Body fluids

Course: Physiology
Prepared by
Dr. A. Chebotarova, MD, PhD
 INTENDED LEARNING OBJECTIVES
To the end of the lecture students must be able to:
1. Contrast the following units used to describe concentration: mM, mEq/l, mg/dl, mg%.
2. List the typical value and normal range for plasma Na+, K+, H+ (pH), HCO3-, Cl-, Ca2+, and glucose, and the typical
intracellular pH and concentrations of Na+, K+, Cl-, Ca2+, and HCO3-.
3. Describe the polar structure of water, and explain how the formation of hydrogen bonds permits the
dissociation of salts (such as NaCl), saccharides, and other polar molecules. Contrast the definitions of
hydrophobic and hydrophilic related to water polarity.
4. Given the body weight and percent body fat, estimate the a) total body water, b) lean body mass, c)
extracellular fluid volume, d) intracellular fluid volume, e) blood volume, and f) plasma volume. Identify normal
extracellular fluid (plasma) osmolarity and concentrations of Na+, K+, Cl-, HCO3-, proteins, creatinine, and urea,
and contrast these values with those for intracellular fluids.
5. Contrast the movement between intracellular and extracellular compartments caused by increases or decreases
in extracellular fluid osmolality.
6. Given the composition and osmolality of a fluid, identify it as hypertonic, isotonic, or hypotonic. Predict the
change in transcellular fluid exchange that would be caused by placing a red blood cell in solutions with varying
tonicities.
7. Identify major routes and normal ranges for water intake and loss, and predict how changes in intake and loss
affect the distribution of total body water.
8. Demonstrate the ability to use the indicator dilution principle to measure plasma volume, blood volume,
extracellular fluid volume, and total body water, and identify compounds used to measure each volume
9. Predict the changes in extracellular volume, extracellular osmolality, intracellular volume, and intracellular
osmolality caused by infusion of three liters of 0.9% NaCl, 0.45% NaCl
10. Identify the site of erythropoietin production, the adequate stimulus for erythropoietin release, and the target
tissue
Dr. Alisa for erythropoietin
Chebotarova, MD, PhD action.
 Introduction
• A significant percentage of the human body is water,
which includes intracellular and extracellular fluids.
• It makes up a significant percentage of the total
composition of a body. Water is a necessary
component to support life for many reasons. All cells in
the human body are made mostly of water content in
their cytoplasm.
• Water is the medium of the internal environment and
constitutes a large percentage of the body weight.
• The maintenance of a relatively constant volume and a
stable composition of the body fluids is essential for
homeostasis
• Some of the most common and important problems in
clinical medicine arise because of abnormalities in the
control systems that maintain this constancy of the
body fluids.
Dr. Alisa Chebotarova, MD, PhD
 Fluid Intake and Output
• Daily Intake of Water:
• 1. water is ingested in the form of liquids or water in
the food - 2100 ml/day
• 2. water is synthesized in the body as a result of
oxidation of carbohydrates - 200 ml/day.
• Daily Loss of Body Water:
• 1. Insensible Water Loss (independently of sweating) -
700 ml/day:
• evaporation from the respiratory tract
• diffusion through the skin
• 2. Fluid Loss in Sweat - 100 ml/day – 1-2 L/day
• 3. Water Loss in Feces - 100 ml/day
• 4. Water Loss by the Kidneys – 1500 ml/day
Dr. Alisa Chebotarova, MD, PhD
 Overall Water Content
• The total amount of water in a human of average weight (70 kilograms) is
approximately 40 liters
• In a newborn infant, this may be as high as 79 percent of the body weight, but it
progressively decreases from birth to old age, with most of the decrease
occurring during the first 10 years of life.
• Obesity decreases the percentage of water in the body, sometimes to as low as
45 percent.
• The water in the body is distributed among various fluid compartments that are
interspersed in the various cavities of the body through different tissue types.

Dr. Alisa Chebotarova, MD, PhD

 Body Fluid Compartments ✭
• The total body fluid - 50%–70% of body weight, average value - 60%:
• Women - lower percentages of water than men (because women have the higher
percentage of adipose tissue).

• 1. the extracellular fluid (ESF) - approximately 1/3 of total body water (30-40%
of of total body water), or 20% of body weight
• interstitial fluid (ISF) - 3/4 of the extracellular fluid (25% of total body water)
• blood plasma - 1/4 of the extracellular fluid (5-10% of total body water)
• transcellular fluids (synovial, peritoneal, pericardial, intraocular cerebrospinal fluids)
• 2. the intracellular fluid (ICF) - approximately 2/3 of total of body water (60-
70% of total body water), or 40% of body weight

Dr. Alisa Chebotarova, MD, PhD

 Body Fluid Compartments ✭

Dr. Alisa Chebotarova, MD, PhD

 Body Fluid Compartments
- 60-70% - 30-40%

TBW

25 %
5-10 %

cell membrane – capillary membranes –

barriers for Na+ barriers for plasma proteins

Dr. Alisa Chebotarova, MD, PhD serve as barriers

 Intracellular Fluid
• The intracellular fluid is separated from the
extracellular fluid by a cell membrane that is
highly permeable to water but not to most of
the electrolytes in the body.

• The water inside the cells in which all

intracellular solutes are dissolved
• the major cations “+” are potassium (K+) and
magnesium (Mg2+)
• the major anions “-” are proteins and organic
phosphates - adenosine triphosphate (ATP),
adenosine diphosphate (ADP), and adenosine
monophosphate (AMP)
Dr. Alisa Chebotarova, MD, PhD
 Extracellular Fluid
• The water outside the cells
• the major cation of ECF is sodium (Na+)
• the major anions are chloride (Cl−) and bicarbonate (HCO3−)

Plasma is the aqueous component of blood. Interstitial fluid is an ultrafiltrate of plasma

It is the fluid in which the blood cells are
suspended - 55% of blood volume
Plasma proteins constitute about 7% of
plasma by volume
Blood cells constitute 45% of blood volume -
hematocrit 0.45 (0.48 in males, 0.42 in
females)
It has nearly the same composition as
plasma, excluding plasma proteins and
blood cells.
Pores in the capillary wall permit free
passage of water and small
solutes

Dr. Alisa Chebotarova, MD, PhD

 Body fluids pH:

• The negative logarithmic term that is used to express H+ concentration.

• pH decreases as the concentration of H+ increases

• pH increases as the concentration of H+ decreases

Dr. Alisa Chebotarova, MD, PhD

 Composition of Body Fluid Compartments
• Sample problem.
• Two men, Subject A and Subject B, have disorders that cause excessive acid production in the body.
The laboratory reports the acidity of Subject A’s blood in terms of [H+] and the acidity of Subject B’s
blood in terms of pH. Subject A has an arterial [H+] of 65 x 10−9 Eq/L, and Subject B has an arterial
pH of 7.3.
Which subject has the higher concentration of H+ in his blood?
• Solution:
Subject A pH = - log 10 [H+]
pH = - log 10 (65 x 10−9 Eq/L) = - log 10 (6,5 x 10−8 Eq/L) =
log 10 6,5 = 0,81
log 10 10−8 - 8,0
log 10 6,5 x 10−8 = 0,81 + (- 8,0) = 7,19
pH = -(-7,19) = 7,19
• Subject A has a blood pH of 7,19 computed from the [H+], and Subject B has a reported blood pH of
7,3.
•Dr.Subject A has a lower
Alisa Chebotarova, MD, PhDblood pH, reflecting a higher [H ] and a more acidic condition.
+
 Measuring Volumes of Body Fluid
Compartments
• Measured by the dilution method:
• a marker substance is distributed in the body fluid compartments according to its physical
characteristics.
• Steps:
• 1. Identification of an appropriate marker substance
• 2. Injection of a known amount of the marker substance
• 3. Equilibration and measurement of plasma concentration
• 4. Calculation of the volume of the body fluid compartment

Dr. Alisa Chebotarova, MD, PhD

 Measuring Volumes of Body Fluid
Compartments ✭
• 1. Identification of an appropriate marker substance
• a large molecular weight substances cannot cross cell membranes, distributed in ECF but
not in ICF
• some substances will be distributed everywhere that water is distributed and it is used as a
marker for total body water.
• The markers for total body water are substances that are distributed wherever
water is found:
• isotopic water (Deuterium oxide - D2O and tritiated water - THO)
• antipyrine - lipid soluble, has the same volume of distribution as water does
•
• The markers for ECF volume are substances that distribute throughout the ECF
but do not cross cell membranes:
• mannitol and inulin - large molecular weight sugars
• sulfate - large molecular weight anion
Dr. Alisa Chebotarova, MD, PhD
 Measuring Volumes of Body Fluid
Compartments ✭
• 1. Identification of an appropriate marker substance
• Markers for plasma volume are substances that distribute in plasma but not in
interstitial fluid:
• radioactive albumin
• Evans blue - a dye that binds to albumin

• ICF and interstitial fluid volumes cannot be measured directly because there are
no unique markers for these compartments

Dr. Alisa Chebotarova, MD, PhD

 Measuring Volumes of Body Fluid
Compartments
• 2. Injection of a known amount of the marker substance:
• The amount of marker substance injected into the blood is measured in
milligrams (mg), millimoles (mmol), or units of radioactivity (millicuries)

• 3. Equilibration and measurement of plasma concentration:

• The marker is allowed to equilibrate in the body fluids,
• correction is made for any urinary losses during the equilibration period,
• the concentration of the marker is then measured in plasma

Dr. Alisa Chebotarova, MD, PhD

 Measuring Volumes of Body Fluid
Compartments ✭
• 4. Calculation of the volume of the body fluid compartment:
• Because the amount (mg) of marker present in the body is known (amount
originally injected minus the amount excreted in urine) and the concentration
(mg/ml) is measured, the volume of distribution of the marker substance can be
calculated as follows:

Dr. Alisa Chebotarova, MD, PhD

 Measuring Volumes of Body Fluid
Compartments ✭

D2O, THO

ICF volume = TBW - ECF

mannitol, inulin, sulfate
radioactive albumin,
Evans blue

Dr. Alisa Chebotarova, MD, PhD ISF volume = ECF - Plasma volume
 Measuring Volumes of Body Fluid
Compartments
• Sample Problem:
• A 65-kg man is participating in a research study for which it is necessary to know
the volumes of his body fluid compartments. To measure these volumes, the man
is injected with 100 mCi of D2O and 500 mg of mannitol. During a 2-hour
equilibration period, he excretes 10% of the D2O and 10% of the mannitol in his
urine. Following equilibration, the concentration of D2O in plasma is 0.213
mCi/100 mL and the concentration of mannitol is 3.2 mg/100 mL

• What are his total body water, his ECF volume, and his ICF volume? Is the man’s
total body water appropriate for his weight?

Dr. Alisa Chebotarova, MD, PhD

 Measuring Volumes of Body Fluid
Compartments
• Solution:
• Amount of D2O injected = 100 mCi
for measuring of TBW
• Amount of D2O excreted = 10% of injected = 10% of 100 mCi = 10 mCi

• Amount of mannitol injected = 500 mg for measuring of ECF

• Amount of mannitol excreted 10% of injected = 10% of 500 = 50 mg

• ICF volume cannot be measured directly, but it can be calculated as the difference between
total body water and ECF volume

Dr. Alisa Chebotarova, MD, PhD

 Measuring Volumes of Body Fluid
Compartments
• Solution:
Amount of D2O injected !Amount of D2O excreted
• TBW = Concentra]on of D2O in plasma =

100 mCi – 10 mCi 100 mCi – 10 mCi 90 mCi

= = = = 42.3 L
0.213 mCi/100ml 2.13 mCi/L 2.13 mCi/L
Amount of mannitol injected !Amount of mannitol excreted
• ECF = Concentra]on of mannitol in plasma =
500 mg – 50 mg 500 mg – 50 mg 450 mg
= = = = 14.1 L
3.2 mg/100ml 32 mg/1 L 32 mg/L
• ICF = TBW – ECF = 42.3 L – 14.1 L = 28.2 L

• The man’s total body water is 42.3 L, which is 65.1% of his body weight (42.3 L is approximately
42.3 kg; 42.3 kg/65 kg = 65.1%). This percentage falls within the normal range of 50%–70% of
Dr.body weight. MD, PhD
Alisa Chebotarova,
 Osmosis
• The distribution of fluid is determined by the osmotic
movement of water.
• Osmosis is the diffusion of water across a Effective osmole: If a solute doesn’t easily cross a
semipermeable or selectively permeable membrane. membrane, then it is an “effective” osmole for that
• Water diffuses from a region of higher water compartment, it creates an osmotic force for
concentration to a region of lower water
concentration. water:
• The concentration of water in a solution is • plasma proteins do not easily cross the capillary
determined by the concentration of solute. membrane - effective osmoles for the vascular
• The greater the solute concentration is, the lower the compartment
water concentration will be.
• Osmolarity - concentration of particles per liter of • Na+ doesn’t penetrate the cell membrane, but it
solution
does cross the capillary membrane - effective
• Osmolality - concentration of particles per kg of osmole for the extracellular compartment
solvent

Osmolarity - Concentration of particles (mOsm/L)

g - Number of particles per mole in solution (Osm/mol)
Dr. Alisa Chebotarova, MD, PhD C - Concentration (mmol/L)
 Plasma osmolarity
• The normal value for osmolarity of the body fluids is 290 mOsm/L, or, for
simplicity, 300 mOsm/L.
• Plasma osmolarity can be estimated from the plasma Na+ concentration, plasma
glucose concentration, and blood urea nitrogen (BUN), as these are the major
solutes of ECF and plasma
• In the extracellular fluid, the main dissolved substance that cannot penetrate the cell
membrane is sodium
• Glucose penetrates membranes slowly and contributes some osmotic effect, particularly
with hyperglycemia.
• Urea easily penetrates most membranes, but not all (blood-brain barrier, sections or
nephron).
• Some include urea in the ECF effective osmolarity; others ignore it.

Dr. Alisa Chebotarova, MD, PhD

 Plasma osmolarity ✭ ✭

The Na+ concentration is multiplied by 2 because Na+ must be balanced by an equal

concentration of anions. (In plasma, these anions are Cl− and HCO3−)
The glucose concentration in mg/dL is converted to mOsm/L when it is divided by 18.
The BUN in mg/dL is converted to mOsm/L when it is divided by 2.8.

Dr. Alisa Chebotarova, MD, PhD

 Plasma osmolarity
• The osmolar gap is defied as the difference between the measured osmolality
and the estimated osmolality
• Normal ≤ 15

• If this gap falls within an acceptable range, then it is assumed that sodium,
glucose, BUN are the major dissolved ions and molecules in the serum.
• If the calculated gap is above an acceptable range, then it is an indication that
there is something else dissolved in the serum that is producing an osmol gap,
which can be a major clue in determining what is ailing the patient:
• Alcohols (ethanol intoxication, methanol ingestion, ethylene glycol ingestion, isopropyl
alcohol ingestion, propylene glycol toxicity, acetone ingestion)
• Sugars (mannitol, sorbitol)
• Lipids (Hypertriglyceridemia)
• Proteins (Hypergammaglobinemia)
Dr. Alisa Chebotarova, MD, PhD
 Composition of Body Fluid Compartments
• Substances aren’t in equilibrium, but there is a balance
• there is a difference between the basic constituents of the body-fluid compartments.
This means that homeostasis is not about reaching equilibrium, but about
maintaining a steady-state. Since the system is not necessarily in equilibrium energy
expenditure is required to maintain a steady state.

Dr. Alisa Chebotarova, MD, PhD

 Water Content Regulation
• Body water is regulated largely by the renal and neuro-endocrine systems. Water
content regulation is one of the most important parts of homeostasis due to its
influence on blood pressure and cardiac output.
• Much of this regulation is mediated by hormones, including anti-diuretic
hormone (ADH), renin, angiotensin II, aldosterone, and atrial natriuretic peptide
(ANP).

Dr. Alisa Chebotarova, MD, PhD

 Shifts of Water Between Body Fluid
Compartments

Dr. Alisa Chebotarova, MD, PhD

 Shifts of Water Between Body Fluid
Compartments
• In the steady state, intracellular osmolarity is equal to extracellular osmolarity -
osmolarity is the same throughout the body fluids.
• To maintain this equality, water shifts freely across cell membranes.
• If a disturbance occurs to change the ECF osmolarity, water will shift across cell
membranes to make the ICF osmolarity equal to the new ECF osmolarity.
• After a brief period of equilibration (while the shift of water occurs), a new steady state will
be achieved and the osmolarities again will be equal.

• Solutes such as NaCl and NaHCO3 and large sugars such as mannitol are the ECF
compartment (do not readily cross cell membranes), if one ingests a large
quantity of NaCl, that NaCl will be added only to the ECF compartment and the
total solute content of the ECF will be increased.
Dr. Alisa Chebotarova, MD, PhD
 Darrow- Yannet Diagram
Osmolarity (Concentration of Solute) The Darrow-Yannet
diagram is a standard
model to display changes
in body osmolarity and ECF
versus ICF volume
ICF Volume ECF Volume Volumes are on the X-axis
2/3 1/3 Body osmolarity on the Y-
axis
Water always equilibrates
Volume Volume across the cell membrane.
Extracellular volume - When there is a net gain of fluid by the body, this compartment always enlarges. A net loss of body fluid
decreases extracellular volume.
Intracellular volume - This varies with the effective osmolality of the extracellular compartment. Solutes and fluids enter and
leave the extracellular compartment first (sweating, diarrhea, fluid resuscitation, etc.). Intracellular volume is only altered if
extracellular osmolality changes
Concentration of solutes - At steady-state, the intracellular concentration of water equals the extracellular concentration of
water.
Dr. If Chebotarova,
Alisa ECF osmolalityMD,
increases,
PhD cells lose water and shrink. If ECF osmolality decreases, cells gain water and swell.
 Shifts of Water Between Body Fluid
Compartments
• To understand the events that occur in some disturbances, a three-step approach
should be used:
1. identify any change occurring in the ECF:
• was solute added to the ECF?
• was water lost from the ECF?

2. decide whether that change will produce an increase, a decrease, or no change in ECF
osmolarity

3. if there is a change in ECF osmolarity, determine in which direction water must shift
• Into or out of the cells
• If there is no change in ECF osmolarity, no water shift will occur !!!!!
• If there is a change in ECF osmolarity, then a water shift must occur !!!!!

Dr. Alisa Chebotarova, MD, PhD

 Disturbances of body fluids:
Some definitions
• Volume contraction means a decrease in ECF volume.
• Volume expansion means an increase in ECF volume.
• The terms isosmotic, hyperosmotic, and hyposmotic refer to the osmolarity of
the ECF.
• an isosmotic disturbance means that there is no change in ECF osmolarity;
• a hyperosmotic disturbance means that there has been an increase in ECF osmolarity;
• a hyposmotic disturbance means that there has been a decrease in ECF osmolarity.

Dr. Alisa Chebotarova, MD, PhD

 Isosmotic (isotonic) Volume Contraction ✭
• Diarrhea (except infant)
• Vomiting
• Hemorrhage
• Patient shows loss of extracellular volume with no change in osmolality.

• Since extracellular osmolality is the same, then intracellular volume is

unchanged.
• The decrease in ECF volume means that blood volume (a component of ECF) also is
reduced, which produces a decrease in arterial pressure
• Increased hematocrit and increased plasma protein concentration

• In the new steady state, ECF volume decreases and the osmolarities of ECF and
ICF are unchanged
Dr. Alisa Chebotarova, MD, PhD
 Isosmotic (isotonic) Volume Contraction ✭
Diarrhea (except infant) Osmolarity (Concentration of Solute)
Vomiting ECF Volume ↓
Hemorrhage After
Osmolarity - no change
ICF - no change

ICF ECF Increased hematocrit

and increased plasma
protein concentration

Before
Dr. Alisa Chebotarova, MD, PhD
 Isosmotic (isotonic) Volume Contraction ✭
• In diarrhea:

• one loses a large volume of fluid from the gastrointestinal tract. The osmolarity of
the fluid lost is approximately equal to that of the ECF - it is isosmotic
• there is no need for a fluid shift across cell membranes and ICF volume remains
unchanged

Dr. Alisa Chebotarova, MD, PhD

 Isosmotic (isotonic) Volume Contraction
• Compensation:

• Loss of extracellular volume -> ↑ RAAS and ↑ ADH

Dr. Alisa Chebotarova, MD, PhD

 Hyperosmotic Volume Contraction ✭
• Inadequate water intake
• Water Deprivation
• Sweating
• Diabetes Insipidus (Hypotonic water loss from the urine)

• Patient shows loss of extracellular volume with rise in osmolality -> loss of
intracellular volume.
• net loss of water - greater loss of water than osmoles
• the plasma protein concentration is increased but the hematocrit is unchanged:
• Water moves from ICF to ECF, means moves from RBC either

Dr. Alisa Chebotarova, MD, PhD

 Hyperosmotic Volume Contraction ✭
Water Deprivation Osmolarity (Concentration of Solute)
Sweating ECF Volume ↓
diabetes insipidus
Osmolarity - ↑
ICF volume - ↓
the plasma protein
ICF ECF concentration is
increased but the
hematocrit is
unchanged:
Water moves from
ICF to ECF, means
moves from RBC
Before either
Dr. Alisa Chebotarova, MD, PhD
 Hyperosmotic Volume Contraction ✭
• In excessive sweating:

• sweat is hyposmotic relative to ECF - hyposmotic fluid is lost from the ECF, ECF
volume decreases and ECF osmolarity increases.
• ECF osmolarity is transiently higher than ICF osmolarity, and this difference in
osmolarity causes water to shift from ICF into ECF.
• Water will flow until ICF osmolarity increases and becomes equal to ECF
osmolarity
• This shift of water out of cells decreases ICF volume.

Dr. Alisa Chebotarova, MD, PhD

 Hyperosmotic Volume Contraction
• Compensation:

• Decreased extracellular volume -> ↑ RAAS.

• This drop in extracellular volume -> ↑ ADH (if possible), as does the rise
osmolarity.
• These setting would be a strong stimulus for ADH.

Dr. Alisa Chebotarova, MD, PhD

 Hyposmotic Volume Contraction ✭
• Adrenal Insufficiency:
• Lack of mineralcorticoids - aldosterone

• net loss of hypertonic fluid - more osmoles lost than fluid

• Patient shows decrease in extracellular volume and osmolality -> increase in
intracellular volume.
• The rise in intracellular volume is the result of the decreased ECF osmolality

• In the new steady state, both ECF and ICF osmolarities will be lower than
normal and equal to each other, ECF volume will be decreased and ICF volume
will be increased
Dr. Alisa Chebotarova, MD, PhD
 Aldosterone ✭
• One of the fundamental functions of aldosterone is to increase sodium
reabsorption in principal cells of the kidney.
• This reabsorption of sodium plays a key role in regulating extracellular volume.
• Aldosterone also plays an important role in regulating plasma potassium -
increases the secretion of this ion in principal cells.
• The 2 primary factors that stimulate aldosterone release are:
• Plasma angiotensin II (Ang II)
• Plasma K+

Dr. Alisa Chebotarova, MD, PhD

 Hyposmotic Volume Contraction ✭
• In adrenal insufficiency:

• One has a deficiency of several hormones including aldosterone, a hormone that

normally promotes Na+ reabsorption in the distal tubule and collecting ducts.
• excess NaCl is excreted in the urine -> decreased ECF volume and osmolarity
• water reabsorption does not depend exclusively on Na+ reabsorption, net loss of salts
exceeds the loss of water
• water shifts from ECF to ICF until ICF osmolarity decreases to the same level as
ECF osmolarity

Dr. Alisa Chebotarova, MD, PhD

 Hyposmotic Volume Contraction ✭
Adrenal Insufficiency: Osmolarity (Concentration of Solute)
Lack of aldosterone ECF Volume ↓
Osmolarity - ↓
ICV - ↑

ICF ECF

Before

Dr. Alisa Chebotarova, MD, PhD

 Hyposmotic Volume Contraction
• Compensation:

• Although the only cause to consider is adrenal insufficiency, if this scenario were
to occur, then the drop in extracellular volume -> ↑ RAAS.
• It is difficult to predict what happens to ADH in this setting.
• The drop in extracellular volume stimulates, but the fall in osmolality inhibits, thus it
depends upon the magnitude of the changes.

Dr. Alisa Chebotarova, MD, PhD

 Isosmotic Volume Expansion ✭
• Infusion of 0.9% NaCl
• drinking significant quantities of an isotonic fluid
• infusion of an isotonic colloid
• excess aldosterone (both water and salts will be reabsorbed)
• Patient shows increase in extracellular volume with no change in osmolality or
intracellular volume
• net gain of isotonic fluid - equal increase fluid and osmoles
• In infusion of isotonic NaCl:
• all of the isotonic NaCl solution is added to the ECF
• increase in ECF volume but no change in ECF osmolarity
• no shift of water between ICF and ECF because there is no difference in osmolarity
between the two compartments.
•Dr.plasma protein concentration and hematocrit will decrease
Alisa Chebotarova, MD, PhD
 Isosmotic Volume Expansion ✭
Infusion of 0.9% NaCl Osmolarity (Concentration of Solute) ECF Volume ↑
drinking of isotonic fluid
infusion of an isotonic colloid Osmolarity - no change
excess aldosterone ICV - no change

plasma protein
concentration
ICF ECF and hematocrit
will decrease

Before

Dr. Alisa Chebotarova, MD, PhD

 Isosmotic Volume Expansion
• Compensation:

• The rise in extracellular volume inhibits both:

• ↓ RAAS
• ↓ ADH

Dr. Alisa Chebotarova, MD, PhD

 Hyperosmotic Volume Expansion ✭
• High-NaCl intake
• Hypertonic infusion of solutes (saline, mannitol)
• Hypertonic infusion of colloids (dextran)
• Patient shows gain of extracellular volume, increase in osmolality, and a decrease in
intracellular volume
• net gain of solute - increase in osmoles greater than increase in water
• Ingesting dry NaCl:
• increase the total amount of solute in the ECF
• ECF osmolarity increases
• water shifts from ICF to ECF, decreasing ICF volume and increasing ECF volume.
• plasma protein concentration and hematocrit will decrease

• In the new steady state, both ECF and ICF osmolarities will be higher than normal and
equal to each other, ICF volume will decrease and ECF volume will increase.
Dr. Alisa Chebotarova, MD, PhD
 Hyperosmotic Volume Expansion ✭
High-NaCl intake
Hypertonic infusion of solutes
Osmolarity (Concentration of Solute)
ECF Volume ↑
Osmolarity - ↑
ICV - ↓

plasma protein
ICF ECF concentration and
hematocrit will
decrease

Before

Dr. Alisa Chebotarova, MD, PhD

 Hyperosmotic Volume Expansion
• Compensation:

• The rise in extracellular volume -> ↓ RAAS.

• It is difficult to predict what will happen to ADH in this setting.
• The rise in extracellular volume inhibits, but the rise in osmolality stimulates, thus it will
depend upon the magnitude of the changes.
• In general, osmolality is a more important factor, but significant changes in vascular
volume/pressure can exert profound effects.

Dr. Alisa Chebotarova, MD, PhD

 Hyposmotic Volume Expansion ✭
• Syndrome of inappropriate antidiuretic hormone (SIADH)
• Drinking significant quantities of water (polydipsia),
• Drinking significant quantities of a hypotonic fluid,
• Hypotonic fluid infusion (0.45% NaCl in water, dextrose in water)

• Patient shows increase in extracellular and intracellular volumes with a

decrease in osmolality.
• net gain of water - more water than osmoles

• plasma protein concentration is decreased by dilution, the hematocrit is

unchanged
Dr. Alisa Chebotarova, MD, PhD
 Hyposmotic Volume Expansion ✭
SIADH
polydipsia
Osmolarity (Concentration of Solute)
ECF Volume ↑
Drinking of a hypotonic fluid Osmolarity - ↓
Hypotonic fluid infusion
ICV - ↑

ICF ECF plasma protein

concentration
is decreased by
dilution, the
hematocrit is
Before
unchanged
Dr. Alisa Chebotarova, MD, PhD
 ADH (AVP) ✭
• Also called arginine vasopressin (AVP).
• ADH stimulates water reabsorption in principal cells of the kidney via the V2
receptor.
• By regulating water, ADH plays a pivotal role in regulating extracellular osmolality.
• In addition, ADH vasoconstricts arterioles (V1 receptor) and thus can serve as a
hormonal regulator of vascular tone.
• The 2 primary regulators of ADH are:
• Plasma osmolality (directly related): an increase stimulates, while a decrease inhibits
• Blood pressure/volume (inversely related): an increase inhibits, while a decrease
stimulate

Dr. Alisa Chebotarova, MD, PhD

 Hyposmotic Volume Expansion ✭
• In SIADH:

• secretes inappropriately high levels of antidiuretic hormone (ADH), which

promotes water reabsorption in the collecting ducts.
• too much water is reabsorbed and the excess water is retained and distributed
throughout the total body water
• if an extra 3 L of water is reabsorbed by the collecting ducts, 1 L will be added to the ECF
and 2 L will be added to the ICF

Dr. Alisa Chebotarova, MD, PhD

 Hyposmotic Volume Expansion
• Compensation:

• The rise in extracellular volume -> ↓ RAAS and ↓ ADH.

• In addition, the fall in osmolality inhibits ADH.

Dr. Alisa Chebotarova, MD, PhD

 Disturbances of Body Fluids

Dr. Alisa Chebotarova, MD, PhD

 Calculation of fluid volume and osmolarity
after disturbances
Sample Problem
• A woman runs a marathon on a hot September day and drinks no fluids to
replace the volumes lost in sweat. It is determined that she lost 3 L of sweat,
which had an osmolarity of 150 mOsm/L. Before the marathon, her total body
water was 36 L, her ECF volume was 12 L, her ICF volume was 24 L, and her body
fluid osmolarity was 300 mOsm/L. Assume that a new steady state is achieved
and that all of the solute (i.e., NaCl) lost from her body came from the ECF. What
are her ECF volume and osmolarity after the marathon?

58
Dr. Alisa Chebotarova, MD, PhD
 Calculation of fluid volume and osmolarity
after disturbances
Solution:
• Values before the marathon will be called old, and values after the marathon will be called
new. To solve this problem, first calculate the new osmolarity of the total body water because
osmolarity will be the same throughout the body fluids in the new steady state. Then calculate
the new ECF volume using the new, calculated osmolarity.
• To calculate the new osmolarity, calculate the
total number of osmoles in the body after
the fluid is lost in sweat (New osmoles = Old
osmoles − Osmoles lost in sweat). Then
divide the new osmoles by the new total
body water to obtain the new osmolarity.
(Remember that the new total body water is
36 L minus the 3 L lost in sweat.)
59
Dr. Alisa Chebotarova, MD, PhD
 Calculation of fluid volume and osmolarity
after disturbances
Solution:
• To calculate the new ECF volume, assume that all of the solute (NaCl) lost in sweat comes from
the ECF. Calculate the new ECF osmoles after this loss, then divide by the new osmolarity
(previously calculated) to obtain the new ECF volume.

60
Dr. Alisa Chebotarova, MD, PhD
 Calculation of fluid volume and osmolarity
after disturbances
Solution:
• To summarize the calculations in this example, after the marathon the ECF osmolarity increases
to 313.6 mOsm/L because a hyposmotic solution is lost from the body (i.e., relatively more
water than solute was lost in sweat). After the marathon, the ECF volume decreases to 10 L
(from the original 12 L).
• Therefore some, but not all, of the ECF volume lost in sweat was replaced by the shift of water
from ICF to ECF. Had there been no shift of water, then the new ECF volume would have been
even lower (i.e., 9 L).

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Dr. Alisa Chebotarova, MD, PhD