Electrolytes

Introduction
Electrolytes are ions capable of carrying an electric

charge.
They are classified as anions or cations based on
the type of charge they carry.
These names were determined years ago based on
how the ion migrates in an electric filed.
Anions have a negative charge and move toward
the anode whereas cations migrate in the direction
of the cathode because of their positive charge.
Cation(+) Cathode.
Anion(-) Anode.

Functions of electrolytes
1. Osmotic pressure and fluid volume
2.
3.
4.
5.
6.

regulation(Na+, K+, Cl-).

Coagulation factors (Mg2+, Ca2+).
Enzyme co-factors (Mg2+, Ca2+, Zn2+).
Neuromuscular excitability (K+, Mg2+,
Ca2+).
Myocardial rhythm and contraction (K+,
Mg2+, Ca2+).
Production and transfer of energy (ATP).

Water
The average water content of the human body

varies 40-75% of total body weight with values

declining with age and especially with obesity.
Women have lower average water content than
men as a result of a higher fat content.
Water is the solvent for all processes in the human
body.
It transports nutrients to cells , determines cell
volume by its transport into and out of cells ,
removes waste products by way of urine , and acts
as the bodys coolant by way of sweating.
Water is located in intracellular and extracellular
compartments.

 Intracellular fluid(ICF)
Is the fluid inside the cells and accounts for

about two thirds of total body water.

Extracellular fluid(ECF)
Accounts for the one third of total body water
and can be subdivided in the intravascular
extracellular fluid (plasma) and the interstitial
cell fluid that surrounds the cells in the tissue.
Normal plasma is about 93% water with the
remaining volume occupied by lipids and
proteins.

The concentrations of ions with in cells and in

plasma are maintained both by energyconsuming active transport processes and by

diffusion or passive transport processes.
Active transport is a mechanism that requires
energy to move ions across cellular membranes.
For example maintaining a high intracellular
concentration of potassium and a high
extracellular(Plasma) concentration of sodium
requires use of energy from ATP in ATPasedependent ion pumps.
Diffusion is the passive movement of ions
across a membrane.

It depends on the size and charge of the ion

being transported and on the nature of the

membrane through which it is passing.
The rate of diffusion of various ions also may
be altered by physiologic and hormonal
process.
By maintaining the concentration of proteins
and electrolytes in a controlled yet somewhat
flexible environment the distribution of water
in these compartments also can be controlled.

Because most biological membranes are

freely permeable to water but not to ions or

proteins the concentration of ions and
proteins on one side of the membrane or the
other will influence the flow of water across a
membrane (an osmoregulator).
In addition to the osmotic effects of sodium
other ions , proteins and blood pressure
influence the flow of water across a
membrane.

Osmolality

Osmolality is a physical property of a solution

that is based on the concentration of solutes

(expressed as millimoles) per kilogram of
solvent(W/W).
Osmolality is related to several changes in the
properties of a solution relative to pure water
such as freezing point depression and vapour
pressure decrease.
The colligative properties are basis for routine
measurements of osmolality in the laboratory.

The term osmolarity is still occasionally used with

results reported in milliosmoles per liter (W/V) but it

is inaccurate in cases of hyperlipidaemia or
hyperproteinaemia for urine specimens or in the
presence of certain osmotically active substances
such as alcohol or mannitol.
Both the sensation of thirst and antidiuretic
hormone (ADH) secretion are stimulated by the
hypothalamus in response to an increased
osmolality of blood.
The natural response to the thirst sensation is to
consume more fluids increasing the water content
of the ECF diluting the elevated solute (sodium)
levels and decreasing the osmolality of the plasma.

Content of the ECF diluting the elevated solute

(sodium) levels and decreasing the osmolality of

the plamsa.
Thirst therefore is important in mediating fluid
intake.
The other means of controlling osmolality is by
secretion of ADH(vasopressin).
This hormone is secreted by the posterior
pituitary gland and acts on the cells of the coltion.
As water is conserved osmolality decreases
turning off ADH secretion.

Clinical significance of
osmolality
Osmolality in plasma is important because it is

the parameter to which the hypothalamus

responds.
The regulation of osmolality also affects the
sodium concntration in plasma largely because
sodium and its associated anions account for
approximately 90% of the osmotic activity in
plasma.
Another important process affecting the sodium
concentration in blood is the regulation of blood
volume.

 As discussed later although osmolality and

volume are regulated by separate mechanism

( except for ADH and thirst)they are related
because osmolality (sodium) is regulated by
changes in water balance whereas volume is
regulated by changes in sodium balance.
To maintain a normal plamsa osmolality(275235mosm/kg of plasma H2O) osoreceptors in
the hypothalamus respond quickly to small
changes in osmolality.

A 1-2% increase in osmolality causes a 4-flold

increase in the circulation concentration of

ADH and a 1-2% decrease in osmolality shuts
off ADH productions.
ADH acts by increasing the reabsorption of
water in the cortical and medullary collecting
tubules.
ADH has a half-life in the circulation of only
15-20minutes.
Renal water regulation by ADH and thirst play
important roles in regulating plasma

Renal water excretion is more important in

controlling water excess whereas thirst is

more important in preventing water deficit or
dehydration.
Consider what happens in several conditions.

Water load
As excess intake of water(e.g. in polydipsia)

begins to lower plasma osmolality both ADH

and thirst are suppressed.
In the absence of ADH water is not
reabsorbed causing a larger volume of dilute
urine to be excreted as much as 10-20L daily
well above any normal intake of water.
Therefore hypoosmolalilty and hyponatraemia
usually occur only in patients with impaired
renal excretion of water.

Water Deficit
As a deficit of water, plasma osmolality begins

to increase plasma osmolality both ADH

secretion and thirst are activated.
Although ADH contributes minimizing renal
water loss, thirst is the major defense against
hyperosmolality and hypernatraemia.
Although hypernatraemia rarely occurs in a
person with a normal thirst mechanism and
access to water it becomes a concern in
infants, unconscious patients, or anyone who is
unable to either drink or ask for water.
Osmotic stimulation o thirst progressively
diminishes in people who are older than age 60.

In the older patient with illness and

diminished mental status dehydration

becomes increasingly likely.
As an example of the effectiveness of thirst in
preventing dehydration a pateint with
diabetes insipidus (no ADH) may excrete 10 l
of urine per day however because thirst
persists water intake matches output and
plasma sodium remains normal.

Regulation of blood
volume
Adequate blood volume essential in maintaining

blood pressure and ensure perfusion to all tissue

and organs.
Regulation of both sodium & water are interrelated
in controlling blood volume.
The Renin-angiotensin-aldosterone system of
hormones that respond to decrease in blood volume
and help maintain the correct blood volume.
Renin is secreted near the renal glomeruli in
response to decreased renal blood flow(decreased
blood volume or blood pressure).

Renin converts angiotensinogen to angiotensin I

which then becomes angiotensin II .

Angiotensin II causes vasoconstriction which
quickly increases blood pressure and secretion of
aldosteron which increases retention of sodium
and the water that accompanies the sodium.
Changes in blood volume(actually pressure) are
initially detected by a series of stretch receptors
located in areas such as the cardiopulmonary
circulation , carotid sinus , aortic arch and
glomerular arterioles.

These receptors then activate a series of

response (effectors) that restore volume by

appropriately varying vascular resistance ,
cardiac output and renal sodium and water
retention.
Four other factors affect blood volume:1. Atrial natriuretic peptide (ANP) relapsed from
the myocardial atria in response to volume
expansion , promotes sodium excretion in
the kidney(B-type natriuretic peptide[BNP]
and ANP act together in regulating blood
presure and fluid balance).

2. Volume receptors independent of osmolality

stimulate the release of ADH which conserves

water by renal reabsorption.
3. Glomerular filtration rate (GFR) increases with
volume expansion and decreases with volume
depletion.
4. All other things equal an increased plasma
sodium will increase urinary sodium excretion
and vice versa.
.The normal reabsorption of 98-99% of filtered
sodium by the tubules conserves nearly all of the
150l of glomerular filtrate produced daily.
.A1-2% reduction in tubular reabsortion of sodium
can increase water loss by several litres per day.

Urinary osmolality values may vary widely

depending on water intake and the

circumstances of collection on water intake
and the circumstances of collection.
However it is generally decreased in diabetes
insipidus (inadequate ADH) and
polydipsia(excessive H2O intake) and
increased in conditions such as (SIADH) and
hypovolaemia( although urinary Na+ is
usually decreased).

Determination of osmolality
Specimen:May be measured in serum or urine.
Plasma use is not recommended because

osmotically active substances may be introduced

into the specimen from the anticoagulant.
Discussion:The methods for determining osmolality are based
on properties of a solution that are related to the
number of molecules of solutes per kilogram of
solvent(colligative properties) such as changes in
freezing point and vapor pressure.

An increase in osmolality decreases the freezing point

temperature and the vapor pressure decrease

(actually the dew point) are the two most frequently
used methods of analysis.
Sample must be free of particulate matter to obtain
accurate results.
Turbid serum and urine samples should be centrifuged
before analysis to remove any extraneous particles.
If reusable sample cups are used they should be
thoroughly cleaned and dried between each use to
prevent contamination.

Osmometers that operate by freezing point

depression are standardized using sodium

chloride reference solutions.
After calibration the appropriate amount of
sample is pipetted into the required cuvet or
sample cup and placed in the analyzer.
The sample is then supercooled to -7C and
seeded to initiate the freezing process.
When temperature equilibrium has been
reached the freezing point is measured with
results for serum and urine osmolality reported
as milliosmosmoles per kilogram.

Calculation of osmolality has some usefulness either

as an estimate of the true osmolality or to determines

the osmolal gap which is the difference between the
measured osmolality and the calculated osmolality.
The osmolal gap indirectly indicates the presence of
osmotically active substances other than sodium ,
urea or glucose such as ethanol , methanol , ethylene
glycol , lactate or -hydroxybutyrate.
Two formulas are presented each having theoretic
advantages and disadvantages. Both are adequate for
the purpose previously describe.

glucose(mg /dl) BUN(mg/dl)

2Na

20
3

glucose BUN
1.86Na

9
18
2.8

Sodium

Sodium is the major cation of extracellular fluid

representing almost one-half the osmotic

strength of plasma.
It therefore plays a central role in maintaining
the normal distribution of water and osmotic
pressure in the extracellular fluid compartment.
The normal daily diet contains 8 to15g (130
to260mmol) of NaCl which is absorbed nearly
completely from the gastrointestinal tract.
The body requires only 1to2mmol/day.
The kidneys which are the ultimate regulators
of the amount of Na+ (and thus water) in the
body excrete the excess.

Sodium initially is filtered freely by the glomeruli.

Then 70%to80% of the filtered Na+ load in the

proximal tubules with Cl- and water passively

following in an is iso-osmotic andelectrically
neutral manner.
Another20% to 25% is reabsorbed in the loop of
Henle a long with Cl- and more water.
In the distal tubules interaction of the
adrenocortical hormone aldosterone with the
coupled Na+ , k+ and Na+ , H+ exchange
systems results directly in the remaining 5% to
10 % of the filtered Na+ determines the amount
of Na+ excreted in the urine.

Clinical applications
I. Hyponatraemia:.Defined as a serum/plasma level <135mmol/l.
.Levels below 130mmol/l are clinically significant.
A.
1.
2.
3.
4.
5.
6.
7.

Increased sodium loss:Hypoadrenalism.

Potassium deficiency Why?
Diuretic use(thiazides)
Ketonuria
Salt-losing nephropathy.
Prolonged vomiting or diarrhea
Sever burns.

B.
1.
2.
3.
4.
C.
1.
2.
3.

Increased water retention:Renal future.

Nephrotic syndrome.
Hepatic cirrhosis.
Congestive heart failure.
Water imbalance:Excess water intake
SIADH.
Pseudohyponatraemia.

 Symptoms of hyponatraemia:Depend on the serum level.

Between 125 and 130mmol/l symptoms are

primarily gastrointestinal (GI).

More severe neuropsychiatric symptoms are
seen below 125 mmol/l including nausea and
vomiting , muscular weakness , headache ,
lethargy and ataxia.
More sever symptoms also include seizures ,
coma and respiratory depression.

II. Hypernatraemia
.Hypernatraemia (increased serum Na+

concentration) results from excess loss of

water relative to Na loss, decreased water
intake, or increased Na+ intake or retention.
.Hypernatraemia is less commonly seen in
hospitalized patients than hyponatreamia.
A. Excess water loss:1. Diabetes insipidus.
2. Renal tubular disorder.
3. Prolonged diarrhea.
4. Profuse sweating.
5. Severe burns.

B.
1.
2.
3.
C.
1.
2.
3.

Decreased water intake

Older persons.
Infants.
Mental impairment.
Increased intake or retention:Hyperaldosteronism.
Sodium bicarbonate excess.
Dialysis fluid excess.

 Symptoms of hypernatraemia
Symptoms most commonly involve the CNS

as a result of the hyperosmolar state.

These symptoms include altered mental
status, lethargy, irritability, restlessness,
seizures, muscle twitching, hyperreflexes,
fever, nausea or vomiting, difficult respiration,
and increased thirst.
Serum Na+ of more than 160 mmol/L is
associated with a mortality rate of 60%75%.

Determination of Sodium
Specimen:Serum, plasma, and urine are all acceptable

for Na+ measurements.

When plasma is used, lithium heparin,
ammonium heparin, and lithium oxalate are
suitable anticoagulants.
Haemolysis does not cause a significant
change in serum or plasma values as a result
of decreased levels of intracellular Na+.

However, with marked hemolysis,levels may

be decreased as a result of a dilutional

effect.Whole blood samples may be used with
some analyzers.
Consult the instrument operation manual for
acceptability.
The specimen of choice in urine Na+
analysesis a 24-hour collection.
Sweat is also suitable for analysis.

 Methods:Through the years, Na has been measured in

various
ways, including chemical methods, flame emission
spectrophotometry (FES), atomic absorption
spectrophotometry (AAS), and ISEs.
Chemical methods are outdated because of large
sample volume requirements and lack of precision.
ISEs are the most routinely used method in clinical
laboratories.
ISE method uses a semipermeable membrane to
develop
a potential produced by having different ion
concentrations on either side of the membrane.
In this type system, two electrodes are used.

One electrode has a constant potential, making it

the reference electrode.

The difference in potential between the reference
and measuring electrodes can be used to calculate
the concentration of the ion in solution.
However, it is the activity of the ion, not the
concentration that is being measured.
Most analyzers use a glass ion-exchange
membrane in its ISE system for Na+ measurement.
There are two types of ISE measurement, based on
sample preparation:-direct and indirect.
Direct measurement provides an undiluted sample
to interact with the ISE membrane.

With the indirect method, a diluted sample is

used for measurement.

There is no significant difference in results,
except when samples are hyperlipidemic or
hyperproteinemic.
Excess lipids or proteins displace plasma
water, which leads to a falsely decreased
measurement of ionic activity in millimoles
per liter of plasma, whereas the direct method
measures in plasma water only.

In these cases, direct ISE is more accurate.

One source of error with ISEs is protein buildup on

the membrane through continuous use.

The protein coated membranes cause poor
selectivity, which results in poor reproducibility of
results.
Vitros analyzers (Ortho-Clinical Diagnostics) use a
single-use direct ISE potentiometric system.
Each disposable slide contains a reference and
measuring electrode.
A drop of sample fluid and a drop of reference fluid
are simultaneously applied to the slide, and the
potential difference between the two is measured
which is proportional to the Na+ concentration.

 Reference Ranges:-

Potassium

Potassium is the major intracellular cation.

In tissue cells , its average concentration is

150mmol/l and in erythrocytes the concentration is

105mmol/l(23times its concentration in plasma).
High intracellular concentrations are maintained
because k+ diffuses very slowly outward through
the cell membrane while the Na+ , k+ ATPase
pump which is fueled by oxidative energy
continually transports k+ into the cell against the
concentration gradients.
This pump is a critical factor in the maintenance
and adjustment of the ionic gradients on which
nerve impulses transmission and contractility of
cardiac and skeletal muscle depend.

Diffusion of k+ from the cell into the plasma

exceeds pump-mediated K+ uptake when

ever pump activity is decreased.

The bodys requirement for k+ is satisfied by a

dietary intake of 50 to150mmol/day.

Potassium absorbed from the gastrointestinal tract
is distributed rapidly by the kidneys.
Potassium filtered through the glomeruli is almost
completely reabsorbed in the proximal tubules and
is then secreted in the distal tubules in exchange
for Na+ under the influence of aldosterone.
Factors that regulate distal tubular secretion of K+
are:
1. Intake of Na+ and K+ .
2. Plasma concentration of mineralocorticoids .
3. Acid-base balance.

Diminished glomerular filtration rate and the

consequent decrease in distal tubular flow

rate is an important factor in the retention of
K+ seen in chronic renal failure.
Renal tubular acidosis and metabolic and
respiratory acidoses and alkaloses also effect
renal regulation of K+ excretion.

Clinical applications
I. Hypokalaemia:.Hypokalemia is a plasma k+ concentration

below the lower limit of the reference range.

.Causes of hypokalaemia:A. GI loss:1. Vomiting.
2. Diarrhea.
3. Gastric suction.
4. Intestinal tumour.
5. Malabsorption.
6. Cancer therapy.
7. Large doses if laxatives.

B.
1.
2.
3.
4.
5.
6.
7.
C.
1.
2.

Renal loss:Diuretics drugs.

Nephritis.
Renal tubular acidosis(RTA).
Hyperaldosteronism.
Cushings syndrome.
Hypomagnesemia.
Acute leukemia.
Cellular shift:Alkalosis.
Insulin overdose.

 Symptoms of hypokalaemia:Symptoms (e.g., weakness,fatigue, and

constipation) often become apparent asplasma K

decreases below 3 mmol/l.
Hypokalaemia can lead to muscle weakness or
paralysis, which can interfere with breathing.
The dangers of hypokalaemia concern all
patients, but especially those with
cardiovascular disorders because of an
increased risk of arrhythmia, which may cause
sudden death in certain patients.
Mild hypokalaemia (3.03.4 mmol/L) is usually
asymptomatic.

II. Hyperkalaemia:-Hyperkalemia elevated levels of

A.
1.
2.
3.
4.
B.
1.
2.
3.
4.
5.

potassium in the blood above the normal range.

Decreased renal excretion:Acute or chronic renal failure (GFR, 20 mL/min).
Hypoaldosteronism.
Addisons disease.
Diuretics.
Cellular shift:Acidosis.
Muscle/cellular injury.
Chemotherapy.
Leukemia.
Haemolysis.

C. Increased intake:-Oral or IV potassium

replacement therapy.
D. Artifactual:1. Sample haemolysis.
2. Thrombocytosis.
3. Prolonged tourniquet use or excessive fist
clenching.
.Symptoms of hyperkalemia:.Hyperkalemia can cause muscle weakness,
tingling, numbness, or mental confusion by
altering neuromuscular conduction.

Muscle weakness does not usually develop

until plasma K+ reaches 8 mmol/l.

Hyperkalemia disturbs cardiac conduction,
which can lead to cardiac arrhythmias and
possible cardiac arrest.
Plasma K+ concentrations of 67 mmol/l may
alter the electrocardiogram, and
concentrations more than 10 mmol/l may
cause fatal cardiac arrest.

Determination of potassium
Specimen:Serum, plasma, and urine may be acceptable for

analysis.
Haemolysis must be avoided because of the high
K+ content of erythrocytes.
Heparin is the anticoagulant of choice.
Whereas serum and plasma generally give similar
K+ levels, serum reference intervals tend to be
slightly higher.
Significantly elevated platelet counts may result
in the release of K+ during clotting from rupture
of these cells, causing a spurious hyperkalaemia.

In this case, plasma is preferred.

Whole blood samples may be used with some

analyzers.
Consult the instruments operations manual for
acceptability.
Urine specimens should be collected over a 24-hour
period to eliminate the influence of diurnal
variation.
Methods:As with Na+,the current method of choice is ISE.
For ISE measurements, a valinomycin membrane is
used to selectively bind K+,causing an impedance
change that can be correlated to K concentration.
KCl is the inner electrolyte solution.

 Reference Ranges:-