1. Nephrology Core Curriculum Hyperosmolar States

2. 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

3. 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 H20H20 H20H20 H2OH2O H2OH2O Glucose Osmotic pressure

4. 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 H20H20 H20H20 H2OH2O H2OH2O Glucose Osmotic pressure

5. 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 H20H20 H20H20 H2OH2O H2OH2O Glucose Osmotic pressure

6. Osmotic pressure Ineffective 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 H2OH2O H2OH2O Urea Osmotic pressure Urea

7. 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

8. 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+.

9. 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?

10. Osmotic pressure Example #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 Extracellular 280mosmol/kg H20H20 H20H20 K+ = 140meq/l 25 liters 17 liters Na+ = 140 Intracellular Extracellular 290mosmol/kg H20H20 K+ = 145meq/l 24.1 liters 17.9 liters Na+ = 145 Pre- Post-420meq/Na

11. Osmotic pressure Example#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 Intracellular Extracellular 280mosmol/kg H20H20 H20H20 K+ = 140meq/l 25 liters 17 liters Na+ = 140 Intracellular Extracellular 290mosmol/kg H20H20 K+ = 145meq/l 24.1 liters 17.9 liters Na+ = 145 Pre- Post-420meq/Na

12. Osmotic pressure Example #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 Intracellular Extracellular 280mosmol/kg H20H20 H20H20 K+ = 140meq/l 25 liters 17 liters Na+ = 140 Intracellular Extracellular 270mosmol/kg K+ = 135meq/l 25.9 liters 17.6 liters Na+ = 135 Pre- Post-1.5 liters of water H20H20

13. Osmotic pressure Example #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 Intracellular Extracellular 280mosmol/kg H20H20 H20H20 K+ = 140meq/l 25 liters 17 liters Na+ = 140 Intracellular Extracellular 280mosmol/kg K+ = 140meq/l 25 liters 18.5 liters Na+ = 140 Pre- Post-1.5 liters of NS H20H20 H20H20

14. 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

15. Osmotic Pressure One final point-- notice that the intracellular volume varies inversely with the plasma Na+ concentration –decreased in hypernatremia –increased in hyponatremia Neurologic symptoms are 2nd to these changes

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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