FLUID COMPARTMENTS

30. Fluid compartments

Describe the major fluid
compartments of the body in
the adult.
> Total body water (TBW) varies depending on age, size, gender
and fat content. It is approximately 60% of body weight (BW) in the
average adult male (i.e. 42 L) and 50% in the average adult female.
The remainder of the weight is made up of protein, minerals and fat.
The main components of TBW are the extracellular and intracellular
compartments.
> Intracellular fluid (ICF) makes up two-thirds of TBW (i.e. 28 L), and is
contained within the phospholipid bilayer of the cell membrane.
> Extracellular fluid (ECF) makes up one-third of TBW (i.e. 14 L). This is
divided into:
• interstitial fluid (ISF), which makes up 75% of the ECF (i.e. 9.5 L)
and lies between cells, but outside the cell membrane
• plasma, making up 25% of the ECF (i.e. 3.5 L), contained within the
vasculature
• transcellular fluids (TCF) (i.e.1 L), which are secreted fluids that are
separated from the plasma by an epithelial layer (pleural, peritoneal,
gastrointestinal fluids, CSF, intra-ocular fluids, sweat, saliva and bile),
the so-called ‘third space’
> Total blood volume (TBV) consists of plasma and red cell volume, and
is 5–6 L.

Table 30.1  Fluid compartments for a 70 kg male

Compartment % BW % TBW % ECF Volume (L)

TBW ±60 42
ICF 40 67 28
ECF 20 33 14
• ISF 15 10.5 75 9.5
• plasma 5  3.5 25 3.5
• TCF <1 1.0

Compare the adult with the Table 30.2  Comparison of neonatal and adult fluid compartments
neonate fluid compartments.
Compartment Adult Neonate
TBW (% BW) 60 75–85
Fat (% BW) 20–25 5–15
ECF (% BW) 20 30–45
ICF (% BW) 40 <40
Plasma (% BW) 5 5
Note that in premature babies, ECF exceeds ICF.

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 01 PHYSIOLOGY
Describe the cell membrane
and capillary barriers and the
movement of molecules across
them.
How are the body compartment
volumes estimated?
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Cell membrane: this is a selectively permeable membrane that separates
the intracellular contents from the extracellular environment. It consists
of a phospholipid bilayer with hydrophobic heads on either side of the
membrane and hydrophilic tails facing inwards. This arrangement allows fat-
soluble molecules to diffuse easily across the membrane, but prevents the
movement of polar molecules (amino acids, nucleic acids, carbohydrates,
proteins and ions), which is enabled by transmembrane protein complexes
such as pores, channels and gates. The movement of substances can be
either ‘passive’ or ‘active’, i.e. with or without the expenditure of energy. The
transport mechanisms involved include:
> Passive osmosis and diffusion across a concentration gradient:
small molecules/ions such as CO2 and O2 can move across the plasma
membrane by diffusion. The concentration gradient also sets up an
osmotic flow for water.
> Transmembrane protein channels and transporters: molecules
such as sugars, amino acids and certain products of metabolism may:
• Passively diffuse through protein channels (such as aquaporins in the
case of water) in facilitated diffusion, or
• Actively be pumped across the membrane by transmembrane
transporters.
> Endocytosis: cell membrane creates a vesicle, capturing the substance
and internalising it, e.g. phagocytosis. This is a form of active transport.
> Exocytosis: the membrane of a vesicle fuses with the plasma
membrane, expelling its contents into the extracellular environment, e.g.
hormones and enzymes.
Capillary wall: consists of a single layer of simple squamous epithelium
and a basement membrane (basal lamina). Capillaries connect arteries and
veins within organ systems across a branched network called the capillary
bed. The more metabolically active an organ is, the larger the capillary bed.
Small molecules (<3 nm) such as water, oxygen and carbon dioxide cross
the capillary wall through the space between cells (paracellular transport),
while larger molecules (>3 nm) such as albumin and other large proteins
pass through transcellular transport carried inside vesicles. There are three
main types of capillaries:
> Continuous: uninterrupted lining with tight junctions and complete basal
lamina. Allow passive diffusion of lipid-soluble molecules and movement
of small molecules such as water and ions through intercellular clefts.
Skeletal muscle and skin have numerous transport vesicles, whereas
CNS (blood–brain barrier) has few, so sealing the paracellular space.
> Fenestrated: endothelial cells have pores or windows (60–80 nm
in diameter) and a complete basal lamina. Allow a limited amount of
proteins to diffuse. They are located in intestines, pancreas, endocrine
glands and renal glomeruli.
> Sinusoidal: large open-pore (30–40 µm in diameter) capillaries, large
gaps between cell junctions and a discontinuous basal lamina. Allow red
and white blood cells (7.5–25 µm diameter) and serum proteins to pass.
Present in bone marrow, lymph nodes, liver, spleen and adrenal glands.
Dilutional techniques are used to estimate compartment volumes.
An indicator dye is injected into the compartment to be measured. The dye
should distribute throughout that compartment, but remain contained within
it. The concentration of the dye is measured and the mass administered is
known. Thus, using the formula for volume of distribution (Vd = mass of dye/
concentration), the compartment volume can be estimated.
Some compartments are derived (ICF, ISF and TBV).
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 FLUID COMPARTMENTS
Table 30.3  Methods of measurement of fluid compartments

Compartment Characteristic of indicator Indicator

TBW Freely diffusible substance Deuterium oxide
Antipyrine
ECF Substances that do not enter cells Inulin
Thiocyanate
Thiosulphate
ICF TBW – ECF
Plasma Substances confined to plasma Radiolabelled albumin
Evan’s blue dye
Red cell volume Radiolabelled red cells
TBV Plasma volume × 100/(100 – haematocrit)
Interstitial fluid ECF – plasma volume

What factors regulate Water balance governs the ICF, and sodium balance regulates the ECF
body water? compartments. (mnemonic WISE: Water regulates Intracellular; Sodium
regulates Extracellular)
The control of TBW is linked to the secretion of antidiuretic hormone (ADH/
vasopressin) by the posterior pituitary.
ADH is secreted in response to:
> Hyperosmolarity (threshold 1–2%) detected by osmoreceptors in the
hypothalamus, outside the blood–brain barrier. Similarly, osmoreceptors
stimulate thirst
> Volume depletion (ECF) detected by low-pressure baroreceptors in great
veins, atria and pulmonary vessels, and high-pressure baroreceptors in
the carotid sinus and aortic arch (threshold 7% change in volume)
> Angiotensin II (AGII)
> Other: pain, exercise, stress, emotion, nausea and vomiting, standing,
nicotine, morphine, barbiturates, carbamazepine.
ADH secretion is reduced in response to:
> Low osmolarity
> Increased ECF volume
> Alcohol
The renal effects of ADH on water balance include:
> Increased water permeability in cortical collecting tubule (V2 receptors)
> Increased water and urea permeability in medullary collecting tubule
> Increased retention of water
> Reduced urine volume
Other ADH effects include:
> Release of factor 8 by the endothelium (V2)
> Platelet aggregation and degranulation (V1)
> Arteriolar vasoconstriction (V1)
Sodium balance governs the ECF volume (as water passively diffuses across
membranes when sodium is reabsorbed) and is regulated by:
> Dietary sodium intake
> ECF volume (baroreceptors) and ADH secretion
> GFR and tubuloglomerular feedback.
> Renin–angiotensin–aldosterone system:
• Efferent arteriolar vasoconstriction to maintain GFR
• Direct sodium reabsorption
• Secretion of aldosterone from adrenal cortex
• Increased ADH
• Increased thirst (water retention)
• Negative feedback on renin release

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What is the effect of a sudden IV
infusion of 5% dextrose?
What is the effect of an IV infusion
of 1 L 0.9% saline solution?
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> Aldosterone and other adrenocortical hormones:
• Reabsorption of NaCl (30–90 minute latent period)
• Excretion of K+
• Secretion of H+
• Accompanied by changes in ADH.
> Rate of tubular secretion of K+ and H+
> Atrial natriuretic peptide (ANP) and other natriuretic hormones:
• Secreted by atrial myocytes in response to atrial stretch due ECF
expansion (from high NaCl intake or IV infusion of saline)
• Actions include natriuresis (by an increase in GFR and tubular
excretion of sodium), reduction in BP (by reduced responsiveness of
vascular smooth muscle to vasoconstrictors) and reduced secretion of
aldosterone, ADH, renin and consequently AGII.
> 5% dextrose is a hypotonic solution and therefore gets distributed
equally throughout all the fluid compartments. It can be thought of as
water because the dextrose gets metabolised leaving behind water,
which diffuses freely.
> Intravascular volume will thus increase only minimally (by approximately
70 mL if 1 L was administered).
> This is less than the 7–10% threshold needed to stimulate the
baroreceptors.
> However, the plasma osmolarity will decrease enough to stimulate
the osmoreceptors (1–2% threshold) and therefore ADH secretion will
decrease, increasing renal water excretion.
This is an isotonic solution and results in ECF expansion, diuresis and
natriuresis as explained below:
> Sodium will diffuse from areas of high concentration to those of lower
concentrations and will be followed by water
> The cell membrane is impermeable to sodium and thus the distribution
of the saline (water) administered will be confined to the ECF with 75%
(750 mL) in the ISF and 25% (250 mL) in the plasma
> The plasma expansion from 3.5 to 3.75 L is enough (7% increase) to be
detected by the baroreceptors and ADH secretion is reduced
> The increased sodium load and ECF expansion will cause an increase in
ANP secretion and natriuresis, and inhibition of the renin–angiotensin–
aldosterone system.
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