TOTAL BODY WATER (TBW)

-Body composition in a 70 Kg young adult male:

✔ Water = 60% (of the total weight which is 70 kg)
✔ Proteins = 18%
✔ Fats = 15%
✔ Minerals = 7%
✔ Carbohydrates < 1%
Therefore: water is the most important constituent in
the body.
-With total deprivation of water, survival is limited to a
few days, whereas total food deprivation is tolerated
for at least a month.

-Total body water (in a 70 kg,adult male): = 60 % of

the total body weight

= 42 Kg (60/100 x 70) = 42 L
 Body Fluid Compartments
Total body water is divided into two compartments:

1) Intracellular fluid (ICF): = 2/3 of the total body

water or 40% of the total body weight (TBwt).

2) Extracellular fluid (ECF): = 1/3 of the total body

water or 20% of the total body weight (TBwt).
ECF is further divided into:
a) Interstitial fluid: = 75% of ECF or 15% of TBwt.
b) Intravascular fluid: = 25% of ECF or 5% of TBwt.
c) Trans-cellular fluid: Negligible.
In a 70 Kg adult male:

– Total body water = 42 L (60% of the total body

weight)

• ICF = 28 L (= 40% of total body weight)

• ECF = 14 L (= 20% of total body weight)

– ISF = 10.5 L (= 15% of total body weight)

– IVF (Plasma) = 3.5 L (= 5% of total body weight)
Question:
Calculate the expected body fluid compartments in an
average 60 kg adult male

Answer:
Total body weight= 60Kg,
therefore: Total body water = 60/100 x 60 = 36L,

ICF = 40/100 x 60 = 24 L, ECF = 20/100 x 60 = 12 L,

ISF = 15/100 x 60 = 9 L and IVF = 5/100 x 60 = 3 L.

 Differences between ECF & ICF:

❖ ECF has: lower volume, higher pH and higher

concentrations of sodium, calcium, chloride &
bicarbonate. Sodium is the main cation and chloride
is the main anion.

❖ICF has: higher volume, lower pH and higher

concentrations of potassium, magnesium, phosphate,
sulphate and protein. Potassium is the main cation
and non-diffusible anions (like organic phosphate and
protein) are the main anions.
Factors Affecting Body Fluid Compartments
Body fluid compartments are affected by:
1. Osmosis
2. Diffusion
3. Gibbs Donnan equilibrium
4. Sodium-potassium pump
5. Starling's forces
6. Abnormalities of water balance
1- Osmosis
- Osmosis is the movement of water molecules across a
semi-permeable membrane, from a region of lower
concentration of a solute to a region of higher
concentration of the solute.
All cell membranes and capillaries are
semi-permeable membranes (permeable to water and
generally not permeable to solute).
- For osmosis to occur there should be a difference in
solute concentration between the two sides of the
membrane, i.e. difference in osmolarity.
Osmolarity, Osmolality & Tonicity

Osmolarity
- Osmolarity is the number of osmoles of solute per
one liter of solution.
- It is used to describe concentrations of osmotically
active particles in a solution.
- If a solute dissociates into ions to form an ideal
solution, each liberated ion is an osmotically active
particle.
- For example: dissociation of one mole of (NaCl)
gives one osmole of sodium and one osmole of
chloride (i.e. 2 osmoles).
- Osmotic pressure is defined as the pressure necessary
to prevent solvent migration (i.e. prevent osmosis).
Osmolality
- Osmolality is the number of osmoles per one
kilogram of solvent.
- It is more accurate than osmolarity since it depends
on mass (which is constant) rather than volume

- In body fluids, where the solvent is water, the

concentration of solutes is very low (highly diluted);
therefore one liter and one kilogram are equal. More
over, temperature and pressure are constant under
normal physiological conditions; that’s why
osmolality and osmolarity are equal in body fluids.
-Osmolality of plasma = (280-300) mosm/L.

- Na+ and its anions are responsible for most of this

value (Na+ determines ECF osmolality).

-Osmolality of intracellular fluid = (280-300) mosm/L.

-K+ and its anions are responsible for most of this value
(K+ determines ICF osmolality).
Tonicity

-This term is used when describing osmolality of a

solution relative to osmolality of the plasma.

- Accordingly, solutions may be:

o Isotonic (with osmolality similar to plasma)
o Hypotonic (with osmolality lower than plasma)
o Hypertonic (with osmolality higher than plasma)

- Intravenous (I.V.) infusion of each type of these

solutions affects volumes and osmolarities of body
fluid compartments.
- I.V. infusion of an isotonic solution increases volume
of ECF with no effect on its osmolarity, and no effect
on volume or osmolarity of ICF (i.e. no effect on cells).
- I.V. infusion of a hypotonic solution increases
volumes of ECF and ICF and decreases osmolarities
of ECF and ICF.
- I.V. infusion of a hypertonic solution increases
volume and osmolarity of ECF, and decreases volume
of ICF while its osmolarity is increased.
Calculation of osmolality:
A. From the Freezing Point Depression
- One osmole depresses the freezing point of a solution
by 1.86 οc
- One milliosmole depresses the freezing point by
0.00186 οc
- Number of milliosmoles per liter in a solution =

The freezing point depression/0.00186

Q: Calculate the osmolality of normal human plasma if
the freezing point = - 0.55 οc
Answer: Plasma osmolality = 0.55/0.00186 = 295 mosm/L
B. From the Molarity

Number of osmoles = Number of moles x number of particles

(liberated by a single molecule)

Q: Calculate the osmolarity of 0.9% NaCl solution and mention

the effect of this solution on volume and osmolarity of ICF after
its infusion in the plasma? (Molecular weight of NaCl = 58.5).

Answer: 0.9% NaCl = 0.9 g/dL, (x 10) = 9 g/L

Molarity = [conc. g/L] / MWt of NaCl = 9 / 58.5 mol/L
= 0.154 mol/L, (x 1000) = 154 mmol/L
Osmolarity = 154 x 2 = 308 mosm/L
(Isotonic, has no effect on ICF)
Q: Calculate the osmolarity of 3% NaCl
solution and mention the effect of this
solution on volume and osmolarity of ICF
after its infusion in the plasma?
(Molecular weight of NaCl = 58.5).
Q: Calculate the osmolarity of 5% glucose solution. If one
liter of this solution is infused intravenously, mention the
immediate and the later effects on the cells? (MWt
glucose = 180).

Answer: 5% glucose = 5g/dL = 50 g/L

Molarity = [Conc. g/L]/MWt
= 50/180 = 0.278 mol/L
(x 1000) = 278 mmol/L
Osmolarity = 278 x 1 = 278 mosm/L (Isotonic)
Immediate effect on cells: no effect because it is
isotonic

Later effect on cells: After uptake of glucose by

cells the solution becomes hypotonic; water
enters cells, it increases volume & decreases
osmolarity of ICF.
C. Using a formula
Osmolarity of the plasma can be calculated using the
following formula: Plasma Osmolarity = 2([Na] + [K])
+ [glucose] + [urea]
(All concentrations are in mmol/L)
Q: Calculate the osmolarity of the plasma if [Na] = 140
mmol/L, [K] = 4 mmol/L, [Glucose]= 5 mmol/L and
[Urea]= 7 mmol/L.
Answer: Osmolarity = 2(140 + 4) + 5 + 7
= 300 mosm/L (isotonic).
2- Diffusion
- It is expansion or passage of a substance through a
cell membrane down its chemical or electrical
gradient, due to continuous random movement of its
molecules.
- Water follows osmotically active particles to inside or
to outside the cell, this affects volumes of body fluid
compartments.
3- Gibbs Donnan equilibrium
- The presence of non-diffusible anions (protein and
organic phosphate) within the cell affects distribution
of diffusible ions (both anions and cations); it allows
entry of diffusible cations (e.g. Na+) into the cell and
prevents entry of diffusible anions (e.g. Cl-).
- At equilibrium:
1- Total cations = total anions (on either side of the membrane)
2- The product of diffusible ions on one side equals the product of
diffusible ions on the other side of the membrane
4- The Sodium-Potassium Pump
- Found in all cells of the body.
- Transports sodium and potassium actively against
their chemical gradients (3 Na+ ions to outside and 2
K+ ions to inside the cell).
Functions of the Na+/K+ pump
- Participates in genesis of the resting membrane
potential (i.e. generates negative charges towards the
inner side of the cell membrane (see chapter two)).
- Prevents swelling and rupture of cells by removing
excess sodium ions to outside

Regulation of the pump

- The pump is activated by accumulation of Na+ ions
intracellularly.
- Activity is increased by:
o Insulin, Aldosterone and thyroid hormones
- Activity is inhibited by:
o Dopamine and digitalis
5- Starling's forces
- As mentioned above, movement of water
across cell membranes depends on osmosis.
However, movement of water across the walls
of capillaries depends, in addition to that, on 4
primary forces (known as Starling’s forces)
that control fluid exchange between plasma and
interstitium.
 Starling forces include:
1- Capillary hydrostatic pressure (HPc)
-It is the pressure of plasma acting on the lateral
wall of the blood vessel

- For filtration (from plasma to ISF)

= 35 mmHg at the arteriolar end of capillaries
= 15 mmHg at the veniolar end of capillaries
2- Capillary Oncotic pressure (OPc):
- The osmotic pressure of plasma proteins (also known
as colloid osmotic pressure or oncotic pressure)
- It is exerted mainly by albumin
- For absorption (from ISF to plasma)
= 25 mmHg throughout the capillaries (proteins are not
filtered and therefore their oncotic pressure is not
changed)
 3- Interstitial fluid hydrostatic pressure HPISF:
-Acts in the opposite side to HPC;(i.e. against
filtration)

4- Interstitial fluid oncotic pressure OPISF:

- Acts in the opposite side to OPC; (i.e. against
absorption)
- Calculation of filtration pressure:
- Both hydrostatic pressure of ISF and oncotic
pressure of ISF are of low magnitude, they act against
each other and therefore they cancel each other.
- The filtration pressure is calculated by subtracting
the capillary oncotic pressure from the capillary
hydrostatic pressure as follows:
o At the arteriolar end= (35-25)= +10 mmHg (i.e. net
filtration)
o At the veniolar end= (15-25)= -10 mmHg (i.e. net
absorption)
Edema
- Edema is defined as abnormal accumulation of fluid
in the interstitial space. It is caused by many diseases
through one or more of the following mechanisms:

1- Increased capillary hydrostatic pressure (HPC)

When the HPC becomes higher than the OPC , the return of
the filtered fluid to the capillaries is prevented causing edema.
- Examples include:
o Heart failure
o Venous obstruction
 2- Decreased oncotic pressure (OPC)
Some diseases may lower the level of proteins in the plasma.
This decreases OPC.

o Malnutrition
Decreased protein intake (e.g. Kwashiorkor)
Results in generalized edema
o Malabsorption
Decreased absorption of protein

o Liver disease (chronic disease like liver cirrhosis)

Decreased synthesis of plasma proteins

3- Lymphatic obstruction
- Obstruction of lymphatics results in accumulation of
the fluid that’s supposed to be absorbed by the
lymphatics to be removed from the interstitium.
Therefore, it accumulates causing edema.

Surgical removal of lymph nodes

Filaria
 4- Increased permeability of capillaries:

o Inflammation
The increased permeability is due to mediators of
inflammation released by white blood cells and the nearby
tissues

o Burn
The increased permeability is due to the high temperature
Results in localized edema

o Allergy
The increased permeability is due to histamine which is
released by mast cells and basophils
 Types of edema:
1- Pitting edema
- The finger leaves a mark (a pit) on the skin
-The mark appears because the fluid escapes away
from the site of pressure and returns slowly

-Causes of pitting edema include:

All causes of high capillary hydrostatic pressure

All causes of low capillary oncotic pressure
 2- Non pitting edema
- The finger does not leave a mark on the skin because
the escaped fluid returns rapidly.
-This is because it is attracted by proteins that are
filtered to the interstitium

- Causes of non pitting edema include:

All causes of increased permeability
All causes of lymphatic obstruction
6- Abnormalities of water balance
Water balance
- In normal physiological conditions, the body loses
water in urine to excrete waste products of metabolism
and in addition to that, there is insensible loss of water
through the skin and in expired air.
- These water losses should continuously be replaced by
water intake to maintain normal water content of the
body.
- if water intake is higher than the daily requirement of
the body, the excess water should be excreted.
water loss should equal water intake
Normal water intake occurs through:
o drinking 1.3L/day
o solid food 0.9L/day
o metabolism 0.3L/day

Net = 2.5L/day

Normal water output occurs through:

o urine 1.5 L/day
o stool 0.1 L/day
o sweating & insensible loss 0.9 L/day

Net= 2.5 L/day

Note
- The average water intake = the average water loss =
2.5 L/day
- The above values vary greatly in different
physiological and pathological conditions:
Examples of the physiological conditions:
1- Type of work
E.g. heavy work increases sweating= increased water
loss
2- Exercise
E.g. strenuous exercise increases sweating and causes
hyperventilation (increases insensible water loss in
expired air) = increased water loss
3- Degree of water intake

Affects urine volume as follows:

- High water intake increases urine volume
- Low water intake decreases urine volume
 Examples of the pathological conditions:
1- Abnormal water intake through:
- increased metabolism (fever, hyperthyroidism)
- increased drinking (psychogenic polydypsia)
- excess intravenous fluids (fluid overload)
-complete water deprivation

2- Abnormal water loss through:

- vomiting
- diarrhea
- polyuria (diabetes mellitus, diabetes insipidus)
- excessive sweating (heat exhaustion)
- hyperventilation (metabolic acidosis)
Oligo urea: decreased uring
output
Polyurea: increased urine out
put
Anuria : No urine at all
Regulation of water balance
- As mentioned earlier, maintenance of
constancy of ECF is the goal of all systems in the
body.
- Variation in water intake or water loss
produces minor changes in extracellular fluid
volume and osmolarity. These changes stimulate
certain receptors (e.g. volume receptors &
osmoreceptors) that activate multiple regulatory
mechanisms to restore back the constancy of the
ECF.
-The regulatory mechanisms include:

1- Mechanisms for control of water intake

-act principally through control of thirst

2- Mechanisms for control of water loss

- act principally through control of urine
volume
Thirst
- Defined as the subjective perception that
provides the urge for humans and animals
to drink fluids.
- Also defined as the conscious desire for
water.
- Regulated by thirst center located in the
hypothalamus.
- There are 4 major stimuli to thirst:
Angiotensin II: This is an octa-peptide hormone
produced in the plasma following release of renin
enzyme from the "Juxta-glomerular apparatus" in the
kidney.
- It acts directly on specific receptors located in the
brain to stimulate thirst.
Hypertonicity: Small increases of 1-2% of the
effective osmotic pressure of plasma causes shrinkage
of osmoreceptors in the hypothalamus (due to osmosis
from the osmoreceptors to the ECF).
 Hypovolemia: The volume of ECF is sensed via
volume receptors located at the low pressure side of
the circulation (i.e. the venous side, at the junction of
the right atrium and the vena cava and at the entry of
the pulmonary vein into the left atrium).
Hypotension: The blood pressure is sensed via
baroreceptors located at the high pressure side of
the circulation (i.e. the arterial side, at the carotid
sinus and the aortic sinus which are found at the
bifurcation of the common carotid artery and the
aortic arch respectively).
Control of water loss
- Under normal environmental and
physiological conditions, the amount of water
lost by sweating, respiration and through the
skin is almost constant whereas the amount lost
by urine is variable. The minimal volume of
urine that can be excreted to eliminate the
metabolic waste products = 0.5 L/day. The
maximal volume depends on water intake.
Renal function
- The functional unit of the kidney is the
"nephron" which consists of: glomerulus, for
filtration & tubules: for reabsorption and
secretion.
- About 180 L of fluid pass through the
glomeruli of the kidney each day. However,
only 1.5 L is excreted in urine indicating that
the renal tubules reabsorb more than 99% of
the filtered fluid.
Hormonal activity
ADH

- Antidiuretic hormone, also known as vasopressin

- It is a nona-peptide hormone synthesized in the
hypothalamus and stored in the posterior pituitary
gland
- It is released in response to the same major stimuli of
thirst, through similar mechanisms:
Functions of ADH
- ADH acts on the collecting ducts in the kidney
causing water retention. It facilitates reabsorption of
7-13% of the filtrate
- When ADH level in plasma is high, it also causes
vasoconstriction resulting in elevation of the blood
pressure
Abnormalities of ADH:
- Deficiency of ADH causes polyuria and excessive
thirst due to hypovolemia. Urine volume may reach up
to 23 L/day. The condition is known as diabetes
insipidus (DI).
Excessive ADH secretion causes reduction in urine
volume, hypertension and edema due to water
retention. The condition is known as syndrome of
inappropriate ADH secretion (SIADH). It is caused by
many problems; these include head trauma, lung
tumors, pneumonia and pancreatitis.
 Aldosterone
- Steroid hormone synthesized in the adrenal cortex
- It is released in response to the following stimuli:
o Hyperkalemia
Directly stimulates aldosterone release from the
adrenal cortex.
o High level of ACTH

o The renin-angiotensin-aldosterone system

 Atrial natriuretic peptide (ANP)
- A peptide hormone released by atria in response to
hypervolemia.
- It reduces ECF volume through the following effects:
o Inhibition of the effect of angiotensin II on thirst
o Inhibition of the effect of aldosterone on the kidney
o Increasing the rate of glomerular filtration
o Increasing excretion of sodium in urine