1. Calcium Metabolism and its clinical significance
Dr. RohiniC Sane

3. Calcium metabolism
99 % bone
qBody content = (1.0 -1.5 kg )
1% ECF
qSources: milk (cow -100mg/100ml ,human milk -300mg/100ml ),
cereals à major source
qDaily requirement –
Individual Daily requirement
Adult 500mg
Children 1200 mg
Pregnancy 1500 mg
Old age 1500 mg /day calcium + 20 microgram /day vitamin D

4. Calcium metabolism-Absorption of Calcium
First & second part of duodeneum
Active transport
Carrier protein –calcium dependent ATPase

5. Factors affecting Calcium Absorption
Increase calcium absorption
1. Vitamin Dà increase in Calbindin à Calcium
absorption
2. Parathyroid Hormone
3. acidity-favors calcium absorption
4. Amino acids ( Lysine & Arginine)
à Calcium absorption
Decrease calcium absorption
1. Phytic acid ( hexa phosphate Inositol )à
fermentation decrease Phytatecontent
2.Oxlate à present in leafy vegetables
3.Steatorrhoea à fatty acid not absorbed
Calcium fatty acid complex not absorbed
4.High phosphate content à calcium
phosphate is not precipitates ,not absorbed

6. Calcium metabolism
q optimum Ratio for maximum absorption :
Calcium : phosphorous à ( 1: 2 to 2:1 )
Daily intake (500mg )
loss of calcium : stool (400 mg ) urine (100mg )

8. Calcium metabolism
qDistribution of Calcium in human body
qIntra cellular concentration : 10 micromole/ lt
qExtra cellular concentration : 2.5 mmol/ lt
qInflux :
1. Na ⁺ /Ca ²⁺ exchange –low affinity for calcium
2. Ca ²⁺ /H⁺ ATPase exchange
1. 2.
Ca ²⁺ Ca ²⁺ ECF
Na ⁺ H⁺
ICF

9. Calcium balance in a human body

10. Functions of Calcium
q1.Activation of enzymes (1) through “Calmodulin ”
qCalcium + Calmodulin à Calcium- Calmodulin
Kinase Active kinase
Enzyme Phosphorylated enzyme
Biological effect

11. Indirect activation ( through Calmodulin )

12. Indirect activation ( through Calmodulin )

13. Functions of Calcium
q1.Activation of Adenylate Cyclase : Indirect activation ( through Calmodulin )

15. Indirect activation ( through Calmodulin )

16. Direct activation ( without Calmodulin )

18. Functions of Calcium
v2. Secretion of hormones : Ca²⁺ mediated hormones
eg Insulin ,Parathyroid hormone ,Calcitonin ,Vasopressin

19. Functions of Calcium- Insulin secretion

20. Functions of Calcium
v3. Second messenger of hormones : Ca²⁺ mediated hormones
eg Parathyroid hormones , ADH
HORMONES à
C Amp à Ca²⁺
à Effect

21. Functions of Calcium : Calcium mediated phosphorylation of
myosin
v4. Excitation & contraction of muscle fiber
v De phosphorylated myosin light chain kinase
phosphorylated inactive myosin light chain kinase
Calcium –Calmodulin myosin light chain kinase
Myosin relaxed + ATPà myosin phosphorylated ( contraction )+ADP
PHOSPHTASE
ATP
ADP
C Amp activated protein kinase
(+ ) Ca²⁺ -Calmodulin

22. FUNCTIONS OF CALCIUM
• B. Calsequestrin:
(1) Calcium binding protein
(2) Active transport of Ca²⁺
Calcium decreases “neuromuscular irritability”
Calcium deficiency causes “ Tetany”

23. Role of Calsequestrin in Calcium Metabolism

24. FUNCTIONS OF CALCIUM
• 5.Microfilament regulated processes
• Cell mobility
• Endocytosis Regulated by Calcium Calmodulin complex
• Secretory vesicle
• Degranulation

25. 5.Microfilament regulated processes

26. Role of calcium in endocytosis

27. Role Of Calcium in Micro-tubular Function

28. Functions of Calcium
• 7. permeability of serum through capillary is decreased by Ca²⁺
Therefore used to reduce allergic exudates

30. Functions of Calcium
• 8. blood coagulation ( CALCIUM = FACTOR IV )

31. Functions of Calcium
• 9. Prolonged systole in myocardium :therefore intravenous administration
should be slow

32. Functions of Calcium
• 10.bone & teeth formation
Osteoblast: bone deposition
Osteoclast à demineralization

34. Ionized form
5mg/dl
Metabolically
active
Diffusible
Complexes
With anion
1mg/dl
Complexes with
PO₄⁻³ &
bicarbonate
HCO₃⁻
Diffusible
Bound to protein
4mg/dl
BOUND TO
Albumin (3mg )
& Globulin(1mg )
Non diffusible
Total serum Calcium: 9-11 mg/dl = 5 mequ/lt = 2.5 mmol/lt
Colorimetric Method for estimation of Total serum Calcium : using Naphthalhydroxamic acid ,Ortho cresol thalein
Method of estimation of IONIZED FORM : ION SELECTIVE ELECTRODES

35. SERUM CALCIUM
= 9-11 mg/dl
SALKOWITCH
TEST
Fine cloudy ppt
Physiological
SERUM CALCIUM
= 7.5 mg/dl
SALKOWITCH
TEST
No ppt
Hypocalcaemia
SERUM CALCIUM
>11 mg/dl
SALKOWITCH
TEST
Heavy white ppt
Hypercalciuria
SALKOWITCH TEST
ESTIMATION OF URINARY CALCIUM USING TURBIDOMETRIC METHHOD ( AMMONIUM OXLATE )

36. Factors regulating blood calcium levels
1. VITAMIN D
2. PTH
3. CALCITONIN Major factors
4. PHOSPHOROUS LEVELS
5. SERUM PROTEIN
6. ACIDOSIS /ALKALOSIS
7. KIDNEY FUNCTION Minor factors
8. AGE

38. Role of Thyroid and parathyroid hormones in Calcium balance

39. Factors regulating blood calcium levels
1. VITAMIN D
Target organs
Bone
Intestine
Kidney
↑ activity alkaline phosphatase, NO &
osteoblasts
Absorption dietary Calcium
Reabsorption Calcium from filtrate
Vitamin D à increase synthesis calcium binding protein à increase absorption of Calcium
Hyper vitaminosis à Hyper-calcemia

42. Factors regulating blood calcium levels
2. SERUM PTH ( Parathyroid hormone ): 10-60 mg/dl ( normal level )
FOUR Para thyroid glands à chief cells synthesize PTH( ionic Ca²⁺controls
secretion by negative feed back )
115 AMINO ACIDS PRE PRO PTH❶
90 AMINO ACIDS PRO PTH❷
84 AMINO ACIDS PTH ( ACTIVE) ❸
↑PTH à ↑ Calcium
SITE OF ACTION à BONE ,KIDNEY,INTESTINE STORAGE OF PTH FOR SEVERAL HOURS NOT DAYS

43. Factors regulating blood calcium levels
2A. SERUM PTH ( Parathyroid hormone—100 ng/l )& Calcium: in bones
↑PTH ànumber of osteoblast ↑
↑Activity of pyro phosphatase
↑demineralization
↑Calcium levels

44. Factors regulating blood calcium levels
2B . SERUM PTH ( Parathyroid hormone )& Calcium:bone
↑PTH à↑ LACTATE
↑solubiIization of Calcium into surrounding
medium

45. Factors regulating blood calcium levels

46. Factors regulating blood calcium levels
2C . SERUM PTH ( Parathyroid hormone )& Calcium:bone
↑PTH à↑ secretion of Collagenase
Loss of matrix & bone reabsorption
Mucopolysaccharide & Hydroxy Proline in Urine

47. Factors regulating blood calcium levels
SERUM PTH ( Parathyroid hormone ) & Calcium : Kidney
①↓ Renal excretion of Calcium (↑Ca ²⁺ Hypercalcemia )
②↑Renal absorption of Calcium( ↑Ca ²⁺- Hypercalcemia )
③ ↑ Excretion of phosphorous ( ↓ phosphorus )
④Hydroxylation of 25 hydroxy Calciferol ( Indirect absorption )
Hyperparathyroidism à Hyper-calcemia à decrease phosphorous

48. Factors regulating blood calcium levels
SERUM PTH ( Parathyroid hormone )& Calcium: intestine
①↑PTH à↑Hydroxylation of 25 hydroxy calciferol
②↑DHCC ( DI HYDROXY CHOLECALCIFEROL )
③ ↑CALCIUM BINDING PROTEIN
④↑ CALCIUM ABSORPTION FROM DIETARY SOURCES
Hyper-parathyroidismà Hyper-calcemia à decrease phosphorous

49. Factors regulating blood calcium levels
Calcitonin : by para follicular cells of thyroid gland
①32-34 amino acids ( depending species)
②Calcitonin secretion is stimulated by serum Calcium Gastrin ,Glucagon .biological amines
③↓SERUM CALCIUM LEVELS
4a.↓ calcium reabsorption of bone 4b. ↓ activity of osteoblast 4c. Activity of osteoblast 4d. ↓ PTH ( PTH & CALCIUM are antagonist )
5. Kidney : ↑ phosphorous excretion through urine
6. Promote bone growth

51. Factors regulating blood calcium levels
IV Serum inorganic phosphorous :
“ reciprocal relationship” with CALCIUM
Ca X P = 40 ( adult )
Rickets : Ca X P < 40
Children : Ca X P = 50
Renal insufficiency : calcium decreases ( calcium excretion increases ) &
phosphorous increases ( phosphorous excretion decreases )

52. Factors regulating blood calcium levels
V SERUM PROTEIN :
Nephritis ,malnutrition à Hypo-albuminemia à serum calcium decreases
Decrease in Albumin by 1 g à decrease in serum calcium by 0.8 mg/ dl (
calcium bound to Albumin )
Metabolic active :ionized form is normal. Therefore no deficiency manifestation.
VI Alkalosis & Acidosis :
Alkalosis à favors Calcium + protein : decrease ionized form
Acidosis àFavors ionization of Calcium
VII Kidney Threshold :
Kidney threshold : 10mg/dl
Calcium intravenous injection à urinary excretion
Calcium ( Ca ²⁺) ,Magnesium ( Mg ²⁺) , proton ( H ⁺) prevents tetany .

53. Serum calcium levels
Hypercalcemia : > 11mg/ dl ( Normal serum Calcium: 9-11 mg/dl )
Causes :
a) Hyper parathyroidism-MAJOR CAUSE
b) Metastatic carcinoma of bone
c) Hyper vitaminosis D ( Vitamin D toxicity )
d) Lithium therapy
e) Thiazide diuretics MINOR CAUSES
f) Paget disease
g) Multiple myeloma

56. Kidney stones : a cause of renal dysfunction

58. Hyper parathyroidism
MAJOR CAUSE of Hypercalcemia : > 11mg/ dl ( Normal serum Calcium: 9-11 mg/dl )
Causes :
a) Parathyroid –Adenoma
b) Ectopic secreting tumors
Signs & Symptoms :
1. Osteoporosis
2. Punch out areas of bone reabsorption
3. Calcium excretion in urine ( Calciuria )
4. Calcium precipitate in urine à urinary calculi
5. Retention of chloride à Hyper chloremic acidosis à polyuria ( increased solutes
in urine )
6. Anorxia ,mucle weakness ,short Q-T interval in in ECG
7. Ectopic calcium in eal tissue , pancreas ,arterial wall ,muscle tissue ,ossificans )

61. Serum calcium levels
v Hypocalcemia : < 8.8 mg/ dl ( Normal serum Calcium: 9-11 mg/dl )
Tetany : < 7.5 mg/dl
Mild tremors : 8.5 mg/dl
qCauses
1.Tetany :
2. Fanconi’s syndrome
3.Pseudohypothyroididism
4.Renal tubular acidosis
5. Renal tubular avidosis

62. Tetany-1
q Causes of Tetany :
1. Decrease in Dietary intake
2. Surgical removal of parathyroid gland
3. Auto immune disease
qSigns & symptoms :
a) Neuro- muscular irritability
b) Carp pedal spasm
c) Laryngismus à DEATH
d) Chvostek’ s sign à tapping of 5th cranial nerve ,facial contraction
e) Trousseau’s sign à inflammation of blood pressure causes carpopedal
spasm
f) Increases Q-T interval in ECG

64. Signs and Symptoms of TETANY

65. Trousseau’s sign indicate calcium deficiency

66. Chvostek’s sign indicate calcium deficiency

67. Tetany-2
q LABORATORY TESTS / FINDINGS :
1. Serum calcium ↓
2. Serum inorganic phosphorous ↑
3. Urinary excretion of Calcium & inorganic phosphorous↓
qTreatment : Intra venous injection of Calcium salt

68. Hypocalcemia
q Fanconi’s syndrome
1. Glycosuria
2. Aminoaciduria
3. Decrease SERUM Calcium & increase inorganic phosphorous
4. Hypercalciuria

69. Hypocalcemia
q.Pseudo hypo thyroidism
a) X linked dominant condition
b) PTH levels normal
c) Lack of end organ response to PTH
d) Hypocalcemia ,Hypophosphatemia
e) Shortening of 4th &5th metacarpal & metatarsal bones

70. Hypocalcemia
qRenal tubular acidosis
a. Inherited abnormality
b. H⁺ production deficient ( urinary p H > 5 )
c. Loss of bicarbonate ,Sodium Potassium ,Calcium ,Magnesium ( ↓Serum
levels of HCO₃⁻ , Na⁺ ,K ⁺ , Ca ⁺ ²,Mg ⁺² )
d. Renal Rickets à Bone simillar to Rickets

71. Hypocalcemia
qVitamin D deficiency ( not Tetany )-Rickets –marginal decrease in serum
Calcium levels ,Medullary Thyroid carcinoma , dietary deficiency ,
Malabsorption , Serum Calcitonin increases
qMild decrease in serum Calcium observed in renal diseases ( decrease
Calcitonin formation )

73. Long QT

74. Comparison of Calcitonin & Calcitriol
Calcitonin
Peptide
hormone
Synthesis-by
thyroid gland
Action—
decrease serum
calcium level
Calcitriol
Steroid
hormone
Synthesis by
skin ,Liver
,Kidney
Action –
increase serum
levels

75. Factors regulating blood calcium levels
Decrease in Serum CALCIUM
Calcitonin inhibited,
PTH stimulated
Bone demineralization( influx of
CALCIUM in bone
Increase in Serum CALCIUM
Increased Calcitonin secretion,
PTH inhibited
Bone mineralization( out flux of
CALCIUM from bone )

76. Bone mineralization & de mineralization
• Bone mineralization & de mineralization need
Calcium
Phosphorous
Proteins
Vitamins: A , D, C
Enzyme : Alkaline phosphatase
Hormones : PTH, Calcitonin ,sex hormones
Normal renal function ( for synthesis of Calcitriol )
Osteoblast ( for mineralization )/& osteoclast (for demineralization )

77. Process of Bone mineralization
Vitamin D à activity of Alkaline phosphatase increases
Calcium & Phosphorous liberation from substrate
Ionic concentration of ( calcium x phosphorous ) increased
Calcium & phosphorous get deposited
Hydroxy apatite formation
Dynamic equilibrium with serum calcium
Bone reservoir & matrix of triple stranded Collagen molecule participate

78. Osteoporosis
a) Age30 years àMaximum calcium content in bone
b) Age 45-50 years à Calcium absorption decreases ,calcium excretion
increases ( negative balance )à demineralization ( OSTEOPENIA )
c) Age 60 years à
Absorption of vitamin D ↓
Androgen & Estrogen ↓
Serum Calcium ↓
Reduced bone stregth
Repeated bone fractures à OSTEOPOROSIS
OSTEOPOROSIS : WOMEN > MEN , INDIANS > WESTERNERS

79. Osteoporosis-bone demineralization

80. Osteoporosis-bone demineralization

81. Role of Calmodulinkinase in Calcium Metabolism