MINERAL METABOLISM - calcium, Phosphorus, Iron. for Allied Health Sciences

INERAL METABOLISM - Calcium, Phosphorus, Iron, for First year Allied Health Sciences, RGUHS syllabus

1. Mineral metabolism
Ca, P, Fe
P. Santosh Kumar

2. Mineral metabolism- Syllabus
Name the macro/Micro minerals
Iron: Sources, RDA, functions and disorders of
deficiency and excess
Calcium and phosphorus: Sources, RDA, functions,
normal serum levels and hormones regulating their
levels.

3. Definition: Minerals are elemental atoms that are
Essential nutrients required for normal growth
and maintenance of the body.

4. Mineral Classification: These minerals are broadly
classified based on requirement into
•Major minerals or macro minerals,
•Minor minerals or micro minerals also called as trace
elements
•Non-essential trace elements
•Possibly essential trace elements

5. Macro minerals: If the requirement of the mineral is more
than 100mg/day called as macro minerals.
Ex: Calcium, Phosphorus, Sodium, Potassium, Chloride,
Magnesium, Sulphur
Micro minerals- If the requirement of the mineral is less
than 100mg/day called as micro minerals.
Ex: Iron, Cupper, Zinc, Iodine, Selenium, Manganese,
Fluoride, Molybdenum, Chromium,

6. Possibly essential trace elements: Some of the minerals
are necessary for the body but their exact role is not
known.
Ex: Bromism, Lithium, Nickel, Vanadium, Cadmium
Non-essential trace elements. Certain minerals are toxic
to the body and they should be avoided in the diet-
Ex: Lead, Mercury, Aluminium Boron, Silver, And
Bismuth etc..

7. Functions of Minerals
•Calcification of bone, Blood coagulation (Ca)
•Nerve & muscle function (Ca, Na, K)
•Some minerals have structural functions (Ca, P in bone; S in
keratin)
•Acid-base and water balance (Na, K, Cl) Fluid balance and
osmotic regulation.
•Some participate with enzymes in metabolic processes
(cofactors)(Mg, Mn, Cu, Zn, K)
•Integral components of biologically important compounds,
Unique functions e.g., heme(Fe), B12 (Co), thyroid
hormones(Iodine)

9. Calcium
•Major mineral mainly present in bones and teeth
•Total calcium in the human body is about 1 to 1.5 kg,
99% of which is seen in bone and 1% in extracellular
fluid.
•Calcium present in the body is of three types about 50%
in ionized calcium, 40% protein bound and remaining
10 % is complexed calcium with bicarbonate, phosphate
etc.

10. •Three Forms of Circulating Ca
2+

11. Metabolism of calcium is under following
headings.
•Sources,
•RDA,
•Absorption, Transportation, excretion,
•Biochemical functions,
•Regulation and
•Clinical significance

12. Sources of Calcium
Good source: Milk. Calcium
content of cow’s milk is about
100 mg/100 mL.
Medium sources: Egg, fish and
vegetables
Poor sources: Cereals (wheat, rice)

13. RDA of calcium
•Adult : 500 mg/day
•Children : 1200 mg/day.
•Pregnancy and lactation: 1500 mg/day
•After the age of 50, there is a general tendency for
osteoporosis,
–which may be prevented by increased calcium (1500
mg/day) plus vitamin D (20 μg/day).

14. Mechanism of Absorption of Calcium
Absorption, transportation and excretion: calcium is
absorbed from first and second part of duodenum.
•It is absorbed against a concentration gradient with help
of calcium pump (carrier protein) and requires energy
and helped by calcium-dependent ATPase.

15. -Calcitriol –active form
of vitamin, increases the
absorption of calcium by
inducing the synthesis of
calcium binding protein
calbindin.
Factors increases the absorption of calcium

16. -Parathyroid Hormone (PTH) - increases the absorption
of calcium by increasing the transport of calcium from
the intestinal cells
-Acidity- increases the absorption of calcium
-Amino acids- like lysine and arginine, sugar and acids
also increases the absorption of calcium

17. Factors decreases the absorption of calcium
1.Phytates (present in cereals) and oxalates (leafy
vegetables) present in various foods form insoluble salts
and interfere with Ca absorption.
2.High content of dietary phosphate results in the
formation of insoluble calcium phosphate and prevents
Ca uptake. The dietary ratio of Ca and P between 1:2 and
2:1 is ideal for optimum Ca absorption by intestinal cells.
3.The free fatty acids react with Ca to form insoluble
calcium soaps. This is particularly observed when the fat
absorption is impaired (malabsorption syndrome).

18. Factors decreases the absorption of calcium
4.Alkaline condition (high pH) is unfavorable for Ca
absorption.
5.High content of dietary fiber interferes with Ca
absorption.
6.Optimum ratio of Ca to P which allows maximum
absorption is 1:2 to 2:1 as present in milk.

19. Functions of calcium:
1.Plays an important role in calcification (mineralization) of
bones and teeth.
2.Necessary for Regulation certain enzymes;
–activation of enzymes like calcium- glycogen synthase,
PDH, amylase, myosin kinase, magnesium ATPase,
Adenylate cyclase, and protein kinases,,
–inhibits the enzymes like pyruvate kinase, Trypsin etc.
3. Calcium increases contraction and excitation of muscles by
activating the activity of actin and myosin

20. Functions of calcium:
4.Ca++ prolongs systole. In hypercalcemia, cardiac arrest is
seen in systole.
5.Calcium is coagulation factor-IV, calcium plays an
important role in blood coagulation by converting
prothrombin to thrombin.
6.Acts as second messenger for hormones action- Ex:
glucagon.
7.Plays an important role in release of certain hormones
like insulin, vasopressin, PTH etc.

21. 8.Necessary for transmission of nerve impulses from
pre-synaptic to post-synaptic region.
9.Involved in secretary process like endocytosis and
exocytosis
10.Calcium plays an important role in permeability in gap
junction
11.Plays an important role in vascular permeability-
Calcium decreases the passage of serum through
capillaries. Thus, calcium is clinically used to reduce
allergic exudates.

22. Regulation of blood calcium level:
•Normal blood calcium level ranges from 9-11mg/dl.
•Blood calcium level is regulated by three hormones
namely
–Calcitriol
–Parathyroid hormone (PTH)
–calcitonin
•acted mainly on three main organs Bone, Kidney, Intestine.
•Calcitriol and PTH increases blood calcium level where as
calcitonin decreases blood calcium level

23. Overview of calcium homeostasis
(Parathyroid hormone)

24. Homeostasis of Blood Calcium Level
Calcitriol, parathyroid
hormone (PTH) and calcitonin
are the major factors that
regulate the plasma calcium.
When serum calcium is low,
PTH is stimulated, resulting in
increased calcium release from
bone and decreased renal
calcium excretion. PTH also
stimulates increased production
of calcitriol, which acts to
increase absorption of calcium
from intestine.

25. Homeostasis of Blood Calcium Level
When serum calcium is
high, Calcitonin (CT)
secreted by parafollicular cells
of thyroid gland.
calcitonin promotes
calcification by increasing the
activity of osteoblast.
Decreases bone resorption and
increases the excretion of Ca
into urine.
CT, therefore, has a
decreasing influence on blood
calcium.

26. Regulate the plasma calcium by Calcitriol,
parathyroid hormone (PTH) and calcitonin in
detail

27. •Calcitriol: it is a hormone formed from cholecalciferol.
Cholecalciferol undergoes hydroxylation in the liver to form 25-
OH cholecalciferol with the help of an enzyme 25-hydroxylase.
25-OH cholecalciferol undergoes further hydroxylation in kidney
with the help of an enzyme α-hydroxylase to form 1,25
dihydroxycholecalciferol.
•Calcitriol increases blood calcium level by
•Inducing the synthesis of calcium binding protein calbindin in the
intestinal cells genetically.
•By increasing the number and activity of osteoblasts and there by
leading to the mineralization of bones
•By increasing the reabsorption of calcium and phosphorus by
renal tubules

28. •Parathyroid hormone (PTH)- secreted by chief cells of
parathyroid glands, secreted as pre-prohormone with 115 amino
acids converts to pro-hormone with 90 amino acids and finally to
hormone with 84 amino acids.
•It concentration is increased in primary and secondary
hyperparathyroidism.
•PTH increases blood calcium level by
–Increasing the demineralization and decalcification of bones
–By Increasing the reabsorption of calcium from renal tubules
–By increasing the synthesis of calcitriol in the kidney by
stimulating the activity of an enzyme α-hydroxylase which in
turn increases absorption of calcium in the intestine.

29. •Calcitonin- secreted by para-follicular cells of thyroid and thymus
gland, single polypeptide chain with 32-34 amino acids, secretion
is stimulated by glucagon, gastrin and other gastrointestinal
peptides.
•Calcitonin decreases blood calcium level by decreasing the
activity of osteoclasts and increasing that of osteoblasts and also
by increasing the excretion of calcium through kidneys
✓Inducing the synthesis of calcium binding protein calbindin in
the intestinal cells genetically.
✓By increasing the number and activity of osteoblasts and there
by leading to the mineralization of bones
✓ By increasing the reabsorption of calcium and phosphorus by
renal tubules.

30. Clinical significance:
•Normal blood calcium level ranges from 9-11mg/dl.
•Estimated by O-Cresolphthalein complexone (OCPC) and also by
Arsenezo-II method.
Disorders of calcium metabolism
Hypocalcemia: decreased blood calcium level below the normal
range is called as hypocalcemia
Causes for hypocalcemia: Rickets, Osteoporosis,
Hypoparathyroidism, Medullary carcinoma of thyroid, Acute
pancreatitis, Intestinal malabsorption, Renal tubular acidosis,
Nephrotic syndrome, renal failure and hepatic diseases are some
of the important causes for hypocalcemia

31. •Symptoms and signs of hypocalcemia: convulsions, muscle
cramps, spasm (involuntary contraction of muscle), neuromuscular
irritability, stridor (high pitched whistling sound while taking a
breath) and bradycardia (slow heart rate).
•Tetany: occurs when blood calcium goes below 7.0 mg/dl. It is
also due to surgical removal of parathyroid gland and autoimmune
diseases.
•The three major symptoms of Tetany are carpopedal spasm with
tingling around mouth and distal parts of limbs.

32. Contraction of facial muscle in response
to tapping the facial nerve
Chvostek’s
sign
Carpal spasm occurring after occlusion of
the brachial artery with BP cuff for 3 min
Trousseau’s
sign

35. Laboratory changes in tetany:
•Decreased blood calcium level along with phosphate
•There is increased excretion of both calcium and phosphate in
urine
•There is increased QT interval
Treatment: intravenous administration of 10% 10 ml of calcium
gluconate and also followed by oral supplementation of calcium
along with vitamin D

36. Hypercalcemia: increased blood calcium level more than the normal
range is called as Hypercalcemia
Causes for Hypercalcemia :
Hyperparathyroidism, Multiple Myeloma, Metastatic Carcinoma of
Bone, Thyrotoxicosis, Addison’s Disease, Tuberculosis, Leprosy,
Paget's disease of bone.

37. Signs and Symptoms of hypercalcemia:
•Polyurea, polydipsea, osteoporosis and pathological fractures,
renal stones are some of the important symptoms and signs of
hypercalcemia.
Laboratory changes:
•Increased blood calcium level
•Decreased serum phosphate level
•Increased ALP
•Increased excretion of calcium in turn causes Increased excretion
of chloride leading to hyperchloremic acidosis.

38. Calcium Deficiencies
•Rickets
–in growing Children
•Osteomalacia (osteoporosis)
–in adults

39. •Disorder of defective calcification of bones.
•May be due to low levels of vit. D in the body.
•Or due to dietary deficiency of Ca and P or both.
•Conc. of serum Ca and p are below normal.
•Increase in activity of alkaline phosphatase (ALP) is
characteristic feature.

41. •Associated with damage to renal tissue.
•Causes impairment in synthesis of calcitriol.
•Treated with administration of calcitriol.

42. Osteoporosis
•Characterized by demineralization of bone. Progressive loss of bone mass.
•Occurs in elderly people (above 60 yr) in both the sexes.
•Most predominant in post menopausal women.
•Frequent bone fractures occur.
Etiology – largely unknown, but it is believed that several causative factors
occur as follows –
•Ability to produce calcitriol from vit. D is reduced.
•Deficiency of sex hormones in women has implicated in development of
osteoporosis.
Treatment – estrogen is administered along Ca to post menopausal women.
•High dietary intake of Ca is recommended.

43. PHOSPHORUS

44. Metabolism of phosphorus-
•Also macro mineral, intra cellular ion and the total body
content of phosphorus is about 1kg of which 80%
present in bones and teeth and remaining 10% is present
in muscles.

45. Sources:
good source :Milk
moderate sources: Cereals, nuts and meat eggs, cheese,
cereals and nuts.
RDA of phosphorus in adults : 500 – 700 mg/day
During pregnancy and lactation the requirement is 1200
mg/day.

46. •Dietary phosphorus is absorbed from small intestine and
the absorption is affected by different factors as that of
calcium absorption, increased by both PTH and
calcitriol. Excess use of antacids decreases the
absorption of phosphorus.
•About 90% of filtered phosphorus is reabsorbed by renal
tubules and remaining excreted through i.e. about 0.8 -
1.3 gm of phosphorus excreted through urine.

47. Functions of phosphorus :
1.Formation of bone and teeth
2.Production of high energy phosphate compounds such as
ATP, CTP, GTP, CPK, PAPS etc.
3.Synthesis of nucleoside coenzymes such as NADP
+
and
NADPH
+
4.DNA and RNA synthesis, (phosphodiester linkages)
5.Formation of phosphate esters, such as glucose-6-phosphate
6.Formation of phosphoproteins, e.g. casein
7.Activation of enzymes by phosphorylation
8.Phosphate buffer system in blood. The ratio of Na
2HPO4:
NaH
2PO4 in blood is 4:1 at pH of 7.4

48. Hormonal regulation of serum phosphate levels
•Serum phosphate level is regulated by calcitriol, PTH
and calcitonin.
•Calcitriol increases the serum phosphate level by
increasing its absorption from intestines and kidneys
•Plasma phosphate concentration is controlled by the
kidney, where tubular reabsorption is reduced by PTH.
•The phosphate which is not reabsorbed in the renal
tubule acts as an important urinary buffer.

49. Disorders associated with phosphorus/ Clinical
importance of phosphorus.
Normal serum inorganic phosphate concentration:
Adults: 3-4 mg/dl.
Children: 5-6 mg/dl higher than adults because of
increased bone turnover
It is estimated by Fiske Subbarao method

50. •Hyperphosphatemia and hypophosphatemia are the two disorders
associated with phosphorus
•Hyperphosphatemia- Increased serum/plasma phosphorus
concentration above the normal is called as Hyperphosphatemia.
Causes of hyperphosphatemia
•Hypoparathyroidism,
•Hypervitaminosis- D,
•Diabetes mellitus (DM),
•Renal diseases
•Malignancy and Hemolysis,
•Symptoms of Hyperphosphatemia are because of increased serum
phosphate and decreased in calcium level. Tetany and seizers are the two
important symptoms of Hyperphosphatemia

51. Hypophosphatemia- Decreased serum/plasma phosphorus concentration
below the normal levels is called as Hypophosphatemia.
Causes of Hypophosphatemia
•Hyperparathyroidism,
•Vitamin D deficiency,
•Renal rickets,
•Liver diseases,
•Starvation,
•Vomiting,
•Malabsorption syndrome
Symptoms of Hypophosphatemia are muscle pain, weakness, respiratory
failure and decreased myocardial output.

52. Iron (Fe)

53. Iron metabolism: Important trace element in the body
•Total body content of iron is about 3-5 gms,
•out of which about 75% present in the RBCs constituent
of Hemoglobin (Hb).
•Remaining present in liver, bone marrow and muscles.
•It is present in almost all the cells.
•Heme is the most predominant iron-containing
substance. It is a constituent of several
proteins/enzymes (hemoproteins)

54. Functions of iron : Iron mainly
exerts its functions through the
compounds in which it is present.
Iron containing compounds includes
– Heme and Non-heme
compounds
Heme iron containing compounds
are
•Hb- transport of oxygen to the
tissues and CO
2 from tissues to the
lungs

55. •Myoglobin (Mb) – storage site of oxygen in muscles
•Cytochrome b (Cyt–b), Cyt–c and cytochrome
oxidase- involved in ETC (Electron Transport chain).
•Catalase – catalyses the conversion of H
2O
2 to H
2O
and superoxide.
•Tryptophan pyrrolase – involved in tryptophan
metabolism
•Cyt p450 – detoxification process

56. •Non-heme iron compounds are
–Xanthine oxidase – conversion of hypoxanthine to
xanthine and finally to uric acid.
–Transferrin – transport of iron into plasma
–Ferritin – storage form of iron
–Iron sulfur proteins- involved in ETC (Electron
transport chain).

57. Sources:
Richest source : Jaggery, other rich sources includes
meat, eggs, fruits - apple, and yeast.
Moderate sources: Green leafy vegetables, pulses,
cereals, fish.
Very poor source: Milk and milk product.

58. RDA:
–Adult men – about 20 mg/day
–Children – 20 to 30 mg/day
–Pregnancy and lactation - 40 mg/day

59. Absorbed by upper part of duodenum.
Iron is one way substance because iron homeostasis is
maintained by regulation at the level of absorption and
not by excretion.
Only ferrous form of iron is absorbed.
Factors that increase the iron absorption are:
•Gastric HCl, vitamin C, cysteine and sulfhydryl group
of proteins favour the absorption of iron by converting
ferric form iron to ferrous form and
•also iron deficiency increases the absorption of iron.

60. Factors that decreases the iron absorption are :
Presence of phytates (in cereals) and oxalates (in leafy
vegetables) present in cereals and leafy vegetables,
ingestion of antacids, gastric surgery, lead and
phosphates etc.

61. Iron Absorption and Transport in Gastro intestinal tract :

62. •In the lumen of GIT ferric form of iron present in the food first
converts to ferrous form by gastric HCl and vitamin C. then the
ferrous iron enters into the mucosal cells of GIT.
•In the mucosal cells of GIT, ferrous iron in oxidized to ferric form
with the help of an enzyme ferro-oxidase, then the ferric from
combines with apo-ferritin which is a temporary storage form of
iron in mucosal cells.
•Ferritin in the mucosal cells converts to ferrous form with the help
of an enzyme ferro-reductase. Then the ferrous from the mucosal
cells of the GIT enters into plasma.
•In the plasma ferrous form is oxidized to ferric form by copper
containing protein cerruloplasmin which has ferro-oxidase
activity.

63. •The ferric form of iron in the plasma binds with specific iron
binding protein apo-transferrin to form transferrin. Each
transferring molecule binds with two atoms of ferric iron.
•The transferrin may be stored in the liver, spleen and bone
marrow in the form of ferritin. And to some extent also stored
in bone marrow, muscles and other tissues. Under normal
conditions iron is stored as ferritin. When iron is in excess it is
stored as hemosiderin.
•It is mainly excreted through faeces- 0.7mg/day and very little
excreted through urine – 1 mg/day. Increased loss of iron in urine
occurs in nephrotic syndrome, because of loss of transferrin.

64. Disorders associated with iron metabolism are
•Iron deficiency anemia and
•Iron excess (iron toxicity)
Iron deficiency anemia- most prevalent world wide nutritional
disorder including developed countries.
Most commonly occurs in growing children, adolescent girls,
pregnancy and lactating women.
Strict vegetarians are most prone for iron deficiency anemia because
of presence of inhibitors of iron absorption in vegetarian foods.

65. •Iron deficiency is characterized by microcytic
hypochromic anemia. Anemia is diagnosed when
hemoglobin level is <10 g/dL and/or ferritin level is below
12 μg/dL.
•Some of the important causes of iron deficiency anemia
are
–Nutritional deficiency of Iron
–Hookworm infestation
–Repeated pregnancies
–Chronic blood loss may be due to Hemorrhoids (piles),
peptic ulcer, menorrhagia (Prolonged Bleeding)

66. –Decreased absorption
–Gastrectomy and Hypochlorhydria
–Gastrectomy and Hypochlorhydria
–Lead poisoning: Iron absorption and hemoglobin
synthesis are reduced. In turn, iron deficiency causes
more lead absorption
–Nephrosis: Haptoglobin, hemopexin and transferrin are
lost in urine, along with loss of iron.
–Chronic inflammatory conditions etc.

67. Signs and symptoms iron deficiency anemia:
•excessive tiredness, generalized weakness, lethargy
(lack of energy), apathy (lack of feeling or emotion)
giddiness, fatigue, head ache, loss of weight and
appetite, tingling sensations and inability to concentrate.
•Pallor, oedema, sore tongue and angular stomatitis and
koilonychia (spoon nail).

68. Hookworm infection

69. Iron deficiency anemia
Clinical Manifestations:
•Anemia , Apathy
•Impaired attention, irritability, lowered
memory
Nail changes
–Brittle/fragility
–Koilonchia/spooning
–Hair loss
–Glossitis
–Angular stomatitis
Koilonychia or “spoon nail” in
chronic iron deficiency anemia.
Anglular stomatitis
Glossitis

70. Microscopy
•Peripheral blood smear
microcytic – hypochromic anemia
Normal Peripheral Smear
Iron Deficiency Anemia
H=hypochromic RBC; p=pencil RBC; T=target RBC; M=microcytic RBC
The Lancet 2000;355:1260
Iron Deficiency Anemia

71. Biochemical changes in iron deficiency anemia:
•Hb decreased,
•MCV (Mean corpuscular volume) Decreased,
•Peripheral smear shows microcytic hypo chromic picture.
•Total serum iron concentration is decreased, (100-150 µg/dl)
•TIBC – total iron binding capacity increased (250-400 µg/dl)
•Transferrin concentration is increased (200 -360 mg/dl)
•Ferritin concentration is decreased (2-25 µg/dl)
•Soluble transferrin receptors level increased

72. Treatment of iron deficiency anemia: Includes
•Treatment of underline cause
•Administration of iron preparations orally/ parenteraly
•Folic acid, vitamin C and vitamin E along with iron preparation
Iron toxicity/ iron over load: are of two types
•Hemosiderosis and
•Hemochromatosis
•Hemosiderosis is the initial stage of iron overload associated
with increased iron stores as hemosiderin without associated
tissue injury, where as Hemochromatosis is increased iron stores
as hemosiderin with tissue injury.

73. •Hemosiderosis is may be due to genetic defect in which iron
absorption is increased and transferrin level is also increased.
Cooking in iron vessels increases the availability of iron.
•Hemochromatosis may be primary or secondary. In primary
Hemochromatosis there is increased absorption of iron and iron
is deposited as hemosiderin in liver, pancreas, heart and other
organs. Secondary Hemochromatosis is due to acquired causes
like chronic iron over load, parenteral administration of iron,
repeated blood transfusion alcohol abuse etc.

74. Clinical symptoms of Hemochromatosis- are related to organs
involved like may be cirrhosis of liver, fibrosis of pancreas with
diabetes mellitus and skin pigmentation.
•Cirrhosis of liver, hemosiderin deposition under the skin causing
yellow brown coloration of skin, pancreatic cell death leading to
diabetes collectively called as Bronze diabetes
•accumulation of iron in joints leads to arthritis, in heart leading to
arrhythmias
Treatment of Iron toxicity- phlebotomy and administration of iron
chelating agent Deferoxamine.

75. Minerals- Assignment Questions
Long assays:
1.Write the Sources, RDA, functions and disorders associated
with iron deficiency, add a note on excess iron load in the body.
2.Write the Sources, RDA, functions, normal serum levels and
disorders associated with calcium metabolism
3.Write the Sources, RDA, functions, normal serum levels and
disorders associated withphosphorus.
Short Answer:
4.What are minerals and how they are classified?