Water and Electrolyte Balance

R. C. GuptaM.D. (Biochemistry)

Jaipur (Rajasthan), India

Water is the most abundant component ofour body

Need for water is more urgent than that forany other nutrient

Humans beings can live one month without food but only six days without water

EMB-RCG

EMB-RCG

In adults, water accounts for:

70% of the total body weight in males

60% of the total body weight in females

EMB-RCG

Water content depends on age:

Infants: 75%

Adults: 60-70%

Elderly: 45%

EMB-RCG

Water content differs in different tissues:

Muscles: 70%

Adipose tissue: 30%

Bones: 10%

Water content is more in muscular

persons than in obese persons

Water:

Bathes all cells

Gives shape and form to cells

Serves as a lubricant

Is the solvent for all ions and molecules

Transports materials to and from cells

Is the medium for all biochemical reactions

Latent heat of evaporation

Specific heat

Dielectric constant

Solvent power

Some properties of water which make it

an ideal medium for body fluids are its:

Water has been chosen as the universal

solvent for all living organisms

Solvent power

Water is an efficient and suitable solvent for most of the solutes present in our

body

Some compounds which do not dissolve readily in water can form colloidal

solutions

Water has a high dielectric constant

A large number of oppositely charged particles can co-exist in water due to this

Dielectric constant

Specific heat

Water has a very high specific heat which means that a large amount of heat is

required to raise the temperature of water

Due to this, body temperature doesn’t rise appreciably when thermal energy is

released during oxidation of nutrients

Latent heat of evaporation

Water has a high latent heat of evaporation relative to other liquids

A large amount of thermal energy is required for evaporation of water

When water evaporates from skin and lungs, a large amount of heat is lost

This prevents a rise in body temperature

Distribution of water

Compartment Water

Total water in an

average man 50 litres

Water in intra-cellular

compartment 35 litres

Water in extra-cellular

compartment 15 litres

Un-exchangeable fluid

The water present outside the cells is

known as extra-cellular fluid (ECF)

The ECF is further distributed into some

sub-compartments:

Trans-cellular fluid

Interstitial fluid

Plasma

Sub-compartment Volume

3 litresPlasma (vascular compartment)

Interstitial fluid (in between cells) 7 litres

Trans-cellular fluid (in cavities) 1 litre

4 litres

Un-exchangeable fluid (in bones,

cartilages, dense connective tissue etc)

Osmolality

Concentration of solutes/particles in fluid, expressed in milliosmol (mosm) per kg

Determines distribution of water in different compartments

Water moves from lower to higher osmolality

The major osmotically active solutes in

body fluids are:

Electrolytes have more osmotic power asthey dissociate into at least two particles

Non-electrolytes e.g. glucose, lipids etc

Electrolytes e.g. inorganic salts and proteins

Intracellular Interstitial Plasma

fluid fluid

CATIONS (mEq/L)

Sodium 10 137 142

Potassium 160 5 5

Magnesium 24 3 3

Calcium 6 5 5

Total 200 150 155

ANIONS (mEq/L)

Chloride 5 113 100

Bicarbonate 5 27 27

Sulphate 15 1 1

Inorganic phosphate 25 2 2

Organic phosphates 70 – –

Organic anions 15 5 5

Proteins 65 2 20

Total 200 150 155

Effective osmolality of a compartment isdetermined by the solutes restricted tothat compartment

Effective osmolality of the compartment isalso known as its tonicity

Selective distribution of ions in differentcompartments is maintained by specificion channels and ion pumps

A lot of energy is spent for maintaining thedifferential distribution of ions in differentcompartments

Cations

Sodium is the major cation in extracellularfluid

Potassium is the major cation in intracellularfluid

This differential is maintained by Na+, K+-exchanging ATPase

EMB-RCG

Anions

The major anions in extracellular fluid arechloride and bicarbonate

The major anions in intracellular fluid arephosphates and proteins

Proteins

Proteins are present in a:

Fairly high concentration in intracellular fluid

Smaller but significant concentration in plasma

Negligible concentration in interstitial fluid

Effective osmolality is determined by:

Sodium and its associated anions in the extracellular fluid

Potassium and its associated anions in the intracellular fluid

The ions and molecules have specificdistribution in the intracellular fluid

These are vital for the functioning of thecells, and are zealously maintained

Changes in osmolality are usually due toshift of salts (mainly sodium)

When salts shift, water follows salts

Shrinkage of cells due to shifting of waterout of the cells can seriously affect thefunctioning of cells

Swelling of cells due to shifting of waterinto the cells can also seriously affect thefunctioning of cells

Hyper-osmolality of extracellular fluiddraws water out of cells into the extra-cellular compartment

Hypo-osmolality of extracellular fluiddrives water from extracellular compart-ment into the cells

Osmolality of plasma is 275-290 mosmol/kg

A 0.9% solution of NaCl in water hasthe same osmolality (or tonicity) as plasma

A 5% solution of glucose in water also hasthe same osmolality (or tonicity) as plasma

These two are said to be isosmotic orisotonic with plasma

Oncotic pressure

Osmotic pressure exerted by proteins iscalled oncotic pressure

It is also known as colloid osmotic pressure

The normal oncotic pressure of plasma isabout 25 mm of Hg

A decrease in the concentration of proteins inplasma decreases oncotic pressure of plasma

Water is forced out of capillaries at the arterialend due to greater hydrostatic pressure

It cannot re-enter at the venous end if the oncoticpressure is less than the hydrostatic pressure

This will result in oedema

Water intake and output

Water balance of the body depends uponthe relative intake and output of water

Water is taken in as drinking water and inthe form of food and beverages

Some water is formed in the body duringoxidative reactions (metabolic water)

Metabolic water

Oxidation of 1 gm of carbohydrate produces 0.60 gm of water

Oxidation of 1 gm of fat produces 1.07 gm of water

Oxidation of 1 gm of protein produces 0.41 gm of water

In a temperate climate, intake of water is:

Source Volume

Drinking water about 1.5 L /day

Water in food and beverages about 1.0 L /day

Metabolic water about 0.3 L /day

Total intake about 2.8 L /day

Route Volume

Urine about 1.5 L /day

Faeces about 0.1 L /day

Water vapour in expired air about 0.4 L /day

Water loss in the form of sweat about 0.8 L /day

Total output about 2.8 L /day

Water is lost from the body in the form of:

In hot climates, sweat loss is much more

This is compensated by increased intake ofdrinking water

If it is not compensated, urine output willdecrease

However, urine output cannot decreasebelow a certain level

Normal excretion of solutes by the kidneysis about 600 milliosmol/day

Minimum water required to dissolve 600milliosmol solutes is 500 ml

If urine output is below 500 ml/day,excretion of metabolic waste decreases

A urine output below 500 ml/day is calledoliguria

Regulation of water balance

Water balance is maintained by:

The thirst centre in hypothalamus

Antiduretic hormone of posterior pituitary

These two receive signals about osmolality of plasma from osmoreceptors located in

the hypothalamus

Osmo-receptors can perceive a change of

even 1-2% in the osmolality of plasma

If there is an increase in the osmolality of plasma:

Thirst centre is stimulated which increases water

intake

Posterior pituitary secretes anti-

diuretic hormone which decreases

urine output

ADH secretion begins when the osmolalityof plasma reaches about 285 mosmol/kg

The thirst centre is stimulated when theosmolality of plasma reaches about 295mosmol/kg

When blood circulates through the kidneys,125 ml of glomerular filtrate is formed perminute

About 180 litres of glomerular filtrate isformed in 24 hours

Glomerular filtration rate

When the filtrate passes through the

tubules, a large amount of solutes and

water are absorbed

The re-absorption can be divided into:

Obligatory re-absorption

Facultative re-absorption

Tubular re-absorption

A large amount of solutes is absorbed

when the filtrate passes through proximal

convoluted tubules and loop of Henle

A corresponding amount of water is re-absorbed due to osmotic effect of solutes

This is known as obligatory re-absorption

Obligatory re-absorption

Obligatory re-absorption equals:

About 85% of the glomerular filtrate

Or about 153 litres per day

Cells of distal convoluted tubules andcollecting ducts are not permeable to waterin the absence of ADH

Binding of ADH to its receptors (V2

receptors) on the surface of these cellsactivates adenylate cyclase

Facultative re-absorption

Active adenylate cyclase increases theintracellular concentration of cAMP

cAMP activates protein kinase A

Active protein kinase A phosphorylatessome cytosolic proteins

The phosphorylated proteins translocateaquaporins from cytosol into cell membrane

Aquaporins are water channels

Water moves into the cell through thesewater channels

Movement of water into distal convoluted

tubules and collecting ducts is proportional

to plasma ADH concentration

The ADH-regulated re-absorption is knownas facultative re-absorption of water

Normally, this is about 25.5 litres/day

About 1.5 litres of water is not absorbed bytubules

This is excreted in the form of urine everyday

Facultative re-absorption can be adjustedto maintain the water balance of the body

Electrolyte balance

Sodium, potassium and chloride are the major electrolytes

Their plasma levels are:

Sodium: 135 -145 mEq/L

Potassium: 3.5 - 5.0 mEq/L

Chloride: 96 -106 mEq/L

Sodium

The most important cation in regulation of fluid and electrolyte balance

The most abundant cation in the ECF

Contibutes significant osmotic pressure

Potassium

Critical to maintenance of membrane potential

Compensates for shifts of hydrogen ions in or out of cells

Chloride

The most abundant anion in the ECF

Contributes significant osmotic pressure

Regulation of sodium

Aldosterone promotes tubular re-absorption of sodium

Oesrogens have a similar but weakereffect

Atrial natriuretic peptide inhibits release ofaldosterone

Plasma K+ level regulates potassium balance

High plasma K+ level promotes tubular

secretion of potassium

Low plasma K+ level inhibits tubular secretion

of potassium

Aldosterone increases potassium secretion

Regulation of potassium

Regulation of chloride

Chloride is the major anion associated with sodium

It moves with sodium

Aldosterone increases the tubular reabsorption of chloride

Dehydration can result from diminished intake of water or excessive loss of

water

Excessive water loss is a far more common cause of dehydration

Dehydration

Excessive water loss can be due to:

• Excessive sweating

• Vomiting

• Diarrhoea

• Haemorrhage

• Burns

Excessive water loss can also occur inuncontrolled diabetes mellitus

To dissolve the glucose being excretedin urine, urinary water output increases

Excess water loss in urine may also occurin renal diseases

This happens when the kidneys fail toreabsorb water e.g. in chronic glomerulo-nephritis

Extremely severe water loss can occur in diabetes insipidus

Diabetes insipidus can be:

Central diabetes insipidus

Nephrogenic diabetes insipidus

Central diabetes insipidus is due todecreased secretion of ADH

Nephrogenic diabetes insipidus is dueto decreased responsiveness of targetcells to ADH

Dehydration is corrected by administra-tion of fluids

The fluids may be given orally or intra-venously

The composition of the fluid givenshould be similar to that of the fluid lost

Correction of dehydration

Excessive retention of water can occurin acute renal failure

Kidneys fail to excrete water in acuterenal failure

Sometimes, it can result from over-administration of intravenous fluids

Water intoxication

Hypersecretion of ADH is a rare causeof water retention

Apart from treatment of the primarycause, diuretics may be used toincrease the output of urine

Most diuretics act by inhibiting thetubular reabsorption of some solutes

Water is lost in urine to dissolve theextra solutes

Diuretics

Some commonly used diuretics are:

• Acetazolamide

• Spironolactone

• Thiazides

• Furosemide

• Ethacrynic acid

• Mannitol

Acetazolamide is a competitive inhibitorof carbonic anhydrase

It decreases the formation of carbonicacid in proximal convoluted tubules

Normally, carbonic acid dissociates intoH+ and HCO3

–

Acetazolamide

H+ is secreted into tubular fluid inexchange for Na+

By disrupting this exchange, acetazola-mide increases urinary Na+ excretion

Extra water is excreted to dissolve Na+

Excessive use of acetazolamide cancause acidosis due to H+ retention

Spironolactone is a structural analogueof aldosterone

Due to structural resemblance, it bindsto aldosterone receptors

This prevents the action of aldosteroneon distal convoluted tubules

Spironolactone

When the action of spironolactone isblocked, excretion of sodium andchloride increases

Water excretion is increased due to theosmotic effect of sodium and chloride

Thiazides inhibit sodium re-absorptionin the distal convoluted tubules

They also increase potassium loss

Thiazides

Furosemide decreases reabsorption of sodium and chloride in the loop of Henle

Hence, it is known as a loop diuretic

It is a potassium-sparing diuretic as itdoes not cause potassium loss

Furosemide

Action of ethacrynic acid is very similarto that of furosemide

This is also a potassium-sparing loopdiuretic

Ethacrynic acid

Mannitol is an osmotic diuretic

It is filtered by the glomeruli but isnot re-absorbed by the tubules

Extra water is lost in urine due tothe osmotic effect of mannitol

Mannitol

Dehydration described earlier is neverdue to a pure water loss

The fluids lost from the body containelectrolytes also

The loss usually occurs from the extra-cellular compartment as the intracellularfluid is tightly protected

ECF contraction and expansion

Dehydration results in a decrease in ECF volume (ECF contraction)

Depending upon the osmolality of the fluid lost, ECF contraction can be:

Isotonic Hypotonic Hypertonic

Retention of water causes an increase in the volume of ECF (ECF expansion)

ECF expansion can be:

Isotonic Hypotonic Hypertonic

Isotonic contraction or expansion of ECFdoes not affect the ICF

If ECF becomes hypotonic or hypertonic,secondary changes occur in the ICF

Isotonic fluid is lost from the body

Can occur in diarrhoea due to loss of isotonic secretions

Can occur in intestinal obstruction due to collection of secretions in the gut

Isotonic ECF contraction

Hypertonic fluid is lost from the body

Can occur in Addison’s disease due to excessive loss of sodium and chloride in urine

Hypotonic ECF contraction

Hypotonic fluid is lost from the body

Can occur in fevers and heat exposure due to excessive sweating or insensible perspiration

Hypertonic ECF contraction

Isotonic fluid accumulates in interstitial tissue

Can occur due to oedema caused by hypertension, congestive heart failure, nephrotic syndrome, cirrhosis of liver etc

Isotonic ECF expansion

More water is retained than solutes

Can occur in acute glomerulonephritis due to decreased glomerular filtration

Hypotonic ECF expansion

Retention of solutes is more than that of water

Can occur in primary aldosteronism and Cushing’s disease due to retention of sodium and chloride

Hypertonic ECF expansion

ECF contraction clinically manifests as adecrease in blood volume (hypovolaemia)

Sudden and excessive loss of fluids fromthe body can cause life-threatening hypo-volaemia

Hypovolaemia

But hypovolaemia is not always due toloss of fluids

It can occur when the total body water isnormal, or even increased

It may be due to shifting of water fromthe vascular compartment into interstitialtissue

A decrease in blood volume decreases the blood pressure

Restoration of blood volume and blood pressure requires the actions of:

Renin-angiotensin system

Aldosterone

ADH

Compensatory mechanisms may be unable to correct hypovolaemia:

If it is too severe

If the pathological condition causing hypovolaemia persists

Pathological conditions causing hypovolaemia may do so by causing:

Fluid loss

Redistribution of water

Renal Na and H2O loss can

occur in:

• Chronic renal diseases

• Diabetes mellitus

• Addison’s disease

• Diabetes insipidus etc

Extra-renal Na and H2O loss can occur in:

• Fevers

• Vomiting

• Diarrhoea

• Intestinal obstruction

• Haemorrhage

• Burns etc

A shift of water from the vascular compartment into interstitial tissue (oedema) can cause hypovolaemia

Redistribution of water

Oedema can occur due to a decrease

in oncotic pressure of plasma or due

to an increase in capillary permeability

Common causes of

oedema are:

Congestive heart failure

Nephroticsyndrome

Cirrhosis of liver

Hypovolaemia

can be:

Isotonic

Hypotonic

Hypertonic

Isotonic hypovolaemiacan occur due to:

Diarrhoea

Intestinal obstruction

Hypotonic hypovolaemiacan occur due to:

Chronic renal disease

Excessive use of diuretics

Addison’s disease

Congestive heart failure

Nephrotic syndrome

Cirrhosis of liver

Hypertonic hypovolaemiacan occur due to:

Fevers

Heat exposure

Severe burns

Treatment of hypovolaemia should comprise:

Treatment of the primary cause

Correction of fluid balance

In hypovolaemia due to shifting of waterfrom vascular compartment, correctionrequires salt restriction and diuretics

In hypovolaemia due to sodium andwater loss, correction requires oral orintravenous administration of fluids

Oral rehydration is preferable if hypo-volaemia is mild

Severe cases require intravenous fluids

In isotonic hypovolaemia, isotonic (0.9%)saline should be given

In hypotonic hypovolaemia, hypertonic(3%) saline is preferable

In hypertonic hypovolaemia, hypotonic(0.45%) saline or 5% GDW (glucose indistilled water) is preferable

Intravenous fluids

While giving intravenous fluids, a watchshould be kept on serum potassium

Care should be taken not to over-hydrate the patient

Fluid imbalance may be accompaniedby disturbances in acid-base balance

Acid-base imbalance should also becorrected along with the fluid imbalance