Mineral Metabolism- Notes Biochemistry And Clinical Pathology

Mineral Metabolism:
Living beings have organic and inorganic types of chemical constituents. The organic
constituents i.e. proteins, carbohydrates, fats etc. are made up of C, H, O and N. The
inorganic constituents described as ‘minerals’ comprise of the elements present in the body
other than C, H, O and N. Although they constitute a relatively small amount of the total
body tissues, they are essential for many vital processes.
There are 31 elements present in the body.
They are divided into two classes:
(1) Essential elements and
(2) Non-essential elements.
Essential elements:
Those which are essential to maintain the normal living state of a tissue.
They are again divided into two sub groups:
Macro elements:
They are required to be present in the diet, more than 1 mg.
Ex. Ca, P, Mg, Na, K, CI and S.
Micro elements:
They are 8 in number and utilized in trace quantities (in microgram or Nano-gram). Hence
they are called trace elements. These are Fe, Cu, Zn, Co, Mo, F, I and Mn.
Non-essential elements:
They are 8 in number. They are present in tissues but their functions if any are not clearly
defined. They include Al, B, Se, Cr, Br, As, Ti and Pb. Four additional elements, Ni, Tin,
Vanadium and Silicon have been suggested as essential trace elements in nutrition but their
implications for human nutrition are unknown.
The mineral elements present in the body are supplied in the diet. In poor diets consumed by
a large majority of people, calcium and iron deficiency occur commonly. Iodine deficiency
occurs in people living in certain hilly tracts, where the soil and water are deficient in iodine.
In tropical countries, addition of sodium chloride in the diet is of great importance, because
of the loss of NaCl in sweat. The deficiencies of other minerals do not occur normally in
average diets.
i. Sodium, potassium and chlorine are involved mainly in the maintenance of acid-base
balance and osmotic control of water metabolism.

ii. Calcium, phosphorus and magnesium are constituents of bone and teeth.
iii. Phosphorus is the constituent of body cells of the tissues, such as muscle, liver etc.
iv. Sulphur is present in cysteine, methionine, thiamine, biotin, lipoic acid and coenzyme A.
Calcium:
Source:
Milk (0.2 gm./100 ml) and cheese are important dietary sources. Other sources-are egg yolk,
lentils, nuts, cabbage, cauliflower and asparagus, etc.
Requirement:
(1) Men and women after 18 years of age require 800 mg/day.
(2) During lactation and in pregnancy of 2nd
and 3rd
term 1.2 gm./day is required.
(3) Infants under 1 year require-360-540 mg/day.
(4) Children of 1-18 years need 800-1200 mg/day.
Absorption:
Calcium is taken in the diet as calcium phosphate, carbonate, tartarate and oxalate. Calcium is
absorbed actively in the upper small intestine. The active process is regulated by 1, 25
dihyrocholecalciferol, a metabolite of vitamin D which is produced in the kidney in response
to low plasma Ca++
concentrations. Absorption of calcium by the intestine is never complete.
Ca is absorbed by an active transport process occurring mainly in the upper small intestine.
Calcium absorption is influenced by the following factors:
1. Vitamin D promotes absorption of Ca.
2. Acidic pH favous calcium absorption because Ca salts (phosphate and carbonates) are
quite soluble in acid solution arid are relatively insoluble in alkaline solutions. Hence an
increase in acidophilic flora, e.g. lactobacilli is recommended to lower pH which favours the
absorption of Calcium.
3. Organic acids, lactose and basic amino acids in the diet favour calcium absorption.
4. Higher levels of proteins in the diet help to increase the absorption of calcium. On a high
protein diet, about 15% of the dietary calcium is absorbed, compared with 5% absorption on
a low protein diet. Certain calcium salts are much more soluble in aqueous solution of amino
acids than in water and thus absorption of calcium is increased in presence of amino acids.
5. If calcium: phosphorus ratio is much high, Ca3(PO4)2 will be formed and absorption of
calcium is reduced. The optimal ratio for both elements is about 1:1 (1:2 to 2:1) and with
ratios outside these limits, absorption is decreased. This is because of formation of insoluble
calcium phosphate.

6. When fat absorption is impaired much free fatty acids are formed due to hydrolysis. These
fatty acids react with free calcium to form insoluble calcium soap and then Ca is lost in
faeces.
7. Absorption of calcium is inhibited by a number of dietary factors that cause formation of
insoluble calcium salts, i.e. phytate (cereal grain), oxalate, phosphate and iron, etc.
8. High concentration of Mg in the diet decreases absorption of Ca.
9. Presence of excess fibre in the diet interferes with the absorption of Ca.
10. Percentage of calcium absorption decreases as its intake increases.
11. Parathyroid hormone increases the intestinal absorption of calcium.
12. Adrenal glucocorticoids diminish intestinal transport of Ca.
13. After the age of 55 to 60 there is gradual diminution of intestinal transport of calcium.
During menopause many women develop negative calcium-phosphorus balance leading to a
type of osteoporosis. This is usually accompanied by pain and fractures. The negative balance
of calcium and phosphorous are markedly improved by administration of estrogen or by
androgens such as testosterone. A combination of estrogen and androgen is more effective.
14. Kidney threshold regulates the blood calcium level. In a normal adult any extra calcium
absorbed from the intestine is readily excreted in the urine. In hypocalcaemia kidney
threshold also becomes abnormal.
15. Excess of iron also dis-favours absorption of calcium and phosphorus, as ferric phosphate
is highly insoluble. The net result is an upset in the Ca:P ratio.
16. Oxalate in certain foods precipitate calcium in the intestine as insoluble calcium oxalate.
The phytic acids of food form insoluble salt with calcium and reduce calcium absorption.
17. Vitamin D increases calcium and phosphorus absorption from the intestine. Vitamin D
promotes synthesis of specific calcium binding protein which participates in the active
transport of calcium across the small intestinal mucosa. Lack of vitamin D, excess of
phytates, low Ca/P ratio in diet, increased pH of upper intestine and malabsorption
syndromes influence the amount of calcium absorption adversely.
Biological role:
Calcium is involved in the following biological processes:
1. Constituent of bones and teeth:
Calcium along with phosphate constitutes the mineral part of the skeleton and teeth where it
is present to the extent of 99% of the total calcium present in the body. It is primarily in the
form of crystals of hydroxyapatite, while some is in combination with phosphate (calcium
phosphate) in the form of amorphous crystals.
2. Neuromuscular functions:

This involves excitability of nerve function, neural transmission, and contractility of cardiac
and skeletal muscle. Normal concentration of calcium ions is required for the normal
excitability of heart muscle.
3. Blood coagulation:
It plays a vital role in blood clotting process since it activates the enzymic conversion of
prothrombin into thrombin and production of thromboplastin. The removal of calcium from
the blood can prevent blood coagulation and because of this reason EDTA, oxalates, citrates
are used as anticoagulant because these ions can precipitate calcium into the respective
insoluble salts.
4. Membrane function:
It controls the permeability of all membranes and is often bound by lecithine in the
membrane, i.e. it decreases the permeability and balances the opposite action of sodium and
potassium capillary permeability. This involves transfer of inorganic ions across cell
membranes and release of neurotransmitters at synaptic junction.
5. Selected enzymatic reactions:
Calcium acts as activator for number of en2ymes like ATPase, succinic dehydrogenase,
lipase, etc. It also antagonizes the effect of magnesium on many enzymes. It releases cellular
enzymes such as amylase from the parotid and increases the level of activity of intracellular
enzymes such as—Isocitric dehydrogenase, phosphorylase and phosphofructokinase.
6. Regulation of secretion of certain peptide hormones:
Pituitary hormones, parathyroid hormone, calcitonin and vasopressin are regulated through
calcium ionic concentration. Calcium along with zinc plays a vital role in release of insulin
from pancreas. Calcium homeostasis: Normal blood values are 9.5-10.5 mg/100 ml. 35-45%
of this is bound to proteins, mostly to the albumin fraction. In the extracellular fluid nearly all
the calcium is in ionized form (55-65%). 0.5 (5-10%) mg is complexed to organic acids,
phosphate, citrate, etc., while in renal failure, it may be complexed to other organic ions as
well.
The skeleton is in a dynamic state of equilibrium to maintain calcium homeostasis. 4-8 gm. of
calcium in bone is rapidly exchangeable with that in plasma and is present on the surface of
the bone crystals—labile calcium storage pool. The remaining 99% of bone calcium is more
firmly fixed in bone tissue and exchanges at a very slow rate.
Metabolism:
The blood cells contain very little amount of calcium, most of the blood calcium is
therefore, in the plasma, where it is present in 3 fractions:
(1) Ionized about 2 mg/100 ml.
(2) Non-diffusible (protein bound) above 3.5 mg/100 ml.

(3) A small amount as calcium complex of citrate and phosphate.
All these forms of calcium in the serum are in equilibrium with one another. A decrease in
ionized calcium in the serum causes tetany. This may be due to an increase in the pH of blood
or lack of calcium because of poor absorption from the intestine, decreased dietary intake,
increased renal excretion as in nephritis or parathyroid deficiency.
Factors influencing blood calcium level:
1. Parathyroid hormone:
In fasting condition or state there is no absorption from the intestine, the normal plasma Ca
concentration is maintained by its rate of excretion and its mobilization from bones through
the action of the parathyroid hormone.
2. Vitamin D:
It enhances absorption of Ca from the intestine and thus maintains normal Ca concentration.
3. Plasma proteins:
Half of the blood Ca (non-diffusible) is bound to plasma proteins and thus any decrease in
these proteins will be accompanied by a decrease in the total calcium level.
4. Plasma phosphate:
A reciprocal relationship exists between the concentration of Ca and phosphate ions in
plasma. The marked increase in serum phosphate causes a fall in serum calcium concentra-
tion.
5. Calcitonin:
An increase in the ionized Ca levels in the plasma is the stimulus for the production of
calcitonin which then causes a deposition of Ca in bone.
Excretion:
Calcium is excreted in the urine, bile and digestive secretion. About 75% of dietary calcium
is absorbed and rest is excreted as fecal calcium. Nearly 10 g of Ca is filtered by the renal
glomeruli in 24 hours. But only 200 mg appear in the urine, which is in the ionic state as well
as in the complexes with citrate and other organic anions. A very small amount of Ca is
excreted into the intestine after absorption. About 15 mg of Ca is excreted in the sweat.
Vigorous physical exercise increases the loss of Ca by way of sweat.
Disease state:
Calcium metabolism is highly influenced by parathyroid hormones. In hyperparathyroidism
serum calcium rises (12-22 mg/100 ml) (hypercalcaemia), phosphatase activity is increased,
urinary calcium is decreased and phosphorus rises in serum. The calcium, phosphorus ratio is
important in ossification. In the serum the product of calcium and phosphorus (in mg/100 ml)
is normally 50 in children and may be below 30 during rickets.
The following are the diseases related to calcium in the body:

(a) Effects of parathyroid:
1. In hyperparathyroidism, the following changes occur:
(i) Hypercalcemia (12-22 mg/dl).
(ii) Decrease in serum phosphate.
(iii) Diminished renal tubular reabsorption of phosphate.
(iv) Increased phosphatase activity.
(v) Renal urinary Ca and phosphorus found from bone decalcification and dehydration.
(vi) ExtraCa and P are lost from soft tissue and bones by increased bone destroying activity.
2. In hypoparathyroidism, the following changes occur:
(i) The concentration of serum Ca may drop below 7 mg/100 ml.
(ii) Increased serum phosphate and decreased urinary excretion of calcium and phosphorus.
(iii) Normal or occasionally raised serum phosphatase activity.
(iv) Normal acid-base equilibrium.
(v) Probably increased bone density.
(b) Tetany:
Decreased ionized fraction of serum Ca causes tetany.
This may be due to:
1. Increase in the pH of blood.
2. Poor absorption of Ca from the intestine.
3. Decreased dietary intake of Ca.
4. Increased excretion of Ca as in hepatitis.
5. Parathyroid deficiency.
6. Increased retention of phosphorus as in renal tubular disease.
Symptoms:
• Muscle spasms- Muscles lose tone and become flabby, Affects the face, hands and
feet.
• Laryngospasm — which causes muscle spasms in your vocal cords, making speaking
and breathing difficult.
• Numbness in your hands and feet.
• Seizures.
• Heart problems.
(c) Rickets:
This is characterized by faulty calcification of bones in children showing serum phosphate
values of 1 to 2 mg/100 ml.
This may be due to:

1. Vitamin D deficiency.
2. A deficiency of Ca and P in the diet or a combination of both.
3. Poor absorption of Ca from the intestine.
4. Parathyroid deficiency.
5. Increased alkaline phosphatase activity.
Symptoms:
• Delayed growth.
• Delayed motor skills.
• Pain in the spine, pelvis and legs.
• Muscle weakness.
• it can cause skeletal deformities such as: Bowed legs or knock knees, Thickened wrists
and ankles
(d) Osteoporosis:
This disease occurs in adults due to the following causes:
1. Decalcification of bones as a result of Ca deficiency in the diet.
2. Hypoparathyroidism.
3. Low vitamin D content of the body.
Symptoms:
• Many people have no symptoms until they have a bone fracture.
• Loss of height over time.
• A stooped posture.
• Fractures of the brittle bones occur even after minor accidents. A bone that breaks much
more easily than expected.
• Pain due to fracture of vertebrae (may radiate round the trunk, to the buttocks or down the
legs).
Renal rickets:
It is a hereditary disease. It is called familial hypophosphatemia rickets. Affected persons
show severe rickets with hypophosphatemia.
The causes are:
(i) Defective transport of phosphate by the intestine and the renal tubules
(ii) Lowered serum phosphorus and hyperphosphaturia
(iii) Reduced intestinal absorption of calcium and phosphorus. Vitamin D in ordinary doses
does not relieve the disease. Hence, it is referred to as vitamin D resistant rickets.
Phosphorus:
Source:
Phosphorus is present in nearly all foods therefore a dietary deficiency is not known to occur
in man. Dairy products, cereals, egg yolk, meat, beans and nuts are usually rich sources. The
daily average intake is 800-1000 mg and is about twice that of calcium.

Absorption:
Like calcium, phosphorus is also absorbed by upper small intestine and factors influencing
the absorption are also similar. The normal range for plasma inorganic phosphorus is 3.0-4.5
mg/dl. In children values are higher (5-6 mg/dl) and remain so up-till puberty.
Distribution:
Phosphorus is distributed more widely than calcium. 15% is found in muscle and other soft
tissues and 85% in the inorganic mineral phase of bone. It is an integral part of many
macromolecules. Ex. Phospholipids, phosphoproteins and nucleic acids.
Functions:
It has no physiological effects comparable to that of calcium but it has many other
functions which are as follows:
1. Formation of bone and teeth.
2. Formation of phospholipids essential to every cell.
3. Formation of nucleic acids and derivatives.
Ex. Adenylic acid and is thus significant in (RNA and DNA) protein synthesis and from
genetics point of view.
4. Formation of organic phosphates as intermediate in metabolic processes.
Ex. In glycolysis, Glucose + ATP → G-6-P + ADP.
5. Formation of energy rich phosphate compounds.
Ex. ATP (energy currency of the cell).
6. Both inorganic and organic phosphates can take part in buffering the cell.
Ex, Sodium-potassium-phosphates.
7. Formation of coenzymes.
Ex. TPP, NADP.
8. Formation of phosphoprotein.
Ex. Casein.
Excretion:
Urinary excretion is equivalent to dietary phosphate intake. It varies diurnally, more being
excreted at night. The usual daily loss is 600-800 mg, tubular resorption being 85-95%. Renal
loss of phosphate can be of significant magnitude to lower serum phosphorus values and
enhance osteoid demineralization.
Disease state:
The following are the disease states of phosphorus in the body:
1. In rickets, serum phosphate is as low as 1-2 mg/100 ml (There is a temporary decrease in
serum P during absorption of carbohydrates and some fats).
2. Organic P content is low but inorganic content is high in the serum in diabetes.

3. P retention causes acidosis in severe renal diseases. This results in increase of serum P.
4. Serum P levels are increased in hypoparathyroidism and decreased in hyperparathyroidism
and celiac disease.
5. In renal rickets, blood P is very low with an increased alkaline phosphatase activity.
6. The deficiency of vitamin D is the cause of low serum P and the defects in the calcification
of bones (referred to as vitamin D resistant rickets).
Magnesium:
Source:
Magnesium is present in milk, egg, cabbage, cauliflower etc.
Daily requirement:
Infants—100-150 mg; Children—150-200 mg and Adults—200-300 mg.
Absorption:
A greater part of the daily ingested Mg is not absorbed. A very high intake of fat, phosphate,
calcium and alkalies diminish its absorption. Parathyroid hormone increases its absorption.
Distribution:
Whole blood it is 2-4 mg/dl, CSF it is 3 mg/100 ml and muscle it is 2 mg/100 ml.
Functions:
1. 70% of the total magnesium content (21g) of the body is combined with calcium and
phosphorus in the complex salts of bone. The remainder is in the soft tissues and body fluids.
It is the principal cation of the soft tissue.
2. Magnesium ions act as activators for many of the phosphate group transfer enzymes.
3. It is found in certain enzymes, such as co-carboxylase.
4. It functions as a cofactor for oxidative phosphorylation.
Disease state:
The following are the disease states of magnesium in the body:
1. Magnesium deficiency causes depression, muscular weakness and liability to convulsions.
Its deficiency has also been observed in chronic alcoholics with low serum mg and muscular
weakness.
2. Low in Kwashiorkor, causing weakness.
Low levels of Mg are reported in uremia, normal and abnormal pregnancy, rickets, growth
hormone treatment, hypercalcemia and recovery phase of diabetic coma.
Sodium, Potassium, Chloride:
Substances whose solutions conduct an electric current are called ‘electrolytes’. They are
about 11 in general. Na, K, Ca and Mg are cations whereas CI, HCO3, HPO4, SO4, organic
acids and proteins are anions. Among these sodium, potassium and chloride are important in

the distribution and the retention of body water, thus have close relationship among them.
Hence these three elements appear as a single question in the university exams.
Source:
The most important source of Na and CI in the diet is common table salt (NaCl). The good
source of K are chicken, calf flesh, beef liver, dried apricot, dried peaches, bananas, the juice
of orange and pineapple, potatoes etc.
Absorption:
Normally Na, K and CI are completely absorbed from the gastro-intestinal tract. About 95%
of sodium which leaves the body is excreted in the urine.
Distribution:
In the tissues both Na and K occur in a relatively large amount as compared to chloride and
other inorganic salts as well as protein and organic salts. Sodium is present in extra cellular
fluid and in a very low concentration inside the cells whereas potassium is mainly found
inside the cells and in a very low concentration in the extracellular fluid.
Functions of sodium and potassium:
These electrolytes maintain normal osmotic pressure in the body and protect the body against
excessive loss of fluid.
1. They maintain the acid base balance in the body. Sodium bicarbonate, sodium phosphate,
potassium phosphate form the buffer system of extracellular and intracellular fluids.
2. They maintain normal water balance.
3. Na also functions in the preservation of normal excitability of muscle and the permeability
of the cells. K inhibits ‘muscular contraction’ in general.
4. High intracellular potassium concentrations are essential for several important metabolic
functions, including protein biosynthesis by ribosomes.
5. Sodium and Potassium chlorides maintain the viscosity of blood. A number of enzymes
including glycolytic enzymes, such as pyruvate kinase, require K+
for maximal activity.
6. Na helps in the formation of the gastric juice. NaCl takes part in the series of reactions as a
result of which HC1 is manufactured by the stomach.
7. K of KHb in the red cells helps in carbon dioxide transport.
8. K ions inhibit cardiac contraction and prolong relaxation.
9. K ions exert important effect on the function of nervous system.
Functions of chloride:
1. It provides 2/3rd
of the anion of plasma and is the main factor for regulating body reactions.

2. NaCl and KCl are important agents in regulation of osmotic pressure in the body.
3. HCl of gastric juice is ultimately derived from the blood chlorides.
4. Chloride ions are essential for the action of ptyalin and pancreatic amylase.
5. It is essential in acid-base regulation. Chloride plays a role in the body by chloride shift
mechanism.
Metabolism:
The metabolism of these elements is influenced by the following factors:
Hormones:
Mainly adrenocortical steroids and some of the sex hormones facilitate the retention of
sodium and chloride in the body and excretion of potassium by kidneys in the urine. In
adrenocortical deficiency, serum sodium decreases because excretion increases.
Temperature:
When atmospheric temperature is high as in summer, large amounts of sodium and chloride
are lost in perspiration (sweating) and this loss may be checked when temperature is low (in
winter).
Renal function:
In renal disease, with acidosis, Na and CI ion excretion in urine is increased due to poor
tubular reabsorption of sodium whereas that of K ion is decreased leading to hyponatraemia
and hypochloraemia but hyperkalaemia.
Average requirement of Na and K in human body is 5-15 and 4 gm. per day, respectively.
Disorders:
Hyponatraemia:
On sodium deficient diet, young ones grow slowly, lack fat deposit, there is muscle and
testicular atrophy, lung infection and deficiency of osteoid tissues. There will also be loss of
water, which will be evident by rapid weight loss.
Hypokalaemia:
Extreme potassium depletion in circulating blood causes hypokalemia in young one, they
grow slowly and both sexes become sterile. The heart rate is slow, muscle weakness,
irritability and paralysis are seen. Bone growth is retarded and in becomes excessively fragile
and kidney hypertrophy is exhibited.
Hyperkalemia:
Hyperkalemia paralysis occurs due to excessive amount of potassium in blood. The disease is
characterized by periodical attacks of weakness or paralysis. The symptoms of hyperkalaemia
are chiefly cardiac and central nervous system depression. They are related to the elevated
plasma potassium level and not to increase in intracellular potassium levels.

A dietary chlorine deficiency produces no symptom except a subnormal growth rate. Under
normal dietary condition human beings are not subject to a deficiency of sodium, potassium
or chlorine. However excessive diarrhoea, vomiting or extreme sweating over long period
may bring about a NaCl deficiency. Sometimes the metabolism of individual minerals is
asked as a separate question in the university exams. Hence each one is described separately
in detail, hereunder.
Sodium:
Physiological functions:
1. Major component of extracellular fluids and exists in the body in association with anions
chloride, bicarbonate, phosphate and lactate.
2. In association with chloride and bicarbonate it plays a role in acid base equilibrium.
3. Maintains osmotic pressure of the body fluids and thus protects the body against excessive
fluid loss.
4. Plays an important role in the absorption of glucose and galactose from small intestine.
5. Maintains normal water balance and distribution.
6. Maintains the normal neuromuscular function.
7. Functions in permeability of cells.
Distribution:
About 1 /3rd
of the total sodium content of the body is present in the inorganic portion of the
skeleton. Most of the sodium is present in the extracellular fluid.
Plasma — 330 mg/100 ml
Muscles — 60 to 160 mg/100 gm.
Cells — 85 mg/100 gm.
Nerve — 312 mg/100 gm.
Daily requirement:
Adults require 5-15 gms/day. In temperate region, NaCl intake is less. In tropical region,
NaCl intake is more. Hypertension patients should not take more than 1 gm. of Na per day.
Absorption:
Normally, Na is completely absorbed from gastro-intestinal tract. Less than 2% is eliminated
in feces. In persons suffering from diarrhoea, large amounts are lost in feces.
Excretion:
Urine — 5-35 gm.
Skin — 25-50 mg
Stool — 10-125 mg
Excessive loss of Na by sweating causes heat arrays.

Disease state:
1. Adrenal cortical steroids regulate the metabolism of Na. Insufficiency of adrenal cortical
steroids decreases serum Na level with an increase in sodium excretion.
2. In chronic renal disease when acidosis exists, Na depletion occurs due to poor tubular
reabsorption of Na as well as to the loss of Na in the buffering acids.
3. In persons not adapted to high environmental temperature large amount of Na is lost in the
sweat, developing muscular cramps of extremities, oedema, headache, nausea and diarrhoea.
4. Hyponatremia causes dehydration and reduced blood pressure, decreased blood volume
and circulatory failure.
This may be due to:
(a) Prolonged vomiting and diarrhoea resulting in excessive loss of digestive fluid.
(b) Chronic renal disease with acidosis due to poor tubular reabsorption of Na.
(c) Adrenocortical insufficiency.
(d) Loss of weight due to loss of water.
5. In Hypernatremia, serum Na is high.
This occurs in:
(a) Hyperactivity of adrenal cortex as in Cushing’s syndrome.
(b) Prolonged treatment with cortisone and ACTH as well as sex hormones, this results in—
(i) Increased retention of water in the body.
(ii) Increase in blood volume,
(iii) Increase in blood pressure.
6. Steroid hormones cause retention of Na and water in pregnancy.
Potassium:
Physiological junctions:
1. Potassium is largely present in intracellular fluid and it is also present in small amounts in
the extra cellular fluid because it influences the cardiac muscle activity.
2. It plays an important role in the regulation of acid-base balance in the cell.
3. It maintains osmotic pressure.
4. It functions in water retention.
5. It is essential for protein biosynthesis by ribosomes.
6. The glycolytic enzyme pyruvate kinase requires K+
for maximal activity.
Sources:
High content of potassium is found in chicken, beef, liver, bananas, orange juice, pineapple,
yam, potatoes etc.
Distribution:
Plasma — 20 mg/100 ml

Cells — 440 mg/100 gm.
Muscles — 250-400 mg/100g
Nerves — 530 mg/100g.
Daily requirement:
Normal intake of K+
in food is about 4 gm. It is so widely distributed that its deficiency is
rare except in pathological condition.
Blood potassium:
Normal level of serum K is 14-20 mg/100 ml. Erythrocytes contain large amounts of K which
avoids hemolysis. Serum K decreases during increased carbohydrate utilization following
glucose or insulin administration. Aldosterone decreases serum K.
Absorption:
Normally, K is practically completely absorbed from gastrointestinal tract and less than 10%
of K is eliminated in the feces. In subjects with diarrhea large amounts are lost in feces.
Excretion:
K is normally eliminated almost entirely in urine and a small amount in the feces. Aldos-
terone exerts an influence on potassium excretion. In normal kidney function; K is very
promptly and efficiently removed from the blood.
Disease state:
1. K is not only filtered by the kidney but is also secreted by the renal tubules. Excretion of K
is greatly influenced by changes in acid-base balance and also by adrenal cortex. The
capacity of kidney to excrete K is very great and therefore hyperkalaemia does not occur
even after ingestion of K, if kidney function is impaired K should not be given intravenously
unless, circulatory collapse and dehydration are corrected.
2. Hyperkalaemia occurs in patients in the following conditions.
(a) Renal failure
(b) Severe dehydration
(c) Addison’s disease due to decreased excretion of K by the kidney
K deficiency occurs in chronic wasting diseases like malnutrition, prolonged negative
nitrogen balance, gastrointestinal losses and metabolic alkalosis.
Chlorine:
1. As a component of sodium chloride, chloride ion is essential in acid-base balance.
2. As Cl–
it is also essential in water balance and osmotic pressure regulation.
3. It is also important in the production of HCl in the gastric juice.
4. Cl–
ion is an activator of amylase.
Sources:

Mainly as NaCl salt (table salt).
Distribution:
Plasma — 365 mg/100ml
Cells — 190 mg/ 100mg
CSF — 440 mg/100ml
Muscle — 40 mg/100g
Nerve — 171 mg/100g
Daily requirement:
5-20 gms. Excess consumption of NaCl increases blood pressure in hypertensive patients.
Causes edema in protein deficiency.
Absorption:
Normally CI is practically completely absorbed from the GI tract.
Excretion:
CI is chiefly eliminated in the urine, also in sweat. Its concentration in sweat is increased in
hot climates and decreased by aldosterone.
Diseases state:
1. CI deficit also occurs when losses of Na are excessive in diarrhoea, sweating and certain
endocrine disturbances.
2. Loss of CI due to loss of gastric juice by vomiting or pyloric or duodenal obstruction.
3. Hypochloremia alkalosis may develop in Cushing’s syndrome or after administration of
ACTH or cortisone.
Sulphur:
Sources:
Sulphur is taken mainly as cysteine and methionine present in proteins. Other compounds in
the diet contribute small amounts of sulphur.
Absorption:
Inorganic sulphate is absorbed as such from intestine into the portal circulation. Small
amount of sulphide may be formed in the bowel by the action of bacteria, but if absorbed into
the blood stream, it is rapidly oxidized to sulphate.
Sulphur in blood (serum):
Inorganic — 0.5-1.1 mg/100 ml
Ethereal sulphate — 0.1-1.0 mg/100 ml
Neutral sulphur — 1.7-3.5 mg/100 ml

1. Sulphur is present primarily in the cell protein in the form of cysteine and methionine.
2. Cysteine plays important part in the protein structure and enzyme activity.
3. Methionine is the principal methyl group donor in the body. The ‘activated’ form of
methionine, s-adenosyl methionine is the precursor in the synthesis of a large number of
methylated compounds which are involved in intermediary metabolism and detoxification
mechanism.
4. Sulphur is a constituent of coenzyme A and lipoic acid which are utilized in the synthesis
of acetyl-CoA, malonyl CoA, Acyl-CoA and S-acetyl lipoate (involved in fatty acid oxidation
and synthesis).
5. It is a component of a number of other organic compounds such as heparin, glutathione,
thiamine, pantothenic acid, biotin, ergothionine, taurocholic acids, sulphocyamides, indoxyl
sulphate, chondroitin sulphate, insulin, penicillin, anterior pituitary hormones and melanin.
Excretion:
Excreted in urine in 3 forms. Total sulphate excretion may be diminished in renal function
impairment and is increased in condition accompanied by excessive tissue breakdown as in
high fever and increased metabolism.
Disease state:
Serum sulphate is increased in renal function impairment, pyloric and intestinal obstruction
and leukemia.
Marked sulphate retention in advanced glomerulo-nephritis causes the development of
acidosis.
Increase in blood indica (indoxyl potassium sulphate) may occur in uremia.
Iron:
Iron is present in all organisms and in all the cells. It does not exist in the free state, instead is
always present in organic combination, usually with proteins. It exists in two forms i.e.
Fe2+
(ferrous) and Fe3+
(ferric). It serves as an oxygen and electron carrier and is incorporated
into redox enzymes and substances which carry out the function of oxygen transport such as
haemoglobin and cytochromes.
Total iron content in normal adult is 4 to 5 grams. 60-70% is present in hemoglobin, 3% in
myoglobin and 0.1% in plasma combined with β-globulin transport protein transferrin.
Hemoprotein and flavoprotein make up to less than 1% of total iron. Rest is stored as ferritin.
Source:
Rich – Liver, heart, kidney, spleen.
Good – Egg yolk, fish, nuts, dates, beans, spinach, molasses, apples, bananas, etc.
Poor — Milk, wheat flour, polished rice, potatoes etc.

Daily requirement:
Only about 10% of ingested iron is absorbed.
i. Infants – 10-15 mg..
ii. Children – 1-3 years 15 mg.
iii. 4-10 years – 10 mg.
iv. Older children and adults of 11 to 18 years — 18 mg.
v. 19 years and above — 10 mg.
vi. Females between 11 and 50 years of age and during pregnancy or lactation – 18 mg.
vii. After 51 years of age — 10 mg.
viii. In adult women the average loss of iron with blood during menstrual period is 16-32 mg
per month or an additional loss of 0.5 to 1.0 mg per day. This amount is easily obtained from
diet.
ix. In excessive menstrual blood loss and in chronic iron-deficiency anemia, a supplement of
100 mg of iron per day is sufficient to replenish.
x. During growth, pregnancy and lactation iron demand is more.
xi. In healthy adult male or post menopause women dietary iron requirement is negligible
unless any deficiency or loss of iron occurs.
xii. Iron deficiency occurs as a result of malabsorption from gastro-intestinal tract.
xiii. A defect in hemoglobin synthesis in anemia is commonly found in copper deficiency.
Biologically active compounds that contain iron:
1. Haemic compounds:
In these compounds the protoporphyrin is combined with iron to form haem (divalent iron)
and haematin.
Ex. Hemoglobin, myoglobin, cytochromes, catalases and peroxidases.
2. Non-haemic compounds:
These include Transferrin (siderophilin) to transport iron, ferritin and haemosiderin which are
the stored forms of iron and miscellaneous compounds like enzymes.
Absorption:
Very little (less than 10%) of dietary iron is absorbed. Excretion in the urine is minimal.
Infants and children absorb more iron as compared to adults. Iron deficiency in infants is due
to dietary deficiency. Iron deficient children absorb approximately twice as much as normal
children do. Absorption mainly occurs in the duodenum and the proximal jejunum.
(a) Most of the iron in food occurs in the ferric form (Fe3+
), ex. either as ferric hydroxide or
as ferric organic compounds. Acidic pH of the gastrointestinal tract favours the absorption
whereas alkaline pH decreases it. In an acid medium, these compounds are broken down into
free ferric ions or loosely bound organic iron, reducing substances such as —SH groups ex.

cysteine and ascorbic acid which convert ferric iron into the reduced (ferrous) state, in this
form iron is more soluble and should therefore be more readily absorbed.
(b) A diet high in phosphate, phytic acid and oxalic acid decreases iron absorption since these
substances form the insoluble compounds with iron. Conversely, a diet very low in phosphate
markedly increases iron absorption.
(c) The extent of absorption depends on the degree of saturation of the tissue, ex. anemic
individuals absorb more than normal individuals.
(d) Iron absorption is enhanced by protein, possibly as a result of the formation of low
molecular weight digestive products (peptides, amino acids) which can form soluble iron
chelates.
(e) It is also increased in pernicious anaemia and in hypo plastic anaemia.
(f) Impaired absorption takes place in patients who have total removal of stomach or a
removal of considerable amount of the intestine.
(g) Achlorhydria, administration of alkali, copper deficiency decrease iron absorption.
(h) Alcohol ingestion favours iron absorption.
Mechanism of Iron Absorption:
Ferrous ion on entering the mucosal cells is oxidized to ferric state and then combines with
apoferritin forming ferritin which contains 23% of iron by weight. When apoferritin gets
saturated with iron no further iron can be taken up by the mucosal cells to store it in the form
of ferritin. Heme enters the mucosal cells without being released from the porphyrin ring.
Heme is broken down in the mucosa and iron appears in the plasma transferrin.
Transport:
In the plasma, the iron is bound to transferrin which is only partially saturated. Plasma iron is
also in exchange with interstitial and intra-cellular compartments. The iron in these
compartments is generally referred to as ‘labile iron pool’ and is estimated to be in the order
of 80 to 90 mg. Here the iron may stay briefly on the cell membrane before its incorporation
into haem or storage compounds. Nearly all the iron released from the mucosal cell enter the

portal blood mostly in the ferrous state (Fe2+
). In the plasma, Fe2+
is oxidized rapidly to the
ferric state (Fe3+
) and then incorporated into a specific protein.
Storage:
Stores of iron are maintained chiefly in the liver, spleen and bone marrow in the form of
ferritin and haemosiderin. Women have lower stores than men and therefore, develop
anaemia much more frequently than men. Iron stores are increased in haemochromatosis,
severe haemolytic anaemias, aplastic anaemia and in persons receiving multiple blood
transfusions, prolonged oral or parenteral iron therapy.
The normal content of protein bound iron (FBI) in plasma of males is 120-140 jig/100 ml; in
females it is 90-120 pg/100ml. However, the total iron binding capacity (TIBC) is about the
same in both sexes i.e. 300-360 pg/100 ml.
Excretion:
Physiological excretion of iron is minimal. The normal routes of excretion are urine, bile,
faeces, cellular desquamation, and sweat. Daily excretion in an adult male is estimated to be
about 1 mg. In women of reproductive age, additional loss through menstruation averages to
1 mg per day.
Abnormal iron metabolism:
Ferritin and hemosiderin, the storage forms of iron act as internal iron reserve to protect
against sudden loss of iron by bleeding. Ferritin is present not only in the intestine but also in
liver (about 700 mg) spleen and bone marrow. If excess iron is administered parenterally
exceeding the capacity of the body to store it as ferritin, it accumulates in the liver as
hemosiderin, a form of colloidal iron oxide in association with protein.
Iron metabolism is disturbed mainly by the following causes:
(a) Decreased formation of hemoglobin.
(b) Decrease in circulating hemoglobin.
(c) Abnormalities in the serum iron concentration
(d) Abnormal deposition of iron-combining pigments in the tissues.
1. Iron functions mainly in the transport of oxygen to the tissues.
2. Involved in the process of cellular respiration.
3. Essential component of hemoglobin, myoglobin, cytochromes and the respiratory enzyme
systems (cytochrome oxidase, catalase and peroxidase).
4. Non-heme iron is completely protein-bound (storage and transport).

5. Non-heme iron is utilized in the structure of xanthine dehydrogenase (xanthine oxidase)
and succinate dehydrogenase and also in the iron sulphur proteins of the respiratory chain.
Iron deficiency:
Iron deficiency is the commonest cause of nutritional anaemia and is prevalent all over the
world. Causes of iron deficiency:
(1) Dietary deficiency:
The iron content in the diet is sufficient to meet the daily requirements, but excessive amount
of phytates in cereals, is responsible for non-absorbability of this iron. Hence higher daily
intake of iron is recommended for vegetarians.
(2) Lack of absorption:
This may be seen in malabsorptive syndromes.
(3) Increased demand:
This occurs during rapid growth in infancy and pregnancy.
(4) Poor stores at birth:
These are found in premature birth and twin pregnancy.
(5) Pathological blood loss:
With loss of 1g of haemoglobin 3.4 mg of iron is lost. Hook-worm infestation is the most
important factor responsible for blood loss. Other sources of blood loss are bleeding piles,
peptic ulcer, hiatus hernia, cancer of gastrointestinal tract, chronic aspirin ingestion, and
oesophageal varies.
(6) Iron deficiency anemia:
Iron deficiency anemia is widely prevalent among children, adolescent girls and nursing
mothers. The hemoglobin content of the blood during iron deficiency anemia is 5 to 9 g/100
ml.
(a) Women of child bearing age:
The clinical symptoms are breathlessness on exertion, giddiness and pallor of the skin. In
severe cases, there may be edema of the ankles.
(b) Weaned infants and young children:
The hemoglobin level is 5 to 9 g/100 ml of blood. The children are dull and inactive and
show pallor of the skin. The appetite is poor and growth and development are retarded.
Treatment of iron deficiency anaemia:
Anaemia responds to oral iron therapy. The commonly used preparations are ferrous sulphate,
ferrous fumarate and ferrous gluconate. Iron dextran can be administered both
intramuscularly and intravenously, iron sorbitex is given intramuscularly, and saccharide iron
oxide is given intravenously.

Anemic women should take ferrous sulphate tablet. For a child below 12 months, a mixture
of ferrous ammonium citrate sweetened with glycerine and for children of 1 to 5 years ferrous
ammonium citrate mixture should be given for curing.
Iron overload:
Hypersiderosis may occur as a primary disorder (Idiopathic haemochromatosis) or secondary
with excessive entry of exogenous, iron into the body.
1. Siderosis:
When excessive amounts of iron are released in or introduced into the body beyond the
capacity for its utilization, the excess is deposited in various tissues, mainly in the liver. This
may occur due to repeated blood transfusions, excessive breakdown of erythrocytes in
hemolytic types of anemia and inadequate synthesis of hemoglobin as in pernicious anemia.
2. Nutritional siderosis:
This disorder is found among Bantus in South Africa. Bantus cook their food in large iron
pots and consume iron-rich food. The absorption of iron appears to be high, leading to the
development of nutritional siderosis. Livers of the Bantus contain large amounts of iron.
Hemochromatosis:
Hemochromatosis is a rare disease in which large amounts of iron are deposited in the tissues,
especially the liver, pancreas, spleen and skin producing various disorders. Accumulation of
iron in the liver, pancreas and skin produces hepatic cirrhosis, bronze diabetes and bronze-
state pigment respectively.
Copper:
Source:
Richest sources:
Liver, kidney, other meats, shell fish, nuts and dried legumes.
Poor sources:
Milk and milk products. The concentration of copper in the fetal liver is 5-10 times higher
than that in liver of an adult.
Daily requirements:
Infants and children – 0.05 mg/kg body weight
Adults – 2.5 mg
A nutritional deficiency of copper has never been demonstrated in man, although it has been
suspected in case of nephrosis.

Absorption:
About 30% of the normal daily diet of copper is absorbed in the duodenum.
Blood copper:
The normal concentration of copper in serum is 90 µg/100 ml. Both RBC and serum contain
copper. 80% of RBC copper is present as superoxide dismutase (erythrocuperin), Plasma
copper occurs as firmly bound form and loosely bound forms. The firmly bound copper
consists of ceruloplas-min. Loosely bound copper is called ‘directly reacting copper’ and is
bound to serum albumin. The plasma copper levels increase in pregnancy because of their
estrogen content. Oral contraceptives have a similar effect.
1. It has important role in hemoglobin synthesis.
2. It is required for melanin formation, phospholipids synthesis and collagen synthesis.
3. It has a role in bone formation and in maintenance of the integrity of myelin sheath.
4. It is a constituent of several enzymes such as tyrosinase, cytochrome oxidase, ascorbic acid
oxidase, uricase, ferroxidase I (ceruloplasmin), ferroxidase II, superoxide dismutase, amino
oxidase and dopamine hydroxylase.
5. Three copper containing proteins namely cerebrocuperin, erythrocuperin and
hepatocuperin are present in brain, RBC and liver respectively.
Excretion:
Only 10 to 60 mg of copper is excreted in the urine. 0.5 to 1.3 mg is excreted through bile
and 0.1 to 0.3 mg is excreted by intestinal mucosa into the bowel lumen.
Effects of copper deficiency:
1. Although iron absorption is not disturbed but the release of iron into the plasma is
prevented due to the decreased synthesis of ceruloplasmin. As a result, hypoferremia occurs
which leads to the depressed synthesis of heme developing anemia in severe deficiency of
copper.
2. The experimental animals on a copper deficient diet lose weight and die.
3. In copper deficient lambs, low cytochrome oxidase activity results in neonatal ataxia.
4. Copper deficiency produces marked skeletal changes, osteoporosis and spontaneous
fractures.
5. Elastin formation is impaired in the deficiency of copper. Because a copper containing
enzyme plays an important role in the connective tissue metabolism, especially in the
oxidation of lysine into aldehyde group which is necessary for cross linkage of the
polypeptide chains of elastin and collagen.

6. Copper deficiency results in myocardial fibrosis in cows. It is suggested that reduction in
cytochrome oxidase activity may lead to cardiac hypertrophy.
Disorders of copper metabolism:
Wilson’s disease (hepatoreticular degeneration):
Wilson’s disease is a rare hereditary disorder of copper metabolism.
The following disorders have been observed in this disease:
(a) The absorption of copper from the intestine is very high (about 50 percent); whereas 2 to
5 percent copper is absorbed in normal subjects.
(b) Ceruloplasmin formation is very less. Hence a greater part of serum copper remains
loosely bound to serum protein-notably albumin and therefore, copper can be transported to
the tissues, such as brain and liver or to the urine.
(c) Excessive deposition of copper in the liver and the kidney causes hepatic cirrhosis and
renal tubular damage respectively. The renal tubular damage results in the increased urinary
excretion of amino acids, peptides and glucose.
Iodine:
Source:
Rich sources are sea water, marine vegetation and vegetables as well as fruits grown on the
sea board. Plants grown at high altitudes are deficient in iodine because of its low
concentration in the water. In such regions, iodide is commonly added to the drinking water
or table salt in concentrations of 1:5000 to 1:200000.
Daily requirement:
Adults – 100 to 150 μg
In adolescence and in pregnancy – 200 μg
Distribution:
Normal iodine content of body is 10 to 20 mg. 70 to 80% of this is present in thyroid gland.
Muscles contain large amount of iodine. The concentration of iodine in the salivary glands,
ovaries, pituitary gland, brain and bile is greater than that in muscle. Iodine in saliva is
inorganic iodide, while most of the iodine present in tissue is in the organic form.
Blood Iodine:
Practically all the iodine in the blood is in the plasma. The normal concentration in plasma or
serum is 4 to 10 μg/100 ml. 0.06 to 0.08 μg/100 ml is in inorganic form, 4 to 8 μg/100 ml is
in the organic form bound to protein, precipitated by protein precipitating agents. 90% of the
organic form consists of thyroxine and the remainder tri and di-iodothyronine. About 0.05%
of thyroxine is in the free state. RBC contains no organic iodine.

Absorption:
Iodine and iodide are absorbed most readily from the small intestine. Organic iodide
compounds (di-iodothyronine and thyroxine) are partly absorbed as such and a part is broken
down in the stomach and intestines with the formation of iodides. Absorption also takes place
from outer mucus membrane and skin.
Storage:
90% of the iodine of the thyroid gland is in organic combination and stored in the follicular
colloid as ‘thyroglobulin’ a glycoprotein containing thyroxine, di-iodothyronine and smaller
amounts of triiodothyronine.
On demand these substances are mobilized and thyroxine as well as triiodothyronine is
passed into the systemic circulation. They undergo metabolic degradation in the liver.
Excretion:
1. Inorganic iodine is mostly excreted by the kidney, liver, skin, lungs and intestine and in
milk.
2. About 10% of circulating organic iodine is excreted in feces. This is entirely unabsorbed
food iodine.
3. 40 to 80 % is usually excreted in the urine, 20 to 70 μg daily in adults, 20 to 35 μg in
children. The urinary elimination is largest when the intake is lowest.
4. Urinary iodine is increased by exercise and other metabolic factors.
Iodine is required for the formation of thyroxine and triiodothyronine hormones of the
thyroid gland. These thyroid hormones are involved in cellular oxidation, growth,
reproduction and the activity of the central and autonomic nervous systems. Triiodothyronine
is more active than thyroxine in many respects.
Iodine deficiency:
1. In adults the thyroid gland is enlarged producing goiter. If treatment is started very early,
the thyroid becomes normal. If treatment is delayed, the enlargement persists.
2. In children, severe iodine deficiency results in the extreme retardation of growth causing
cretinism.
Prevention of goiter:
Goiter can be prevented by the regular use of iodized salt or iodine added to the drinking
water.
Goitrogenic substances in foods: Cabbage, cauliflower and radish contain substance like
vinyl-2- thiooxazolidone which makes iodide present in the food unavailable by reacting with
it. Such substances are called ‘goitrogenic’ substances.

Selenium:
i. Good dietary sources are kidney cortex, pancreas, pituitary and liver.
ii. It is rapidly absorbed mainly in duodenum.
iii. It is distributed in liver 0.44 μg/gm in skin 0.27 μg/gm and in muscle 0.37 μg/gm.
iv. In the cells it is present as selenocystinenadselenomethionine.
v. Selenium along with Vitamin E plays an important role in tissue respiration.
vi. Selenium is involved in biosynthesis of coenzyme Q (ubiquinone), which is involved in
respiratory chain.
vii. Selenium acts as an antioxidant providing protection against peroxidation in tissues and
membrane.
viii. It is an essential component of glutathione peroxidase, an enzyme which catalyzes the
conversion of reduced glutathione to its oxidized form.
ix. Selenium is excreted in faeces, urine and via exhalation.
x. It causes toxic effect called selenosis.

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