nephrology core curriculum hyperosmolar states. osmotic pressure osmotic forces are the prime...

Nephrology Core CurriculumHyperosmolar 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

• 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

H20

H20

H2O

H2O

Glucose

Osmotic

pressure

Osmotic pressure

• 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

H20

H20

H2O

H2O

Glucose

Osmotic

pressure

Osmotic pressure

• 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

H20

H20

H2O

H2O

Glucose

Osmotic

pressure

Osmotic pressureIneffective osmoles

• The osmo must be unable to cross the membrane to be an effective osmo

• Example-- urea– 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

H2O

H2O

Urea

Osmotic

pressure

Urea

Urea

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 pressureExample #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 pressureExample #1 addition of NaCl without water

• 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

Intracellular Extracellular280mosmol/kg 280mosmol/kg

H20 H20

K+ = 140meq/l25 liters 17 liters

Na+ = 140


H20

K+ = 145meq/l24.1 liters 17.9 liters

Na+ = 145

Pre-

Post-420meq/Na

Osmotic pressureExample#1 Addition of NaCl without water

• 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


H20 H20


Na+ = 140


H20


Na+ = 145

Pre-

Post-420meq/Na

Osmotic pressureExample #2-- Add 1.5 liters of free water to

the EC space • 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


H20 H20


Na+ = 140



Na+ = 135

Pre-

Post-1.5 liters of water

H20

Osmotic pressureExample #3-- Add 1.5 liters of NS to the EC

space • If NS given, no change in osmolality

and no water movement across the cell membrane-- fluid remains in the EC space


H20 H20


Na+ = 140


K+ = 140meq/l25 liters 18.5 liters

Na+ = 140

Pre-

Post-1.5 liters of NS

H20H20

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 increased- yet 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 amounts- therefore 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

SubstanceAdded

PlasmaOsmo

Plasma Na EC volume IC volume Urine Na

NaCl

Water

IsotonicNaCl

Neurologic symptoms

are 2nd to these changes

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 OsmolalityWater 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

nephrology core curriculum hyperosmolar states. osmotic pressure osmotic forces are the prime...

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