Major extra and intracellular electrolytes. Pharmaceutical Inorganic chemistry UNIT-II (Part-II) Electrolyte: Intracellular fluid Interstitial fluid Plasma (Vascular fluid) Anionic electrolytes- HCO₃⁻, Cl⁻, SO₄²⁻, HPO₄²⁻ Cationic electrolytes- Na⁺, K⁺, Ca²⁺, Mg²⁺ Concentration of important Electrolytes: Electrolytes used in the replacement therapy: Sodium chloride*, Potassium chloride, Calcium gluconate* and Oral Rehydration Salt (ORS), Physiological acid base balance.

1. Pharmaceutical Inorganic chemistry
UNIT-II (Part-II)
Major extra and intracellular electrolytes
Presented By
Ms. Pooja D. Bhandare
(Assistant Professor)
DADASAHEB BALPANDE COLLEGE OF PHARMACY BESA NAGPUR

2. • Electrolyte is a substance that ionizes when dissolved in a suitable ionising solvent such as water.
• This includes most soluble acids, bases & gases.
• An electrolyte may be defined as concentrated if it has high concentration of ions or dilute if it has
low concentration of ions.
• The electrolyte concentration is maintained constant in the body fluids.
• If a person undergoes surgery or remain ill or under undesirable condition for a long time, the body
cannot maintain the electrolyte balance, then it is done by external administration which is termed
as Replacement therapy.
• Electrolytes are used for the correction of acid-base balance in various body fluids.
Electrolyte:

3. • The electrolyte concentration of body fluids have been different in various body fluid
compartments. They are
1. Intracellular fluid:- The fluid which is present inside the cell. Ex- Cytoplasm
• It constitutes 40-50% of body weight & its volume is 30 litres.
2. Interstitial fluid:- The fluid which is present between the cells.
• It constitutes 12-15% of body weight & its volume is 10 litres.
3. Plasma (Vascular fluid):- The fluid which is present within the blood vascular system.
• This constitutes 4-5% of body weight & its volume is 3-5 litres.
• The fluids present in the interstitial & vascular compartments are referred to collectively as
Extracellular fluid (ECF).

4. • Electrolytic Fluid Compartments:
•  Body contain 60-70% of water
Body Fluids
• Intracellular Fluid Extracellular Fluid
(Fluid inside the cell)
[45-50% of body weight]
Interstitial Fluid
(Between the cell)
[12-15% of body
weight]
Plasma or Vascular
fluid (Fluid within
blood vascular system)
[4-5% of body weight]

5. • Sodium & chloride are the main ions of ECF while potassium & phosphate are
the major ions of ICF.
• The three fluid compartments are demarcated from each other by membranes
which are permeable to water & certain inorganic & organic components
present in the body fluids.
• These membranes do not permit the transfer of certain molecules like proteins.
• For certain ions like Na, K, Mg the membrane shows selective permeability.
Thus the composition & concentration of various solutes in body fluids have
been definite but different from one another.
• The body fluids are having various inorganic ions which are either anionic or
cationic.
• Anionic electrolytes- HCO₃⁻, Cl⁻, SO₄²⁻, HPO₄²⁻
• Cationic electrolytes- Na⁺, K⁺, Ca²⁺, Mg²⁺

6. Concentration of important Electrolytes

7. • The fluid in each compartment is ionically balanced.
• Body has the capacity to adjust slight variations in electrolytic
concentration of the fluid compartments.
• If concentration of electrolytes changes – water will migrate across the
cell membrane to re-establish Osmotic equilibrium.

10. 1. SODIUM –
• Location- extracellular compartment as a salt (90%).
• Normal plasma level- 136-142 mEq/L
• Normal intake of NaCl per day- 5-20g
• Daily requirement – 3-5g
• Excess quantity of salt consumed gets excreted in the urine.
• The sodium level in the blood is controlled by aldosterone.
• Food sources- table salt, milk, baking powder, meat & some vegetables.
• Functions-
1. Regulates acid-base equilibrium.
2. Along with chloride maintain osmotic balance of various fluids.
3. Plays an important role in permeability of cell
4. Transmission of nerve impulse.

12. 2. POTASSIUM –
• Normal intake of KCl-5-7g/day
• Daily requirement – 1.5-4.5g
• Sources- milk, certain vegetables, meat & whole grains.
• It is rapidly absorbed from diet & rapidly excreted through kidneys.
• Maintains electrolyte composition of various body fluids.
• Influences acid-base balance & water retention.cc

13. Condition Hyperkalaemia Hypokalaemia
Elevated K⁺ levels Low K⁺ levels
Reason Renal failure, Dehydration or
shock, Addison’s disease
Prolonged diuretic therapy,
Inadequate intake, Severe
diaphoresis, Use of laxative,
vomiting, Excess insulin, Excess
stress, Hepatic disease, Acute
alcoholism
Symptoms Apathy, Confusion, Numbness/
paraesthesia of extremities,
Abdominal cramps, Nausea, Flaccid
muscles, Diarrhoea, Oliguria,
Bradycardia, Cardiac arrest
Anorexia, Nausea, vomiting,
Drowsiness, lethargy, confusion,
Leg cramps, Muscle weakness,
Hyperreflexia (overactive or
overresponsive reflexes).,
Hypotension, Cardiac
dysrhythmias, Polyuria

14. 2. CALCIUM –
• The total calcium content in body is about 22g/kg body weight
• Daily requirement – 0.8g
• 99% of calcium is found in bones and 1% in ECF
• Sources- milk, cheese, green vegetables, eggs, some fish.
• It can be absorbed from all parts of small intestine by an active transport mechanism.
• Greater amounts of calcium are needed in children and during pregnancy, lactation
• The normal range for total plasma calcium – 2.2 to 2.6m mol/litre
• About half of this is bound to plasma proteins, a small fraction gets complexed with
• citrate and phosphate and remaining amount circulates in blood as ionised calcium
• Ionised calcium plays a vital role in the functioning of nerves, blood clotting and muscle
contraction
• The level of calcium ions in plasma is regulated by parathyroid hormone and calcitonin

15. • FUNCTIONS –
• Normal functioning of ANS and voluntary system
• For cardiac function
• Important factor in coagulation of blood
• For the formation of bones
• Muscle contraction and maintenance of muscle tone
• Transmission of nerve impulses across synapse
• Release of certain neurotransmitters(Ach)

16. Condition Hypercalcemia Hypocalcaemia
Elevated Ca⁺² levels Low Ca⁺² levels
Reason Hyperparathyroidism, Excess vit D
intake
Decreased calcium absorption,
Hypoparathyroidism, vit D
deficiency, Cushing’s syndrome,
Osteoblastic metastasis
Symptoms Fatigue, muscle weakness,
constipation, Anorexia, Cardiac
irregularities
Titanic spasms, convulsions

17. 3. Magnesium –
• Second most abundant cation in the ICF
• The adult human body having 25gms of Mg about 54% is present in the bones
along with P, Ca, about 45% is in ICF and about 1% is in ECF
• Daily requirement – 350mg
• Source – nuts, soyabeans, whole grains, sea foods
• Functions –
(a). Activates enzymes which are involved carbohydrates and protein metabolis
(b). Important in neural transmission, myocardial function, neuromuscular
activity
(c). Needed for the operation of Na⁺- K⁺- ATPase pump system
(d). It is a cofactor for phosphate transferring enzymes
(e). Constituent of teeth and bones

19. 4. Chloride –
• Major extracellular anion
• Total chloride ion present in the body – 50mEq/kg body wt.
• Daily requirement – 5 to 10g
• Source – common table salt
• It readily gets absorbed throughout GIT.
• Mainly excreted through urine & through skin during sweating.
• Functions –
• Chloride ion along with sodium ion maintain osmotic balance between different
body fluids.
• Maintains charge balance between the body fluids i.e. ICF & ECF both as they
can pass through all membranes.
• Maintains acid-base balance & also take part in the formation of gastric HCl.
• Maintains proper hydration.

20. • Chloride Imbalance –
• Hypochloremia- due to metabolic acidosis
diabetic mellitus &
excessive vomiting.
• Hyperchloremia- due to dehydration
Excess chloride intake
CHF
 Severe renal failure

21. 5. Bicarbonate –
• Second largest anion in the ECF.
• Along with carbonic acid, it acts as one of the important buffer system in
the maintenance of acid-base balance.
• A lack of bicarbonate causes metabolic acidosis while an excess of
bicarbonate causes metabolic alkalosis.

22. 6. Phosphate –
• The phosphate ions such as H₂PO₄⁻, HPO₄⁻², PO₄⁻³ are the major anions of ICF.
Among these HPO₄⁻² is most important for maintaining pH at 7.4.
• Normal plasma phosphate concentration is 1.7 to 2.6 mEq/litre.
• Almost 4/5 of the total body phosphate is present in teeth & bones along with
calcium.
• Rest of the phosphate ion is covalently bound with lipids, proteins, carbohydrates,
nucleic acids, ATP.
• Functions-
• Plays a vital role in maintaining pH of body fluids.
• HPO₄⁻²/ H₂PO₄⁻ is an important biochemical buffer.
• Essential for normal bone & tooth development & proper calcium metabolism.
• Serum inorganic phosphate plays an important role in regulating erythrocyte
glucose metabolism.
• Under normal conditions, deficiency of phosphate ions does not occur. However
since the serum phosphate levels are usually correlated with serum calcium levels,
any change in the normal serum calcium levels may result in change in normal
serum phosphate levels

23. • Hypophosphatemia –
• Seen in vit D deficiency (Rickets),
• hyperparathyroidism &
• lack of phosphate reabsorption by kidney tubule due to infections,
• cancer in patients consuming a large amount of antacids specifically Al(OH)₃
• Hyperphosphatemia-
• Occur due to inappropriate excretion as a result of renal failure,
• increase in absorption due to hypervitaminosis D &
• hypoparathyroidism.
• Hyperphosphatemia leads to formation of phosphatic urinary calculi ( a form
of kidney stone).

24.  ELECTROLYTE REPLACEMENT THERAPY
• It is also called as electrolyte replenisher. Due to serious symptoms of the loss of
electrolytes, it is essential to maintain the normal level by external supply of
electrolytes, this therapy is called as electrolyte replacement therapy.
• There are two types of electrolyte solutions are used in replacement therapy-
I) Electrolyte solution for rapid initial replacement-solutions contains electrolyte
with concentration resemble with the electrolyte concentration found in extracellular
fluids.
II) Electrolyte solution for subsequent replacement-lower concentration of electrolyte
in solution.

25. 1. Sodium replacement-
• The depletion of sodium cause various forms of hyponatremias. A patient who suffers
severe symptoms cause by hyponatremia should receive either 3% or 0.9% sodium
chloride solution, until severe symptoms resolve
• The main objective of replacement to raise the serum sodium concentration to 120
mEq/L. there are various sodium chloride preparations are available.
1. Sodiumchloride:
• Formula: NaCl Molecular weight-58.44
• Standards : Sodium chloride not less than 99.0% and not more than 100.5% of NaCl,
calculated with reference to the dried substance.

26. • Method of Preparation: In laboratory it is prepared from common salt in
water by passing hydrochloric acid gas. The crystals are precipitated out.
• Industrially it is prepared by 1) by evaporating purified saline (sea water)
deposits & further purification. 2) and by purifying rock salt.
• It can also be prepared in laboratory in small scale by the acid-base reaction. In
which strong acid (HCl) reacts with strong base ( NaOH) & finally it gives
sodium chloride.
• Properties:
• Physical properties: it is colorless crystals or white, crystalline powder.
• It is freely soluble in water & slightly more soluble in boiling water, practically
insoluble in ethanol.
• Chemical properties:
• With oxidizing agent, it gets oxidized & liberates chlorine gas.
• 2Cl + MnO2 + 2H2SO4 Mn + 2SO4 + 2H2O +Cl2

27. • Identifications: It gives reactions characteristics of sodium and chloride.
• Test of purity: It has tested for acidity and alkalinity, Ba, Ca and Mg, Fe and
heavy metals, bromide, iodide, sulphate and loss on drying.
• Assay: The 0.1 g of substance is dissolved in 50ml of water in a glass stoppered
flask. To it, 50ml of 0.1 N silver nitrate solution, 3ml of nitric acid, 5ml of
nitrobenzene & 2ml of ferric ammonium sulphate solution are added. Now the
solution is shaken well and is then titrated with 0.1 N ammonium thiocyanate
solution until the water becomes reddish-yellow.
• Each ml of 0.1 N AgNO3 = 0.005844 g of NaCl.
• Storage: It is stored in tightly closed container in dry place as it absorb
moisture.
• Uses:
1. it can be used as electrolyte replenisher, as it is isotonic solution.
2. In combination with other electrolyte & dextrose, it is used as dialysis solution
in renal failure.
3. It is used as a saline diuretic in the form of enteric coated tablet.

28. Sodium chloride preparations:
1. sodium chloride injection I.P ( normal saline)
• It contains 0.9% sodium chloride without any antimicrobial agent (PH 4.5-7.0)
2. Sodium chloride hypertonic injection I.P-
It contains 1.6% w/v sodium chloride (PH 5-7.5)
3. Compound sodium chloride injection ( ringer solution)
• It contain following ingredients:
• Sodium chloride-0.869 g
• Potassium chloride-0.030 g
• Calcium chloride-0.048 g
• Water for injection q. s. 100ml
4. Bacteriostatic sodium chloride injection USP.
• It is sterile solution of sodium chloride (0.9% w/v) in water for injection containing
suitable antimicrobial agent. It is used as sterile vehicle.

29. 5. Sodium chloride & Dextrose Injection I.P
• It is solution of dextrose & sodium chloride in water for injection containing no
antimicrobial agent (PH 3.5-6.5). It is used as a nutrient & as an electrolyte
replenisher.
6. sodium chloride tablet I.P
• It contain 95.0 to 105 % w/v of sodium chloride and is available in strength of 180,
300 & 500 mg of sodium chloride. It is used as an electrolyte replenisher.
7. Sodium chloride and mannitol injection.
• It is sterile solution of sodium chloride and mannitol in water for injection. It is used
as a diuretic agent.

30. 2. Potassium chloride
• Formula: KCl Molecular weight-74.55
• Standard: potassium chloride contains not less 99.0% and not more than 100.5 % of
KCl, calculated with reference to the dried substance.
• Preparation:
• 1.It is prepared from natural mineral, carnallite (KCl, MgCl2.6H2O). The raw mineral
is ground and then treated with hot water. The less soluble KCl precipitate out. The
process is repeated till all the KCl is recovered from liquid.
• 2.On laboratory scale, it is prepared by action of HCl on potassium carbonate or
bicarbonate.
• K2CO3 + 2HCl 2KCl + H2O + CO2
• KHCO3 + HCl KCl + H2O + CO2
• 3. It can also be prepared in the laboratory in small scales by reacting potassium
hydroxide (KOH) with hydrochloric acid (HCl).
• KOH + HCl KCl + H2O

31. Properties:
• It is colorless crystalline, or white crystalline powder; odorless. It has a saline taste. It melts at 772
C. the 10% aqueous solution is neutral to litmus.
• It is freely soluble in water; practically insoluble in ethanol and ether.
Uses:
• It is used in prevention and treatment of potassium depletion and hypokalemia and diuretic-induced
hypokalemia.
• Potassium chloride is sometimes used as an excipient in pharmaceutical formulations.
• It is used in diabetic ketoacidosis.
• It is used in hypertension, potassium supplementation results in reduction of both systolic and
diastolic blood pressure.

32. Preparations of Potassium chloride:
1. Potassium chloride and Dextrose Injection:
• Potassium chloride and dextrose, intravenous infusion, is a sterile solution of potassium
chloride and either anhydrous glucose, in water for Injections.
2. Potassium chloride, sodium chloride and dextrose Injection:
• Potassium chloride, sodium chloride and dextrose Injection intravenous infusion.
3. Bumetanide and slow potassium tablets:
• This preparation is official in BP 2007. It contains bumetanide and potassium chloride. They
are formulated so that the potassium chloride is released over a period of several hours.
4. Sterile potassium chloride concentrate:
• It is sterile solution of potassium chloride in water for Injections.

33. 3. Calciumgluconate
Formula: C12H22CaO14. H2O Molecular weight: 448.40
Structure: calcium gluconate is calcium D-gluconate monohydrate.

34. Physical properties:
White crystals, granules or powder, stable in air, does not lose its
( C12H22O14Ca. H2O) water of crystallization on drying.
Neutral to litmus paper.
Chemical properties:
When treated with dil. HCl, it is decomposed into gluconic acid and calcium chloride.
Method of Preparation:
It is prepared by boiling a solution of gluconic acid with Calcium carbonate.
Product is filtered and dried.

35. Assay:
Principles: Complexometric titration.
0.5 g sample is dissolved in warm water, cool and add 5 ml of 0.05 M MgSO4 and 10
ml of strong ammonia solution.
Titrant: 0.05 M Disodium EDTA
Indicator: Mordant Black II mixture.
End point: until deep blue color develops.
 From the volume of 0.05 M disodium EDTA required, subtract the volume of the
MgSO4 solution added for actual reading.
 Factor: 1 ml 0.05 M disodium EDTA= 0.02242 g of Calcium gluconate.
Uses: It is used in management of hypocalcemia and calcium deficiency state.
In insect bite: calcium gluconate 10 % solution, is given intravenously as an alternative
to the use of conventional muscle relaxant, for the management of pain and muscle
spasm associated with insect bite.
In severe acute hypocalcemia.

36. Preparations of calcium gluconate:
1. Calcium gluconate injection:
• Calcium gluconate injection is a sterile solution of calcium gluconate in
water for Injection. Not more than 5 % of the calcium gluconate may be
replaced with a suitable calcium salt as stabilizing agent.
2. Calcium gluconate tablets:
• Usual strengths: 325 mg; 500 mg; 650 mg; 1 g
3. Effervescence calcium gluconate tablets:

37. Oral Rehydration Salts (ORS):-
• Oral rehydration therapy was developed in 1940
• ORS came in market from 1970.
• Recommended by World Health Organization (WHO)
• Oral Rehydration Salts – is a fluid replacement for the condition called dehydration,
electrolyte imbalance due to diarrhea.
• It works by increase the uptake of sodium and water by the intestine.
• Potassium is very important it promote the water and sodium absorption.
• A large number of formulation of oral rehydration preparations are available in
market, which contains glucose, sodium chloride, potassium chloride, and either
sodium bicarbonate or sodium citrate. These dry powder preparations are to be
mixed in specific amount of water and are used for oral rehydration therapy.

38. • ORS contains anhydrous glucose, NaCl, KCl & either NaHCO₃ or Sodium
citrate.
• These dry powder preparations are to be mixed in specific amounts of
water along with certain flavouring gent and a suitable agent for free flow
of the powder.
• These are used for oral rehydration therapy.
• In ancient times, homemade ORS is used which constitutes of 1
tablespoonful of salt, 2 tablespoonful of sugar in 1 litre of water.
• The following 3 formulations are usually prepared.
• When glucose is used, NaHCO₃ is packed separately.
• The quantities given below are for preparing 1 litre solution.

39. The formula II & III are recommended by WHO & UNICEF for control in
diarrhoeal diseases.

40. Physiological Acid-Base balance
• The number of hydrogen-ions present in the solution may be regarded as a
measure of the acidity of the solution. But pH is related to negative logarithm of
acidity of (H+) ion concentration. Thus, pH may be considered to measure the
acidity of the solution.
• All body fluids have definite pH values which must be maintained within
relatively narrow limits (within which the cells functions normally).The normal
range of pH values of few selected fluids are:

41. The pH values of certain body fluids are:-
• The pH of blood of a healthy person remains constant around 7.35
• If the pH of blood becomes low (high H⁺ concentration) acidosis results.
• If the pH of blood becomes high (low H⁺ concentration) alkalosis results.
• The range of pH of the blood compatible with life is 7-7.8.
• Since the kidneys help to remove excess acid from the body, urine can be quite acidic.

42. • The intracellular fluids also have varying pH depending upon the types of the
cell. For Eg in osteoblasts it may be slightly alkaline (pH 8.0) and in cells of
prostate gland it may be acidic (pH 5.0).
• The individual pH in an organ is maintained by secretions of alkalis or acids to
suitoptimum level.
• The low pH in the stomach is best to the functioning of the enzyme pepsin
present in gastric juice which breakdown proteins. Saliva has a pH range 6.4-
7.4 which is the optimum value for the action of ptyalin (the enzyme present in
saliva which initiates the digestion of carbohydrates)
• The metabolic process of the body cells produces acids or acidic substances
(for eg. Carbonic acid from CO2 and water, sulphuric acid and phosphoric acid
from, proteins and phosphoproteins, lactic acid and pyruvic acid from
anaerobic metabolism) and alkalis (for eg. Bicarbonate ions from salt of
organic acids c.f. citrate, lactate etc) which tend to alter the pH of the tissue
fluid and blood.

43. • The term Alkalosis refers to excess removal of H+ from the body fluid, in
contrast to the excess addition of H+, which is referred to as Acidosis.
• There are mainly three regulatory mechanisms which maintain the pH of the
each system and equilibrium with one another. These are:
1. Buffer of the body fluids
2. Respiratory mechanism
3. Renal regulation

44. 1. Buffer System:
• Buffers are the chemicals capable to maintain a constant pH. Buffer system is
consists of a weak acid and the salt of that acid.
• They resist the rapid change in the pH of body fluid by converting strong acids and
bases into weak acids and bases. Buffer is thus able to remove excess H+ from the
body fluid but not from body.
• The major buffer systems existing in the body fluids are as follows:
i. Carbonic acid-Bicarbonate Buffer system (H2CO3/NaHCO3):
ii. Phosphate Buffer System (Na2HPO4/NaH2PO4):
iii. Protein (Hemoglobin) Buffer System:

45. i. Carbonic acid-Bicarbonate Buffer system
(H2CO3/NaHCO3):
• It occurs in plasma and kidneys. Important regulator of blood pH. If there
occurs an excess of H+, the bicarbonate (HCO3-) ion acts as a weak base and
accept H+ to form carbonic acid. They latter dissociate further to yield CO2
and water molecules.
H+ + HCO3- H2CO3 H2O + CO2
• While if there occurs shortage of H+, the carbonic acid (another compound of
buffer system) ionises to release more H+ and maintain the pH.
• H2CO3 H+ + HCO3-

46. ii. Phosphate Buffer System
(Na2HPO4/NaH2PO4):
• This buffer system mainly works in cells and kidneys and helps to maintain the
physiological pH 7.4. Higher concentration of phosphate ions are found in intracellular
fluid, thus consider as an important regulator of pH of cytosol.
• The system consists of monohydrogen phosphate/ dihydrogen phosphate (HPO42-/H2PO4-)
anions.
• If there occur an excess of H+, the monohydrogen phosphate ion acts as the weak base by
accepting the proton
• HCl + Na2HPO4 NaCl + NaH2PO4
• While dihydrogen phosphate ions can act as the weak acid and is able to neutralize the
alkaline condition
• NaOH + NaH2PO4 H2O + Na2HPO4

47. iii. Protein (Hemoglobin) Buffer System:
• It is considered to be the most abundant buffer in body cells and plasma. Protein is
compound of amino acids that are having at least one carboxyl group (COOH) and at least
one amino (NH2) group.
• When there occurs an excess of hydrogen ions, the amino group acts as a base and accept
the proton.
• Thus, proteins are able to serve both the functions of acid and base components of a buffer
system due to its amphoteric nature. At physiological pH, histidine and cysteine are
considered to be the most important amino acid buffer. Since hemoglobin which is a
protein is composed of 37 histidine in the structure, it is effective physiological buffer.

48. 2. Respiratory mechanism:
• When respiration is decreased, there is an accumulation of CO2 in the body
which used up the alkali reserve of the blood resulting in the acidosis.
• On the other hand, if thereis “over-breathing”, which results in excessive
excretion of CO2, the condition of alkalosis may develop. Thus, acidity and
CO2 increases are both powerful stimulants of respiratory mechanism and
cause an increase in the rate and depth of respiration.

50. 3. Renal mechanism:
• Kidneys have the ability to form ammonia which combines with the acids
produced during the protein metabolism and is excreted in urine.
• The pH of urine is highly variable between 4.8 to 8.0. Normally, it is towards
acid side but varies with the nature of diet, exercise etc. While unstable
H2CO3 is removed mainly by respiratory mechanism, the fixed acids like
phosphoric, sulphuric and hydrochloric acids have to be remove through
kidneys.

51. Thank You !