Elements essential for the body Manik

Elements Essential for the Body
Arranged By- Md. Imran Nur Manik; B.Pharm.;M.Pharm.;(Thesis) RU Page 1
Prepared By- Shadid Uz Zaman At Tadir, B.pharm.;M.Pharm.;(Professional) DU
Major Intra & Extracellular electrolytes
Introduction:
The body fluids are solutions of inorganic and organic solutes. The concentration
balances of the various components are maintained in order for the cells and tissues to have a
constant environment. In order to maintain the internal homeostasis there are regulatory
mechanisms in the body which control pH, ionic balances, osmotic balances etc.
There are also a large number of products (under the heading of “replacement therapy”) which
can be used by a physician when the body is unable to correct an electrolyte imbalance due to
change in composition of its fluids. These products include electrolytes, acids and bases, blood
products, carbohydrates, amino acids and proteins. Under the above heading we shall discuss
the major electrolytes used in replacement therapy.
Body fluid:
The electrolyte concentrations vary with a particular fluid. There are three types of fluid
compartment in our body – cell, interstitial space and blood vessels having following figures-
Fluid type Compartment % body weight
Intracellular fluid Cell 45-50
Extracellular fluid Interstitial space and blood vessels
A) Interstitial fluid Interstitial space 12-15
B) Plasma or vascular fluid Blood vessels 4-5
These three compartments are separated from each other by membranes which are
permeable to water and any inorganic and organic solutes. They are selectively permeable to
certain ions like Na+
, K+
and Mg2+
etc. So each compartment has a distinct solute pattern. For
example Na+
and Cl─
are found in plasma and interstitial fluid while K+
and HCO3
─
are found
in intracellular fluid. Conc. of major electrolytes in different types of fluid is given below-
Type of
electrolyte
Conc. in plasma
(mEq/L)
Conc. in interstitial fluid
(mEq/L)
Conc. in intracellular fluid
(mEq/L)
Cations
Na+
142 145 10
K+
4 4 160
Ca2+
5 3
Mg2+
3 2 35
Totals 154 154 205
Anions
HCO3
¯ 27 30 8
Cl─
103 115 2
HPO4¯ 2 2 140
SO4¯ 1 1
Organic acids 5 5
Proteins 16 1 55
Total 154 154 205
Md.
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Physiological acid-base balance:
Before discussing the electrolytes used in acid-base balance, the systems in the body
which maintain the acid-balance needs to be discussed. Three systems work together to
maintain the acid-base balance of the plasma (or body).
1. The buffers of the body fluid and RBC
2. The pulmonary excretion of excess CO2
3. The renal excretion of either acid or base, whichever is excess.
Buffer systems:
Among various buffer systems in the body the major are the 323 COHHCO /
(found in
the plasma and kidney) and 
424 POHHPO /2
(cells and kidney) along with hemoglobin buffer
(RBC).
The bicarbonate/carbonic acid buffer and hemoglobin buffer function together as following-
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Although there are other buffer systems in the plasma, the bicarbonate/carbonic acid
system is by far the most the important plasma buffer. At a given pH, the ratio of the
concentrations of the two substances is constant. If an excess of acid is liberated in the body, it
is neutralized by some of the sodium bicarbonate.
323 COHNaNaHCOH  
The excess carbonic acid decomposes into water and carbonic dioxide and the latter is
excreted by the lungs until the normal bicarbonate/carbonic acid ratio is achieved.
 2232 COOHCOH
If an excess of alkali occurs in the body, it combines with carbonic acid to form
bicarbonate, and more carbonic acid is formed from CO2 and water to restore the balance.
OHHCOCOHOH 2332
-
 
3222 COHOHCO 
It may be noted that at pH 7.4 the ratio of
32
3
COH
HCO
is 20:1.
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Phosphate buffer is also an effective system in maintaining physiological pH.
At pH 7.4 the


42
4
POH
HPO 2
ratio is approximately 4:1. At pH 6.8 the ratio is 1:1. In the kidneys,
the pH of the urine can drop to 4.5-4.8 corresponding to the ratios of 1:99 to 1:100.
Pulmonary excretion:
The lungs perform in the acid-base balance by excretion of CO2. This is best illustrated in
the figure above labeled “O2 loading and CO2 unloading in external respiration”.
Renal excretion:
The steps of acid excretion in the kidneys occur as follows-
a. Sodium salts of mineral and organic acids are removed from the plasma by glomerular
filtration.
b. Sodium is preferentially removed from the renal filtrate or tubular fluid, and in tubular
cells, reacts with carbonic acids formed by the carbonic anhydrase catalyzed reaction of
CO2 and water. This is sometimes called Na+
-H+
exchange.
c. The sodium bicarbonate returns to the plasma (eventually being removed in the lungs as
CO2) and the protons enter the tubular fluid, forming acids of the anions that originally
were sodium salts (H2PO4¯, lactate etc.).
d. The formation of NH3 from protein and amino acid metabolism is another mean of
removing protons. The NH3 is secreted by the tubular cells into the tubular fluid where it
combines with protons from carbonic acid to form NH4
+
.
The “consumption” result is that protons and toxic NH3 are excreted, physiological pH
is maintained and sodium is reabsorbed from the tubular filtrate.
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Acid-base imbalances:
Metabolic acidosis:
Metabolic acidosis refers to all types of acidosis other than the one caused by excess CO2
in the body fluids. It is the primary decrease in HCO3¯ concentration. Metabolic acidosis is
treated with sodium salts of bicarbonate, lactate, acetate and occasionally citrate.
Administration of bicarbonate increases the HCO3¯/H2CO3 ratio when there is
bicarbonate deficit. Lactate, acetate and citrates are normal components of metabolism. They
degrade to CO2 and water by TCA cycle. The CO2 will form bicarbonate by action of carbonic
anhydrase and thereby reduce the bicarbonate deficit.
Metabolic alkalosis:
Alkalosis caused by a primary increase in bicarbonate concentration is called metabolic
alkalosis. Metabolic alkalosis is treated with ammonium salts. They function in the kidneys and
retard Na+
-H+
exchange.
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The following is all the types of acid-base imbalances in the human body.
Condition Cause
Metabolic acidosis Primary HCO3¯ deficit.
Metabolic alkalosis Primary HCO3¯ excess.
Respiratory acidosis Primary H2CO3 excess
Respiratory alkalosis Primary H2CO3 deficit.
Drugs used in regulating acid-base balance:
1. Sodium acetate
2. Potassium acetate
3. Sodium bicarbonate
4. Potassium bicarbonate
5. Sodium biphosphate
6. Sodium citrate
7. Potassium citrate
8. Sodium lactate
9. Ammonium chloride
Sodium bicarbonate USP:
Synonyms:
Also known as sodium acid carbonate, sodium hydrogen carbonate, baking soda, bicarbonates
of soda.
Properties:
1. It occurs as white, crystalline powder which is stable in dry air but slowly decomposes in
moist air.
2. It is soluble in water and insoluble in alcohol.
3. Its solutions with freshly prepared cold water without shaking are alkaline to litmus. The
alkalinity increases as the solutions stand, are agitated or are heated.
4. When heated the salt loses water and CO2 and gets converted into the normal carbonate.
5. CO2 is liberated when the salt is treated with acids. The liberated CO2 bubbling through
the liquid us termed effervescence.
acidcitricacidtartariclikeorganicusuallyacidAny ,,

HA
OHCONaAHANaHCO 223
The above decomposition takes place when the dry salt or a solution is heated. This is one of
the major difficulties in attempting to sterilize either the dry salt or its solution.
Dosage form:
1. Sodium bicarbonate tablets
2. Sodium bicarbonate injections
Both USP and BP recognize an injection of NaHCO3 as a sterile solution of NaHCO3 in
water for injection. Although the USP is silent about this, BP states that the solution can be
sterilized by bacteriologic filtration or autoclaving.
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Autoclaving is performed by passing CO2 through the solution for 1 minute and then
placing the solution in gas-tight containers for the autoclaving process. This causes an
equilibrium control on degradation reaction resulting it to be reversed.
After 2 hours of cooling at room temperature, the solution is assayed by titration to make
sure that no decomposition has taken place. If so the pH can be adjusted by passing in CO2.
Use:
i. To combat gastric hyperacidity
ii. To combat systemic acidosis
iii. Miscellaneous use
iv. Sterile injection of the salt is used in emergency situations. For this purpose 7.5%
NaHCO3 solution is made in disposable syringes which can be stored in refrigeration
for 60-90 days or 7-30 days in room temperature. But pH should be checked
frequently.
Problem Administering NaHCO3:
In emergency situations, NaHCO3 is administered parenterally. For this purpose
sterilization is required at 250-260⁰C. But NaHCO3 decomposes to Na2CO3 in presence of heat.
This is problematic because Na2CO3 is much more alkaline than wanted.
Electrolyte combination therapy:
In short term therapy, infusion of a standard glucose and saline solution may be
adequate but when deficits are severe solutions containing additional electrolytes are needed.
Combinations compounded according to need to each individual patient are ideal but this is not
possible considering cost and sterility. But there is a broad selection of commercial electrolyte
infusion solutions with differing amount of electrolytes available one of which should fit the
need of a patient.
There are two types of combination products as follows-
Fluid maintenance therapy: Intended to supply normal requirements for water and electrolytes
to patients who can’t take them orally. The composition of such products is
Dextrose → at least 5%(To minimize the buildup of those metabolites associated with
starvation, urea, phosphate and ketone bodies)
In addition there is also
Na → 25-30 mEq/L
K → 15-20 mEq/L
Cl → 22 mEq/L
HCO3¯ (or lactate or acetate) → 20-23 mEq/L
Mg → 3mEq/L
P → 3 mEq/L
Electrolyte replacement therapy:
It is needed when there is heavy loss of water and electrolytes in cases like prolonged
fever, severe vomiting & diarrhea. There are usually two types of solutions used in replacement
therapies
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i. Solution for rapid initial replacement
The concentrations of the electrolytes are more or less similar to that of ECF.
Typical concentration ranges are
Na → 130-150 mEq/L
K → 4-12 mEq/L
Cl─
→ 98-109 mEq/L
HCO3
─
(or equivalent lactate/gluconate/acetate) → 28-55 mEq/L
Ca → 3-5 mEq/L
Mg → 3-5 mEq/L
ii. Solution for subsequent replacement
Electrolyte concentrations in subsequent replacement solutions are-
Na → 40-121 mEq/L
K → 16-35 mEq/L
Cl─
→ 30-103 mEq/L
HCO3
─
(or equivalent lactate/acetate) → 16-53 mEq/L
Ca → 0-5 mEq/L
Mg → 3-6 mEq/L
P → 0-13 mEq/L
Such products are
Ringer’s injection:
Each liter contains
NaCl → 8.6 g
KCl → 0.3 g
CaCl2 (as dehydrate) → 0.33 g
This is equivalent to
Na → 147 mEq/L
K → 4 mEq/L
Ca → 4.5 mEq/L
Cl → 155.5 mEq/L
Ringer’s injection is usually available in 500 and 1000 ml injections.
Lactated ringer’s injection:
Each 100 ml contains
NaCl → 600 mg
Na-Lactate → 310 mg
KCl → 30 mg
CaCl2 (as dehydrate) → 20 mg
This is equivalent to
Na → 130 mEq/L
K → 4 mEq/L
Ca → 2.7 mEq/L
Cl → 109.7 mEq/L
Lactate → 27 mEq/L
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Lactated ringer’s injection is usually available as 150, 250, 500 and 1000 ml injections.
Both of these products are usually administered intravenously in 1 litre dose.
Iron and hematinic preparations:
Introduction:
Iron is present in some form in higher animals. In the body it is essential to the
elementary metabolic processes and in respiratory chain as electron carrier. Below iron and
some its preparations termed hematinic preparations are discussed-
Absorption of iron from intestinal lumen:
There have been three postulates suggested to explain the controls of intestinal iron
absorption. They are
1. The mucosal block hypothesis
2. The active transport hypothesis
3. The iron-chelate hypothesis
The mucosal block theory:
This theory suggests that
i. Dietary administered iron is reduced to ferrous form as iron must be in ferrous form to
cross the mucosal membrane.
ii. Ferrous form diffuses into mucosal cell of intestine and gets reoxidized to form ferric
form (to bind with apoferritin – a condition of ferritin where iron is not bound to it).
iii. Ferric ion combines with apoferritin to form stable ferritin.
iv. Ferritin travels across the cell and iron is released to be reduced again to ferrous form.
v. Ferrous ion diffuses across the serosal membrane.
vi. After entering inside the serosal membrane it is reoxidized to ferric ion and combines
with iron-transport protein Transferrin.
vii. In the form of transferrin iron is transported to liver or bone marrow.
This theory asserts that only small amount of ferritin can be formed in a cell and once
the full complement of ferritin is formed the cell can’t pick up iron regardless of its
concentration in the lumen of intestine.
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Active transport mechanism:
It can be illustrated as following
According to this theory
i. Dietary administered iron is reduced to ferrous form and it enters the mucosal cell by
diffusion.
ii. In the cell it combines with endogenous low molecular weight ligands or is stored as
ferritin.
iii. Iron crosses the serosal membrane by a specific transport system intimately linked to
ATP.
iv. After passing the serosal membrane it combines with transferrin and transported to liver
and bone marrow.
The iron-chelate hypothesis:
This hypothesis state-
i. Exogenous or endogenous ligands or chelating agents bind with dietary administered
iron (in both ferric and ferrous form) to produce low molecular weight complexes. This
complex passively diffuses through the mucosal cell membrane.
ii. Within the cell the iron is stored as ferritin or transferred to new endogenous ligands.
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iii. Iron may diffuse across the serosal membrane as chelate of original chelating material or
the new endogenous ligands.
iv. After passing the serosal membrane iron is transferred to transferring and stored in liver
or goes to bone marrow for erythropoiesis.
Iron in the body:
The daily requirement of iron in human body is as follows-
Male → 10-12 mg
Female → 12-18 mg.
From this amount iron intake only 5-10% is absorbed from the intestine. This iron in our
body is associated with two types of protein.
a) Hemoproteins:
Hemoproteins are those iron-containing proteins which are responsible for respiration
(respiratory enzymes) and carrying O2.
Cytochrome C is an example of respiratory enzyme which has a heme (porphyrin ring) system
bonded to polypeptide. Here the iron functions as an electron carrier. Other examples
respiratory enzymes having iron are catalase and peroxidase.
On the other hand hemoglobin and myoglobin represents O2 transporting hemoproteins.
b) Iron transport or storage proteins:
These proteins are responsible for handling body’s requirements of iron.
Ferritin and hemosiderin are iron storage proteins. Ferritin is a water soluble crystalizable iron
protein which stores iron in Fe3+
form but releases it as Fe2+
. On the other hand hemosiderin is
water insoluble and can be regarded as dehydrated ferritin.
Transferrin, a glycoprotein is the major iron transporting protein in our body. It releases iron in
RBC precursor and sends iron to liver.
Official iron products:
Ferrous fumarate:
Properties:
i. Occur as reddish orange to red-brown odorless powder.
ii. It is slightly soluble in water and very slightly soluble in alcohol.
iii. It dissolves in dilute HCl with precipitation of fumaric acid.
Use as drug: It is better than ferrous sulphate or ferrous gluconate because-
i. It is resistant to oxidation on exposure to air.
ii. Resistant to oxidation even on exposure to a hot humid atmosphere over an extended
period of time.
iii. Conversion to the ferric form is little.
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Dose:
200 mg, two or three times a day.
Ferrous gluconate:
Properties:
i. It occurs as a yellowish gray or pale greenish yellow fine powder or as granules
having a slight odor of burnt sugar.
ii. Its 1 in 20 solution is acid to litmus.
iii. It is soluble in water but practically insoluble in alcohol.
Use as drug:
It has good bioavailability but doubtfully no less irritant than ferrous sulphate or ferrous
fumarate when equivalent dose of iron is administered.
Dose:
300 mg, three times a day.
Ferrous sulphate:
FeSO4.7H2O
Properties:
i. It occurs as pale, bluish green crystals or granules which are odorless.
ii. It oxidizes readily in the air to form brownish yellow ferric sulphate [Fe4(OH)2(SO4)5]
iii. Its (ferrous sulphate USP) 1 in 10 solution is acid to litmus having a pH of about 3.7.
Use as drug:
It is used orally as tablets and syrup. It is the most widely used oral iron preparation and
is the drug of choice in treating uncomplicated iron-deficiency anemia.
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But due its oxidizing property USP carries the warning “Do not use ferrous sulphate that
is coated with brownish yellow basic ferric sulphate”.
It may be irritating to the GI mucosa due to the astringent action of the soluble iron.
Dose:
300 mg, two or three times a day.
Iron dextran injection:
Properties:
i. Iron dextran injection is a sterile, colloidal solution of ferric hydroxide [Fe(OH)3]
complexed with partially hydrolyzed dextran (glucose polymer) of low molecular
weight in Water For Injection (WFI).
ii. The pH of the injection is between 5.2 and 6.5.
Use as drug:
i. It is for intramuscular injections only.
ii. It is used only in confirmed cases of severe iron-deficiency anemia where oral therapy
is contraindicated, ineffective or when oral medication can’t be relied upon.
iii. It is efficient only when bone marrow iron stores are depleted.
Dose:
1M intramuscular injection containing 100 mg of iron once a day.
Essential & trace elements:
The elements discussed below have specialized biochemical functions and may show a
specific deficiency syndrome.
Potassium:
Introduction:
Potassium is a major intracellular cation and it is present in a concentration
approximately 23 times higher than the concentration in the extracellular fluids.
Cation
Extracellular fluid conc. (mEq/L)
Intracellular fluid conc. (mEq/L)
plasma Interstitial fluid
K+
4 4 160
This concentration differential is maintained by an active transport mechanism.
During transmission of a nerve impulse, potassium leaves the cell and sodium enters the cell. It
is currently believed that an active transport mechanism reestablish the concentration
differential after transmission of the nerve impulse. This active transport mechanism has been
called the sodium potassium pump.
Dietary source:
Vegetables, fruits, whole grains, meat, milk etc.
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Absorption and excretion:
Potassium in the diet is rapidly absorbed (in the intestine). Any excess potassium is
rapidly excreted by the kidneys. Potassium salts have been used for their diuretic action because
of this efficient excretion of potassium by the kidneys, since a certain volume of fluid will be
excreted in order to keep the potassium salt in solution.
Role in our body:
1. Maintain the osmotic integrity of cells and osmotic pressure in ICF
2. Maintain acid-base balance through potassium-hydrogen exchange
3. Contribute to the reactions that take place in cells. It functions to-
◦ Transform carbohydrates into energy
◦ Convert amino acid to protein
◦ Change glucose into glycogen
4. Play a critical role in the excitability of skeletal, cardiac, and smooth muscle (through
action potential).
5. In sodium reabsorption through Na+
-K+
ATPase.
Abnormal conditions:
Hypokalemia (hyperpotassemia)
It refers a condition when the potassium level in plasma is decreased below 3.5 mmol/L.
It can occur due to vomiting, diarrhea, burns, hemorrhage, diabetic coma, intravenous
infusion of solutions lacking in potassium (dilution effects), overuse of thiazide diuretics and
alkalosis.
The effects of hypokalemia include changes in myocardial function, flaccid and feeble
muscle and low blood pressure.
Hyperkalemia (hyperpotassemia)
It is the condition of the body where the potassium level in the plasma increases above
5.0 mmmol/L.
It is less common as kidneys readily excrete excess potassium. It occurs during certain
types of kidney damages and in certain acidotic conditions where potassium is retained due to
interference with sodium and potassium proton exchange.
Effects of hyperkalemia include possible cessation of heart beat (potassium arrest). It is
thought that potassium may be displacing calcium in the cardiac muscle, since a decrease in
calcium will produce a similar pattern in the heart muscle and may explain why calcium
gluconate is effective in hyperpotassemic conditions.
Copper
Introduction:
Copper is indispensable for normal metabolism in man and most animals. But unlike
iron, most of the population obtain adequate amount of from food and water (and cooking
utensils). Thus copper supplements are probably not necessary.
The adult human contains about 2 mg/kg of Cu distributed mostly in enzymes and other
proteins. The daily average intake of copper is 2-5 mg.
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Dietary source:
Among food whole grains, beans, nuts, potatoes, and organ meats (kidneys, liver) are
good sources of copper. Also water is another good source.
Absorption, excretion and distribution:
Absorption
Copper is solubilized in the acidic stomach and absorbed from the stomach and upper
small intestine. Approximately 30% of daily intake (5 mg) that is 2 mg is absorbed in the body.
Distribution:
From the intestine Cu enters the blood serum where it exists first as Cu-albumin
complex. Copper is transported in this form to liver, RBC, bone marrow, kidney and tissue.
In the liver copper is stored, incorporated into a copper protein named ceruloplasmin or
excreted through bile.
In the RBC 60% of the copper is found as erythrocuprein and 40% is found as labile
nonerythrocuprein fraction. The copper of erythrocuprein may come from bone marrow during
formation of normoblast, a RBC precursor.
At equilibrium, 93% of serum copper is in ceruloplasmin and 7% in albumin. Copper
from ceruloplasmin is not released unless the protein is catabolized.
Excretion:
Of the amount absorbed
80% is excreted through the bile
16% is emptied directly back to intestine through the gut walls
4% is excreted in urine.
Role in our body:
1. Hemoglobin formation: Despite an adequate supply of iron, Cu is required to prevent
anemic conditions as-
a) Cu could facilitate iron absorption
b) Cu could be stimulatory to the enzymes in the heme and/or globin biosynthetic
pathway
c) Cu helps in the mobilization of stored iron which could be incorporated into the
hemoglobin molecule. Ceruloplasmin is a ferrioxidase enzyme. It oxidizes ferrous
iron to ferric iron for binding by transferrin. Transferrin then releases its iron to
the RBC precursor.
2. Oxidative phosphorylation (ATP production by cellular respiration): Cu is constituent of
cytochrome oxidase, the terminal oxidase in electron transport mechanism.
3. Formation of aortic elastin: Cu is necessary for amine oxidase activity and may play a role
in the formation of cross linkage of elastin of aorta.
4. Component of tyrosinase: Cu is a component of tyrosinase, an enzyme responsible for
conversion of tyrosine to the black pigment, melanin. A Copper deficiency in animals
causes loss of hair color due to reduced tyrosinase activity.
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Since copper intake of man and animal is sufficient, the abnormal conditions are rarely
observed. But the following two may be mentioned.
Neutropenia and other symptoms in infants:
This is due to copper deficiency in the infant. The primary symptoms include
neutropenia (Neutrophil leucocyte deficiency) with or without iron-deficiency anemia. In
protracted (prolonged) cases, regenerative anemia and scurvy like bone lesion may appear.
Wilson’s disease:
It is a rare (4 or 5 per million subjects) genetic disorder where the patient have excess Cu
level (storage) in liver, brain, kidney and cornea. The symptoms of this disease are
1. Hepatic cirrhosis
2. Brain damage
3. Demyelination
4. Kidney defects
It can be treated by chelating agent penicillamine.
Official copper preparations:
There is no official preparation for copper deficiency as it is rare. Copper preparations
are used topically as fungicides and astringents. The only official copper salt is Cupric sulphate
which is an antidote for phosphorus poisoning.
Calcium
Introduction:
Calcium is one of the major physiological ions in human body. About 91% of body
calcium is found in the bones and the rest is found in extracellular fluid.
Dietary source:
Milk and dairy products are the best source of calcium.
Absorption and control of calcium:
Calcium is absorbed from the upper part of the small intestine where the intestinal
contents are still acidic. Absorption of calcium (active control of calcium) is regulated by the
followings-
i. Vitamin D3 obtained from diet and sun
ii. Parathyroid hormone (PTH) from parathyroid gland
iii. Calcitonin from thyroid gland
iv. & skeletal loading of calcium
Vitamin D3:
Vitamin D3 is obtained from diet as cholesterol which is converted to cholecalciferol in
skin in the presence of sunlight. It is initially stored in liver and it is converted to
25-hydroxycholecalciferol. The concentration of it is regulated by feedback control.
25-hydroxycholecalciferol is converted to 1, 25-dihydroxycholecalciferol (Calcitriol) which is
the active form of vitamin D in kidney. This occurs under the feedback control of PTH.
Calcitriol stimulates absorption of calcium from intestine as following figure-
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Calcitriol performs the following functions-
1. Promotes intestinal absorption of calcium
2. May act as a gene activator causing synthesis of calcium-binding protein which
transfer the calcium cation across the intestinal wall
3. Has slight effect to increase calcium re-absorption in kidneys
4. Works with PTH to cause calcium absorption from bone
Parathyroid hormone (PTH):
It is polypeptide with 84 amino acid residues (M.W. 9,500 dalton) which is secreted from
parathyroid gland in rapid (minutes) response to reduced calcium in blood.
The peptide fragments of the hormone can be active for periods measured in hours. The
hormone operates via cAMP 2nd
messenger.
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The effects of PTH are-
1. Increases calcium resorption from bone. For this purpose existing osteoclasts are
activated and new osteoclasts are formed (days to weeks) to digest bone and release
calcium
2. Decreases excretion of calcium by kidneys. This is important to prevent bone
deterioration
3. Increases calcium absorption manifested via Vitamin D3. PTH produces most active
form of D3 in the kidney (1, 25-dihydroxy-cholecalciferol) which stimulates calcium
absorption.
Calcitonin:
Calcitonin acts directly on the bone to reduce the number of osteoclast cells and acts
indirectly on kidney to increase urinary excretion of phosphates. Thus it inhibits the absorption
of calcium from intestine.
Skeletal loading:
In bone there are two types of cells osteoblasts (build the bone by absorbing Ca from
blood) and osteoclasts (break the bone and release Ca into blood). They affect Ca absorption.
Role in our body:
Form bone structure:
As bones begin to form, calcium salts form crystals called hydroxyapatite (HA, is a
naturally occurring mineral form of calcium apatite with the formula Ca5(PO4)3(OH), but is
usually written Ca10(PO4)6(OH)2 to denote that the crystal unit cell comprises two entities. Up to
50% of bone by weight is made up of a modified form of hydroxyapatite) on a matrix of
collagen (a group of naturally occurring proteins found in animals, especially in the flesh and
connective tissues of mammals such as tendon, ligament and skin, and is also abundant in
cornea, cartilage, bone, blood vessels, the gut. The fibroblast is the most common cell which
creates collagen). During mineralization, as the crystals become denser, they give strength and
rigidity to maturing bones. At the age of 30 peak bone mass occurs.
The bone also serves as a calcium bank.
Nerve function:
Calcium is necessary for release of acetylcholine from preganglionic nerve endings.
Muscle contraction:
Calcium gives rise to muscle contraction. Its action is this is associated with cAMP.
Blood clotting:
Calcium is one of the factors involved in blood clotting (blood coagulation factor IV).
Cellular metabolism:
This is a complicated mechanism. Some hormones activate a signal cascade based on the
membrane lipid phosphatidylinositol. To understand this few things are essential to know.
G protein→ G proteins are ones in which protein binds with a guanine neucleotide. Most of the
G proteins are heterotrimaric (α, β and γ subunits).
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G-Protein Coupled Receptor (GPCR)→ they are receptors found in the membrane of
eukaryotes. When some hormones bind with GPCR it activates the associated G protein by
exchanging GDP bound to G protein with GTP (it may be noted that when G protein is bound
to GDP they are “off” and when they are bound to GTP they are “on”).
When GPCR is activated it activates the associated G protein by exchanging GTP for
GDP. The G-protein's α subunit, together with the bound GTP, can then dissociate from the β
and γ subunits to further affect intracellular signaling proteins. In the above diagram it activates
Adenyl Cyclase (AC) which releases cAMP from ATP. cAMP in turn activates Protein Kinase
A (PKA).
Kinases sequentially catalyze transfer of Pi from ATP to OH groups at positions 5 & 4 of
the inositol ring, to yield phosphatidylinositol-4,5-bisphosphate (PIP2).
PIP2 is cleaved by Phospholipase C. Here a G protein Gq (Gq-GTP) activates
phospholipase C. different isoforms of phospholipase C has different regulatory domains and
thus respond to different signals.
AC
hormone
signal
outside
GPCR plasma
membrane
GTP GDP ATP cAMP + PPi
 cytosol
GDP GTPMd.
Imran
Nur
Manik

Cleavage of PIP2, catalyzed by Phospholipase C, yields two second messengers
a) Inositol-1,4,5-triphosphate (IP3)
b) Diacylglycerol (DG)
Diacylglycerol, with Ca++
, activates Protein Kinase C, which catalyzes phosphorylation of
several cellular proteins, altering their activity. IP3 activates Ca++
-release channels in ER
(endoplasmic reticulum) membranes. Thus Ca++
stored in the ER is released to the cytosol
where it may bind calmodulin or help activate Protein Kinase C.
Signal turn-off (Ca++
functions) includes removal of Ca++
from the cytosol via Ca++
-
ATPase pumps, & degradation of IP3.
Osteoporosis:
Osteoporosis is one of the most prevalent diseases of aging, affecting more than
25 million people in the US, most of which are women.
The disease occurs when the bone mineral density becomes so low that the skeleton is
unable to sustain ordinary strains, a condition marked by the occurrence of fractures.
Who are at risk?
The risk factors include aging, female sex, limited intake of bone building nutrients
(Calcium, phosphorus, fluoride, magnesium, potassium, Vitamin A, Vitamin D, Vitamin K are
bone building materials. Possibly iron, copper, zinc, manganese, and boron function in bone
metabolism, but their roles in preventing bone loss are not well established), excessive
consumption of potentially damaging substances (alcohol, tobacco), sedentary lifestyle, lack of
sunlight, decreased estrogen levels, genetics, and race.
O P
O
O
H2C
CH
H2C
OCR1
O O C
O
R2
OH
H
OPO3
2
H
H
OPO3
2
H
OH
H
O
H OH
1 6
5
43
2
PIP2
phosphatidylinositol-
4,5-bisphosphate
O P
O
O
H2C
CH
H2C
OCR1
O O C
O
R2
OH
H
OPO3
2
H
H
OPO3
2
H
OH
H
O
H OH
1 6
5
43
2
PIP2
phosphatidylinositol-
4,5-bisphosphate
cleavage by
Phospholipase C
OH
H
OPO3
2
H
H
OPO3
2
H
OH
H
H OH
OPO3
2
1 6
5
43
2
IP3
inositol-1,4,5-trisphosphate
OHH2C
CH
H2C
OCR1
O O C
O
R2
diacylglycerol
Md.
Imran
Nur
Manik

Why osteoporosis occurs?
1. Decreased calcium absorption from intestine. This may be caused by
- Presence of excessive dietary fiber which may interfere with calcium absorption.
- Caffeine intake may reduce Ca absorption
2. Increased urinary calcium excretion. This may be caused by-
- Excessive animal protein consumption
- High sodium intake especially when coupled with low calcium intake
- Caffeine may also increase calcium excretion
3. High phosphorus intake with low calcium intake may promote bone loss
4. Vitamin D deficiency/inability to hydroxylate vitamin D.
5. Bone dissolution to buffer the fixed acid load from dietary protein
6. Increased sensitivity to parathyroid hormone.
Prevention of osteoporosis:
1. Increase intake of bone-building nutrients
2. Reduce consumption of alcohol, tobacco, caffeine, sodium, and animal protein
3. Engage in regular weight-bearing exercise
Iodine
Introduction:
Iodine is an essential ion necessary for the synthesis of two hormones produced by the
thyroid gland, Triiodothyronine (T3) and thyroxin (T4). It also has pharmacological action as
fibrolytic agent, expectorant and bactericidal agent.
The usual iodine requirement for an average man is 140 µg/day and 100µg/day for an
average woman.
Dietary source:
Today adequate iodine intake is insured by iodized table salts containing 0.01% KI.
Role in our body:
The biggest role of iodine is in the synthesis of T3 & T4 hormone.
Triiodothyronine (T3):
It is a follicular hormone which constitutes about 7% of total secretion of thyroid gland.
Thyroxin (T4):
It is also a follicular hormone constituting 93% of total secretion.
[Another hormone named Calcitonin is also secreted from thyroid gland but this is omitted
here.]
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Synthesis of T3 & T4:
Synthesis of thyroid hormones involves following steps
i. Thyroglobulin synthesis: The thyroid gland is composed of thyroid follicles.
Each follicle has a lining of cells called thyroid follicular cells. From these cells
thyroglobulin is (71 amino acid residues) synthesized and secreted. It enters the follicle
by exocytosis.
ii. Uptake of iodine: From diet I ¯ ion is obtained which enters the follicular cells from
blood via Na/I symporter.
iii. Oxidation of iodide: Iodide ion is secreted outside into the follicle where it is oxidized
to iodine form.
iv. Iodination of tyrosine: Tyrosine is obtained from proteolysis of thyroglobulin. Iodine
is added to tyrosine to form MIT (Mono Iodo Tyrosine) and DIT (Di Iodo Tyrosine).
v. Coupling of MITT & DIT:
4
3
TDITDIT
TDITMIT


After synthesis of the hormones they are secreted into the blood from the follicular cells.
Md.
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Colloid goiter:
When there is a lack of iodine in the diet, T3 and T4 aren’t synthesized since no
iodination of tyrosine takes place. But thyroglobulins are still secreted into the follicles of the
thyroid gland. Also the body tries to make up for the hormone deficiency by increasing the size
of the gland. This results in an enlargement of the thyroid gland.
This is simply known as colloid goiter. This is characterized by a swelling at the neck.
This is prevented by using iodized table salt.
Products of Iodine:
Povidone-iodine (PVP-I) is a stable chemical complex of polyvinylpyrrolidone (also known
as Povidone & PVP) and elemental iodine. It contains from 9.0% to 12.0% available iodine,
calculated on a dry basis.
It is broadly used for the prevention and treatment of skin infections, and the treatment
of wounds.
Iodine has been recognized as an effective broad-spectrum bactericide, and it is also
effective against yeasts, molds, fungi, viruses, and protozoa. Drawbacks to its use in the form of
aqueous solutions include irritation at the site of application, toxicity and the staining of
surrounding tissues.
Zinc
Introduction:
Zinc is an essential trace element for humans, animals and plants. It is vital for many
biological functions and plays a crucial role in more than 300 enzymes in the human body.
These include carbonic anhydrase, glutamate dehydrogenase etc.
Dietary source:
The major sources of zinc are (red) meat, poultry, fish and seafood, nuts and legumes,
whole cereals and dairy products. Zinc is most available to the body from meat. A person on
vegetable diet may not get adequate amounts of zinc because of phytic acid found in vegetable
proteins.
Zinc in the body:
The adult body contains about 2-3 grams of zinc. Zinc is found in all parts of the body: it
is in organs, tissues, bones, fluids and cells. Muscles and bones contain most of the body’s zinc
(90%). Particularly high concentrations of zinc are in the prostate gland and semen.
The recommended daily allowance of zinc varies for different types of people. Babies up
to 6 months old should consume about 2 mg of zinc per day. This increases to 3 mg per day for
children 7 months to 3 years old. Children 4 to 8 years old should get 5 mg of zinc per day.
Children 9 to 13 years old should consume 8 mg
The optimal amount of zinc in a diet differs between men and women after age 14. The
recommended daily allowance for men is 11 mg of zinc per day; women only require 9 mg per
day, except when they are pregnant or lactating. Pregnant women should get 13 mg of zinc per
day, while lactating women should consume 14 mg per day.
The tolerable upper limit for zinc was set at 40 mg per day for adults over 19. Doses up
to 30 mg per day are generally well tolerated.
Md.
Imran
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Manik

Role in our body:
1. Zn is vital for growth and cell division:
Zinc is especially important during pregnancy, for the growing fetus whose cells are
rapidly dividing. Zinc also helps to avoid congenital abnormalities and pre-term delivery.
Zinc is vital in activating growth - height, weight and bone development in infants, children
and teenagers.
2. Zinc is vital for fertility:
Zinc plays a vital role in fertility. In males, zinc protects the prostate gland from
infection and ultimately from enlargement (prostatic hypertrophy). Zinc helps maintain
sperm count and mobility and normal levels of serum testosterone
3. Zinc is vital for the immune system:
a. Among all the vitamins and minerals, zinc shows the strongest effect on our all-
important immune system.
b. Zinc plays a unique role in the T-cells. Low zinc levels lead to reduced and weakened
T-cells which are not able to recognize and fight off certain infections.
c. An increase of the zinc level has proven effective in fighting pneumonia and diarrhea
and other infections. Zinc can also reduce the duration and severity of a common cold.
4. Zinc is vital for taste, smell and appetite:
Zinc activates areas of the brain that receive and process information from taste and
smell sensors. Levels of zinc in plasma and zinc’s effect on other nutrients, like copper and
manganese, influence appetite and taste preference. Zinc is also used in the treatment of
anorexia.
5. Zinc is vital for skin, hair and nails:
Zinc accelerates the renewal of the skin cells. Zinc creams are used for babies to
soothe diaper rash and to heal cuts and wounds. Zinc has also proven effective in treating
acne, a problem that affects especially adolescents, and zinc has been reported to have a
positive effect on psoriasis.
Zinc is also used as an anti-inflammatory agent and can help sooth the skin tissue,
particularly in cases of poison ivy, sunburn, blisters and certain gum diseases.
Zinc is important for healthy hair. Insufficient zinc levels may result in loss of hair,
hair that looks thin and dull and that goes grey early. There are also a number of shampoos
which contain zinc to help prevent dandruff.
6. Zinc is vital for vision:
High concentrations of zinc are found in the retina. With age the retinal zinc declines
which seem to play a role in the development of age-related macular degeneration (AMD),
which leads to partial or complete loss of vision. Zinc may also protect from night blindness
and prevent the development of cataracts.
Zinc deficiency:
Zinc deficiency is a serious problem in many developing countries. Zinc deficiency is
ranked as the 5th leading risk factor in causing disease. Zinc deficiency can lead to-
1. Diarrhea and pneumonia in children, which can lead to high mortality rates in these
underdeveloped regions.
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2. Stunted growth and impaired development of infants, children and adolescents. Early
zinc deficiency also leads to impaired cognitive function, behavioral problems,
memory impairment.
3. In industrialized countries cases of mild zinc deficiency can be observed. The most
common symptoms include dry and rough skin, dull looking hair, brittle finger nails,
white spots on nails, reduced taste and smell, loss of appetite, reduced adaptation to
darkness, frequent infections, delayed wound healing, dermatitis and acne.
Treatment:
Mild zinc deficiency symptoms can usually be corrected by supplying the body with the
right amount of zinc each day. Supplemental zinc not exceeding the recommended daily
allowance might be taken.
Therapies involving larger doses of zinc should always be discussed with your physician.
Therapeutical doses typically range from 20 mg – 30 mg, in some rare cases doses might be
higher.
Effect of excess zinc in the body:
Higher doses may cause-
1. Gastrointestinal reactions including nausea, vomiting, cramps and discomfort.
2. Other adverse reactions include a metallic taste in the mouth, headache and drowsiness.
3. High doses of zinc might also impair the status of other nutrients especially copper,
calcium and iron.
Element and
total amount
in human
body
Best food
sources
Required
Daily
Amount
(RDA)
Absorption
and metabo-
lism
Principal met-
abolic func-
tions
Clinical manifes-
tation of deficien-
cy
Sodium
(Na+
),
1.8g/kg
Table salts,
salty foods,
animal
foods, milk,
baking soda
powder,
some vege-
tables.
About 3-
5g
Readily ab-
sorbed, ex-
tracellular,
excreted in
urine and
sweat; aldos-
terone in-
creases reab-
sorption in
renal tubules.
Buffer constit-
uent, acid-base
balance, water
balance, os-
motic pressure,
CO2 transport,
cell membrane
permeability,
muscle irrita-
bility.
i. Dehydration
ii. Acidosis
iii. Tissue atrophy
iv. Excess leads
to edema, hy-
pertension.
Potassium
(K+
),
2.6g/kg
Vegetables,
fruits,
whole
grains,
meat, milk,
legumes.
About
1.5-4.5 g
Readily ab-
sorbed, intra-
cellular; ex-
creted by
kidney.
Buffer constit-
uent, acid-base
balance, water
balance, CO2
transport,
membrane
transport, neu-
romuscular ir-
ritability.
i. Acidosis
ii. Renal dam-
age
Md.
Imran
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Manik

Calcium
(Ca++
),
22g/kg
Milk, milk
products,
fish bones
(cooked).
0.8 g
Poorly ab-
sorbed (20-
40%) accord-
ing to body’s
need; absorp-
tion is aided
by vitamin
D, lactose,
acidity; hin-
dered by ex-
cess fat,
phosphate,
oxalate; ex-
creted in fe-
ces; parathy-
roid hormone
mobilizes
bone Ca++
.
Formation of
apatite in
bones, teeth;
blood clotting;
cell membrane
permeability;
neuromuscular
irritability.
i. Rickets
(child) and
poor growth
ii. Osteoporosis
(adult)
iii. Hyper excit-
ability.
Phosphorus
(PO4
3
),
12g/kg
Milk, milk
products,
egg yolk,
meat,
whole
grains, leg-
umes, nuts.
0.8 g
Readily ab-
sorbed; ex-
creted by
kidney.
Constituent of
bones, teeth;
constituent of
buffers; con-
stituent of
ATP, NAD,
FAD etc.; con-
stituent of met-
abolic interme-
diates, nucleo-
proteins, phos-
pholipids,
phosphopro-
teins.
i. Osteomala-
cia(rare)
ii. Renal rickets
iii. Cardiac ar-
rhythmia
Magnesium
(Mg++
),
0.5g/kg
Chloro-
phyll, nuts,
legumes,
whole
grains.
350 mg
Absorbed;
competes
with Ca++
for
transport.
Cofactor for
PO4
3—
transferring
enzymes; con-
stituent of
bones, teeth;
decreases neu-
romuscular ir-
ritability.
i. Magnesium
conditioned
deficiency
ii. Muscular
tremor,
choreiform
(involuntary
dancing)
movements,
iii. Confusion
iv. Vasodilation
v. Hyper irrita-
bility
Iron (Fe++
or
Fe+++
),
75mg/kg
Liver,
meats, egg
yolk, green
leafy vege-
10 mg in
male; 18
mg in fe-
male.
Absorbed ac-
cording to
body need;
aided by
Constituent of
hemoglobin,
myoglobin,
catalase, fer-
i. Hypochromic
Anemia
ii. Pregnancy
demands
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tables,
whole
grains, en-
riched
bread and
cereals.
HCl, ascor-
bic acid.
ridoxin, cyto-
chromes; elec-
tron transport,
enzyme cofac-
tor.
iii. Excess causes
hemochroma-
tosis.
Iodine (I─
)
Seafoods,
iodized
salt.
140 µg in
male; 100
µg in fe-
male.
Concentrates
in thyroid;
transported
as PBI.
Constituent of
thyroxin, triio-
dothyronine;
regulator of
cellular oxida-
tions.
i. Endemic (sim-
ple) goiter (hy-
pothyroid-
dism).
ii. Cretinism
Zinc (Zn++
),
28mg/kg
Liver, pan-
creas, shell-
fish, widely
distributed
in animal
and plant
tissue.
10-15 mg
1-2 mg ab-
sorbed; phyt-
ate decreases
absorption.
Constituent of
insulin, carbon-
ic anhydrase,
carboxypepti-
dase, lactic de-
hydrogenase,
alcohol dehy-
drogenase, al-
kaline phos-
phatase.
i. Anemia
ii. Stunned growth
iii.Hypogonadism
in male
Copper
(Cu++
),
2mg/kg
Liver, kid-
ney, egg
yolk, whole
grains.
2-3 mg
Limited ab-
sorption;
transport by
ceruloplas-
min; stored
in liver; ex-
cretion via
bile.
Formation of
hemoglobin
(increases iron
utilization);
constituent of
oxidase en-
zymes (tyrosi-
nase, cyto-
chrome oxi-
dase, ascorbic
acid oxidase).
i. Hypochromic
anemia
ii. Excessive he-
patic storage
in Wilson’s
disease.
Cobalt
(Co++
),
3mg
Liver, pan-
creas,
mush-
rooms.
1-2 mg
Limited ab-
sorption;
stored in liv-
er; excretion
via bile.
Constituent of
vitamin B12.
i. Anemia in an-
imals
ii. Deficiency as
vitamin B12
causes perni-
cious anemia
iii. Excess causes
polycythemia
Manganese
(Mn++
),
20mg
Liver, kid-
ney, wheat
germ, leg-
umes, nuts.
3-9 mg
Stored in liv-
er, mito-
chondria,
and bone;
excreted via
bile.
Cofactor for
number of en-
zymes – ar-
ginase, carbox-
ylase, kinases
etc.
i. Unknown in
man, in ani-
mals it causes
decreased glu-
cose toler-
ance, perosis,
congenital
ataxia.
Md.
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Molybdenum
(Mo),
5mg
Liver, kid-
ney, whole
grains, leg-
umes, leafy
vegetables.
Trace
Readily ab-
sorbed; ex-
creted in
urine and
bile.
Constituent of
xanthine oxi-
dase, aldehyde
oxidase.
Unknown
Chromium
(Cr+++
)
Liver, ani-
mal and
plant tissue.
Trace
Involved in
carbohydrate
utilization.
i. Unknown.
Deficiency in
diabetes
claimed
ii. Decreased
glucose toler-
ance in rats
iii. Possible rela-
tion to cardi-
ovascular dis-
ease.
Selenium
(Se)
Liver, kid-
ney, heart.
Trace
Excreted in
urine.
Constituent of
factor 3; acts
with vitamin E
to prevent liver
necrosis and
muscular dys-
trophy in ani-
mals; inhibits
lipid hyperoxi-
dation.
i. Unknown
ii. Excess causes
alkali disease
in cattle,
sheep
Chloride
(Cl─
)
50 mEq/kg
Animal
foods, table
salts.
Intake 5-
10 g as
NaCl.
Rapid ab-
sorption; ex-
creted in
urine; high
renal thresh-
old; not
stored
Electrolyte,
osmotic bal-
ance; gastric
HCl; acid-base
balance.
Hypochloremic
alkalosis (perni-
cious vomiting)
Fluoride (F)
Seafoods,
some drink-
ing water.
1 mg (1
ppm in
drinking
water)
Easily ab-
sorbed; ex-
creted in
urine, depos-
ited in bones
and teeth.
Constituent of
fluoroapatite –
tooth enamel.
i. Dental caries
ii. Osteoporosis
iii. Excess (5-8
ppm in water)
causes mott-
led enamel
Sulfur (SO4
-2
)
Plant and
animal pro-
teins as cys-
teine and
methio-
nine.
2-3 g
Derived from
metabolism
of cysteine
and methio-
nine; excret-
ed in urine,
Constituent of
proteins, mu-
copolysaccha-
rides, heparin,
thiamine, bio-
tin, lipoic acid;
detoxication.
i. Cystinuria
ii. Cystine renal
calculi.
Md.
Imran
Nur
Manik

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