Regulation of Body Fluids

Dr Mar Mar Lwin

MBBS MMedSc
DipMedEd PhD
 Learning Objectives

 List the various fluid compartments of the body

 the composition & measurement methods

 Explain how the volume of these fluid compartments are

maintained, especially the blood volume

 Explain the basics of the homeostatic mechanism

 Identify the control systems of the body

 Explain the feedback mechanism and their working

 Describe the control mechanisms that make the body capable of

adapting to the environment
 Body Fluids
• About 60% of the adult human body is fluid, mainly water
solution of ions and other substances
• the fluid inside the cells is called intracellular fluid (about 2/3)
• about 1/3 is in the spaces outside the cells and is called
extracellular fluid which is in constant motion throughout the
body
• the ions and nutrients needed by the cells stays in the
extracellular fluid. Thus, the extracellular fluid is the internal
environment of the body
• Cells are capable of living, growing, and performing their special
functions as long as the proper concentrations of oxygen,
glucose, ions, amino acids, fatty substances and other
constituents are available in this internal environment
 Body Fluids
• The maintenance of a relatively constant volume and a stable
composition of the body fluids is essential for homeostasis
• The relative constancy of the body fluids is remarkable because
there is continuous exchange of fluid and solutes with the
external environment as well as within the different
compartments of the body

• Total body fluid = 60% of total body weight

• Average male (70 kg of body weight)

60
Total body water = 70 kg X = 42 L
100
 Body fluid compartments

28L

70 Kg
42L
10.5L

14L
3.5L
 TOTAL BODY FLUID
(60% OF BODY WEIGHT), 42L

2/3 1/3

ICF ECF
(40% OF BW,28L) (20% OF BW, 14L)

TRANSCELLULAR
GLANDULAR

ISF IVF (plasma)

(15% OF BW, 10.5L) (5% OF BW, 3.5L)
• In average young adult male
7% of BW  mineral
15%  fat
18%  protein & related substances
60%  water
• This percentage can change depending on age, gender, and
degree of obesity (body fat)
• TBW is 10% lower in females due to relatively greater amount
of fat
• infants TBW  65-75% of body wt, due to body constituted by
different tissues
infants brain (water content=80%) forms larger part of body wt &
bone (water content=20%) smaller part of body wt
The total body fluid is distributed mainly between two
compartments:

• the extracellular fluid and the intracellular fluid

Intra cellular fluid (ICF) compartment

• comprises 2/3 of the body's water, 40% of body weight
• Fluid within body cells contains its individual mixture of different
constituents, but the concentrations of these substances are
similar from one cell to another
Extra cellular fluid compartment (ECF)
• All the fluids outside the cells are collectively called the ECF
• account for about 20 % of the body weight,
• Plasma
• interstitial fluid
• transcellular fluid (specialized type of extracellular fluid)

(1) Plasma
• fluid part of blood, 25% of ECF  3.5L, 4-5% body wt
• Plasma volume can be calculated from blood volume &
hematocrit (PCV (packed cell volume)

100-PCV
Plasma Volume = Blood volume X ------------
100
Blood volume =plasma + cells that filling vascular system
 Blood Volume

• Blood is contained in a closed chamber of its own

(circulatory system)

• contains both extracellular fluid (plasma) & intracellular fluid

(fluid in red blood cells)

• Average blood volume of normal adult is 5L (7%of body weight)

(3L plasma & 2L red blood cells)

• Hematocrit (Packed Red Cell Volume (PCV) is the fraction of the blood composed
of red blood cells, as determined by centrifuging blood in a “hematocrit tube”
until the cells become tightly packed in the bottom of the tube
(2) Interstitial fluid (millieu interior)
• thin layer of fluid surrounding cells forming their immediate
environment & this fluid constitutes internal environment of body
• outside vascular system & surrounds all cells & includes lymph
(lymph constitutes 2-3% of TBwt)

• Its temperature, pH, osmolarity, ionic concentration,O2 & CO2

tension & other vital features should be within narrow range for
optimal function & even survival of cells which it surrounds

(3)Transcellular fluid
• fluid in lumen of structure lined by epithelium
• about 1L, (1.5% of B wt)
• include CSF, aqueous & vitreous humor, synovial fluid, GIT
secretions, pleural, peritoneal, pericardial, bile, cochlea &
fluid in urinary tract
 Major cations and anions of the ICF and ECF

• the ECF contains large amounts of Na+, Cl- and HCO3 ions,
oxygen, carbon dioxide, glucose, fatty acids, amino acids and
other cellular waste products that are being transported to the
kidneys for excretion.
• only small quantities of K+, Ca++, Mg++, PO4 & organic acid ions
• the composition of ECF is regulated by various mechanisms,
especially by the kidneys

• the ICF contains large amounts of K+, Mg++ ,PO4 ions and
large amounts of protein,

• only small quantities of Na+ and Cl- ions and almost no Ca++ ions
Measurement of Various body fluid compartment
• The volume of a fluid compartment in the body can be measured by
placing an indicator substance in the compartment,
• allowing it to disperse evenly throughout the compartment’s fluid, and
then analyzing the extent to which the substance becomes diluted,
“indicator-dilution” method
• These methods must fulfil the following requirements:
1. All the indicator administered remains in the volume to be measured;
2. Uniform distribution of the indicator follows an adequate time for
mixing;
3. The indicator does not alter the volume of the compartment;
4. The indicator does not enter the system by another route.

The volume of the compartment = (the amount of the indicator

administered - the amount of indicator excreted) / concentration of
indicator in the volume being measured
 Indicators for measurement of body compartments
Plasma volume – use a substance that binds to plasma albumin
Total body water – use a substance that diffuses freely into all fluid compartments
ECF volume – use non-metabolised substances

Volume Indicators

Total body water 3H

2O
(radioactive water,tritium) 2H2O (heavy water,
deuterium), antipyrine

Extracellular fluid 22Na, 125I-iothalamate, thiosulfate, inulin, Mannitol, Sucrose

Intracellular fluid Calculated as Total body water – ECF volume

Plasma volume 125I-albumin, Evans blue dye (T-1824)

Blood volume 51Cr-labeled

red blood cells, or calculated as
Blood volume = Plasma volume/(1 - Hematocrit)

Interstitial fluid Calculated as Extracellular fluid volume - Plasma volume

• Antipyrine is lipid soluble and can rapidly penetrate cell membranes and distribute
uniformly throughout the intracellular and extracellular compartments
• inulin is proportionally distributed between plasma volume and interstitial volume
• radioactive albumin or by Evans blue - neither leave the vascular system nor
penetrate the erythocytes
Regulation of fluid exchange and osmotic equilibrium
between intracellular and extracellular fluid
• The distribution of fluid between intracellular and extracellular
compartments is determined mainly by the osmotic effect of the
solutes especially sodium, chloride, and other electrolytes acting
across the cell membrane

• the cell membranes are highly permeable to water but relatively

impermeable to ions such as sodium and chloride

• Therefore, water moves across the cell membrane rapidly, so that the
ICF remains isotonic with the ECF

 Osmolarity - the number of solute particles per liter of solution

(osmoles per liter of solution)
 Osmolality - the number of solute particles per kg of water (osmoles
per kilogram of water)
 In dilute solutions such as the body fluids, these two terms can be
used almost synonymously because the differences are small
 Osmosis is the net diffusion of water across a selectively permeable
membrane from a region of high water concentration to a lower water
concentration.

 Osmotic Pressure - Osmosis of water molecules can be opposed by

applying a pressure in the direction opposite of the osmosis. The
pressure required to prevent the osmosis is called the osmotic
pressure. Osmotic pressure is an indirect measurement of the water
and solute concentrations of a solution

 The higher the osmotic pressure of a solution means the higher solute
concentration and the lower water concentration

 The osmotic pressure of a solution is directly proportional to the

concentration of osmotically active particles in that solution
 Diagrammatic representation of osmosis

A B
Water molecules are represented by small circles, solute molecules by large solid
circles.
In the diagram A, water is placed on one side of a membrane permeable to water
but not to solute, and an equal volume of a solution of the solute is placed on the
other.
Water molecules move down their concentration gradient into the solution, and

In the diagram B, the volume of the solution increases.

As indicated by the arrow on the right, the osmotic pressure is the pressure that
would have to be applied to prevent the movement of the water molecules.
 • The osmotic pressure is proportional to the number of particles in
solution per unit volume of solution. So, the concentration of
osmotically active particles is usually expressed in osmoles.

• One osmole (Osm) equals the gram molecular weight of a substance

divided by the number of freely moving particles that each molecule
liberates in solution. For biological solutions, the milliosmole (mOsm;
1/1000 of 1 Osm) is commonly used.
• whether the solute is a large molecule or a small molecule. (Eg; one
molecule of albumin with a molecular weight of 70,000 has the same osmotic
effect as one molecule of glucose with a molecular weight of 180)
• One molecule of sodium chloride has two osmotically active particles, Na+ and
Cl–, and therefore has twice the osmotic effect of an albumin molecule or a
glucose molecule

Non-ionizing glucose: osm. = no. of glucose molecules

1 mole of glucose = 1 osm
ionizing NaCl: 1 mole of NaCl = (Na+ + Cl-) = 2 osm
Na2SO4 = Na+ + Na+ + SO4- = 3 osm
 TONICITY is the osmolality of a solution relative to plasma.
(Effective Osmolality)
• Isotonic - same osmolality as body fluids /plasma
• Hypertonic - greater than plasma
• Hypotonic - lower than plasma
Plasma osmolality 290 mosm/L → 270 - Na+ and Cl- & HCO3-
< 5 - Plasma protein
10 - Glucose, urea/major
non electrolytes

• The tonicity of solutions depends on the concentration of

impermeant solutes
• Tonicity of a solution is related to the effect of the concentration
of the solution on the volume of a cell
• Isotonic means that the solution does not change the volume of
the cell
• Hypotonic - the solution causes a cell to swell
• Hypertonic - the solution causes a cell to shrink
Effects of (A) isotonic, (B) hypertonic, and (C) hypotonic solutions on cell
volume
• If a cell is placed in a solution of osmolarity of 285 mOsm/L the
cells will not shrink or swell because the water concentration in the ICF
and ECF is equal. Such a solution is said to be isotonic because it
neither shrinks nor swells the cells

• Examples of isotonic solutions include a 0.9% NaCl solution

• If a cell is placed into a hypotonic solution that has a lower osmolarity

(< 285 mOsm/L) water will diffuse into the cell causing it to swell;
Solutions of sodium chloride with a concentration of less than 0.9% are
hypotonic and cause cells to swell.

• If a cell is placed in a hypertonic solution having a higher osmolarity (>

285 mOsm/L) water will flow out of the cell into the extracellular
fluid, the cell will shrink until the two concentrations become equal.
Solutions of greater than 0.9% are hypertonic
 Effect of adding saline solution to the ECF
• If an isotonic saline solution is added to the ECF compartment,
the osmolarity of the ECF does not change; therefore, no
osmosis occurs through the cell membranes. The only effect is an
increase in ECF volume.

• If a hypertonic solution is added to the ECF, the osmolarity of

ECF increases and causes osmosis of water out of the cells into
the ECF compartment to achieve osmotic equilibrium. The net
effect is an increase in ECF volume, a decrease in ICF volume,
and a rise in osmolarity in both compartments.

• If a hypotonic solution is added to the ECF, the osmolarity of the

ECF decreases and some of the extracellular water diffuses into
the cells until the ICF and ECF compartments have the same
osmolarity. Both the intracellular and the extracellular volumes
are increased, although the intracellular volume increases to a
greater extent & osmolarity reduced
Isosmotic, Hyperosmotic, and Hypo-osmotic Fluids
• The terms isotonic, hypotonic, and hypertonic refer to whether solutions
will cause a change in cell volume. The tonicity of solutions depends on
the concentration of impermeant solutes

• The terms hyperosmotic and hypo-osmotic refer to solutions that have a

higher or lower osmolarity compared with the normal extracellular fluid,
without regard for whether the solute permeates the cell membrane

• Body fluid osmolality is defined by the ratio of total body solute

to total body water
• It is regulated at 285–295 mOsm/L
• Solutions with an osmolarity the same as the cell are called
isosmotic, regardless of whether the solute can penetrate the
cell membrane
• hyperosmotic solution that have a higher osmolarity
• hypo-osmotic solution that have a lower osmolarity compared
with the normal ECF, without regard whether the solute
permeates the cell membrane
ECF osmolality (290 ± 5 mOsm/kg)

Electrolytes Crystalloids Colloids

sodium and anions Glucose and urea Plasma proteins

270 mOsm 10 mOsm 5 mOsm

(90%)

Sodium backbone of ECF

 Regulation of ECF Volume & tonicity

• Regulation of ECFV & tonicity is dependent upon regulation of

water & Na+ balance

• Regulation of ECFV by regulating the total amount of Na+ in the

body (slow process)

• Regulation of the plasma osmolality by regulating the amount of

water in the body (quick; in a matter of minutes)
 Water balance

INTAKE OUTPUT
•Food not so
• Gut obligatory,
variable more or less
•Metabolism • Lungs constant
• Drinking • Skin
• KIDNEYS

• water input is regulated primarily by changes in volume of

water drunk (controlled by thirst mechanism)

• water output is regulated primarily by changes in the volume

of urine (kidney)
 Control of water balance

• Thirst and Vasopressin (ADH) anti diuretic hormone

• Both are controlled by centers in the hypothalamus that are

stimulated primarily by two physiological conditions,

(1) increases in plasma osmolality and

(2) decreases in plasma volume

 Thirst mechanism

• control by hypothalamus
• Drinking is regulated by plasma osmolality and ECFV

• hypertonicity → osmoreceptors in anterior hypothalamus

• hypovolemia → baroceptors in heart & blood vessels

ECFV → AT II → Hypothalamus → thirst

changes in plasma osmolality and changes in ECF volume affect
thirst by separate pathways
 Vasopressin (ADH)

• Secreted by nuclei of hypothalamus,

• transported to and stored in posterior pituitary
• released by :-

1. osmolality of ECF above the normal 285 mosm/kg

(mediated through osmoreceptors in ant. Hypothalamus)

2. Fall in ECFV and systemic arterial pressure (not as sensitive &rapid

as osmoreceptor mechanism)
(mediated by low-pressure baroreceptors in atria, great veins &
pulmonary veins)
 Effects of Vasopressin
•  water reabsorption in the kidney by increasing water
permeability of collecting duct

• Water reabsorption → causing  ECFV;  osm

• Generalized vasoconstriction and raise blood pressure

• presence of vasopressin → concentrated urine & water retained
in excess of solute

• absence of vasopressin → dilute urine & water lost in excess of

solute

• important for body economy & regulation of ECF osmolality

(Note: Kidney can only minimize further loss of fluid,

thirst can makes up the loss)
 Mechanisms for defending ECF tonicity

• When the effective osmotic pressure of the plasma rises, vasopressin

secretion is increased and the thirst mechanism is stimulated; water is
retained in the body, diluting the hypertonic plasma; and water intake is
increased
• Conversely, when the plasma becomes hypotonic, vasopressin secretion
is decreased and “solute-free water” (water in excess of solute) is
excreted. In this way, the tonicity of the body fluids is maintained within
a narrow normal range from 280 mOsm/kg of H2O to 295 mOsm/kg of
H2O
 Water Balance

• Intake-output chart is very important in clinical practice to

ensure adequate intake to match the output

INTAKE = urine volume/24 hours + 1000 ml + Extra Losses

Extrarenal losses

Extra loss = milk, stool, vomitus, sweat, blood, plasma

milk secretion 500-1000ml/day
sweating may be 3 -4 L on a hot day
loss through burns, haemorrhage

Extrarenal losses = from lungs, gut, skin (1000ml)

 Water Gain (L) Water Loss (Output) (L)

From gut - food 1L From gut 0.2L (may be increased in diarrhoea)

- drink 1.3L (stool) (increased loss also in vomiting)

(variable)

From lungs 0.3L (increased in hyperventilation)

From metabolism 0.3L
(metabolic water) From skin 0.6L (insensible perspiration; increased
in sweating, burns)

From 1.5L (may be reduced to 0.5 or increased

kidneys according to the needs of the body)

2.6 L 2.6 L
 Water Balance

OUTPUT > INTAKE DEHYDRATION

rise in plasma osmolality
the eyes sunken, the skin loses its elasticity,
the person is lethargic

INTAKE > OUTPUT

OVERHYDRATION
WATER INTOXICATION
fall in plasma osmolality
 Effects of increasing dehydration on
physical performance
body water loss Effects

0.5% Increased strain on heart

1% Reduced aerobic endurance
3% Reduced muscular endurance

4% Reduced muscle strength, reduced fine motor

skills, heat cramp

5% Heat exhaustion, reduced mental capacity

6% Physical exhaustion, heat stroke, coma

 Regulation of ECF Volume

• It is closely interlinked with sodium balance as sodium

contributes 90 % of the osmolality of ECF and water follows
sodium
• Thus, sodium forms the backbone of ECF

Electrolyte Balance
• Of the electrolytes routinely monitored (sodium, potassium,
chloride, bicarbonate)
• only sodium, potassium will be considered here;
• sodium because its balance is linked with regulation of ECF
volume and tonicity, and
• potassium because its balance is linked to that of sodium
 Sodium Balance
Input Output : via three routes :
1. sweat Na+ loss under
• Diet (varies with types of diet) normal condition is
• Input : not physiologically 2. faeces negligible
regulated
3. Urine - The urinary loss matches
the intake in normal healthy
individuals

• Thus, Na+ output is regulated primarily by changes in the

amount of Na+ excreted in urine
Mechanisms which maintains sodium balance

• RAA system (when ECF volume decreased)

(Renin-angiotensin- aldosterone system)

• thirst mechanism

• ANP (when ECF volume increased)

(atrial natriuretic peptide)

• sympathetic system

• vasopressin
1. Fall in blood volume and pressure results in less stretching of
the baroreceptors and there is AVP release (AVP favours water
reabsorption in the kidney) and

2. Stimulation of sympathetic system causing

i. release of RENIN from the juxtaglomerular apparatus in
the kidneys;
ii. an increase in sodium and water reabsorption in the
proximal tubules.

3. Renin acts on angiotensinogen, which is converted to

angiotensin I and finally to angiotensin II (AT II) which
facilitates water and salt reabsorption in the tubules acting
directly and through aldosterone

4. Stimulation of thirst.
 BP ECF volume BP

Renal perfusion Volireceptor Baroreceptor

pressure (less stretched) (less stretched)

Intrarenal + +
baroreceptor
(less stretched) Hypothalamus
VMC

+ SON,PVN
JG cells Sympathetic
system Thirst
Renin centre
AVP

RAA system
 RAA system activation

Na+ reabsorption in PCT

Thirst stimulation

Na+ reabsorption in DCT

Defense of ECF volume by
angiotensin II
 Sympathetic activation

Sympathetic activity

+ +
JG cell PCT
(direct action)

RAA system
Na+
activation
reabsorption
 Thirst centre

Water intake ECF Volume

Hypertonicity Hypovolemia

Osmoreceptors Baroreceptors

Angiotensin II
HYPOTHALAMUS

THIRST
AVP secretion

Hypothalamus

Blood AVP

Increased water permeability

Increased water reabsorption

All these mechanisms

Na+ and water reabsorption

Water intake

Restore ECF volume back to the

normal
Responses to ECF volume expansion with
reduction in plasma osmolality

• When hypotonic solution is gained e.g. drinking water, the ECF

volume rises and plasma osmolality falls
• If isotonic solution is added, there is volume expansion without
change in osmolality. The excess water is excreted from the
body by the following mechanisms :
1. Inhibition of AVP Release
A rise in ECF volume stimulates volireceptors in the low-
pressure system, resulting in inhibition of AVP release. The fall
in osmoiality also inhibits AVP release via osmoreceptors in the
hypothalamus

2. Release of ANP from the Heart (Atria) atrial natriuretic peptide

A rise in ECF volume stretches the atrial myocardium, releasing
ANP from atrial myocytes.
ANP causes a rise in GFR, vasodilation and reduction in renal
sodium reabsorption, which results in osmotic diuresis.