MINERALS

Classification:

Bulk elements/ macroelements

o Required in >100 mg/day in the diet

Calcium

Potassium

Magnesium

Sodium

Potassium

Chloride

Sulfur

Trace elements

o Required in <100mg/day in diet

Iron

Iodine

Copper

Manganese

Zinc

Molybdenum

Selenium

Fluoride

Cobalt

chromium

Possibly essential trace elements

o Considered to be essential, though actual function is not yet known

Nickel

Tin bromine

Lithium

barium

Unessential but found in diet

Rubidium

Silver

Gold

Bismuth

Toxic minerals

o Found in food but toxic

Lead

Aluminium

Mercury

Arsenic

cadmium

CALCIUM

Sources:

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

Functions:

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)

Blood coagulation

o Factor IV

o Activation of other clotting factors- VIII, IX, X and prothrombin.

Enzyme action

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

Neuromuscular excitability

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

Absorption:

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.

Parathormone (PTH)

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

Malabsorption syndromes

The change in Ca : P ratio from the normal range of (2:1 to 1:2) decreases

absorption

Serum calcium:

Normal : 9-11 mg/dL

Torniquet should not be tied while testing Ca2+ levels as it will give wrong higher

values.

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

Regulation:

1. Effect of Vit D

On intestine: increase synthesis of calbindin thus increasing calcium

absorption

On bone: calcification (deposition of calcium & phosphate in bone

mineralisation) and also increase osteoblast activity thus decreasing serum

calcium level

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

(phosphaturic effect)

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. pH of plasma

Alkalosis – makes ionic Ca bind with protein – ionic Ca decreases – causes

tetany

7. In children, serum Ca level is closer to the upper limit

8. Renal threshold – 10 mg/dL

Hypercalcemia:

Effects:

Deposition in kidneys along with phosphorus – tubular damage and renal

calculi

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.

Causes:

Hyperparathyroidism

Excess intake/ increased absorption of Vit D/ calcium/ both.

Sarcoidosis – increased sensitivity to Vit D – increased Ca absorption

Secondary malignancies (carcinoma) in bone

Leukemias

Paget’s disease

Osteoporosis

Thyrotoxicosis

Drugs like thiazides (diuretic)

Hypocalcemia:

Effects:

Tetany (only when IONIC calcium decreases) – tested using CHVOSTEK’S SIGN

& TROUSSEAU SIGN

Usually asymptomatic

Carpopedal spasm (affects hands, feet, face & larynx)

Causes:

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

Hypoproteinemia

Acute pancreatitis

Renal tubular defects

PHOSPHORUS

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

understood)

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

complexes

Functions:

Component of bones and teeth

Totally, 1 kg of phosphorus is found in body,

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)

Phosphoproteins

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

Serum phosphorus:

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:

PTH

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

Calcitonin

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

Causes:

Excess Vit D

Renal failure

Hypoparathyroidism and pseudohypoparathyroidism

Diabetic ketosis

Healing fractures

Acromegaly

Hypophosphatemia: anorexia, bone pain, muscular weakness, dizziness

Causes:

Hyperparathyroidism

Rickets and osteomalacia

Hyperinsulinism

Steatorrhea – decreases fat absorption – decreases Vit D absorption

Fanconis syndrome

IRON

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

Hb, Mb

Enzymes like cytochromes, tryptophan pyrrolase, catalase,

peroxidase

o Non heme iron proteins

Fe-S centres

Aconitase – activated by iron

Ferritin

Transferrin

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.

Transport:

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

Receptor-transferrin complex

Internalized

Iron liberated

Receptor-apotransferrin complex

Goes back to its membrane site

Receptor remains; apotransferrin returns to blood

Storage : in ferritin

Has 24 subunits

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.

Hemosiderin:

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.

Excretion:

1 to 1.5 mg/day through faeces

Unabsorbed iron and iron from the desquamated mucosal cells.

Disorders:

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.

Causes:

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 Haemorrhoids/piles

o Peptic ulcers

o Menorrhagia

Nephrosis

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

Hypoclorrhydria

Clinical manifestations:

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.

Lab findings:

Hb < 12 g/dL

Serum iron < 100 μg/dL

Increased TIBC

Treatment:

Treating the underlying cause than the symptoms.

Iron and folic acid - 100 mg & 500 μg in pregnants; 20 mg & 100 μg in

children

Iron toxicity:

Hemosiderosis:

Golden brown granules of hemosiderin accumulate in liver and spleen

Seen in patients receiving repeated blood transfusion as in thalassemia,

hemophilia etc.

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

Bantu siderosis:

Found in African Bantu tribe

Due to cooking in iron vessels

MAGNESIUM

Sources: all green vegetables (chlorophyll has Mg)

RDA: 350 mg/day

Total body Mg content: 25 g

Functions:

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

Hypomagnesemia:

Causes:

Severe, prolonged diarrhea

Malabsorption

Protein Calorie Malnutrition (PCM)

Alcoholism and malnutrition

Hypermagnesemia:

CNS depression

Lousiness, lethargia

Causes:

Increased use of Mg containing laxatives and antacids

Renal failure

COPPER

RDA: 2 – 3 mg/day

Total body copper content: 100 mg

Serum concentration: 70 to 140 μg/dL

Transport: bound to albumin

Functions:

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.

Tyrosinase needs copper.

Other enzymes requiring copper are cytochrome oxidase, tryptophan pyrrolase,

dopamine β hydroxylase, monoamine oxidase, δ ALA synthase.

Copper increases HDL concentration.

Disorders:

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

like symptoms

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.

ZINC

RDA: 10 to 15 mg/day

Total body zinc content: 2 to 3 g

Functions:

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

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

Defeciency manifestations:

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

Diarrhea

IODINE

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

Deficiency:

Second major micronutrient deficiency in India (first place for iron, third place

for Vit A)

Goitre

Goitrous belt – areas rich in goitre patients; along the Himalayas

Goitrogens

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

thyroid gland

o Mustard seeds have thiourea inhibits iodination of tyrosine in

thyroglobulin.

FLUORINE

Source:

Drinking water is the main source

Other sources are sea fish, tea, cheese, jowar, toothpaste

RDA: 2 to 4 mg/day

Functions:

Present as fluoride ion.

In places where water has fluoride >1 ppm (0.1 mg/dL), people are resistant to

dental caries

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.

Fluorosis:

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.

MANGANESE

Component of enzymes

o Superoxide dismutase – mitochondrial component

o Arginase

o Isocitrate dehydrogenase

o Cholinesterase

o Enolase

Many kinases, hydrolases, decarboxylases need Mn

Activation of glycosyl transferases, to synthesize oligosaccharides,

proteoglycans and glycoproteins

In animals, for normal reproduction and bone formation.

SELENIUM

Functions:

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

Deficiency:

Liver necrosis and cirrhosis

Cardiomyopathy, muscular dystrophy

Keschan cardiomyopathy:

Seen in Keschan province in China

Soil contains less Se causing deficiency

Cardiac necrosis, arrhythmia

MOLYBDENUM

Component of molybdoflavo enzymes xanthine oxidase and aldehyde oxidase

Also found in sulfite oxidase and nitrite reductase

COBALT

Component of cobalamin

Stimulates formation of erythropoietin

Activates glycyl glycine dipeptidase

CHROMIUM

Role in glucose metabolism – increases glucose tolerance of an individual.