Bulk elements/ macroelements
o Required in >100 mg/day in the diet
o Required in <100mg/day in diet
Possibly essential trace elements
o Considered to be essential, though actual function is not yet known
2. Tin bromine
Unessential but found in diet
o Found in food but toxic
Milk and milk products
Egg, fish and meat
Vegetables, cereals, pulses, nuts
Recommended dietary allowance (RDA):
ADULT: 500 mg/day
Children: 1200 mg/day
Pregnant and lactating: 1500 mg/day
Aged : 1500mg/day; vit D - 20µg/day to facilitate Calcium absorption
All functions are by the ionic form- Ca 2+
Constituent of bones and teeth
o Present as calcium hydroxy apatite crystals
o Provides strength and hardness
o Storehouse of calcium (i.e., if serum calcium level decreases, it can be
supplied by the bones)
o Factor IV
o Activation of other clotting factors- VIII, IX, X and prothrombin.
o Activates enzymes via calmodulin
Eg: adenylate cyclase, phosphorylase kinase, pyruvate carboxylase, pyruvate
dehydrogenase, glycogen synthase etc.
Role in muscle contraction
Role in nerve conduction
o Decreases neuromuscular excitability
o Counteracts the excitatory effects of Na+ and K+
o Decreases serum Ca2+ - spasms – hypocalcemic tetany
In myocardium, it prolongs systole; if calcium level is very high, cardiac arrest
is caused in systole.
Release of stored hormones- insulin, PTH, calcitonin, ADH
Second messenger in hormonal action
o G proteins & inositol triphosphate
Secreted in milk
4. In first and second part of duodenum
Active process- against concentration gradient
Factors favouring absorption:
Vit D- active form- calcitriol- i.e., 1, 25-dihydroxy cholecalciferol
o Increases synthesis of carrier protein CALBINDIN
o Action of Vit D is similar to that of steroid hormones; hence it itself is
considered as a hormone.
o Increases calcium absorption by activating Vit D through 1αhydroxylase
Acidity if increased in intestine favours calcium absorption
The amino acids lysine and arginine also favour absorption.
Factors decreasing absorption:
Phytates like inositol hexaphosphate
Oxalates precipitate calcium as calcium oxalate
The change in Ca : P ratio from the normal range of (2:1 to 1:2) decreases
Normal : 9-11 mg/dL
Torniquet should not be tied while testing Ca2+ levels as it will give wrong higher
Calcium exists in three forms in serum
o Ionic calcium (Ca2+) – 50%
o Anions (phosphate/ citrate/ oxalate/ complexes) < 1 mg
o Bound to albumin (protein bound calcium)- 4mg/dL
o First two are called diffusible calcium
5. 1. Effect of Vit D
On intestine: increase synthesis of calbindin thus increasing calcium
On bone: calcification (deposition of calcium & phosphate in bone
mineralisation) and also increase osteoblast activity thus decreasing serum
On kidney: decreases excretion/ increases reabsorption of calcium thus
increasing serum calcium levels.
Overall : hypercalcemic effect
2. Effect of PTH
On bone: causes resorption/ demineralisation by stimulating osteoclasts
On kidney: increases reabsorption of calcium; excretion of phosphorus
On intestine: increases absorption of calcium
Overall: hypercalcemic effect
3. Effect of calcitonin
Secreted by parafollicular cells of thyroid
32 amino acids
On bone: deposition of calcium & phosphorus (mineralisation)
On intestine: decreases absorption but not prominent
On kidney: not much action, probably increases excretion of calcium
Overall: hypocalcemic effect
In medullary carcinoma of thyroid, calcitonin concentration increases; hence is
used as tumour marker.
4. Phosphorus level inversely affects calcium level.
i.e,. Ca × P = 40, a constant (higher in children)
5. Serum protein levels
1 g decrease in serum albumin leads to 0.8 mg decrease in serum calcium
6. 6. pH of plasma
Alkalosis – makes ionic Ca bind with protein – ionic Ca decreases – causes
7. In children, serum Ca level is closer to the upper limit
8. Renal threshold – 10 mg/dL
Deposition in kidneys along with phosphorus – tubular damage and renal
Deposition in extra osseous tissues
Decrease in neuromuscular excitability characterised by constipation,
abdominal pain, muscular hypotonia
In heart if the level goes beyond 15 mg/dL, cardiac arrest is caused.
Excess intake/ increased absorption of Vit D/ calcium/ both.
Sarcoidosis – increased sensitivity to Vit D – increased Ca absorption
Secondary malignancies (carcinoma) in bone
Drugs like thiazides (diuretic)
Tetany (only when IONIC calcium decreases) – tested using CHVOSTEK’S SIGN
& TROUSSEAU SIGN
7. Usually asymptomatic
Carpopedal spasm (affects hands, feet, face & larynx)
Chronic renal failure
Defecient intake/ dietary defeciency/ decreased absorption of Ca and Vit D
Diseases of pancreas, biliary tract and intestine
Hypoparathyroidism – acquired/ idiopathic
Neonatal hypocalcemia due to maternal hyperparathyroidism
Renal tubular defects
Sources: milk, meat, fish, eggs, vegetables
RDA: 500 mg/day in adults; >1 g in children
Absorption: in mid jejunum as inorganic phosphorus (mechanism not clearly
Factors affecting absorption:
Ca : P ratio of 2:1 to 1:2 has best absorption
Vit D increases phosphorus absorption
PTH increases P absorption
Calcitonin decreases P absorption
Iron and phytic acid decrease absorption by binding with P and forming
Component of bones and teeth
Totally, 1 kg of phosphorus is found in body,
8. o 80% in bones and teeth
o 10% in muscles
o 10% in cells
As components of high energy compounds like ATP, GTP, CTP, carbamoyl
phosphate, creatine phosphate, PEP etc.
Intermediates in carbohydrate metabolism are phosphate derivatives.
In lipid metabolism,
o Intermediates of TAG synthesis are phosphate derivatives
o As components of membranes (phospholipids)
In the nucleotides and nucleic acids, backbone has phosphate
In acid base balance, as phosphate buffer system
Component of coenzymes like TPP, PLP, NAD+, NADP+, FMN, FAD, CoA etc.
Regulation of enzyme activity by phosphorylation and dephosphorylation. eg.,
glycogen synthase and glycogen phosphorylase
Normal: 2.5 – 4.5 mg/dL in adults; 4 – 6 mg/dL in children
To estimate serum P level, hemolysis of collected blood must be avoided.
Regulation of serum P level:
In intestine: increases absorption
In bone: bone resorption
These increase serum P level
In kidneys: phosphaturic effect
This decreases serum P level, which is more pronounced. Therefore, overall
effect if decrease in serum P level
9. In bone: decreases resorption
In intestine: decreases absorption
In kidneys: increases phosphaturia
Overall effect is decrease in serum P level
Calcitriol/ vit D
In intestine: increases absorption
In kidneys: increases reabsorption
These increase serum P level
In bones: increases mineralization
This decreases serum P level. Overall effect is increase in serum P level.
Hyperphosphatemia: no definite symptoms seen
Excess Vit D
Hypoparathyroidism and pseudohypoparathyroidism
Hypophosphatemia: anorexia, bone pain, muscular weakness, dizziness
Rickets and osteomalacia
Steatorrhea – decreases fat absorption – decreases Vit D absorption
Sources: green leafy vegetables, cereals, pulses, jaggery, fish, meat, liver. Milk is a
very poor source.
RDA: males: 20 mg, females: 30 mg, pregnant: 40 mg per day.
Functions: totally, 3 to 5 g of iron is found in body.
Part of proteins. They are of two types:
o Heme proteins
Enzymes like cytochromes, tryptophan pyrrolase, catalase,
o Non heme iron proteins
Aconitase – activated by iron
o 75% in Hb; 5% in Mb; 20% in other proteins.
Absorption: only 10% of iron intake is absorbed from upper duodenum
Factors affecting absorption:
Gastric HCl liberates Fe3+ from food, favouring absorption
G-SH, Vit C, ferrireductase, -SH of cysteine help to convert Fe3+ to Fe2+
Vit C and amino acids form soluble chelates (iron ascorbate and iron
aminoacid) favouring absorption.
In blood, through transferrin
Each transferrin has 2 binding sites for iron
300 mg of transferrin present in 100 mL of blood can bind with 400 μg of Fe3+
(range 250 to 400 μg) – Total Iron Binding Capacity (TIBC)
But, only one third of the sites are used in normal individual. Therefore, total
serum iron is 100 to 150 μg/dL
In liver diseases, TIBC decreases
In iron deficiency anemia, TIBC increases.
Uptake of iron:
By reticulocytes in bone marrow
By receptor mediated process in reticulocyte membrane.
Receptor + transferrin
Goes back to its membrane site
Receptor remains; apotransferrin returns to blood
Storage : in ferritin
Has 24 subunits
13. Can bind to 4000 atoms of Fe3+, but in normal, only 2000 Fe3+ are bound
to one ferritin molecule.
20% of iron is in this form.
Insoluble, amorphous form of iron
37% of iron is in this form
Ferritin in centre, with aggregates of iron on it
Formed only during iron overload.
1 to 1.5 mg/day through faeces
Unabsorbed iron and iron from the desquamated mucosal cells.
Iron deficiency anemia
Most common nutritional deficiency disorder
30% of world’s population is anemic
In India, it is 70%; in pregnants, 80% are anemic
Microcytic, hypochromic type.
Lack of nutrition
o The food may not contain iron
o Phytates and oxalates in food bind to iron and prevent its absorption
Hookworm infection (one worm – 0.3 mL blood/day)
Repeated pregnancies (1 g iron lost per pregnancy)
Chronic blood loss
o Peptic ulcers
14. o Menorrhagia
o Loss of haptoglobin (binds Hb), haemopexin (binds heme) and transferrin
Lead poisoning (it inhibits ALA dehydratase – decreased Hb synthesis)
Lack of absorption after gastrectomy
Person becomes uninterested – apathetic – due to decreased O2
Decreased ATP synthesis as iron is a component of cytochromes
Atrophy of gastric epithelium
Dysphagia – Plummer Wilson syndrome – precancerous condition
Impaired attention, irritability, poor memory – decreased scholastic performance
Person becomes less efficient.
Hb < 12 g/dL
Serum iron < 100 μg/dL
Treating the underlying cause than the symptoms.
Iron and folic acid - 100 mg & 500 μg in pregnants; 20 mg & 100 μg in
Golden brown granules of hemosiderin accumulate in liver and spleen
Seen in patients receiving repeated blood transfusion as in thalassemia,
15. Hemochromatosis/Bronze diabetes:
Total body iron > 30 g (normal 4 to 5 g)
Hemosiderin in large quantity, in liver – liver cirrhosis; in pancreas – diabetes;
in skin – brown appearance
Found in African Bantu tribe
Due to cooking in iron vessels
Sources: all green vegetables (chlorophyll has Mg)
RDA: 350 mg/day
Total body Mg content: 25 g
60% of body’s Mg is found in bones and teeth
Cofactor for enzymes utilizing ATP, like kinases (PFK, alkaline phosphatase,
hexokinase, cAMP dependent kinases.
In body, Mg-ATP complex is found.
Mg-ATP is substrate for adenylate cyclase
to form cAMP
Activation of myosin ATPase
Nucleic acid and protein biosynthesis need Mg as cofactor – polymerases,
aminoacyl tRNA synthetase
Reduces neuromuscular excitability
Mg deficiency – hypomagnesemic tetany
Serum levels: 1.8 to 2.2 mg/dL
Severe, prolonged diarrhea
Protein Calorie Malnutrition (PCM)
Alcoholism and malnutrition
Increased use of Mg containing laxatives and antacids
RDA: 2 – 3 mg/day
Total body copper content: 100 mg
Serum concentration: 70 to 140 μg/dL
Transport: bound to albumin
Role in iron metabolism (component of ceroluplasmin/ferroxidase)
Deficient ceruloplasmin – iron deficiency anemia – CANNOT be treated by oral
iron therapy (normal blood concentration of ceruloplasmin (an acute phase
protein) is 25 to 50 mg/dL
Component of the enzyme superoxide dismutase. This enzyme is of two types:
o Cytosolic – has 2 Zn2+ and 2 Cu2+ per molecule
o Mitochondrial – has 2 Zn2+ and 2 Mn2+ per molecule
For cross linking of collagen, enzyme lysyl oxidase has Cu.
17. Tyrosinase needs copper.
Other enzymes requiring copper are cytochrome oxidase, tryptophan pyrrolase,
dopamine β hydroxylase, monoamine oxidase, δ ALA synthase.
Copper increases HDL concentration.
Wilson’s disease (hepato-lenticular degeneration):
Decrease in plasma ceruloplasmin
Due to defect in gene coding for Cu containing ATPase
Liver cirrhosis due to Cu deposition
In lentiform nucleus of brain, Cu is deposited, leading to Parkinson’s disease
Damage to kidney tubules – aminoaciduria
Deposition in pancreas – diabetes
Deposition in edges of cornea – in Descemet’s membrane, forming golden
brown/blue/green ring (Kayser-Fleischer ring)
Penicillamine – chelating agent
Menke’s kinky/steely hair disease:
Deficient Cu binding ATPase.
RDA: 10 to 15 mg/day
Total body zinc content: 2 to 3 g
Component of enzymes
o More than 300 enzymes need Zn2+ as cofactor.
o Eg., superoxide dismutase, carbonic anhydrase, alcohol dehydrogenase,
LDH, glutamate dehydrogenase, retinine reductase, RNA polymerase.
Vit A metabolism
18. o Stimulates Vit A from liver
o Increases plasma Vit A level and its utilization in Rhodopsin cycle
Role in taste
o Protein gusten in saliva needs Zn
For growth and reproduction
Role in insulin action
o For storage and release of insulin
Promotes wound healing, mechanism not known
Loss of appetite, poor growth, dermatitis, impaired wound healing, decreased
taste sensation (hypogeusia), loss of hair (alopesia), fetal malformations.
Disorder: Acrodermatitis enteropathica
Disorder of Zn absorption
Characterized by acrodermatitis
Skin lesion around mouth, teeth, fingers
Source: commercial salt
RDA: 150 to 200 μg/day
Total body iodine content: 25 to 30 mg; 80% of it is in thyroid gland
Function: component of thyroxin hormones – T3 and T4
Second major micronutrient deficiency in India (first place for iron, third place
for Vit A)
Goitrous belt – areas rich in goitre patients; along the Himalayas
o Present in food
o Decrease iodine utilization
o Present in cassava tubers, bamboo, sweet potato
o Cabbage and tapioca have thiocyanate which inhibits iodine uptake by
o Mustard seeds have thiourea inhibits iodination of tyrosine in
Drinking water is the main source
Other sources are sea fish, tea, cheese, jowar, toothpaste
RDA: 2 to 4 mg/day
Present as fluoride ion.
In places where water has fluoride >1 ppm (0.1 mg/dL), people are resistant to
o Mode of action: fluoride gets incorporated to enamel of teeth and makes
it resistant to organic acids of bacteria
Makes bone resistant to osteoporosis
Inhibits enolase, thus stops glycolysis.
Excess of fluoride (>3 to 5 ppm, also goes as high as 20 ppm) in drinking water
Mottling of teeth
Chalky appearance of teeth, brown pigmentation
Pitting of teeth – pieces of teeth may be lost
Alternate areas of osteosclerosis and osteoporosis.
Component of enzymes
o Superoxide dismutase – mitochondrial component
o Isocitrate dehydrogenase
Many kinases, hydrolases, decarboxylases need Mn
Activation of glycosyl transferases, to synthesize oligosaccharides,
proteoglycans and glycoproteins
In animals, for normal reproduction and bone formation.
Component of glutathione peroxidase, hence acts as antioxidant
It has sparing effect on Vit E and vice versa
Part of 5-deiodinase needed to convert T4 to T3
Component of thioredoxin reductase
Amino acid selenocysteine (SeCys/SeC) is the 21st amino acid
o It has –SeH group instead of –SH group
o It is incorporated into proteins; coded by stop codon UGA
Liver necrosis and cirrhosis
Cardiomyopathy, muscular dystrophy
Seen in Keschan province in China
Soil contains less Se causing deficiency
21. Cardiac necrosis, arrhythmia
Component of molybdoflavo enzymes xanthine oxidase and aldehyde oxidase
Also found in sulfite oxidase and nitrite reductase
Component of cobalamin
Stimulates formation of erythropoietin
Activates glycyl glycine dipeptidase
Role in glucose metabolism – increases glucose tolerance of an individual.