Extra and intracellular electrolytes

By Abir hasan sajid

The body fluids are solutions of inorganic and organic solutes. The concentration balance of the
various components is maintained in order for the cell and tissue to have a constant
environment. In order for the body to maintain this internal homeostasis, (homeostasis means
maintenance of static or constant conditions in the internal environment) there are regulatory
mechanisms which control pH, ionic balance, osmotic pressure etc.

Disturbance of fluid and electrolyte metabolism involve four properties of the body fluid-
volume, osmolarity, hydrogen ion concentration (pH) and the concentration of other specific
ions.

The total body water is divided into three compartments:

1) the intracellular compartment.
2) the extracellular compartment, which consists of the plasma and the interstitial
fluid.
3) the transcellular compartment, which includes the fluid within the
gastrointestinal tract, humor of the eye and the excretory system of the kidneys
and glands, pericardial, peritoneal, synovial, cerebrospinal fluid.

((((All the body fluids intracellular, extracellular (interstitial, plasma or vascular) contains
electrolytes. The electrolyte concentration varies in these fluids. These fluid compartments are
separated from each other by membranes which are permeable to water and many organic and
inorganic solutes. They are nearly impermeable to macromolecules e.g., proteins and
selectively permeable to certain ions e.g. Na+, K+ and Mg+ as a result, each of these fluid
compartments has distinct solute pattern and the solution in each compartment is ionically
balanced.)))

➢ The extracellular fluid contains large amounts of sodium, chloride and bicarbonate ions,
plus nutrients for the cell such as oxygen, glucose, fatty acids and amino acids.
➢ The intracellular fluid contains large amounts of potassium, magnesium and phosphate
ions.

Regulations of electrolyte:

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The electrolyte balance of the body is maintained by a regulation between the intake and
output of water. The intake of water includes the fluid taken orally and the release of water
during the oxidation and other metabolic process in body. Water is eliminated from body by
urine, expiration (lungs)and feces. Excessive loss of water results in concentration of body fluids
which causes rise in osmotic pressure, as a result water moves out from intracellular
compartment to maintain the osmotic pressure in extracellular fluid. This results in dehydration
of cells. Loss of water above 20% may prove to be fatal.

Some Electrolytes
1.Calcium
About 99% of body calcium is found in bones and the remaining is present in extracellular fluid
compartment. Only 10% of the ingested calcium is absorbed from the intestinal tract and the
remainder is excreted with feces. The concentration of calcium in plasma averages about
9.4mg/dl, (9-10mg/dl), calcium level in plasma is regulated within narrow limits by parathyroid
hormone.

The calcium in plasma is present in three forms

I) About 40% is combined with plasma proteins and is non diffusible through the capillary
membrane.
II) About 10% is combined with other substances of plasma and interstitial fluid (citrate,
phosphate for instance) and is diffusible through the capillary membrane in such a manner that
it is not ionized.

III) The remaining 50% calcium present in plasma is diffusible through the capillary membrane
and ionized. This ionic calcium does most of the Physiological role of Calcium

Physiological role of Calcium:

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• Calcium is found mainly in the extracellular fluids whilst phosphorous is found mostly in the
intracellular fluids. Both are important in the maintenance of healthy bone and teeth.

•Calcium is also important in the transmission of nerve impulses across synapses, the clotting of
blood and the contraction of muscles. If the levels of calcium fall below normal level both
muscles and nerves become more excitable.

• In cardiovascular system (CVS) Calcium is essential for contraction coupling in cardiac muscles
as well as for the conduction of electric impulse in certain regions of heart.

•Calcium also plays role in maintaining the integrity of mucosal membrane, cell adhesion and
function of the individual cell membrane as well.

Hypercalcemia: When the level of Calcium rises above normal, the nervous system is
depressed, and the reflux action of CNS can become sluggish. It also decreases the QT interval
of the heart which can lead to cardiac arrhythmia. It causes constipation and lack of appetite
and depresses contractility of the muscle walls of the GIT. The depressive effect begins to
appear when blood Calcium level rises above 12mg/dl and beyond 17 mg/dl calcium phosphate
crystals are likely to precipitate throughout the body. This situation occurs due to
hypoparathyroidism, vitamin D deficiency, Osteoblastic metastasis, steatorrhea (fatty stools),
Cushing syndrome (hyper active adrenal cortex), acute pancreatitis and acute
hypophosphatemia.

Hypocalcemia: Change in blood pH can influence the degree of calcium biding to plasma
proteins. With acidosis less calcium is bound to plasma proteins. When calcium ion
concentration falls below normal, the excitability of the nerve and muscle cells increases
markedly.

Hypocalcemia occurs due to:

1-hypoparathyroidism,
2-vitamin D deficiency,

3-Osteoblastic metastasis,

4-steatorrhea (fatty stools),

5-Cushing syndrome (hyper active adrenal cortex),

6-acute pancreatitis and acute hyperphosphatemia.

2.Sodium

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The sodium and its associated anions, mainly chloride, account for more than 90% of the solute
in extracellular fluid compartment.
The concentration of sodium is 142mEq/l in extracellular fluid, and 10 mEq/l in intracellular
fluid. Plasma sodium is a reasonable indictor of plasma osmolarity under many conditions.

Physiological role of Sodium

• This plays a crucial role in the excitability of muscles and neurones. It is also of crucial
importance in regulating fluid balance in the body.
• Sodium levels are extremely closely regulated by kidney function.
• Sodium is easily filtered in the glomerular portion of the kidneys and most of it is reabsorbed
in the kidney tubules.

• Major factors that control the GFR include the blood pressure at the glomerulus and the
stimulation of renal arteriole by the sympathetic nervous system.
• The amount of sodium reabsorbed in the proximal convoluted tubule remains almost
constantly at around 67%

• It is also a stimulator for aldosterone release from the adrenal glands. Because water has a
close chemical affinity for sodium, it will follow that more water is reabsorbed in the kidney as
well and this will put up the BP to a normal level.

• An increase in the arterial BP will result in the release of atrial natriuretic factor (ANF) from
the left and right atria of the heart.

• This hormone actually inhibits renin and aldosterone release. By so doing the loss of sodium
by the kidneys is enhanced by the decrease of aldosterone stimulated reabsorption.
• As we have already seen that water will follow sodium, it follows that water is lost from the
body allowing the BP to drop to a normal level.

Hyponatremia: can result from loss of sodium chloride from the extracellular fluid. Conditions
that cause hyponatremia owing to loss of sodium chloride include: 1. excessive sweating,

2.diarrhea and vomiting

3.and over use of diuretics that inhibit kidney to conserve sodium.

4.Addison’s disease, which results from decreased secretion of hormone

aldosterone.
Hypernatremia: can be due to:
1.excessive water loss from extracellular fluid, as in ADH deficiency
2.secretion of sodium- retaining hormone aldosterone (cushing syndrome)excessive treatment

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with sodium salts.

3.Potassium
Potassium is a major intracellular cation present in a concentration approximately 23 times
higher than the concentration of potassium present in Extracellular fluid compartment (about
95% in the cells and only 2% in extracellular fluid).

Function: As with sodium it is extremely important in the correct functioning of excitable cells
such as muscles, neurons, sensory receptors etc. It is also importantly involved in the regulation
of fluid levels within the cell and in maintaining the correct pH balance within the body.

Potassium output is usually equal to potassium input. Sodium reabsorption by aldosterone is

usually in exchange for either hydrogen ions or potassium ions. Therefore, if sodium ions are
reabsorbed more potassium is lost and vice versa. Thus, high levels of potassium in the
interstitial fluid stimulate aldosterone response.

Hypokalemia
Diseases such as Cushing's disease (over production of ACTH) and hyperaldosteronism
(overproduction of aldosterone) can lead to a condition known as hypokalemia (symptoms
caused by low potassium levels) which manifests in muscle weakness, flaccid paralysis, cardiac
arrhythmia and alkalosis.

The pH balance of the body also affects potassium levels. In acidosis potassium excretion is
decreased (leads to hyperkaliemia higher than normal levels of potassium) whereas the
opposite occurs in alkalosis.

Maintenance of potassium balance depends primarily on its excretion by kidney because only
5-10 percent is excreted in feces. Both, elevated and low levels of potassium, can be fatal.

Hyperkalemia
Hyperkalemia occurs due to high intake of potassium or in kidney damage, increase in
potassium concentration can cause cardiac arrhythmias and lead to cardiac arrest by fibrillation
while Hypokalemia due to vomiting, diarrhea, burns, diabetic coma, over use of thiazide
diuretics, alkalosis etc.

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4.Chloride
Chloride major extracellular anion is principally responsible for maintaining proper hydration,
osmotic pressure, and normal cation anion balance in vascular and interstitial compartment.
The concentration of chloride is 103mEq/l in extracellular fluid, and 4 mEq/l in intracellular
fluid. Chloride ion has no pharmacological activity, used as a urinary acidifier..

• Chloride ions are able to diffuse easily across plasma membranes and their transport is closely
linked to sodium movement, which also explains the indirect role of aldosterone in chlorine
regulation.
• When sodium is reabsorbed, chlorine follows passively. It helps to regulate osmotic pressure
differences between fluid compartments and is essential in pH balance.
• The chloride shift within the blood helps to move bicarbonate ions out of the red blood cells
and into the plasma for transport. In the gastric mucosa, chlorine and hydrogen combine to
form hydrochloric acid.
Decreased chloride concentration can be the result of:
1.salt losing nephritis, leading to lack of tubular reabsorption of chloride

2.metabolic acidosis such as found in diabetes mellitus and in renal failure

3.prolonged vomiting.

Increased concentration of chloride may be due to:

1.dehydration,
2.decreased renal blood flow found with congestive heart failure (CHF) or

3.excessive chloride uptake.

5.Phosphate
Phosphate is the principal anion of intracellular fluid compartment. Inorganic phosphate in the
plasma is mainly in two forms HPO4-- and H2PO4-, the concentration of HPO4-- is 1.05
mmole/L and the concentration of H2PO4- 0.26 mmole/L. When the total quantity of the
phosphate in extracellular fluid rises so does the concentration of each of these ions. When pH
of the extracellular fluid becomes more acidic there is relative increase in H2PO4- and decrease
in HPO4- - and vice versa.
Phosphorous is essential for:

1.proper metabolism of calcium,

2.normal bone and tooth development.
3.HPO4-- and H2PO4- makes an important buffer system of body

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4.Phosphate is required in the synthesis of nucleic acids and high-energy compounds
such as ATP.

• Hyperphosphatemia can be found in: hypervitaminosis D, renal failure, and in

hypoparathyroidism.

• Hypophosphatemia can be due to : vitamin D deficiency, hyperparathoidism. and

possible long term aluminum hydroxide antacid therapy.

6.Bicarbonate
Bicarbonate is the second most prevalent anion in extracellular fluid compartment. Along with
carbonic acid it acts as body’s most important buffer system.When there is reduction in the
extracellular fluid hydrogen ion concentration (alkalosis) the kidneys fail to reabsorb all the
filtered bicarbonate thereby increasing the excretion of bicarbonate because bicarbonate ions
normally buffer hydrogen in the extracellular fluid. This loss of bicarbonate is as good as adding
a hydrogen ion to the extracellular fluid. Therefore, in alkalosis, the removal of bicarbonate ions
raises the extracellular fluid hydrogen ion concentration back towards normal.

In acidosis the kidneys do not excrete the bicarbonate in the urine but reabsorb all the filtered
bicarbonate and produces new bicarbonate which is added back to the extracellular fluid. This
reduces the extracellular fluid hydrogen ion concentration back towards normal.

Physiological role of Bicarbonate

• Bicarbonate is alkaline, and a vital component of the pH buffering system of the human body
(maintaining acid-base homeostasis).
• 70 to 75 percent of CO2 in the body is converted into carbonic acid (H2CO3), which can
quickly turn into bicarbonate (HCO3−).

• With carbonic acid as the central intermediate species, bicarbonate – in conjunction with
water, hydrogen ions, and carbon dioxide – forms this buffering system, which is maintained at
the volatile equilibrium required to provide prompt resistance to drastic pH changes in both the
acidic and basicdirections.
• This is especially important for protecting tissues of the central nervous system, where pH
changes too far outside of the normal range in either direction could prove disastrous.

• Bicarbonate also acts to regulate pH in the small intestine. It is released from the pancreas in
response to the hormone secretin to neutralize the acidic chyme entering the duodenum from
the stomach.

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7.Magnesium
Magnesium is the second most plentiful cation in the intracellular fluid. About 50% of total
body magnesium is combined with calcium and phosphates in bones. Essential component of
many enzymes involving phosphate metabolism. Also used in functioning of neuromuscular
system. Magnesium has a definite pharmacologic action ,its salts when injected (im or iv) have
powerful general anesthetic action.

Soluble magnesium sulphate used for:

1.CNS depressant in obstetrics.

2 convulsion states (has anticonvulsant activity).

3.symptoms of tetanus.

Due to slow absorption of magnesium orally so used as saline cathartic (laxative).

Physiological role of Magnesium

• Most magnesium is found in the intracellular fluid and in bone Within cells, magnesium
functions in the sodium-potassium pump and as an aid to the action of enzymes.
• It plays a role in muscle contraction, action potential conduction, and bone and teeth
production.
• Aldosterone controls magnesium concentrations in the extracellular fluid. Low Mg++ levels
result in an increased aldosterone secretion, and the aldosterone increases Mg++ reabsorption
by the kidneys.

Replacement Therapy
The basic objective of replacement therapy is to restore the volume and composition of the
body fluids to normal one. Volume contraction is a life threatening condition because it impairs
the circulation. Blood volume decreases, cardiac output falls and the integrity of
microcirculation is compromised. In volume depletion of sufficient magnitude to threaten life, a
prompt infusion of isotonic sodium chloride solution is indicated. In an extreme case,
intravenous therapy at the rate of 100 ml per minute for the first 1000ml has been considered
necessary for the successful treatment of cholera. A general rule is to replace one half of the
estimated volume loss in the first 12-24 hours of treatment.
2 type of supply:

• Rapid initial replacement: solution contains e-lytes with concentration resemble with
the e-lyte concentrations found in extracellular fluids.

• Subsequent replacements: lower concentration of e-lytes in solution

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(1) For Sodium replacement
• NaCl

• Sodium acetate

(2) For Potassium replacement

• Potassium chloride

• Potassium acetate

• Potassium bicarbonate

(1) SODIUM CHLORIDE

Physical properties:

White or colorless powder, saline taste

Soluble in water, insoluble in alcohol

Chemical properties:

◾Oxidized to give chlorine gas

2cr + MnO2 + 2H2SO4 ---------> Mn(+2) + 2S0(-2) + 2H20 + Cl24

◾It react with silver nitrate and gives white ppt of silver chloride

NaCl + AgNO3 -------------> AgCl, + NaNO3

Preparation:
a. From sea water

b. In lab. It is prepared from common salts (impure) in water by passing HCL gas. Crystals of
NaCl are opted out

Assay:

1.about 0.1 g and dissolve in 50 ml of water

2.Add 50.0 ml of 0.1 M silver nitrate, 5 ml of 2 M nitric acid and 2ml of dibutyl phthalate

Titrant: 0.1 M ammonium thiocyanate

Indicator: ferric ammonium sulphate solution

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End point: colour becomes reddish yellow

1 ml of 0.1 M silver nitrate is equivalent to 0.005844 g of NaCl

Storage: tightly closed container, in dry place

Use:

i)Source of sodium and chloride ions (Sodium replacement)

ii)Making other pharmaceutical formulations like Ringer's injection, ORS.

(2) POTASSIUM CHLORIDE

Physical properties:

I) White or colorless powder, saline taste

II) Soluble in water, insoluble in alcohol

Preparation:
a. Lab scale:

Reaction of HCI with K2CO3 or KHCO3

• K2CO3 + 2HCI-----------------> 2 KCl + CO2 + H2O

• KHCO3 + HCI ------------------> KCI + CO2 +H20

b. Industry scale

• From mineral carnallite KCL. MgCl,. 6H,0

• Carnallite is dissolved by treating with hot water.
• Less soluble KCl will crystallizes out on cooling the solution

Assay:
Principle: Mohr's method (Argentometric titration)

about 0.15 g and dissolve in 50 ml of water

Titrant: 0.1 M silver nitrate

Indicator: potassium chromate solution1 ml of 0.1 M silver nitrate is equivalent to 0.007455 g

of KCI

Use:

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I) Source of potassium ions (potassium replacement) Making other pharmaceutical
formulations like Ringer's injection, ORS

II) As diuretic

III) In Myasthenia gravis'

3.Calcium gluconate
Physical properties:
i) white crystals, granules or powder,

ii) stable in air, does not lose its (C12H22O14Ca. H2O) water of crystallization on drying

iii) Neutral to litmus paper

Chemical properties

When treated with dil. HCI, It is decomposed into gluconic acid and calcium chloride.

Preparation:
- It is prepared by boiling a solution of gluconic acid with Ca carbonate

- Pdct is filtered and #ed out from solution.

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Assay:
- Principle: Complexometric titration

- 0.5g sample is dissolved in warm water, cool and add 5.0 ml of

- 0.05 M MgSO4 and 10 ml of strong ammonia solution

- Titrant: 0.05 M disod. edetate

- Indicator: mordant black II mixture

- End Point: until deep blue color develops.

- From the volume of 0.05 M disod. edetate required, subtract the volume of the MgSO,
solution added for actual reading.

- Factor: 1 ml 0.05 M disod. EDTA = 0.02242g of Ca. gluconate

Use: used in calcium deficiency

ELECTROLYTE COMBINATION THERAPY

Combination of electrolytes are prepared and given to the patient according to its
requirements.

Conditions like:

- During surgery

- when the patient unable to take normal diet

- Malnutrition

Formulations:
i) Ringer solution

ii) Ringer lactate solution

iii) ORS

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(1) COMPOUND SODIUM INJECTION
Synonym: Ringer's injection (Ringer's solution)

Composition:
◾Each 100ml of solution is having

I) NLT 0.82g and NMT 0.90g of NaCL

II) NLT 0.0285g and NMT 0.0315g of KCI

III) NLT 0.030g and NMT 0.036g of CaCl2. 6H20

◾ It should be free from microorganism

Preparation:
Ingredients with appropriate quantity are dissolved in WFI

Solution is filtered and filtrate is sterilized by heating in an autoclave.

Amount:

Sodium Chloride .. . 8.6g

Potassium Chloride...... 0.3g

Calcium Chloride.. . 0.33g

WFI q.s. 1000 ml

Assay:
The three salts present in preparation may be assayed individually.

Use: electrolyte replenishes

Oral Rehydration Salt(ORS)

- Oral Rehydration Salts are dry, homogeneously mixed powders containing Dextrose, Sodium
Chloride, Potassium Chloride and either Sodium Bicarbonate or Sodium Citrate for use in oral
rehydration therapy after being dissolved in the requisite amount of water.

- is a combination of oral electrolytes.

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Composition:

- Contains essential electrolytes those are important to maintain the normal functions of the
body.

- Also contains sufficient amount of water.

- The concentration of electrolytes may be varying depending on the level of loss of particular
electrolyte.

Use:
- In heavy loss of water (dehydration) and loss of electrolytes

- Conditions like severe vomiting, diarrhea and prolonged fever.

- The therapy is done with butter milk, rice, light tea, coconut water etc.

Formulation
The total substance concentration (including that contributed by glucose) should be within the
range of 200-310 mmol l

Glucose---> should at least equal that of sodium but should not exceed 111 mmol/l

Sodium --------------------------> should be within the range of 60-90 mEq/l

Potassium------------------------>should be within the range of 15-25 mEq/l

Citrate----------------------------- >should be within the range of 8-12 mmol/l

Chloride---------------------------->should be within the range of 50-80 mEq/l

Conduction and transmission of nerve impulse

A nerve impulse is the electric signals that pass along the dendrites to generate a nerve impulse
or an action potential. An action potential is due to the movement of ions in and out of the cell.

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It specifically involves sodium and potassium ions. They are moved in and out of the cell
through sodium and potassium channels and sodium-potassium pump.

Conduction of nerve impulse occurs due to the presence of active and electronic potentials
along the conductors.

Transmission of signals internally between the cells is achieved through a synapse. Nerve
conductors comprise relatively higher membrane resistance and low axial resistance. The ionic
currents pass through the two cell membrane when the action potential reaches the stage of
such synapse.

Hypertonic solution
A hypertonic solution has a greater concentration of solutes than another solution. In biology,
the tonicity of a solution usually refers to its solute concentration relative to that of another
solution on the opposite side of a cell membrane; a solution outside of a cell is called
hypertonic if it has a greater concentration of solutes than the cytosol inside the cell.

Hypotonic solution
A hypotonic solution has a lower concentration of solutes than another solution. In biology, a
solution outside of a cell is called hypotonic if it has a lower concentration of solutes relative to
the cytosol.

Isotonic solution
A solution is isotonic when its effective osmole concentration is the same as that of another
solution. In biology, the solutions on either side of a cell membrane are isotonic if the
concentration of solutes outside the cell is equal to the concentration of solutes inside the cell.
In this case the cell neither swells nor shrinks because there is no concentration gradient to
induce the diffusion of large amounts of water across the cell membrane.

.9% NaCl is isotonic solution

The osmolarity of normal saline, 9 grams NaCl dissolved in water to a total volume of one liter,
is a close approximation to the osmolarity of NaCl in blood (about 290 mOsm/L). Thus, normal
saline is almost isotonic to blood plasma. Neither sodium nor chloride ions can freely pass
through the plasma membrane, unlike urea.

A 0.9% NaCl solution is said to be isotonic: when blood cells reside in such a medium, the
intracellular and extracellular fluids are in osmotic equilibrium across the cell membrane, and
there is no net influx or efflux of water.

Cell condition in hyper or hypotonic solution

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In hypertonic solution: When a cell is immersed in a hypertonic solution, osmotic pressure
tends to force water to flow out of the cell in order to balance the concentrations of the solutes
on either side of the cell membrane. The cytosol is conversely categorized as hypotonic,
opposite of the outer solution.

In hypotonic solution: Due to osmotic pressure, water diffuses into the cell, and the cell often
appears turgid, or bloated. For cells without a cell wall such as animal cells, if the gradient is
large enough, the uptake of excess water can produce enough pressure to induce cytolysis, or
rupturing of the cell.

Why bicarbonate buffer is important?

The bicarbonate buffering system is important in the body because it:

I) manages the acid and base imbalances produced by both normal and abnormal physiology

II) assists in the handling of carbon dioxide, the waste product of cellular respiration

The equilibria involved are

CO₂ + H₂O ⇌ H₂CO₃

H₂CO₃ + H₂O ⇌ H₃O⁺+ HCO₃⁻

-If there are too many hydronium ions in the blood, the H₃O⁺ will react with bicarbonate to form water
and carbonic acid.

- If there are too few hydronium ions in the blood, the H₂CO₃ will react to form more H₃O⁺ and HCO₃⁻.

This buffering system works with hyper- or hypoventilation to maintain plasma pH.

In the case of excess acid, hyperventilation increases the loss of CO₂ to the atmosphere. This drives the
bicarbonate equilibrium to the left. Plasma acidity decreases.

Hypoventilation decreases the loss of CO₂ to the atmosphere. This drives the bicarbonate equilibrium to
the right and increases the acidity.

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