body Compa 8. Primary adrenal insufficiency This individual will lose both fluid and salt. There will be a partial dietary replacement of both fluid and salt but because fluid replacement exceeds salt replacement, body osmolarity remains below normal Table 1-2-1. Summary of Volume Changes and Body Osmolarity Following Changes in Body Hydration ICF Volu Osmolarity Diagram Loss of isotonic fluid no change no change Diarrhea Vomiting Loss of hypotonic Quid Dehydration Diabetes insipidus Gain of isotonic fluid no change change Isotonic saline Gain of hypotonic auid Hypotonic saline AriyW Gain of hypertonic Quid Hypertonic saline Hypertonic BCF= extracelluar Bud; ICF= intracelular Fluid
BodyCompartments 8. Primary adrenal insufficiency: :--~ ~------- I I I I Figure 1-2-9 This individual will lose both fluid and salt. There will be a partial dietary replacement of both fluid and salt but because fluid replacement exceeds salt replacement, body osmolarity remains below normal. Table 1-2-1.Summary of Volume Changes and Body Osmolarity Following Changes in Body Hydration ~ ECF =extracellular fluid; rCF =intracellular fluid. KAPLA~. meulca I 17 ECF Body ICF D-Y Volume Osmolarity Volume Diagram Loss of isotonic fluid .!. no change no change Hemorrhage Diarrhea LbL Vomiting Loss of hypotonic fluid .!. i J Dehydration Diabetes insipidus Alcoholism Gain of isotonic fluid i no change no change Isotonic saline Gain of hypotonic fluid i .!. i Hypotonic saline I{"v K Water intoxication \J CAt-eA Gain of 1 i i J Hypert< Hypert< 'v\0-,' e/'r5
USMLE Step 1: Physiology SUPPLEMENTAL TOPICS Volume Measurement in the major Fluid Compartments To measure the volume of a body compartment, a tracer substance must be evenly distributed within that compartment. In this situation the volume of the compartment can usually be cal culated by using the following relationship V×C=A V= Volume of the compartment to be measured oncentration of the tracer in the compartment to be measured A= Amount of the tracer Sample problem: 300 mg of a dye was injected intravenously At equilibrium, the concentration in the blood was 0.05 mg/mL Determine the volume of the compartment which contained the dye Answer: 6000 mL Required Properties of the Tracer Tracers are generally introduced into the vascuar compartment, and they will distribute througl body water until they reach a barrier they cannot penetrate. The two major barriers encountered are capillary membranes and cell membranes Required criteria of tracers to measure the following compartments Plasma: not permeable to capillary membranes, e.g., albumin ECF: permeable to capillary membranes but not cell membranes, e.g., inulin, mannitol, Total body water: permeable to capillary and cell membranes, e.g., tritiated water, urea Blood Volume versus plasma Volume Definition of Blood volume Blood volume represents the plasma volume plus the volume of red blood cells(RBCs), which is usually expressed as hematocrit(fractional concentration of red blood ces) Calculation of blood volume The following formula can be utilized to convert plasma volume to blood volume Blood volume plasma volume Hct= hematocrit 18 dical
'" USMLEStep1: Physiology 18 KAPLA~. meulca I SUPPLEMENTALTOPICS VolumeMeasurementintheMajorFluidCompartments Principle To measure the volume of a body compartment, a tracer substance must be evenlydistributed within that compartment. In this situation, the volume of the compartment can usually be calculated by using the following relationship: VXC=A v = Volume of the compartment to be measured C =Concentration of the tracer in the compartment to be measured A =Amount of the tracer Sample problem: 300 mg of a dye was injected intravenously. At equilibrium, the concentration in the blood was 0.05 mglmL. Determine the volume of the compartment which contained the dye. Answer: 6000 mL Required Properties of the Tracer Tracersare generallyintroduced into the vascular compartment, and they willdistribute through body water until they reach a barrier they cannot penetrate. The two major barriers encountered are capillary membranes and cellmembranes. Required criteria of tracers to measure the following compartments: Plasma: not permeable to capillary membranes, e.g., albumin ECF: permeable to capillary membranes but not cell membranes, e.g., inulin, mannitol, sodium, sucrose Total body water: permeable to capillary and cell membranes, e.g., tritiated water, urea BloodVolumeversusPlasmaVolume Definitionof BloodVolume Bloodvolumerepresentsthe plasmavolumeplusthe volumeof redbloodcells(RBCs),which is usuallyexpressedas hematocrit(fractionalconcentrationof red bloodcells). Calculationof BloodVolume The following formula can be utilized to convert plasma volume to blood volume: BI d I plasma volume 00 vo ume = 1 - Hct Hct =hematocrit
Body Compartments Example: Hct=50%(0.50) Plasma volume=3L Blood volume=-3L=6L Note that if the hematocrit is 0.5(or 50%), the blood is half RBCs and balf plasma. Therefore, blood volume will be double the plasma volume Changes in Red blood Cell Volume Principle Changes in red blood cell volume in an in vitro solution are due to the movement of water (osmosis)across the cell membrane. This is determined by the effective osmolarity(concentra- tion of impermeable solutes)of the external fluid. Just remember, water will diffuse from a region of higher water concentration to a region of lower water concentration ffect of isotonic Saline If a normal red blood cell is placed in isotonic saline(300 mOsm NaCl), no change in red cell volume will occur. This is because the effective osmolarity of the solution equals the effective osmolarity inside the red blood cell. As long as the concentration of nonpenetrating particles the external solution is 300 mOsm, there will be no significant change in the volume of the red Problems Involving a Nonpenetrating Solute Predict the changes in cell volume(increase, decrease, no change)when a normal red blood cell previously equilibrated in isotonic saline is placed in the following solutions Assume the fluid volume of the external solution is large, and thus, as water moves in or out of the cell, there is no significant change in the concentration of beaker solutes(answers on the following page 2. 400 mOsm NaCl 3. 150 mM Nacl 4. 300 mM NaCI Effect of Substances That Rapidly Penetrate Cell Membranes The presence of a substance, such as urea, that penetrates the cell membrane quickly does not affect the osmotic movement of water. If the total concentration of nonpenetrating solutes is <300 mOsm the RBC will swell; if it is >300 mOsm the RBC will shrink Problems Involving a Rapidly Penetrating Solute Predict the changes in cell volume(increase, decrease, no change)when a normal red blood cell previously equilibrated in isotonic saline is placed in the following solutions 5. 200 mOsm NaCl and 200 mOsm urea 6. 300 m Osm urea only 7. 500 mOsm urea only medical 19
BodyCompartments Example: Hct=50% (0.50) Plasma volume =3 L 3L Blood volume =- =6 L 1-0.5 Note that if the hematocrit is 0.5 (or 50%), the blood is half RBCs and half plasma. Therefore, blood volume will be double the plasma volume. Changesin RedBloodCellVolume Principle Changes in red blood cell volume in an in vitro solution are due to the movement of water (osmosis) across the cellmembrane. This is determined by the effectiveosmolarity (concentration of impermeable solutes) of the external fluid. Just remember, water will diffuse from a region of higher water concentration to a region of lower water concentration. Effectof IsotonicSaline If a normal red blood cell is placed in isotonic saline (300 mOsm NaCl), no change in red cell volume will occur. This is because the effectiveosmolarity of the solution equals the effective osmolarity inside the red blood cell.As long as the concentration of nonpenetrating particles of the external solution is 300 mOsm, there will be no significant change in the volume of the red blood cell. ProblemsInvolvinga NonpenetratingSolute Predict the changes in cellvolume (increase, decrease, no change) when a normal red blood cell previously equilibrated in isotonic saline is placed in the following solutions. Assume the fluid volume of the external solution is large, and thus, as water moves in or out of the cell, there is no significant change in the concentration of beaker solutes (answers on the following page). 1. 200 mOsm NaCI 2. 400 mOsm NaCI 3. 150 mM NaCl 4. 300 mM NaCI Effectof SubstancesThat RapidlyPenetrateCellMembranes The presence of a substance, such as urea, that penetrates the cell membrane quickly does not affect the osmotic movement of water. If the total concentration of nonpenetrating solutes is <300 mOsm, the RBCwill swell;if it is >300 mOsm, the RBCwill shrink. ProblemsInvolvinga RapidlyPenetratingSolute Predict the changes in cellvolume (increase, decrease, no change) when a normal red blood cell previously equilibrated in isotonic saline is placed in the following solutions: 5. 200 mOsm NaCl and 200 mOsm urea 6. 300 mOsm urea only 7. 500 mOsm urea only KAPLA!!.. meulC8 I 19
USMLE Step 1: Physiology Effect of Substances That Slowly Penetrate Cell Membranes Some substances penetrate cell membranes but do so slowly. Thus, they initially have an osmot ic effect like sodium chloride but no osmotic effect at equilibrium Problem Involving a Slowly Penetrating Solute Predict the changes in cell volume(increase, decrease, no change)when a normal red blood cell initial effect versus the long-term effect then placed in the following solution. Determine the previously equilibrated in isotonic salir 8. 200 mOsm NaCl and 200 mOsm glycerol (a slowly penetrating substance Answers 1 200 mOsm NaC]: Because the effective osmolarity of the solution is <300 mOsm, the RBC will swel. Cells in hypotonic saline swell 2. 400 mOsm NaCl: Because the effective osmolarity of the solution is >300 mOsm, the RBC will shrink. Cells in hypertonic saline shrink 3. 150 mM NaCl: This is equivalent to 300 mOsm NaCl or isotonic saline. There is no change in RBC volume 300 mM NaCl: This is equivalent to 600 mOsm NaCl or hypertonic saline Cells in hyper tonic saline shrink 5. 200 mOsm NaCl and 200 mOsrn urea: The effective osmolarity of the solution is deter- mined only by the nonpenetrating solutes. A penetrating substance, such as urea, will dif- fuse across the membrane and equalize its concentration in the two compartments Therefore, it will not contribute to effective osmolarity. If the effective osmolarity is less than 300, the cell swells. Here the effective osmolarity is 200; therefore, the cell swells 6. 300 mOsm urea only: The effective osmolarity of the solution is zero, which is the same as pure water; therefore, the cell swells 7. 500 mOsm urea only: Again, the effective osmolarity is zero; therefore, the cell swells 8. 200 mOsm NaCl and 200 mOsm glycerol (a slowly penetrating substance): Timing is important in this question. Initially, the glycerol will not penetrate; therefore, it con- mbutes to the initial effective osmolarity of the solution. Because the initial effective osmolarity is 400, the cell will shrink. With time, the glycerol will penetrate the membrane and equalize its concentration in the two compartments. The long-term effective osmo larity will be due to only the Nacl, 200 mOsm. Therefore, over the long term it will swell Chapter Summary Extracellular volume increases with a net gain of fluid and decreases with a net loss of body fluid Extracellular effective osmolarity is generally detemined by twice the sodium concentration(mOsm, mM) Intracellular volume increases with a decrease in ECF osmolarity and decreases with an increase in ECF A comprehensive summary is given in Table 1-2-1
USMLEStep 1: Physiology 20 KAPLAlf il- me leaI Effectof SubstancesThatSlowlyPenetrateCellMembranes Some substances penetrate cellmembranes but do so slowly.Thus, they initially have an osmotic effectlike sodium chloride but no osmotic effectat equilibrium. ProblemInvolvinga SlowlyPenetratingSolute Predict the changes in cellvolume (increase, decrease,no change) when a normal red blood cell previously equilibrated in isotonic saline isthen placed in the following solution. Determine the initial effectversus the long-term effect. 8. 200 mOsm NaCl and 200 mOsm glycerol (a slowlypenetrating substance) Answers 200 mOsm NaCl: Becausethe effectiveosmolarity of the solution is <300 mOsm, the RBC will swell.Cells in hypotonic saline swell. 2. 400 mOsm NaCl: Becausethe effectiveosmolarity of the solution is >300 mOsm, the RBC will shrink. Cells in hypertonic saline shrink. 1 3. 150mM NaCl: This is equivalent to 300mOsm NaCI or isotonic saline.There is no change in RBCvolume. 4. 300 mM NaCI: This is equivalent to 600 mOsm NaCI or hypertonic saline. Cells in hypertonic saline shrink. 5. 200 mOsm NaCI and 200 mOsm urea: The effective osmolarity of the solution is determined only by the nonpenetrating solutes. A penetrating substance, such as urea, will diffuse across the membrane and equalize its concentration in the two compartments. Therefore, it will not contribute to effective osmolarity. If the effective osmolarity is less than 300, the cell swells. Here the effective osmolarity is 200; therefore, the cell swells. 6. 300 mOsm urea only: The effective osmolarity of the solution is zero, which is the same as pure water; therefore, the cell swells. 7. 500 mOsm urea only: Again, the effectiveosmolarity is zero; therefore, the cell swells. 8. 200 mOsm NaCI and 200 mOsm glycerol (a slowly penetrating substance): Timing is important in this question. Initially, the glycerol will not penetrate; therefore, it contributes to the initial effective osmolarity of the solution. Because the initial effective osmolarity is 400, the cell will shrink. With time, the glycerol will penetrate the membrane and equalize its concentration in the two compartments. The long-term effective osmolarity will be due to only the N aCI, 200 mOsm. Therefore, over the long term it will swell. ChapterSummary Extracellularvolumeincreaseswithanetgainoffluidanddecreaseswithanetlossofbodyfluid. Extracellulareffectiveosmolarityisgenerallydeterminedbytwicethesodiumconcentration(mOsm,mM). IntracellularvolumeincreaseswithadecreaseinECFosmolarityanddecreaseswithanincreaseinECF osmolarity. A comprehensivesummaryisgivenin Table1-2-1
Review questions MEMBRANE TRANSPORT/BODY COMPARTMENTS Review Questions Directions: select the one best answer 1. Red blood cells, originally equilibrated in isotonic saline, are suspended in a solution con taining 250 mOsm/L of sodium chloride in water. Ignoring transient changes, intracellu lar red cell volume will C. remain unchanged 2. Two compartments(X and n)of water are separated by a semipermeable membrane. the concentrations of impermeant solute at time zero are shown in the following drawing Which of the drawings below represents the volumes of X and Y when the system reaches quilibrium? X Y X 3. Identify the Quid compartment that contains approximately two-thirds of the total body water transcellular C. interstitial D. intracell E. extracellular medical 21
ReviewQuestions MEMBRANETRANSPORT/BODYCOMPARTMENTS ReviewQuestions Directions: Select the ONE best answer. 1. Redblood cells,originally equilibrated in isotonic saline, are suspended in a solution containing 250 mOsm/L of sodium chloride in water. Ignoring transient changes, intracellular red cellvolume will: A. B. e. mcrease decrease remain unchanged 2. Twocompartments (X and Y) of water are separated by a semipermeable membrane. The concentrations of impermeant solute at time zero are shown in the following drawing: Which of the drawings below represents the volumes of X and Y when the system reaches equilibrium? A B c D E x y x y x y x y x y a a a a a 3. Identify the fluid compartment that contains approximately two-thirds of the total body water. A. transcellular B. plasma e. interstitial D. intracellular E. extracellular iileClical 21 x y a 000 a a 000 a a 000 a a 000 00