Nephrology Core Curriculum
Hyperosmolar States
Osmotic pressure
• Osmotic forces are the prime determinate of
water distribution in the body
– water can freely cross nearly all membranes in
the body
– body fluids are in osmotic equilibrium
• the osmolalities of the intracellular and extracellular
fluids are the same
Osmotic pressure
Osmotic
pressure
Glucose
H20
H2 O
H2 O
H20
• Water molecules exhibit
random motion and freely
diffuse across the membrane
• The addition of solutes
decreases the intramolecular
cohesive forces, thereby
decreasing that random motion
• Flow will occur from areas of
high activity (or concentration)
to low-- flowing into the
glucose compartment
• Theoretically would occur
indefinitely, because the
activity of water is always less
in the glucose compartment
Osmotic pressure
Osmotic
pressure
Glucose
H20
H2 O
H2 O
H20
• However, since the
compartment is rigid-hydrostatic pressure builds
• This hydrostatic pressure tends
to push water back into the
solute-free compartment
• Equilibrium reached when the
hydrostatic pressure (measured
by column height) is equal to
the forces pulling water across
the membrane
• This pressure is the osmotic
pressure
Osmotic pressure
Osmotic
pressure
Glucose
H20
H2 O
H2 O
H20
• Osmotic pressure that is
generated is proportional
to the NUMBER OF
PARTICLES per unit
volume of solute, not the
type, valence, or weight of
the particles
Osmotic pressure
Ineffective osmoles
• The osmo must be unable
to cross the membrane to
be an effective osmo
• Example-- urea
Osmotic
pressure
Urea
Urea
H2 O
Urea
H2 O
– moves down a
concentration gradient into
the solute-free compartment
– new equilibrium state is
characterized by equal urea
concentrations in each
compartment-- not water
movement
– as a result, no osmotic
pressure-- ineffective osmol
Osmotic pressure
• In vivo, osmotic pressure determines the
distribution of water between the
extracellular and intracellular spaces
– your body doesn’t have water pumps-- it moves
osmoles and the water follows
• Each compartment has one solute that is
primarily limited to the compartment
– Na+ salts are the principle extracellular osmoles that act
to hold water in the extracellular space
– K+ salts account for all the intracellular osmoles
Osmotic pressure
• Although the cell membrane is permeable to
both Na+ and K+, they act as effective
osmoles because they are restricted to their
respective compartments by the Na+-K+ATPase pump in the cell membrane
• Net effect the volumes of extracellular and
intracellular fluids are determined by the
amount of water present and the RATIO of
Na+ to K+.
Osmotic pressure
Example #1 addition of NaCl without water
• Assume
– osmolality of body fluids is 280mosmol/kg
• due entirely to 140meq/L of Na+salts extracellularly
or 140meq/L of K+salts intracellularly
• avg 70kg man has a TBW of 42 liters (60%), of
which 25 liters (60%) is intracellular and 17 liters
(40%) is extracellular
– what will happen if 420meq of NaCl without
water is added to the extracellular fluid?
Osmotic pressure
Example
Pre- #1 addition of NaCl without water
Intracellular
280mosmol/kg
H20
K+ = 140meq/l
25 liters
Extracellular
280mosmol/kg
H20
Na+ = 140
17 liters
Post-420meq/Na
Intracellular
Extracellular
290mosmol/kg
290mosmol/kg
H20
K+ = 145meq/l
24.1 liters
Na+ = 145
17.9 liters
•
•
•
•
•
•
•
•
Initial total body solute= 280mosmol/kg
x 42 kg = 11760mosm
Initial EC solute= 280 x 17 kg = 4760
New total body solute= 11760+420=
12180mosom/l
New total body osmo= 12180/42=
290msomol/kg
New EC solute= 4760 + 420 = 5180
mosmol
New EC volume= 5180/290=17.9kg
New IC volume= 42-17.9=24.1kg
New plasma Na= osmo/2= 145meq/l
• Pearl-- that’s why salt
exacerbates hypertension
Osmotic pressure
Example#1 Addition of NaCl without water
Pre-
Intracellular
280mosmol/kg
H20
K+ = 140meq/l
25 liters
Extracellular
280mosmol/kg
H20
Na+ = 140
17 liters
Post-420meq/Na
Intracellular
Extracellular
290mosmol/kg
290mosmol/kg
H20
K+ = 145meq/l
24.1 liters
Na+ = 145
17.9 liters
• Points
– increasing the quantity of
extracellular solute results in the
movement of 900mL of water
from the cells into the
extracellular fluid
• autotransfusion
– osmolality of both compartments
are increased even though the
added solute is restricted to the
extracellular space
– that’s why use total body water in
calculating the volume of
distribution of changes in plasma
osmolality
Osmotic pressure
Example #2-- Add 1.5 liters of free water to
Prethe EC space
Intracellular
280mosmol/kg
H20
K+ = 140meq/l
25 liters
Extracellular
280mosmol/kg
H20
Na+ = 140
17 liters
Post-1.5 liters of water
Intracellular
Extracellular
270mosmol/kg
270mosmol/kg
H20
K+ = 135meq/l
25.9 liters
Na+ = 135
17.6 liters
•
•
•
•
•
•
•
•
•
•
Initial total body solute= 11,760 mosmol
Initial EC solute= 4760 mosmol
Initial IC solute= 280 x 25=
7000mosmol
New total body water= 42 +1.5= 43.5kg
New body osmo= 11760/43.5=
270mosmol/kg
New EC volume= 4760/270= 17.6 kg
New IC volume= 7000/270= 25.9 kg
Ratio of IC volume to TBW=
25.9/43.5= 60%
New EC Na= 270/2= 135 meq/L
Pearl-- that’s why you don’t give D5W
or free water to an intravascularly
depleted patient
Osmotic pressure
Example #3-- Add 1.5 liters of NS to the EC
Prespace
Intracellular
280mosmol/kg
H20
K+ = 140meq/l
25 liters
Extracellular
280mosmol/kg
H20
Na+ = 140
17 liters
Post-1.5 liters of NS
Intracellular
Extracellular
280mosmol/kg
280mosmol/kg
H20
H20
K+ = 140meq/l
25 liters
Na+ = 140
18.5 liters
•
If NS given, no change in osmolality
and no water movement across the cell
membrane-- fluid remains in the EC
space
Osmotic Pressure
• 3 examples illustrate an important, and often
misunderstood concept, the plasma Na concentration is a
measure of concentration and not of volume
• In all three examples the extracellular volume increasedyet the Na concentration increased (with addition of dry
salt), decreased (with addition of free water), and was
unchanged (with the addition of NS).
• This is because the plasma Na concentration reflects the
ratio of solute and water present, not the absolute amountstherefore there is no necessary correlation between the
plasma Na concentration and the extracellular fluid volume
Osmotic Pressure
• One final point-- notice that the intracellular
volume varies inversely with the plasma
Na+ concentration
– decreased in hypernatremia
– increased in hyponatremia
Substance Plasma
Added
Osmo
NaCl
Water
Isotonic
NaCl
Neurologic symptoms
are 2nd to these changes
Plasma Na EC volume IC volume Urine Na
Relation of Plasma Na
Concentration to Osmolality
• Formula
– 2xNa + glucose/18 + BUN/2.8
– multiple Na x 2 to account for the accompanying anions (NaCl etc)
– because osmo is determined by number of particles not size or
charge, must convert glucose and urea (which are milligrams per
deciliter to particles (or osmoles))
• mosmol/kg = (mg/dL x10) / molecular weight
• glucose- molecular weight = 180
– mg/dl of glucose x 180/10 or mg/dl glucose/18
• urea (two nitrogen molecules (mole weight 14 each)= 28
– mg/dl of urea x 28/10 or mg/dl urea/2.8
Normal Serum Osmolality
• Normal values for the formula parameters
• plasma Na+ 137-145
• glucose 60-100mg/dL
• BUN 10-20mg/dL
– Posm = 275-290mosmol/kg
– Effective Posm -- drop urea = 270-285
– Since glucose usually only accounts for 5, simply
equation to: Effective Posm= 2 x Na
– Thus, in most conditions, plasma Na+ concentration is
a reflection of the Posm
Volume regulation versus
Osmoregulation
• Plasma osmolality is determined by the
ratio of solutes to water
• Extracellular volume is determined by the
absolute amounts of Na+ and water present
• Examples
– exercising on a hot day-- loss of dilute fluid as sweat-- net effect is
a rise in plasma osmolality and Na+ concentration, but a fall in EC
volume
– infusion of NS, will increase EC volume, but not change osmo
– infusion of 1/2NS will lower plasma Na and raise EC fluid volume
Regulation of Plasma Osmolality
• Hypoosmolality and hyperosmolality can produce serious
neurologic symptoms and death, primarily due to water
movement into and out of the brain, respectively.
• To prevent this, plasma osmo (primarily determined by
plasma Na) is normally maintained within very narrow
limits by appropriate variations in water intake and water
excretion
• This regulatory system is governed by osmoreceptors in
the hypothalmus that influence both thirst and the secretion
of ADH
Regulation of Plasma Osmolality
Water Balance
• Obligatory Water Output
–
–
–
–
Skin-- 500ml/day
Respiratory tract-- 400ml/day
Stool-- 200ml/day
Urine output
• volume adequate to match intake minus
stool/skin/respiratory losses
Regulation of Plasma Osmolality
• Kidney can excrete up to 10-20 L/day of
water, therefore persistent water retention
resulting in hypoosmolality and
hyponatremia occurs, with rare exceptions,
only in patients with an impairment in renal
water excretion