Body Fluid Homeostasis

Water is the molecule of life. The body must

maintain the proper amount of water to dilute
the ions in the bodily fluids to the proper
concentration for the cellular proteins to
function properly to maintain life.
 Assigned Reading for Body Fluid Homeostasis:
UpToDate®: General principles of disorders of
water and sodium balance.
Read at minimum:
Introduction, Definitions and Summary
Know clinical equations for plasma osmolality and tonicity
https://www-uptodate-com.ezproxylocal.library.nova.edu/contents/general-principles-
of-disorders-of-water-balance-hyponatremia-and-hypernatremia-and-sodium-balance-
hypovolemia-and-edema?search=water+balance&topicRef=2298&source=see_link

Additional resources for Body Fluid Homeostasis

• Berne & Levy Physiology. 7th ed.
• Chapter 1 •Osmolarity Versus Osmolality
•Osmosis and Osmotic Pressure

•Tonicity
•Oncotic Pressure
•Specific Gravity
•Concept of Steady-State Balance
•Volumes and Composition of Body Fluid Compartments
•Movement of Water Between Body Fluid Compartments
• Chapter 2 •Composition of Body Fluid Compartments
•Definition and Volumes of Body Fluid Compartments
•Maintenance of Cellular Homeostasis
•Ionic Composition of Cells
•Regulation of Cell Volume
•Membrane Potential Revised 7/28/2019
Learning Objectives: Body Fluid Homeostasis
1. Define homeostasis and the principles of positive and
negative feedback in physiological systems, and identify
select components involved in maintaining water balance.
2. Identify the 3 major body water compartments, their
composition and relative volumes.
3. Identify the physiological range for plasma pH, osmolarity,
calcium ion, sodium ion and potassium ion concentration.
4. Contrast the intracellular and extracellular concentrations
of sodium, potassium, chloride and calcium ions.
5. Define and correctly use the terms concentration, gradient,
diffusion, osmolality, osmosis, osmotic pressure,
semipermeable, tonicity.
6. Differentiate between osmotic pressure and tonicity and
identify what happens to a cell placed in a hypotonic
solution and a hypertonic solution.
7. Determine the osmolality of a solution and explain the role
of the reflection coefficient in determining effective
osmotic pressure.
Learning Objectives: Body Fluid Homeostasis
8. Use the simplified clinical equations to estimate
plasma osmolality and plasma tonicity from
patient clinical laboratory data.
9. Describe how cells respond to changes in cell
volume caused by altered extracellular fluid
tonicity.
10.Predict the effect of the intravenous infusion of
solutions of various osmolality and tonicity on
the body fluid compartments.
11.Describe the role of plasma proteins in retaining
water in the plasma fluid compartment, and how
hypoalbuminemia can result in edema.
 Water
• Water is the medium within which
most of the molecules of life are
suspended or dissolved
• Water is a polar molecule with a
partial positive and a partial
negative side
• Water can form hydrogen bonds
with itself and other polar
molecules
δ- H
O δ+
H
Homeostasis: The regulation of the
internal environment within a
“normal” physiological range
Blood plasma levels
Albumin: 3.5 - 5 g/dL
Calcium: 8.5 - 10.5 mg/dL
Glucose: 70 – 99 mg/dL
Potassium: 3.5 - 5 mEq/L (mM)
Sodium: 135 - 145 mEq/L (mM)
Chloride: 96 - 107 mEq/L (mM)
pH = 7.35 - 7.45
 Protein Structure Determines Function
• The DNA sequence carries the information
for the structure and function of the body
• DNA→RNA→Protein→Structure = Function
• The amino acid sequence (primary
structure) of a protein determines the
secondary, tertiary and quaternary
structure of the protein and the proper
protein structure is required for the
protein to function
• Proteins will not function properly if pH,
ions, and temperature are not maintained
within the proper physiological range
 Acid Base
Balance

Acid-base homeostasis requires the body

to balance the intake and the metabolic
production of acids & bases with their
elimination to maintain a normal arterial
blood pH ranging between 7.35 and 7.45
(35 - 45 nM H+/L)

Significant variations in the hydrogen ion

concentration of body fluids are not
compatible with life
Which best describes a patient
with a blood pH of 7.47?

A. Normal
B. Acidemia
C. Alkalemia
D. Acidosis
E. Alkalosis
 Define and understand the terms …
[plasma ion concentrations]
• pH = - log10 [H+] = log10 (1/[H+])
• Physiological pH = 7.35 - 7.45
• Acidemia = high [H+]; pH < 7.35
• Alkalemia = low [H+]; pH > 7.45
• Hypernatremia = high [Na+] >145
• Hyponatremia = low [Na+] <135
• Hyperkalemia = high [K+] >5.5
• Hypokalemia = low [K+] <3.5 mM/L
 Water Balance
Input = Output

=
Water gain Water loss
Drinking & Food ~2200 mL Urination ~1500 mL
Metabolism ~300 mL H2O Defecation & Salivation
+ 24 Moles CO2 ~100 mL
Respiration, Sweat & Tears
~900 mL

Input Output
~2500 mL/ 70 Kg ~2500 mL/ 70 Kg

The body controls water balance primarily by

regulating the extracellular fluid osmolality
serum osmolality reference range 275–295 mOsm/kg***

*** NBOME Item-Writing Guide: Reference Range for Osmolality, serum

What is the osmolality of a
100 mM glucose solution?

A.100 mOsmol/Kg
B.200 mOsmol/Kg
C.300 mOsmol/Kg
D.400 mOsmol/Kg
 What is the osmolarity of a
100 mM sodium chloride solution?

A.100 mOsmol/L
B.188 mOsmol/L
C.200 mOsmol/L
D.300 mOsmol/L
E.400 mOsmol/L
Osmolarity = concentration × number of dissociable particles

Examples
Formula weight (FW) of Glucose = 180.0 g/mole
18.0 g glucose/L = 100 mM glucose
100 mOsm/L

NaCl FW = 58.5 g/mole

5.85 g NaCl/L = 100 mM NaCl =
100 mEq/L Na+ & 100 mEq/L Cl-
200 mOsm/L
A 100mM sodium chloride solution has twice the
osmolality of a 100mM glucose solution because there
are twice the number of molecules in the solution.
In reality, 100 mM NaCl = 188 mOsmol/kg H2O, because
NaCl does not completely dissociate in water.
The NaCl value for n is 1.88 rather than 2.
 Homeostasis
• “Set point” (osmolality)
• Sensor that monitors
deviations from set point Water
• Effector signals
Balance
• Effector organs
• Sensitivity (deviation input = output
tolerated)
Modified from: Fig. 2.1 Berne &
Levy Physiology, 7th Ed., 2018
Magnocellular neurons of the hypothalamus receive information about
ECF osmolality and blood pressure and will produce & release
vasopressin (ADH) into the blood vessels of the posterior pituitary to
help maintain osmolality within a narrow physiological range

Vasopressin (ADH) circulates through

the blood and acts mainly on the
kidney to increase water reabsorption Modified from: Fig. 35.3 Berne &
Levy Physiology, 7th Ed., 2018
 Water and Na+ balance
• Proper fluid volume and serum osmolality are
essential for normal cellular function and are
tightly regulated in the human body
• Water balance determines the serum Na+
concentration, and Na+ balance determines the
bodies water volume status
• The kidney regulates water excretion through a
hypothalamic feedback mechanism to maintain a
relatively constant serum osmolality (275 - 290
mOsm/kg) despite day-to-day variations in water
intake
• Serum osmolality is primarily determined by the
serum Na+ concentration which is regulated by the
kidney and complex neural and endocrine
mechanisms to maintain a narrow physiological
range (135 - 145 mEq/L)
 Water Balance
• The hypothalamus receives input from
sensors that monitor osmolality and blood
pressure
• The hypothalamus can stimulate thirst to
regulate water intake and it can regulate
water output by the kidneys by regulating
the release of antidiuretic hormone (ADH;
arginine vasopressin) and by activating
the renin – angiotensin – aldosterone
system (RAAS)
• Several tissues have the ability to sense
excess extracellular fluid volume and
release natriuretic hormones (ANP, BNP,
…) to increase water output
 Water Balance
• In order to maintain proper fluid balance,
the kidney has the ability to excrete either
a dilute urine to eliminate excess water, or
a concentrated urine to conserve water
• When the body needs to conserve water,
antidiuretic hormone (vasopressin) acts on
the kidney to increase water reabsorption
from the filtrate and to excrete a small
volume of concentrated urine
• When the body needs to eliminate excess
water, antidiuretic hormone (vasopressin)
secretion is suppressed and the kidney
excretes an increased volume of dilute
urine
 Sympathetic Nervous System
(SNS) Innervation of the Kidney
• The kidney receives extensive innervation by the
SNS; norepinephrine (and epinephrine) affect
several aspects of renal function
• SNS regulates renal blood flow; vasoconstriction
of interlobar, arcuate, and interlobular arteries,
afferent & efferent arterioles
• SNS stimulation of renin release from
juxtaglomerular (granular) cells; activation of
RAAS
• SNS enhances Na+ reabsorption by the PCT,
ascending limb of the loop of Henle, DCT
Clinical note 1: beta blockers can reduce renin release
Clinical note 2: dopamine produces renal vasodilation and
can be used to increase systemic blood pressure without
compromising renal blood flow
 Hormones regulating blood
pressure and blood volume
Hormone Blood Vessels Kidney Blood pressure
and volume
Natriuretic Dilation Decreased Na+ Decreased
Peptides and water
(ANP, BNP) retention
Angiotensin II Constriction Increased Na+ Increased
and water
retention
Aldosterone Increased Na+ Increased
and water
retention
Vasopressin Constriction Increased Increased
(ADH) water
retention
 Body Compartments
[70 Kg lean male, ~60% of body weight is water]

Interstitial 1/3 Total Intracellular

Fluid (IF) body water Fluid (ICF)
16% of body weight Extracellular 40% of body weight
(~10 liters) Fluid (ECF) (~28 liters)

Plasma 2/3 Total

4% of body weight body water
(~2½ liters) IF
P
ICF
Adipose tissue & Fat
cell membranes
~3-30% of body
Protein
weight
+ other

Body Weight x 0.6 = TBW = 1/3 ECF + 2/3 ICF

 Body Compartments
Fluid compartments - hydrophilic
• Intracellular fluid – inside cells
• Extracellular fluids – outside cells
– Interstitial fluid
– Blood Plasma
• Transcellular fluids (CSF, others)
Lipid compartments - hydrophobic
• Cell membranes
• Adipose tissues (body fat)
 What is the approximate total
body water volume of a 70 kg,
25 year-old normal healthy
male?
A. 22 L
B. 32 L
C. 42 L
D. 52 L
E. 62 L
 What is the approximate
intracellular fluid volume of a 70
kg, 25 year-old normal healthy
male?
A. 18 L
B. 28 L
C. 42 L
D. 38 L
E. 8 L
 TBW = 0.6 x BW
ICF = 0.4 x BW
ECF = 0.2 x BW

ECF is separated from ICF

by the plasma membranes

Interstitial fluid is separated

from plasma by the capillary
endothelium
Fig. 2.2 Berne & Levy Physiology, 7th Edition, 2018
 Body Water Compartments
70 Kg lean male {~60% total body water (TBW)}
Body Weight x 0.6 = TBW
Body Weight x 0.4 = ICF
2/3
Body Weight x 0.2 = ECF Intracellular
1/3 Extracellular Fluid Fluid (ICF)
(ECF) ~ 20% body weight
~40% of
Interstitial body weight
Fluid (IF) (~25 liters)

Cell plasma membrane

Plasma
~16% of
Endothelium

~4% of body body (~2 liters inside red

weight weight blood cells)

(~2½ liters) (~10 liters)

 Body Fluid Volumes
• The extracellular fluid volume is
determined mostly by main effective
osmole = Na+ and the corresponding
anions
Total cations = Total anions
• The intracellular fluid volume is greater
because cells contain a large amount
impermeable molecules, many of which
are anionic (proteins, DNA, RNA,
carbohydrates, phosphates, K+)
• Extracellular fluid osmolality =
Intracellular fluid osmolality
 The Plasma Membrane separates the
intracellular fluid from the extracellular fluid

The selective
permeability of the
membrane allows
the creation of an
ion concentration
gradient across
the membrane

Figure 2-2 Ganong’s Review of Medical Physiology. 25th Edition

Ionic Composition of the 3 major
Body Water Compartments
Extracellular Fluid
Intracellular
Fluid

Cell membrane
Plasma Interstitial
Fluid
Endothelium
K+

Na+

Total cations = Total anions

Figure 1-1B Ganong’s Review of Medical Physiology. 24th Edition

Graphic representation of the relative distribution of select
components in the 3 major water compartments

Plasma proteins are

an important oncotic
component of the
plasma water
compartment

https://textimgs.s3.amazonaws.com/osanp/m46411/2704_Concentration_of_Elements_in_Body_Fluids.jpg
 Extracellular and Intracellular Fluid
Composition (approximate)
Solute Extracellular Intracellular
Na+ 145 12
K+ 4 120
Ca2+ 2.5 0.0001
Mg2+ 1 0.5
Cl− 110 15
HCO3 − 24 12
Phosphates 0.8 0.7
Glucose 5 <1
Proteins (g/dL) 1 30
pH 7.4 7.2
Osmolarity 295 = 295
 Regulation of the Intracellular
Fluid Composition
• The intracellular fluid composition
is determined by the membrane
permeability and the activity of the
cells membrane proteins
– ATPase pumps
– Channels
– Receptors
– Transporters
• The activity of these membrane
proteins is usually highly regulated
SGLUT not
present in
most cells;
most cells
The
express intracellular
GLUT1 fluid
composition
and the
membrane
potential of
each cell is
determined by
the activity of
membrane
proteins
expressed in
the cell

Fig. 2.3 Berne & Levy Physiology, 7th Edition, 2018

 Movement of Water Between
Body Fluid Compartments
• Movement of water between the ICF and
ECF compartments occurs through
aquaporins expressed in the plasma
membrane of cells
• The driving force for this water movement
is an osmotic pressure difference
• The osmotic pressure of both the ICF and
ECF is determined by the molecules/ions
present in these fluids
• Normally ICF, ECF, and plasma are in
osmotic equilibrium and have the same
osmotic pressure
 Osmosis
Osmolality, Tonicity, & Osmosis

Normal serum osmolality is approximately

282 – 303 mOsmol/kg H2O*
278 – 305 mOsmol/kg **
275 – 295 mOsmol/kg ***

*1/27/2012 Quest Diagnostics Manual-Miramar: Reference Range for serum

osmolality by freezing point depression (26922P)
** 7/19/2018 Quest Diagnostics website: Reference Range for serum
osmolality by freezing point depression (CPT Code 83930)
*** NBOME Item-Writing Guide: Reference Range for Osmolality, serum

Revised 7/19/19
 Which is closest to the
osmolality of blood?

A. 100 mOsmol/kg
B. 200 mOsmol/kg
C. 300 mOsmol/kg
D. 400 mOsmol/kg
 Osmolarity and Osmolality
• Osmolarity is the number of osmoles per liter of
solution (eg, plasma)
• Osmolality is the number of osmoles per kilogram
of solvent
• Osmolarity is affected by the volume of the various
solutes in the solution and the temperature, while
the osmolality is not, therefore osmolality is
preferred for biological solutions
• Osmolarity
– 1 mole/liter (M/L) = 1 osmole/L (Osmol/L)
– 1 millimole/liter (mM/L) = 1 mOsmol/L
– mOsm/L = mmol/L × number of particles/mole
• Osmolality
– 1 mole/kg H2O = 1 osmole/kg H2O (Osmol/kg H2O)
– 1 millimole/kg H2O = 1 mOsmol/kg H2O
 The movement of water across cell membranes
occurs by the process of osmosis
Compartment A contains an impermeable At equilibrium,
solute, therefore the water concentration in A is the hydrostatic
less than B, and water moves from B to A down pressure exerted
its concentration gradient to dilute the solute by the column of
water (h) stops
the net
movement of
h = Osmotic
water from
Pressure in cm
compartment B
water or
to A
mmHg

Time

The semipermeable membrane is highly permeable to

water but is impermeable by the solute in solution A
Modified from Fig. 1.8 Berne & Levy Physiology, 7th Edition, 2018
Osmosis is the diffusion of solvent molecules across a
membrane into a region in which there is a higher
concentration of a solute which is impermeable to the
membrane. The osmotic pressure is directly related to
the concentration (osmolality) of the impermeable
solutes

the osmotic pressure

is the pressure that
would have to be
applied to prevent
the movement of the
water molecules
 Osmotic pressure
van’t Hoff’s Law
Osmotic pressure = π = nCRT
R = ideal gas constant
T = absolute temperature (K)
n = number of particles formed by dissociation of a solute molecule
C = molar concentration of solute

A solute does not create a lasting osmotic effect

if it is freely permeable to the membrane and will
equilibrate across the membrane

Effective Osmotic pressure = πeff

πeff = σnCRT
σ = membrane permeability of solute particles (0 for completely
permeable; 1 for impermeable)
 Which 2 of the following are true
statements? [select all that apply]

A. Total body water as a % of body weight

increases with age.
B. The extracellular fluid volume is greater
than the intracellular fluid volume.
C. The extracellular fluid osmolality is
equal to the intracellular fluid osmolality.
D. Plasma osmolality is equal to the plasma
tonicity.
E. [Na+] is greater in extracellular fluid than
intracellular fluid.
 Osmolality of Plasma
• The osmolality of plasma is not as high as expected because
plasma is not an ideal solution and ionic interactions reduce
the number of particles free to exert an osmotic effect
Equations used clinically to estimate plasma
osmolality
Plasma osmolality = 2 x [Na mmol/L] + [glucose
mmol/L] + [urea mmol/L]
or
Plasma osmolality = 2 x [Na mmol/L] + [glucose
mg/dL]/18 + [urea mg/dL]/2.8
• [note: the calculated estimate of plasma osmolality is usually
within +/- 10 mOsmol/kg H2O of the plasma osmolality measured
by freezing point depression. A difference greater than 10 may
indicate the presence of another substance such as ethanol,
methanol, ethylene glycol, etc.]
 Tonicity of Plasma

• A solute does not create a lasting osmotic

effect if it is freely permeable to the
membrane and will equilibrate across the
membrane; therefore urea is not included in
the tonicity calculation

Equations used clinically to estimate plasma

tonicity:
Plasma tonicity = 2 x [Na mmol/L] + [glucose
mmol/L] = effective plasma osmolality
or
Plasma tonicity = 2 x [Na mmol/L] + [glucose
mg/dL]/18 = effective plasma osmolality
 Tonicity
• Tonicity refers to a solutions effect on cell
volume at equilibrium
• The tonicity of a solution describes its ability to
influence the volume of cells (e.g. red blood
cells) immersed in the solution
• Tonicity is measured at steady state and is
determined by the concentration of
impermeable solutes
Isotonic solutions- produce no change in cell
volume (e.g. 0.9% NaCl)
Hypertonic solutions- cause cells to shrink
(crenate)
Hypotonic solutions- cause cells to swell or
burst (lyse)
 Normal Saline (0.9% NaCl)
• Normal Saline is considered to be isotonic and
iso-osmotic
• Normal Saline is 9 g NaCl/L; 9 g/L /58.5 grams per
mole = 154 mmol/L
• 154 mmol Na ions + 154 mmol Cl ions = 308
mOsm/kg (154 x 1.88 = 289.52 mOsm/kg)
• An osmotic coefficient is a quantity which
characterizes the deviation of a solution from
ideal behavior
• The osmotic coefficient of NaCl is about 0.93
• 308 mOsm/kg × 0.93 = 286.44 mOsm/kg

The effective osmolality of normal saline is

approximately 290 mOsm/kg
Which of the following would you expect from
the IV infusion of 1 L isotonic saline into a
patient? [disregard urine output] [select all
that apply]
A. Total body water increases ~ 1 L.
B. Extracellular fluid (ECF) volume increases
~ 500 mL and the intracellular fluid (ICF)
volume increases ~ 500 mL.
C. ECF volume increases ~ 333 mL and the
ICF volume increases ~ 666 mL.
D. ECF volume increases ~ 666 mL and the
ICF volume increases ~ 333 mL.
E. ECF volume increases ~ 1 L.
 Tonicity

http://en.wikipedia.org/wiki/Image:Osmotic_pressure_on_blood_cells_diagram.svg

Hypertonic Isotonic Hypotonic

Net H2O No net H2O Net H2O
movement movement; movement
out of cell; no change into cell;
cells shrink in cell cells swell
volume and may
burst

http://www.youtube.com/watch?v=crpeX8nBgJE&NR=1
RBC Tonicity video (2:20)
 Diffusion, Osmosis and Tonicity
• Diffusion, Osmosis and Tonicity 9:39 (7:40 IV dextran)
– http://www.youtube.com/watch?v=GwYCr0VubNM
• Osmosis 0:47
– http://www.youtube.com/watch?v=sdiJtDRJQEc
• Molarity, Molality, Osmolarity, Osmolality, and Tonicity
4:03 [https://www.khanacademy.org/science/health-and-
medicine/lab-values/v/molarity-molality-osmolarity-
osmolality-and-tonicity-what-s-the-difference]
– http://www.youtube.com/watch?v=o_Bb43LApog
• Tonicity 11:02
[https://www.khanacademy.org/science/health-and-
medicine/lab-values/v/tonicity-comparing-2-solutions]
– http://www.youtube.com/watch?v=VsW6NXZIUCQ
• Isotonic, Hypotonic, Hypertonic 2:48
– http://www.youtube.com/watch?v=4r1G_oLH-Pw
 Which solution will produce the effect
on cell volume seen in curve a?

Change
1. Water solution
from
2. 100mM NaCl isotonic
saline
3. 225 mM NaCl
4. 200mM NaCl +
50mM urea
5. 50mM NaCl +
350mM glucose
Time
 Which solution will produce the effect
on cell volume seen in curve c?

Change
1. Water solution
from
2. 100mM NaCl isotonic
saline
3. 225 mM NaCl
4. 200mM NaCl +
50mM urea
5. 50mM NaCl +
350mM glucose
Time
 Which solution will produce the effect
on cell volume seen in curve d?

Change
1. Water solution
from
2. 100mM NaCl isotonic
saline
3. 225 mM NaCl
4. 200mM NaCl +
50mM urea
5. 50mM NaCl +
350mM glucose
Time

The plasma membrane is permeable to urea and it will

equilibrate across the membrane over time
 Which solution will produce the effect
on cell volume seen in curve b?

Change
1. Water solution
from
2. 100mM NaCl isotonic
saline
3. 225 mM NaCl
4. 200mM NaCl +
50mM urea
5. 50mM NaCl +
350mM glucose
Time

The plasma membrane is permeable to glucose and it will enter

the cell and be metabolized to CO2 and H2O over time
 Regulation of Cell Volume
• Disorders in sodium or H20 balance can cause
the extracellular fluid (ECF) to become hypotonic
or hypertonic
• Differences in tonicity between the cell interior
and ECF cause H20 to flow into or out of the cell
resulting in changes in cell volume
• Changes in cell volume can damage the cell so
cells have compensatory mechanisms to
minimize volume changes
• Cells respond to changes in volume by several
mechanisms
•Regulatory volume decrease (RVD)
•Regulatory volume increase (RVI)
 Regulatory Cell Volume Decrease (RVD)
• RVD is activated by cell swelling caused by
hypotonic ECF, typically hyponatremia
• Activation of several mechanisms result in net
movement of K+ and Cl- out of the cell
– activation of K-selective and/or Cl-selective
channels
– activation of a K-Cl cotransporter
• Due to this compensation mechanism, care should
be taken to avoid rapid correction of long-term
hyponatremia which can result in osmotic
demyelination syndrome, also known as central
pontine myelinolysis, and other harmful CNS
effects. These effects are often irreversible.
Therefore, correction of disorders of water balance
is usually accomplished slowly to avoid this serious
neurological complication.
 When cells are exposed to a hypotonic medium,
they swell and then undergo a volume-regulatory
decrease (RVD). The RVD involves loss of KCl and
organic osmolytes from the cell.

Fig. 2.7 Berne & Levy Physiology, 7th Edition, 2018

 Regulatory Cell Volume Increase (RVI)

• Regulatory Cell Volume Increase (RVI) is

activated by cell shrinkage due to hypertonic
ECF
• Hypertonic ECF may be caused by
hypernatremia, hyperglycemia, or other effective
osmole solutes
• Responses to prevent cell shrinkage may be
both:
– Acute responses (sec to min)
and
– Chronic responses (days)
 Regulatory Cell Volume Increase (RVI)
• Acute responses (sec to min) involve several
mechanism which ultimately result in an
increased intracellular accumulation of K+ and Cl-
• Different mechanisms many be activated in
different types of cells
• Activation of a Na+-H+ exchanger increases Na+
uptake and alkalinizes the cytoplasm activating a
Cl--HCO3 - exchanger
• Activation of Na+ -K+ ATPase extrudes Na+ in
exchange for K+ resulting in a net increase in
intracellular K+ and Cl-
• Activation of a Na+/K+/2Cl- cotransporter also
increases K+ and Cl- inside the cell
 When cells are exposed to a hypertonic medium,
they shrink and then undergo a volume-regulatory
increase (RVI). During the RVI, Na, K, and Cl and
organic osmolytes enter the cell.

Fig. 2.7 Berne & Levy Physiology, 7th Edition, 2018

Regulatory Cell Volume Increase
(RVI)
• Chronic responses (days) to
hypertonic ECF involves generation
of idiogenic osmoles
• The cells produce more particles
from cellular metabolism, known as
idiogenic osmoles (or osmolytes),
and include taurine, glycine,
glutamine, sorbitol and inositol
 Cell adaptation to hypernatremia
• Cells adapt to extracellular fluid tonicity changes
by decreasing or increasing the concentration of
inorganic (potassium ions, chloride ions) and
organic (glutamate, taurine, sorbitol, and
myoinositol) osmolytes
• Extracellular fluid hypertonicity (hypernatremia)
results in generation of intracellular organic
osmolytes within 24 hours of onset, which leads
to an increase in intracellular fluid tonicity that
draws water into cells, thereby limiting the
decrease in cell volume
• Patients with slowly developing chronic
hypernatremia are therefore less likely to present
with symptoms compared to patients with acute
hypernatremia
Caution: correction of disorders of Na+ and
water balance should be done slowly to
avoid serious neurological complications

Rapid correction of long-term

hypernatremia can result in cerebral
edema, seizures, and neurologic damage
Rapid correction of long-term hyponatremia
can result in osmotic demyelination
syndrome, also known as central pontine
myelinolysis, and other harmful CNS effects
To minimize the risk of these
complications, adjustment of the serum Na+
concentration should be done slowly
Other mechanisms of H2O and solute transport
• Bulk flow - hydrostatic pressure differences
moving molecules in the same direction much
faster than can be accounted for by diffusion
• Ultrafiltration - separation by size of solutes in a
solution achieved by forcing the solution
through a filter
– Occurs in capillary beds, especially in the glomerular
capillaries of the kidney
– The driving force for movement is hydrostatic
pressure
– H2O and small solutes are pushed through capillaries
while the endothelium keeps the proteins and cells in
the blood
 Bulk Flow example:
Blood Flow Through Blood Vessels
• Pressure difference (P) = (Pupstream – Pdownstream);
∆P is the driving force for flow to occur. The
pressure difference is generated by the heart
pushing blood into the arterial side while
removing blood from the venous side
• Resistance (R) is all the factors that act to slow
or oppose flow
– Blood vessel radius
– Blood vessel length
– Blood viscosity (‘thickness’)
 Oncotic pressure
• Oncotic pressure is the osmotic
pressure generated by large
molecules (especially proteins) in
solution, and is an important force
keeping fluid inside blood vessels
• Osmotic pressure generated by a
solution of protein does not
conform to van't Hoff's law, but is
higher than what would be
expected based on the protein
molecular concentration
 Relationship between the concentration
of plasma proteins in solution and the
osmotic pressure (oncotic pressure)

The oncotic

Oncotic pressure (mmHg)

pressure exerted
by proteins in
human plasma
has a normal
value of
approximately 26
to 28 mm Hg, and
is higher than
what is predicted
by van’t Hoff’s law Protein (g/dL)

Fig. 1.9 Berne & Levy Physiology, 7th Edition, 2018

Capillary Ultrafiltration Rate (CFR)
CFR = Kf x [Net filtration pressure]

CFR = Kf [(PC – Pisf) – σ(πC – πisf)]

Kf= Ultrafiltration coefficient (product of permeability and

surface area)
PC= Hydrostatic pressure in capillary
Pisf= Hydrostatic pressure in interstitial fluid
σ= Reflection coefficient for protein
πC= Oncotic pressure in capillary (primarily plasma proteins)
πisf = Oncotic pressure in interstitial fluid
 Forces Producing Filtration

Forces pushing/pulling water out of the capillary

• Hydrostatic Blood Pressure

– About 30-35 mmHg at
arteriole end of capillary
– About 13-16 mmHg at
venule end of capillary
• Interstitial Osmotic
Pressure
– About 1-8 mmHg
 Forces Opposing Filtration
(cause reabsorption)
Forces pulling/pushing water into the capillary

• Blood Oncotic (osmotic) Pressure

– About 26-28 mmHg
• Interstitial Hydrostatic Pressure
– About 0 mmHg

There is usually a slight net

filtration (water movement out
of the vascular system)
 Osmotic (oncotic) Pressure
Due to plasma proteins - mainly albumin
Start Equilibrium

14 inches of water
or
26 mmHg
Blood Interstitial
Fluid
Net water
movement

Semi-permeable membrane
 Net loss of Net
Net
fluid to be Reabsorption
Filtration
removed pressure
pressure
by the
lymphatic -9
10 vessels mmHg
mmHg

Colloid osmotic
pressure 26 mmHg
36 mmHg 17 mmHg
Hydrostatic Hydrostatic
pressure pressure
Arteriole side Venule side

Capillary Fluid Exchange

Extracellular fluid not reabsorbed by
capillaries is absorbed by lymphatics
and returned to veins
Veins 7,195 L/day Capillaries
17 L/day
Heart Lymphatics 3 L/day
20 L/day

Arteries 7,200 L/day

~ 20 L of fluid filters out of capillaries
into tissues each day
~ 17 L is reabsorbed by capillaries
~ 3 L is returned to the blood via the
lymphatics

Kidney 180 L/day filtrate - 1.4 L/day urine

 Interstitial Fluid Movement
• A net movement of fluid occurs from
blood into most tissues
• Fluid gained by tissues is removed by
the lymphatic system
• The lymphatic vessels return fluid to the
cardiovascular system via the large
subclavian veins in the thorax
– Lymphatic valves, muscle movements, and
the “respiratory pump” keep the lymph fluid
moving toward the thoracic cavity
• An imbalance with more capillary
filtration than lymph drainage results in
edema (excess interstitial fluid)
Disorders causing Edema
•Hypoalbuminemia (protein
malnutrition, liver disease)
•Congestive heart failure
•Liver disease
•Impaired lymphatic
drainage (post surgery,
parasites)
Which of the following would you expect from
the IV infusion of 1 L 0.45% NaCl (145
mOsm/kg H2O) into a patient? [disregard
urine output]
A. ECF volume increases ~ 500 mL and ICF
volume increases ~ 500 mL.
B. ECF volume increases ~ 333 mL and ICF
volume increases ~ 666 mL.
C. ECF volume increases ~ 666 mL and ICF
volume increases ~ 333 mL.
D. ECF volume increases ~ 1000 mL and ICF
volume increases ~ 0 mL.
E. ECF osmolality increased
0% 0% 0% 0% 0%

A. B. C. D. E.
Which of the following would you expect from
the IV infusion of 1 L 5% dextrose in water
into a patient? [disregard urine output]

A. ECF volume increases ~ 500 mL and ICF

volume increases ~ 500 mL.
B. ECF volume increases ~ 333 mL and ICF
volume increases ~ 666 mL.
C. ECF volume increases ~ 1000 mL and ICF
volume increases ~ 0 mL.
D. ECF volume increases ~ 666 mL and ICF
volume increases ~ 333 mL.
E. ECF osmolality has increased
0% 0% 0% 0% 0%

A. B. C. D. E.
The effect of various solutions on cell volume
a. Water
Change solution
from isotonic saline b. 50mM NaCl +
350mM glucose

c. 100mM NaCl
150mM NaCl
d. 200mM NaCl +
50mM urea

Time e. 225 mM NaCl

(also d with RVI)
 Specific Gravity
• The total concentration of all molecules in a
solution can also be measured as specific
gravity
• Specific gravity is defined as the weight of a
volume of solution divided by the weight of an
equal volume of distilled water, therefore the
specific gravity of distilled water is 1
• Normal human plasma has a specific gravity in
the range of 1.008 to 1.010
• Urine specific gravity can be high (1.040 to
1.050) in patients who have received an injection
of radiocontrast dye even though the urine
osmolality is similar to that of plasma