Distribution of water and electrolytes in different compartments and their regulation

1. Water and Electrolyte
Balance
R. C. Gupta
M.D. (Biochemistry)
Jaipur (Rajasthan), India

2. Water is the most abundant component of
our body
Need for water is more urgent than that for
any other nutrient
Humans beings can live one month without
food but only six days without water
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3. EMB-RCG
In adults, water accounts for:
70% of the total body weight in males
60% of the total body weight in females

4. EMB-RCG
Water content depends on age:
Infants: 75%
Adults: 60-70%
Elderly: 45%

5. 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

6. 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

7. 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

8. 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

9. Water has a high dielectric constant
A large number of oppositely charged
particles can co-exist in water due to this
Dielectric constant

10. 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

11. 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

12. 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

13. 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

14. 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)

15. 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

16. The major osmotically active solutes in
body fluids are:
Electrolytes have more osmotic power as
they dissociate into at least two particles
Non-electrolytes e.g. glucose, lipids etc
Electrolytes e.g. inorganic salts and proteins

17. 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

18. Effective osmolality of a compartment is
determined by the solutes restricted to
that compartment
Effective osmolality of the compartment is
also known as its tonicity

19. Selective distribution of ions in different
compartments is maintained by specific
ion channels and ion pumps
A lot of energy is spent for maintaining the
differential distribution of ions in different
compartments

20. Cations
Sodium is the major cation in extracellular
fluid
Potassium is the major cation in intracellular
fluid
This differential is maintained by Na+, K+-
exchanging ATPase
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21. Anions
The major anions in extracellular fluid are
chloride and bicarbonate
The major anions in intracellular fluid are
phosphates and proteins

22. Proteins
Proteins are present in a:
Fairly high concentration in
intracellular fluid
Smaller but significant
concentration in plasma
Negligible concentration in
interstitial fluid

23. Effective osmolality is determined by:
Sodium and its associated
anions in the extracellular fluid
Potassium and its associated
anions in the intracellular fluid

24. The ions and molecules have specific
distribution in the intracellular fluid
These are vital for the functioning of the
cells, and are zealously maintained

25. Changes in osmolality are usually due to
shift of salts (mainly sodium)
When salts shift, water follows salts

26. Shrinkage of cells due to shifting of water
out of the cells can seriously affect the
functioning of cells
Swelling of cells due to shifting of water
into the cells can also seriously affect the
functioning of cells

27. Hyper-osmolality of extracellular fluid
draws water out of cells into the extra-
cellular compartment
Hypo-osmolality of extracellular fluid
drives water from extracellular compart-
ment into the cells

28. Osmolality of plasma is 275-290 mosmol/kg
A 0.9% solution of NaCl in water has
the same osmolality (or tonicity) as plasma
A 5% solution of glucose in water also has
the same osmolality (or tonicity) as plasma
These two are said to be isosmotic or
isotonic with plasma

29. Oncotic pressure
Osmotic pressure exerted by proteins is
called oncotic pressure
It is also known as colloid osmotic pressure
The normal oncotic pressure of plasma is
about 25 mm of Hg

30. A decrease in the concentration of proteins in
plasma decreases oncotic pressure of plasma
Water is forced out of capillaries at the arterial
end due to greater hydrostatic pressure
It cannot re-enter at the venous end if the oncotic
pressure is less than the hydrostatic pressure
This will result in oedema

31. Water intake and output
Water balance of the body depends upon
the relative intake and output of water
Water is taken in as drinking water and in
the form of food and beverages
Some water is formed in the body during
oxidative reactions (metabolic water)

32. 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

33. 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

34. 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:

35. In hot climates, sweat loss is much more
This is compensated by increased intake of
drinking water
If it is not compensated, urine output will
decrease
However, urine output cannot decrease
below a certain level

36. Normal excretion of solutes by the kidneys
is about 600 milliosmol/day
Minimum water required to dissolve 600
milliosmol 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 called
oliguria

37. 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

38. 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

40. ADH secretion begins when the osmolality
of plasma reaches about 285 mosmol/kg
The thirst centre is stimulated when the
osmolality of plasma reaches about 295
mosmol/kg

41. When blood circulates through the kidneys,
125 ml of glomerular filtrate is formed per
minute
About 180 litres of glomerular filtrate is
formed in 24 hours
Glomerular filtration rate

42. 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

43. 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

44. Obligatory re-absorption equals:
About 85% of the glomerular filtrate
Or about 153 litres per day

45. Cells of distal convoluted tubules and
collecting ducts are not permeable to water
in the absence of ADH
Binding of ADH to its receptors (V2
receptors) on the surface of these cells
activates adenylate cyclase
Facultative re-absorption

46. Active adenylate cyclase increases the
intracellular concentration of cAMP
cAMP activates protein kinase A
Active protein kinase A phosphorylates
some cytosolic proteins

47. The phosphorylated proteins translocate
aquaporins from cytosol into cell membrane
Aquaporins are water channels
Water moves into the cell through these
water channels

49. Movement of water into distal convoluted
tubules and collecting ducts is proportional
to plasma ADH concentration
The ADH-regulated re-absorption is known
as facultative re-absorption of water
Normally, this is about 25.5 litres/day

50. About 1.5 litres of water is not absorbed by
tubules
This is excreted in the form of urine every
day
Facultative re-absorption can be adjusted
to maintain the water balance of the body

51. 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

52. Sodium
The most important cation in regulation
of fluid and electrolyte balance
The most abundant cation in the ECF
Contibutes significant osmotic pressure

53. Potassium
Critical to maintenance of
membrane potential
Compensates for shifts of
hydrogen ions in or out of cells

54. Chloride
The most abundant anion in the
ECF
Contributes significant osmotic
pressure

55. Regulation of sodium
Aldosterone promotes tubular re-
absorption of sodium
Oesrogens have a similar but weaker
effect
Atrial natriuretic peptide inhibits release of
aldosterone

56. 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

57. Regulation of chloride
Chloride is the major anion associated
with sodium
It moves with sodium
Aldosterone increases the tubular
reabsorption of chloride

58. 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

59. Excessive water loss can be due to:
• Excessive sweating
• Vomiting
• Diarrhoea
• Haemorrhage
• Burns

60. Excessive water loss can also occur in
uncontrolled diabetes mellitus
To dissolve the glucose being excreted
in urine, urinary water output increases

61. Excess water loss in urine may also occur
in renal diseases
This happens when the kidneys fail to
reabsorb water e.g. in chronic glomerulo-
nephritis

62. Extremely severe water loss
can occur in diabetes insipidus
Diabetes insipidus can be:
Central diabetes insipidus
Nephrogenic diabetes insipidus

63. Central diabetes insipidus is due to
decreased secretion of ADH
Nephrogenic diabetes insipidus is due
to decreased responsiveness of target
cells to ADH

64. Dehydration is corrected by administra-
tion of fluids
The fluids may be given orally or intra-
venously
The composition of the fluid given
should be similar to that of the fluid lost
Correction of dehydration

65. Excessive retention of water can occur
in acute renal failure
Kidneys fail to excrete water in acute
renal failure
Sometimes, it can result from over-
administration of intravenous fluids
Water intoxication

66. Hypersecretion of ADH is a rare cause
of water retention
Apart from treatment of the primary
cause, diuretics may be used to
increase the output of urine

67. Most diuretics act by inhibiting the
tubular reabsorption of some solutes
Water is lost in urine to dissolve the
extra solutes
Diuretics

68. Some commonly used diuretics are:
• Acetazolamide
• Spironolactone
• Thiazides
• Furosemide
• Ethacrynic acid
• Mannitol

69. Acetazolamide is a competitive inhibitor
of carbonic anhydrase
It decreases the formation of carbonic
acid in proximal convoluted tubules
Normally, carbonic acid dissociates into
H+ and HCO3
–
Acetazolamide

70. H+ is secreted into tubular fluid in
exchange for Na+
By disrupting this exchange, acetazola-
mide increases urinary Na+ excretion
Extra water is excreted to dissolve Na+
Excessive use of acetazolamide can
cause acidosis due to H+ retention

71. Spironolactone is a structural analogue
of aldosterone
Due to structural resemblance, it binds
to aldosterone receptors
This prevents the action of aldosterone
on distal convoluted tubules
Spironolactone

72. When the action of spironolactone is
blocked, excretion of sodium and
chloride increases
Water excretion is increased due to the
osmotic effect of sodium and chloride

73. Thiazides inhibit sodium re-absorption
in the distal convoluted tubules
They also increase potassium loss
Thiazides

74. 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 it
does not cause potassium loss
Furosemide

75. Action of ethacrynic acid is very similar
to that of furosemide
This is also a potassium-sparing loop
diuretic
Ethacrynic acid

76. Mannitol is an osmotic diuretic
It is filtered by the glomeruli but is
not re-absorbed by the tubules
Extra water is lost in urine due to
the osmotic effect of mannitol
Mannitol

77. Dehydration described earlier is never
due to a pure water loss
The fluids lost from the body contain
electrolytes also
The loss usually occurs from the extra-
cellular compartment as the intracellular
fluid is tightly protected
ECF contraction and expansion

78. 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

79. Retention of water causes an increase
in the volume of ECF (ECF expansion)
ECF expansion can be:
Isotonic Hypotonic Hypertonic

80. Isotonic contraction or expansion of ECF
does not affect the ICF
If ECF becomes hypotonic or hypertonic,
secondary changes occur in the ICF

81. 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

82. 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

83. Hypotonic fluid is lost from the body
Can occur in fevers and heat exposure
due to excessive sweating or insensible
perspiration
Hypertonic ECF contraction

84. 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

85. More water is retained than solutes
Can occur in acute glomerulonephritis
due to decreased glomerular filtration
Hypotonic ECF expansion

86. 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

87. ECF contraction clinically manifests as a
decrease in blood volume (hypovolaemia)
Sudden and excessive loss of fluids from
the body can cause life-threatening hypo-
volaemia
Hypovolaemia

88. But hypovolaemia is not always due to
loss of fluids
It can occur when the total body water is
normal, or even increased
It may be due to shifting of water from
the vascular compartment into interstitial
tissue

89. 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

91. Compensatory mechanisms may
be unable to correct hypovolaemia:
If it is too severe
If the pathological condition
causing hypovolaemia persists

92. Pathological conditions causing
hypovolaemia may do so by causing:
Fluid loss
Redistribution of water

93. 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

94. 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

95. Common
causes of
oedema are:
Congestive heart
failure
Nephrotic
syndrome
Cirrhosis
of liver

96. Hypovolaemia
can be:
Isotonic
Hypotonic
Hypertonic

97. Isotonic hypovolaemia
can occur due to:
Diarrhoea
Intestinal obstruction

98. Hypotonic hypovolaemia
can occur due to:
Chronic renal disease
Excessive use of diuretics
Addison’s disease
Congestive heart failure
Nephrotic syndrome
Cirrhosis of liver

99. Hypertonic hypovolaemia
can occur due to:
Fevers
Heat exposure
Severe burns

100. Treatment of hypovolaemia should
comprise:
Treatment of the
primary cause
Correction of
fluid balance

101. In hypovolaemia due to shifting of water
from vascular compartment, correction
requires salt restriction and diuretics
In hypovolaemia due to sodium and
water loss, correction requires oral or
intravenous administration of fluids

102. Oral rehydration is preferable if hypo-
volaemia is mild
Severe cases require intravenous fluids

103. 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 in
distilled water) is preferable
Intravenous fluids

104. While giving intravenous fluids, a watch
should be kept on serum potassium
Care should be taken not to over-
hydrate the patient
Fluid imbalance may be accompanied
by disturbances in acid-base balance
Acid-base imbalance should also be
corrected along with the fluid imbalance