented.
• Vitamin D in smaller quantities promotes
bone calcification.
37
Guyton textbook of medical physiology – 11th edition

38. Parathyroid Hormone
• Parathyroid gland –
• 4 in no.
• located immediately behind the thyroid
gland.
• 6*3*2 mm
• 2 types of cells-
• Chief cells oxyphil cells
38
Secrete PTH Modified or depleted chief
cells that no longer secrete
hormone.
Guyton textbook of medical physiology – 11th edition

39. • Chemistry of PTH –
Preprohormone(ribosomes)(110 A.A’s)
Prohormone (90 A.A’s)
Hormone (ER & GA ) (84 A.A’s)
 Mol. Wt. – 9500
 Normal plasma PTH level – 10-55pg/ml
 Half life – 10 mins
39
Guyton textbook of medical physiology – 11th edition

40. Actions of PTH
1. Increases Calcium and Phosphate
Absorption from the Bone
 2 PHASES –
a. Rapid phase –
• Begins in minutes and increases
progressively for several hours.
• This phase results from activation of the
already existing bone cells (mainly the
osteocytes) to promote calcium and
phosphate absorption. 40
Guyton textbook of medical physiology – 11th edition

41. b. Slow phase –
• Requires several days or even weeks
to become fully developed.
• It results from proliferation of the
osteoclasts, followed by greatly
increased osteoclastic reabsorption
of the bone itself.
41
Guyton textbook of medical physiology – 11th edition

42. 2. Decreases Calcium Excretion and
Increases Phosphate Excretion by the
Kidneys
• increases calcium absorption occurs mainly
in the late distal tubules, the collecting
tubules, the early collecting ducts, and
possibly the ascending loop of Henle to a
lesser extent.
• diminishes phosphate reabsorption.
42
Guyton textbook of medical physiology – 11th edition

43. 3. Increases Intestinal Absorption of
Calcium and Phosphate
• PTH greatly enhances both calcium
and phosphate absorption from the
intestines by increasing the
formation of 1,25-
dihydroxycholecalciferol in the
kidneys.
43
Guyton textbook of medical physiology – 11th edition

44. Control of Parathyroid Secretion
by Calcium Ion Concentration
• Slight decrease in calcium ion
concentration in the ECF
• increase the rate of secretion of the
parathyroid glands within minutes.
• Eg. In conditions like – Rickets
Pregnancy
Lactation 44
Guyton textbook of medical physiology – 11th edition

45. • Conversely, conditions that increase the
calcium ion concentration above normal
cause decreased activity and reduced size
of the parathyroid glands.
• Such conditions include
(1) excess quantities of calcium in the diet
(2) increased vitamin D in the diet
(3) bone absorption caused by factors other
than PTH
45
Guyton textbook of medical physiology – 11th edition

46. Calcitonin
• Peptide hormone secreted by the thyroid
gland.
• 32-amino acid peptide with a molecular
weight of about 3400.
• Synthesis and secretion of calcitonin occur in
the parafollicular cells, or C cells.
• Increased Plasma Calcium Concentration
Stimulates Calcitonin Secretion.
46
Guyton textbook of medical physiology – 11th edition

47. Actions of Calcitonin
• Decreases Plasma Calcium Concentration
• Two ways-
1. The immediate effect is to decrease the absorptive
activities of the osteoclasts and possibly the
osteolytic effect of the osteocytic membrane
throughout the bone, thus shifting the balance in
favor of deposition of calcium in the exchangeable
bone calcium salts.
47
Guyton textbook of medical physiology – 11th edition

48. 2. more prolonged effect of calcitonin
is to decrease the formation of new
osteoclasts
Reduced osteoclastic and osteoblastic
activity and, consequently, very little
but prolonged effect on plasma
calcium ion concentration.
48
Guyton textbook of medical physiology – 11th edition

49. Other Hormones
1. Parathyroid hormone related protein
(PTHrP)
• Produced by different tissues of our body
• Binds to PTH receptors
• Marked effect on growth and development
of cartilage in utero.
• Defect in PTHrP – severe skeletal
deformities.
49
Guyton textbook of medical physiology – 11th edition

50. 2. GLUCOCORTICOIDS
 Inhibit protein synthesis in osteoblasts,
thereby decreases synthesis of organic
matrix of bone.
 Inhibit absorption of Ca and Po4 from the
gut and facilitate its excretion in the
kidneys lowers plasma
calcium level.
50
Guyton textbook of medical physiology – 11th edition

51. 3. Growth Hormone
Increases intestinal absorption of Calcium
“Positive calcium balance”
4.Thyroid Hormone
Hypercalcemia, Hypercalciuria and
Osteoporosis.
5. Estrogens
Prevents osteoporosis by inhibiting
certain cytokines
6. Insulin
Increases bone formation
51
Guyton textbook of medical physiology – 11th edition

52. Clinical Importance
1. Hypercalcemia –
When serum Ca levels exceeds
11.0mg/dl.
52
Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

53. Causes :
A)Primary hyperparathyroidism
May be due to – i) Familial
ii) Hyperplasia of chief cells-15% case
iii) Tumors –
 Solitary adenoma – 80-85% cases
 Multiple adenomas – 2% cases
 Parathyroid carcinoma - <1% cases
53
Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

54.  Extreme osteoclastic activity in the bones.
inc. Ca ion & dec. P ion conc in ECF
 Tendency to form kidney stones.
calcium phosphate & calcium oxalate
 High level of plasma alkaline phosphatase
– diagnostic feature .
54
Guyton textbook of medical physiology – 11th edition

55. • Cause the plasma calcium level to rise to
12 to 15 mg/dl and, rarely, even higher.
• depression of the CNS & PNS, muscle
weakness, constipation, abdominal pain,
peptic ulcer, lack of appetite, and
depressed relaxation of the heart during
diastole.
55
Guyton textbook of medical physiology – 11th edition

56. • Radiographs of the bone show extensive
decalcification and, occasionally, large
punched-out cystic areas of the bone that
are filled with osteoclasts in the form of
so-called giant cell osteoclast “tumors.”
• The cystic bone disease of
hyperparathyroidism is called osteitis
fibrosa cystica.
56
Guyton textbook of medical physiology – 11th edition

57. B) Malignancy –
i) Humoral factors – like PTHrP, TGF,
EGF,PDGF
ii) Direct skeletal involvement by the
tumors
iii) Hematological malignancies.
C) Other endocrine causes –
i) Hyper & hypothyroidism
ii) Acromegaly
iii) Acute adrenal insufficiency
57
Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

58. D) Granulamatous diseases –
i) TB
ii) Sarcoidosis
iii)Berylliosis
E) Overdosage of vitamins –
i) Vit.A intoxication
ii) Hypervitaminosis D
58
Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

59. F) Drug induced –
i) Thiazide diuretics
ii) Spironolactone
iii) Milk alkali syndrome
G) Miscellaneous causes-
i) Idiopathic hypercalcemia of infancy –
Williams syndrome
ii) Hyperalbuminemia & hyperglobulinemia
iii) Renal failure
59
Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

60. 2 . Hypocalcemia
When serum Ca is less than
8.5mg/dl.
60
Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

61. • Causes –
A)Hypoalbuminemia
 Commonest cause
 May be due to- malnutrition
 Nephrotic syndrome
 Chronic liver ds .
B) Hypoparathyroidism
 May be – surgical induced – 90% cases
 Idiopathic
 Bio inactive PTH
61
Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

62. C) Renal diseases & Renal failure
D) Pseudohypoparathyroidism –
PTH is normal
Defect is in PTH receptors
E) Hypoaparathyroidism in association
with other diseases –
i) Addison’s ds
ii) Pernicious anemia
iii) Candidiasis
62
Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

63. F) Miscellaneous causes –
i. Acute pancreatitis
ii. Medullary carcinoma of thyroid
iii. Magnesium deficiency
iv. Iatrogenic – administration of drug
Foscarnate in AIDS pts.
v. Neonatal hypocalcemia - due to
prematurity
vi. Vit.D deficiency or resistance – Rickets &
Osteomalacia
63
Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

64. Vitamin D deficiency
• Rickets
 occurs mainly in children.
 results from calcium or phosphate
deficiency in the ECF, usually caused by
lack of vitamin D.
• Plasma calcium concentration in rickets is
only slightly depressed, but the level of
phosphate is greatly depressed.
64
Guyton textbook of medical physiology – 11th edition

65. During prolonged rickets
marked compensatory increase in PTH
secretion
causes extreme osteoclastic absorption of
the bone
bone becomes progressively weaker and
imposes marked physical stress on the
bone
65
Guyton textbook of medical physiology – 11th edition

66. • In the early stages of rickets, tetany
almost never occurs.
• However, when the bones finally become
exhausted of calcium, the level of calcium
may fall rapidly.
• As the blood level of calcium falls below 7
mg/dl, the usual signs of tetany develop.
66
Guyton textbook of medical physiology – 11th edition

67. • Treatment –
• supplying adequate calcium and
phosphate in the diet.
• administering large amounts of
vitamin D.
67
Guyton textbook of medical physiology – 11th edition

68. Tetany
• Occurs in patients with low levels of
calcium.
• Intermittent spasm of the peripheral
muscles due to increased excitability
of peripheral nerve.
Textbook of medicine – khosla 6th edition
68

69. • Trousseau sign –contraction of
distal muscles of the hands (carpal
spasm with extension of
interphalangeal joints and adduction
and flexion of the meta-
carpophalangeal joints) and feet
(pedal spasm).
• Chovstek’s sign - demonstrated by
tapping anterior to the ear, at the
emergence of the facial nerve. A
resultant twitch of the nose or lips
suggests low calcium levels. 69
Textbook of medicine – khosla 6th edition

70. Sialolithiasis
• It is a common disease of salivary gland
characterized by the obstruction of the
salivary secretion by the calculus.
• These calculi generally consist of mixture
of different calcium phosphates( mainly
hydroxyapatite & carbonate-apatite )
together with an organic matrix.
• More commonly seen in submandibular
gland duct.
70
Textbook of oral medicine by Anil Ghoms 2nd edition

71. Dental Pulp stones
• They are tiny concretions that cab be
found in the pulp chamber, the
vascularized, central portion of the
tooth.
• They contain matrix of organic
material , upon which it deposits
calcium in the form of carbonate
apetite.
• Their presence is usually associated
with old age pulp or poor pulpal
health.
Shafer’s textbook of oral pathology 7th edition
71

72. Calcium channel blockers
• 3 subclasses –
• 1. Phenyl alkylamine – Verapamil
• 2. Dihydropyridines – Nifidepine
• 3. Benzothiazipine – Diltiazem
• Pharmacological action – inhibit Ca
mediated slow channel component of
action potential in smooth/cardiac
muscle cell.
Essentials of medical pharmacology KD Tripathi 6th edition
72

73. • Uses of CCB’S –
1. Angina pectoris
2. Hypertension
3. Cardiac arrythmias
4. Hypertrophic cardiomyopathy
5. Premature labor- Nifedipine
6. Suppress migraine & nocturnal leg
cramps – Verapamil
7. Raynaud’s disease – Nifedipine
73
Essentials of medical pharmacology KD Tripathi 6th edition

74. Conclusion
• Calcium is crucial for body physiological
function.
• It is an essential intracellular signaling
molecule & plays a variety of extracellular
functions , thus the control of bodily
calcium concentrations is vitally important.
• Calcium concentration must be tightly
regulated to maintain the physiological
stability by interaction between major
organs & hormones.
74

75. Bibliography
1. Guyton textbook of medical physiology – 11th
edition
2. Textbook of Medical Biochemistry – M N
Chatterjea & Rana Shinde 6th edition
3. Biochemistry by U Satyanarayana & U.
Chakrapani 3rd edition.
4. Essentials of medical pharmacology KD
Tripathi 6th edition .
5. Fundamentals of biochem – Dr. A.C.Deb
7th edition
75

76. 6.Textbook of oral medicine by Anil Ghoms.
7.Shafer’s textbook of oral pathology 7th edition
8.http://ods.od.nih.gov/factsheets/Calcium-
HealthProfessional/- national institute of
health office of dietary supplements ;
cimsasia.com
9. Textbook of medicine – khosla 6th edition
76

77. Thank you
77