Water Lose

Body Fluids http://cats.med.uvm.edu/physiology/bodyfluids

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The Body's Water

Fluid CompartmentsMeasuring Volumes

Ionic CompositionUnits of MeasureCalculating OsmolarityThe Anion Gap

Clinical ExamplesFluid Movements

Transport MechanismsMembrane TransportOsmosis

ICF-ECF ExchangeCalculating Exchange

ExamplesISF-Plasma Exchange

Capillary PressuresStudy Questions

Answers

Water and its dissolved constituents make up the bulk of your body, and determinethe nature of nearly every physiological process.

In most individuals, approximately 60% of the total weight is water. This percentagevaries between 50% and 70%, with the exact value primarily dependent on aperson's fat content. Since fat has very low water, individuals with more fat will havea lower overall percentage of body weight as water.

In the first sections of this document, we'll examine how the body's water isdistributed into several functional compartments, with significant differences in theionic composition of each.

© 1999, Joe Patlak

Department of Molecular Physiology and Biophysics

University of Vermont ([email protected])


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Fluid Compartments in the BodyThe body's water is effectively compartmentalized into several major divisions.

Intracellular Fluid (ICF) comprises 2/3 of the body's water.

If your body has 60% water, ICF is about 40% of your weight.

The ICF is primarily a solution of potassium and organic anions, proteins etc.(Cellular Soup!).

The cell membranes and cellular metabolism control the constituents of thisICF.

ICF is not homogeneous in your body. It represents a conglomeration offluids from all the different cells.

Extracellular Fluid (ECF) is the remaining 1/3 of your body's water.

ECF is about 20% of your weight.

The ECF is primarily a NaCl and NaHCO3 solution.

The ECF is further subdivided into three subcompartments:

Interstitial Fluid (ISF) surrounds the cells, but does not circulate. Itcomprises about 3/4 of the ECF.

Plasma circulates as the extracellular component of blood. It makes upabout 1/4 of the ECF.

Transcellular fluid is a set of fluids that are outside of the normalcompartments. These 1-2 liters of fluid make up the CSF, Digestive Juices,Mucus, etc.

40% x 70 kg = 28 L water ISF, 10 LPlas-ma,4L

Trans,

1L

Intracellular Water =40% Extracellular=20%

Total Body Water = 60% of weight

The 60-40-20 Rule:

60 % of body weight iswater

40% of body weight isintracellular fluids

20% of body weight isextracellular fluid


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Special Notes:

All the body's fluid compartments are in osmotic equilibrium (exceptfor transient changes).

The ions and small solutes that constitute the ECF are in equilibriumwith similar concentrations in each subcompartment.

The ECF volume is proportional to the total Na content.

Measuring the Volumes of the Body'sCompartments

It is sometimes necessary to know more precisely how water is distributed betweenthe various compartments in a particular individual. The volumes of some of thecompartments can be measured by the dilution method.

For the dilution method, one adds an extrinsic, measurable, compound thatdistributes fully within the compartment of interest. This method relies on theformula:

Concentration = Amount / Volume or:

Volume = Amount Added-Amount Lost / Measured Concentration

Directly Measurable volumes:

Total Body Water: Use D20 or radioactive water (tritiated). Distributes throughout all aqueous solutions.

ECF Volume: Use Inulin (a starch) or Sucrose. These distributethroughout body, but are excluded from cells.

Plasma Volume: Use radioactive albumin or dye (Evans Blue) thatstay in plasma only.

Indirectly Measurable Volumes:There is no practical way to measure only the intracellular or the interstitial volumes. Rather, these are calculated by combining the measured volumes given above.


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Interstitial Volume: Equal to the Extracellular volume minus theplasma volume.

Intracellular Volume: Equal to the Total Water minus theExtracellular Volume.

Ionic Composition of Body Fluids:The following table gives representative values for the primary ionic constituents ofthe major fluid compartments. Also, follow the links at left for additional importantinformation.

Electrolyte Plasma, (mEq/L)[molarity]

Plasma Water(mEq/L)[molality]

Interstitial Fluid (mEq/L)

Intracellular Fluid(mEq/L)

Cations:

Sodium 142 153 145 10

Potassium 4 4.3 4 160

Calcium 5 5.4 5 2

Magnesium 2 2.2 2 26

Total Cations: 153 165 156 198

Anions:

Chloride 101 108.5 114 3

Bicarbonate 27 29 31 10

Phosphate 2 2.2 2 100

Sulphate 1 1 1 20

Organic Acid 6 6.5 7

Protein 16 17 1 65

Total Anions: 153 165 156 198


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Important Notes:

The units of measure given in the table are in equivalents, referred to either litervolume or liter water (plasma). If you are not familiar with the terms molarity,molality, osmolarity, osmolality, equivalents, and tonicity, please review Unitsof Measure.

Plasma has approximately 7% (by volume) proteins and lipids. However, the ionicactivity is limited to the aqueous portion of the solution. Labs report concentrationsas mEq/Liter Plasma. You must correct for the 7% non-aqueous portion toobtain the actual concentrations (if needed). This is why the numbers in thesecond plasma column are higher than the first.

Not all of the reported concentrations are FREE. Some ions are bound to proteins orother ions.

Proteins have many negative charges per molecule. The equivalents given above aretherefore much higher than the molarity of those same proteins.

Units of Measure in Solutions:

Concentrations are often given in terms of weight/volume. For example, mg/L, ormg/100 mL (common clinical units), are used. These units do not depend onknowledge of the molecular structure of the measured substance.

For a substance with a known molecular structure, one can define a "Mole" of thatsubstance. 1 Mole is the weight of 6.23X10^23 molecules, and is commonlycalculated as the sum of the atomic weights of each atom in a molecule.

A Molar Solution is an aqueous solution consisting of one mole of a substance plusenough water to make one Liter of solution.

A Molal Solution is an aqueous solution consisting of one mole of a substance plus 1kg of water (usually very close to 1 L water). The total volume may thus be morethan 1 L.

The difference between molar and molal is important when a solution contains a largeamount of non-aqueous substance. For example, cream has 20% fat (homogenizedin very small droplets). There would be a 20% difference between the molarity ofsalt and its molality. A lab might report a Na concentration of 20 mMolar (moles/Lcream), but really all the Na would be in the 80% that was water. It's "real"concentration (molality) would be 24 mMolal (moles/L water).


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Concentrations of ions are often given in Equivalents (or milliequivalents, mEq)per Liter. The equivalents of an ion is equal to the molarity times the number ofcharges per molecule. Thus Equivalents is the measure of CHARGE concentration.

Osmoles refers to the number of impermeable particles dissolved in a solution,regardless of charge. This will be important for determining the diffusionalmovement of water. For substances that maintain their molecular structure whenthey dissolve (e.g. glucose), the osmolarity and the molarity are essentially thesame. For substances that dissociate when they dissolve, the osmolarity is thenumber of free particles times the molarity. Thus for a pure NaCl solution, a 1Molar solution would be 2 Osmolar (1 for Na, and 1 for Cl).

When measured as osmoles per liter, one obtains the osmolarity. For osmoles perkg water, one obtains osmolality.

Calculating Osmolarity in Complex Solutions:

As described under Units of Measure, the osmolarity of a simple solution is equal tothe molarity times the number of particles per molecule.

Glucose has 1 particle

NaCl has two

MgCl2 has three.

Real solutions can be much more complex:

Proteins with many equivalents/L may only contribute a smallamount to the osmolarity, since they consist of a few very large"particles".

Not all the solution volume is aqueous. For example, plasma has7% dissolved proteins and lipids.

Not all ions are free in a solution. Cations may be bound to otheranions or to proteins.

For complete accuracy, all constituents should be included in thecalculation.


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Shortcut:

The difficulties given above leave many uncertainties when calculating the osmolarityof a solution like plasma.

Plasma osmolarity can be estimated easily, however: Take the reported Naconcentration (mEq/Liter Plasma) and double it. This obviously erroneouscalculation (given all of the above) comes very close, since the errors tend to canceleach other!

In some clinical settings, one must also account for the effects of elevated plasmaglucose or urea.

Osmolarity vs. Tonicity:

Osmolarity measures the effective gradient for water assuming that all theosmotic solute is completely impermeant. It is simply a count of the number ofdissolved particles. Therefore a 300 millimolar solution of glucose, a 300 millimolarsolution of urea, and a 150 millimolar solution of NaCl each have the sameosmolarity.

A cell, placed in each of these solutions, would behave very differently, however. Ina 150 mM NaCl solution, there would be equal osmotic strengths on both sides (NaClis impermeant), and the cell would maintain the same volume.

Urea is very permeable through most cell membranes. It exerts little osmotic forceagainst a real cell and its membrane. A cell placed in 300 mM urea would rapidlyswell as both urea and water entered the cell down their activity gradients.

Tonicity is a functional term that describes the tendency of a solution to resistexpansion of the intracellular volume.

Two solutions are isosmotic when they have the same number of dissolved particles,regardless of how much water would flow across a given membrane barrier. Incontrast, two solutions are isotonic when they would cause no water movementacross a membrane barrier, regardless of how many particles are dissolved.

In the example given above, a 150 mM NaCl solution would be isosmotic to the insideof a cell, and it would also be isotonic--the cell would not swell or shrink whenplaced in this solution. On the other hand, a 300 mM urea solution, while stillisosmotic would cause the cell to swell and burst (due to its permeability). Thisisosmotic ureas solution is not isotonic. Instead it has a lower tonicity (calledhypotonic).


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The Anion Gap:

The equivalents of cations in a solution always balances the equivalents of anions.

However, by tradition, not every ionic constituent is reported by the lab. (Do youreally want to know that much detail in any case?!).

The simplest reports may only give the [Na+], [Cl-], and the [HCO3-].

The "real" balance is given by the equation:

[Na] + [other cations] = [Cl] + [HCO3] + [other anions]

rearranging:

[Na] - ([Cl] + [HCO3]) = [other anions] - [other cations]

= "Anion Gap"

Normal values for the Anion Gap are 8-16 mEq/L plasma

The Anion Gap is a useful shorthand measure, particularly in the differential diagnosisof acid/base disorders.


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Summary of common body fluid distrubances.Most clinical body fluid disturbances fall into one of a small number of classifications.These are summarized in the table below, along with the changes in ECF and ICFvolume and osmolarity.

Note that the nomenclature gives you important clues: It is based on the condition ofthe ECF following the alteration. For example, hypo-osmotic expansion means theosmolality is reduced and the ECF volume has increased. Therefore you canimmediately predict the changes in the EC fluid based on the words used to describethe clinical condition.

Also note that shifts in osmolarity are always in the same direction. This is becausethe EC and IC compartments are always in osmotic equilibrium. Focusing on thename of the disturbance thus gives you three of the four changes listed in the table.

The fourth column is also easy to derive: Since the number of disolved particles inthe intracellular compartment is fixed (they don't cross the cell membrane), the onlyway for IC osmolarity to change transiently is by the addition or subtraction of water. If the osmolarity decreases, then the volume must go up. Note that in the chartbelow, the IC volume arrows are always opposite those for the IC osmolarity.

Condition Example EC Fluid IC Fluid

Osmolality Volume Osmolality Volume

Hyposmoticexpansion

excessivewater intake ↓ ↑ ↓ ↑

Hyposmoticcontraction

salt wasting(Loss bykidneys)

↓ ↓ ↓ ↑

Isosmoticexpansion

IV infusion,edema ↔ ↑ ↔ ↔

Isosmoticcontraction

hemorrhage,burns ↔ ↓ ↔ ↔

Hyperosmoticexpansion

drink conc.saline ↑ ↑ ↑ ↓

Hyperosmoticcontraction

severesweating ↑ ↓ ↑ ↓

In the table, ↓ denotes a decrease, ↑ an increase, and ↔ no change.


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Fluid Movements

This section reviews the basic forces of diffusion, membrane transport of solutes, andthe osmosis of water across membranes. Since the section probably repeatsinformation from your undergraduate studies, you may safely skip it if you feelcompletely comfortable with its definitions and demonstrations.

Fluid movement is caused primarily by the application of pressure. In a macroscopicsense, the application of hydrostatic pressure causes bulk flow, e.g. blood flowingthrough your artieries.

Pressure also moves fluid at a microscopic level. Through pores within cellmembranes, and between the cells, pressure causes water and its dissolved particlesto move. The amount of movement is equal to the pressure gradient, the area, andthe leakiness of the barriers.

The random movement of particles in the presence of a concentration gradient iscalled diffusion, which also acts as a microscopic pressure that causes movementwithin solutions and across membranes.

The mechanism by which water and other solutes move across cell membranes isreviewed here in the section on membrane transport.

Diffusion of water is called osmosis, which is another critical microscopic pressurecontrolling fluid movement.

These forces control the exchange of water and solutes between the intracellular andextracellular fluids as well as between the interstitial and the plasma compartmentsof the ECF.

Follow these sections to examine these forces in more detail.


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Membrane Transport MechanismsThere are four primary means that water and other small molecules cross into or outof cells. They are reviewed here since they play such an important role in body fluidsand many other physiological functions.

Diffusion

Powered by random movement ofmolecules in a solution

Net movement is from regions of highconcentration to low.

Does not saturate as the concentrationor gradient changes

Diffusion of different substances do notinterfere with each other (nocompetition).

Net flux (amount of movement) isproportional to the concentrationdifference and the permeability of anybarrier like a membrane.

Substances can cross membranes bydiffusion if they can dissolve in the oilyinterior of the membrane (hydrophobic)

Diffusion can occur through tightjunctions or within bulk solutions.

Diffusion of water down itsconcentration gradient is calledosmosis.

Anions and cations shown movingat random, as via diffusion in asolution. Put the cursor over thebox above to start the simulation.Click within the box to reset allthe particles to a single point.

For a more extensive review ofDiffusion, Osmosis, and NernstPotentials, see my separatechapter on that subject.


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Facilitated Diffusion

Proteins act as carriers or pores permit fluxof substances that cannot diffuse directlythrough the membrane.

Movement is still passive (like diffusion),from high concentration to low.

Occurs across cell membranes only.

Saturates when substance reaches highconcentrations due to lack of availableprotein.

Related substances can compete for thesame carrier or pore.

Maximum rate of transport (fully saturated)is called Tm, the transport maximum.

Primary Active Transport

Proteins in the membrane canalso act as pumps.

Move ions or small moleculesfrom low concentration to highconcentration (i.e. up theirgradients).

Require cellular energy, usuallyas ATP

Saturates when substancereaches high concentrations dueto lack of available protein.

Example: Na-K ATPase

Present in nearly every cell inthe body


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Pumps 3 Na ions out inexchange for 2 K ions pumpedin (cost=1 ATP)

Other pumps include the Ca-ATPase, and the H-ATPase.

Secondary Active Transport

Uses proteins similar to those forfacilitated diffusion.

Couples the movement of severaldifferent molecules in each cycle.

Saturates when substance reaches high concentrations due to lackof available protein.

Cotransport moves 2 or more molecules in the same direction acrossthe membrane.

Counter transport moves molecules in opposite directions.

The gradient for one molecule can cause the other to move againstits own diffusion gradient.

Normal active transport (Na-K ATPase) makes a strong Na gradient,which in turn powers many secondary active transport mechanisms.

Example: Na-Glucose cotransport.


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Osmosis:Osmosis is the diffusion of water down its concentration gradient. Normally onethinks of water as the solvent, and focuses on the concentration of the solutes, butwater itself has a concentration in any solution. Pure water has a molecular weight of18 grams/mole, so its concentration is approximately 55 Molar!

Solutes take up space that would otherwise have been occupied by water in asolution, and they also associate with a number of the water molecules, furtherlowering its activity (effective concentration). The following demonstration simulatesthe process of dissolving a solute in water. Watch what happens to the concentrationof free water as you use the chooser menu to increase the number of solute particles.

Simulation of Water and Solute in an Aqueous Solution

For a more extensivereview of Diffusion,Osmosis, and NernstPotentials, see myseparate chapter on thatsubject.

This simulation shows the behavior of water andsolute in an idealized, simple solution. Initiallyonly 150 water molecules are present, and theyare exhibiting Brownian motion. Use the pull-down menu at the lower right to increase (ordecrease) the number of solute molecules insolution. Clicking on the large compartment itselfresets the simulation to its starting condtion.

Each additional solute associates with severalwater molecules: in this simulation, 3. When nosolute is present, 150 water molecules are free.When 10 solute atoms are added, and the initialvolume maintained at 150 particles, only 140water molecules are present and 110 of these arefree. What do you think would happen to thesolution, if the solute amount were increased to30? Try it and see!

The other critical component for osmosis is a barrier that permits water to cross, butholds back some or all of the solutes. Under these conditions, a gradient in soluteconcentration means that there is also a gradient in the free water concentration (theother way!). The following demo illustrates this process.


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Simulation of Osmotic Flow Between Two Flexible Compartments

Fluctuating volumes and effectiveMolar concentrations for eachcompartment are depictednumerically across the top of thesimulation. Use the mouse andthe pull-down bar at the right tochange the solute number in theright-hand compartment from 10to 5 particles and describe whathappens. (This experiment maytake as much as 30 minutes toreach equilibrium!) Does themembrane ever return to itsoriginal location? How about achange from 10 to 20? And thenfrom 20 to 5? Repeat theseexperiments several times toobtain a statistical sample.

The demonstration above shows the membrane moving (and the volume changing)as water moves. This is just what would occur between two flexible compartmentsthat always had equal hydrostatic pressure. Cells behave this way, as will bediscussed below

As we have also seen, hydrostatic pressure can also cause water to move. Whenpressure is applied against the direction of osmotic movement, then the osmotic flowwill be slowed or even reversed. When the pressure is just enough to stop theosmotic flow an equilibrium is reached. This pressure, by definition, is called the"Osmotic Pressure" of a solution.


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Exchange between Intracellular andExtracellular Compartments:

The ICF and the ECF are separated by the membranes of the body's cells. Theprotein components of these membranes give them substantial permeability to waterwhile carefully controlling the permeability of selected ions.

Cell membranes are flexible. If water flows into (out of) the cell, it expands(contracts). Hydrostatic pressure therefore does not play a significant role, andosmosis results in flows rather than pressure.

As discussed above, osmosis occurs when there is a gradient of impermeable soluteacross a water-permeable membrane.

In cells, osmotic flow would occur if there were an osmotic gradient between theintracellular and extracellular fluids. In the body, these two compartments arealways in osmotic equilibrium, even though the composition of the fluids in themis very different.

The addition or subtraction of water or solutes from one or more of the body's fluidcompartments will result in water exchange between the ICF and the ECF if there isan alteration in the resulting osmolarity. These relationships were discussed moreextensively in the clinical examples given above, but here you will view more detailregarding how to calculate exactly how much water moves where duringdistrubances.

Calculating Extracellular fluid - intracellular fluidexchange

In the simplest of examples, it is possible to understand intuitively how the bodyfluids move between the intracellular and extracellular compartments. However, formore complex cases, it is often necessary to calculate the exact shifts based on thetotal osmolar content of the two compartments. This section discusses methodologiesfor making such calculations.


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Analytic principles and assumptions

1. Water moves freely between intracellular and extracellular compartments, driven byosmotic pressure differences. Ion movement is variable, but for simplicity of analysis it isreasonable to assume that there are no transient shifts of ions between ECF and ICF .

2. Exchanges of water and solutes with the environment, for example intravenous infusion orwater intake, take place via the ECF. Change of the ICF occurs only by way of fluid shifts,which are seen only if the ECF osmolality is perturbed.

3. The ECF and ICF are in osmotic equilibrium (although the equilibrium may be disrupted bybrief transients that take place over periods of seconds or minutes). Thus one assumesequality of plasma, interstitial fluid, and intracellular fluid osmolality.

4. When one considers the effect of adding or removing water or solutes from the body, massmust be conserved, i.e. neither water nor solutes are created or destroyed as thecompartments come to equilibrium.

See the following for specific examples of such fluid shift calculations. Also, try out yourknowledge on the study questions at the end.

Example of calculations

Assume the standard 70 kg male, in whom the original osmolality of the ECF is 290mOsm/kg water. Consider addition of 2 liters of distilled water to the ECF. Describe inwords the shifts that take place, and calculate the effect of this addition on thevolumes and osmolality of the ECF and ICF.

Addition of water to the ECF increases its volume and reduces its osmolality. Weassume there are no significant movements of solutes across the cell membranes.The cell membranes are permeable to water, and the increased water concentrationin the ECF causes water to enter cells, increasing the volume of the ICF and reducingthe ECF volume (but not returning it to its initial volume). The shift of water results inre-establishment of osmotic equilibrium between ECF and ICF, with both havingincreased volumes and decreased osmolalities.


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Initial conditions:

Initial total body water 0.6 x 70 kg = 42 liters

Initial ICF volume 0.4 x 70 kg = 28 liters

Initial ECF volume 0.2 x 70 kg = 14 liters

Initial total body osmoles

TBW volume x osmolality

42 liters x 290 mOsm/liter

12180 mOsm

Initial ICF osmoles

ICF volume x osmolality


8120 mOsm

Initial ECF osmoles

ECF volume x osmolality


4060 mOsm

Final conditions:

Final osmolality (Total body osmoles)/(new TBW)

12180 mOsm/(42+2) kg water

277 mOsm/kg water

Final ICF volume (ICF osmoles)/(new osmolality)

8120 mOsm/(277 mOsm/kg water)

29.3 kg water = 29.3 liters

Final ECF volume (ECF osmoles)/(new osmolality)

4060 mOsm/(277 mOsm/kg water)

14.65 kg water = 14.65 liters

It will be apparent that one might get these results in other ways (for example, note that the addedtwo liters distributes between the two compartments in proportion to their original size (2/3 to ICF,1/3 to ECF). However, the systematic approach has advantages because it can predict the correctresult even when the body fluid changes include alterations to both water and solutessimultaneously.


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Plasma-Interstitial Fluid Exchange

The aqueous solutions that compose the plasma and the interstitial fluid exchangereadily through the thin walls of most of your body's capillaries. The primary forcesthat govern this exchange are hydrostatic pressure (the blood pressure within thecapillaries), and osmosis.

Hydrostatic Pressure at the Capillary:

The capillary wall acts as a filtration "barrier". Most of the fluid within the capillariesis retained, but some filters through pores between the cells, pushed by the pressuredifference between the capillary blood and the ISF.

Water and small solutes can pass freely through these pores. The net effect of thehydrostatic pressure alone is a net loss of water and solute from plasma to the ISF.

The capillary wall (both cells and pores) are, however, impermeable to the plasmaproteins and lipids. Under normal conditions, these stay within the plasma. Notethat following injury, the capillaries can also leak protein.

The hydrostatic pressure in the capillaries is lower than that of the arteries, anddecreases along the length of the capillary as blood flows through. At the arteriolarend of the capillary, the pressure is usually about 35 mm Hg (due to the pressuredrop caused by the resistance arterioles). On the venule end of the capillary, thepressure is in the range of 15 mm Hg. The mid-capillary pressure profile can beassumed to be linear (see figures below).

Osmotic forces in the capillaries:

Because the capillary wall is permeable to water, but essentially impermeant to theplasma proteins, these molecules generate an osmotic pressure. Furthermore, sincethese proteins are negatively charged, they tend to hold additional cations in theplasma (the Gibbs-Donnan effect), further enhancing an osmotic gradient betweenthe plasma and the interstitial fluid.

The combined effect (osmotic and Gibbs-Donnan) results in a pressure that drawswater out of the interstitium and into the plasma. This pressure is known as theColloid Oncotic Pressure (often shortened to the Oncotic Pressure).

This pressure is proportional to the difference in protein concentration between the


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plasma and the ISF. Compared to pure saline, the plasma exerts about 28 mm HgOncotic pressure, whereas the ISF has only about 3 mm Hg. The net OncoticPressure is thus about 25 mm Hg. This value remains roughly constant over thelength of most capillary beds.

Starling's Relationship

The British physiologist Starling first identified the interrelationship between thehydrostatic pressure and the oncotic forces within the capillary.

Hydrostatic pressure tends to cause fluid to leave the plasma, and oncotic pressurepulls it back. These two forces tend to balance each other.

The hydrostatic forces, however, are gradually decreasing over the length of thecapillary, while the oncotic pressure remains constant. If these pressures weregraphed, they would look approximately like the following figure:

On the arteriole end, the hydrostatic pressure is higher than the oncotic, so there isfluid movement from plasma to interstitium. The magnitude of this water flow isindicated by the light blue area on the left (downward arrows). On the venule end,the hydrostatic pressure has dropped below the oncotic. Fluid moves back from theinterstitium to the plasma. The magnitude of this reverse flow is indicated by thegreen area on the right (upward arrows).

In a normal capillary bed, fluid gain and loss from the plasma are closely balanced, sothere is little or no net change in plasma and ISF volumes. Note that this can beseen graphically, since the blue and green (right and left) regions have equal areas.

Note that a small excess in fluid loss from plasma to ISF is normally drained back tothe circulation via the lymphatics.


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Starling forces in disease:

The balance described above can be altered by changes to the capillary pressure nearthe arterioles or near the venules, as well as alterations in the Oncotic Pressure.

Understanding how changing resistance changes capillarypressures:

The vascular system is a highly branched set of tubes that carry the blood to all partsof the body. Blood pressure results from the pumping of the heart, and affects themovement of fluids throughout the vascular system. This subject will be studied inmore detail in April, but many other systems depend how the blood pressure is "felt"in the capillaries as a function of arterial resistance.

Fluids move through blood vessels (as with any kind of pipe) when there is a pressuredifference between the start and end of the pipe. Just as water moves continuouslydownhill as a river flows, the pressure drops continuously from the start to the end ofa vessel.

Since the capillaries are (in a sense) midway between arteries and veins, theirpressure will be lower than the central arterial pressure and higher than the centralvenous pressure. Also, within the capillaries themselves, the pressure will graduallydrop from their arteriolar side to their venule side.

When a much bigger resistance to flow is introduced in the middle of this pipe (like adamn built on a river, or a "squeeze" on a tube), the pressure upstream from thatresistance will be closer to that near the beginning of the pipe, and the pressuredownstream will be closer to that near the end.

Arterioles squeeze the blood vessels, giving a relatively large resistance to flow. Upstream, the pressure is much closer to central arteriolar pressure, whiledownstream at the start of the capillaries the pressure is about 35 mm Hg.

When the arterioles dilate (and make less resistance), the pressure in the capillariesrises (closer to arterial pressure). When the arterioles constrict (more resistance),then the pressure upstream will rise even more, while it will fall at the capillaries.

These changes in capillary pressure are critical for understanding:

1. Starling Forces of the capillary.

2. Production of saliva and other excretory filtrates.

3. Glomerular filtration in the kidney.


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The following examples illustrate the range ofimbalances that can occur:

Increased Blood Pressure at the capillaries: Vasodilation

Vasodilation reduces the pressure drop across the arterioles, bringing the capillariescloser to the arterial pressure. The venous pressure may not be altered. In thiscase, there is a greater region where fluid leaves the plasma, and a reduced regionswhere it returns.

This imbalance results in a net loss of fluid from the plasma. The result is anexpansion of the interstitial fluid in this tissue. If this expansion continued, it wouldresult in the clinical symptom known as edema.

Decreased Blood Pressure at the Capillaries: Shock


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When the central blood pressure declines, the pressure at the capillaries usually alsodecreases. In addition, most vascular beds will participate in reflex attempts tomaintain the central blood pressure via arteriolar vasoconstriction. This furtherreduces the pressure at the start of the capillary.

The decrease in hydrostatic pressure results in a diminution in the region where fluidis lost from the plasma, and an expansion in the region where fluid returns back tothe plasma. There is a net gain of fluid to the plasma.

This net gain, taken over most of the body's vascular beds leads to an "auto-transfusion" that helps to compensate for plasma loss during hemorrhagic shock.

Increased Venous Pressure: Congestive Heart Failure

When the heart's function is compromised, it cannot pump blood as effectively, sovenous pressure rises. This elevation in venous pressure is also felt at the capillaries,as illustrated above.

This rise in venous pressure diminishes the region where fluid is reabsorbed into theplasma. As with the case (above) of vasodilation, this condition results in a net lossof fluid from plasma to ISF. The resulting edema can be seen in the swollen ankles(and other tissues) that are symptomatic of congestive heart failure.


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Decreased Oncotic Pressure: Protein deficiency and tissuedamage

When the plasma does not contain sufficient protein, or the interstitial fluids containtoo much, then the difference in oncotic forces diminishes. As shown above, thisresults in a net increase in the region where hydrostatic pressure exceeds oncotic. Edema results.

This imbalance can be seen in a number of important conditions. The swollen belliesof children with severe protein malnourishment are due to such edema within theperitoneum. Also, when capillaries are damaged, as in severe burns, they permitproteins to leak into the interstitium. Added to the proteins released from lysed cells,the net result is a diminution of the oncotic pressure difference, and edema.


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BODY FLUIDS - STUDY QUESTIONS

1. What is the concentration of water in pure water?

2. What is the water concentration of a 1 M NaCl solution?

3. Distinguish between "tonicity" and "osmolality." Illustrate the lack of identitybetween "isotonic" and "isosmotic" by an example in which the two clearly aredifferent.

4. The edema of congestive heart failure involves many factors. How might thefinding of increased central venous pressure contribute to this fluid accumulation?

5. A 70 kg male has a body fluid osmolality of 290 mOsm/kg water. Assume 290millimoles of NaCl are added to the ECF. Describe in words what fluid and soluteshifts, if any, take place. Calculate the final osmolality of the body fluids, and the finalECF and ICF volumes.

6. A 70 kg male has a body fluid osmolality of 290 mOsm/kg water. Assume 2 litersof isotonic saline are added to the ECF. Describe in words what fluid and solute shifts,if any, take place. Calculate the final osmolality of the body fluids and the final ECFand ICF volumes.

7. A patient on the renal ward weighed 100 kg, had a plasma osmolality of 290mOsm/kg water, and the following volume distribution:

TBW 60% body weight, ICF volume 40% body weight, and ECF volume 20% bodyweight.

After drinking 5 liters of water rapidly, and following complete absorption but priorto any excretion, what would be the new ICF and ECF volumes (in liters)?

8. In the patient in 7, what would be the new plasma osmolality in mOsm/kg water?


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ANSWERS1. What is the concentration of water in pure water?

1 L water weighs 1000 g. Gram molecular wt water = 18 grams

(1000g/L)/(18grams/mole) = 55.5 moles/L or 55.5 molar

2. What is the water concentration of a 1 M NaCl solution?

1 M NaCl --> 2 osmoles. Each osmole displaces approximately 1 mole of water.Therefore the water concentration is (55.5-2)moles/L, or 53.5 molar.

3. Distinguish between... Tonicity of a particular solution is defined by whether steady-statecell volumes change when they are placed in the solution. Osmolality is determined by thenumber of particles, i.e. ions or molecules, in solution. An "isotonic" solution is one in whichcells neither swell nor shrink in the steady state. An " isosmotic" solution (with respect toplasma) is one that has the same osmolality as plasma. The tonicity of a solution dependsonly on the osmolality of impermeant solutes, whereas the osmolality depends on theconcentrations of all solutes. A solution containing 300 mOsm/kg water of urea is isosmoticwith plasma, because both have the same osmolality, but it is not isotonic because ureapermeates cell membranes easily. Cells placed in a 300 mOsm/kg urea solution will swellas urea and water enter.

4. The edema of congestive heart failure... The central venous pressure is the pressure inthe right atrium and thoracic venae cavae. Heart failure can be defined as any abnormalityin the pumping action of the heart that reduces its ability to perform external work. Centralvenous pressure rises as cardiac output declines. The mean arterial blood pressure maystay normal because of compensatory reflexes (homeostatic control), and only decline inthe late stages of heart failure. Applying the Starling concept of capillary filtration andreabsorption of fluid, normal arterial pressure and increased venous pressure will decreasereabsorption of fluid at the venous ends of capillaries and hence cause edema.


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5. A 70 kg male has a body fluid osmolality... This question was drawn from Berne andLevy, 3rd Ed., pp 756ff. Addition of 290 mMoles of NaCl to the ECF adds 580 mOsm to theECF. We assume NaCl is restricted to the ECF--i.e. does not cross cell membranes. Theosmolality of the ECF will increase, which will cause net water flow from the ICF to theECF. The flow of water increases osmolality of the ICF. Net water flux ceases when theECF and ICF have the same effective osmolality.

Calculations:

Initial conditions:

Initial total body water (TBW): 70 kg x 0.6 = 42 kg or 42 L waterInitial ICV volume: 42x 2/3 = 28 L

Initial ECF volume: 42 x 1/3 = 14 L

Initial total body osmoles: 42 kg x 290 mOsm/kg = 12180 mOsm

Initial ICF osmoles: 28 kg x 290 mOsm/kg = 8120 mOsm

Initial ECF osmoles: 14 kg x 290 mOsm/kg = 4060 mOsm

Final conditions:

Final osmolality = (new total body osmoles)/(TBW) (12180 mOsm + 580mOsm)/(42kg water) = 303.8 mOsm/kg water

Final ICF volume = ICF osmoles/(new osmolality)

8120 mOsm/(303.8 mOsm/kg water) = 26.7 kg or 26.7 L

Final ECF volume = TBW - ICF = 42 - 26.7 = 15.3 L

(Could also have been calculated as follows:)

Final ECF volume = (new ECF osmoles)/(new osmolality)

(4060mOsm + 580mOsm)/(303.8 mOsm/kg water)

4640/303.8 = 15.3 kg water or 15.3 L


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Note that addition of NaCl to the ECF has altered the fractions of the TBW contained in theECF and ICF. The two compartiments no longer contain 1/3 and 2/3 of the TBW.

6. A 70 kg male has a body fluid osmolality... This is also taken from examples in Berneand Levy, 3rd Ed. Addition of isotonic saline to the ECF does not change the effectiveosmolality of the ECF. There is, therefore, no driving force for net water movement. Thetwo liters of saline remains in the ECF. The initial conditions are just as calculated forquestion 5. The final conditions are:

Osmolality of TBW, ECF, ICF unchanged.

Final ECF volume = 14 L + 2 L = 16 LFinal ICF volume = unchanged.

7. A patient on the renal ward...Initial conditions:

Initial TBW = 100 kg x .6 = 60 kg or 60 L water

Initial ICF volume = 100 kg x 0.4 = 40 kg or 40 L water

Initial ECF volume = 100 kg x 0.2 = 20 kg or 20 L water

Initial Total body osmoles = 60 kg x 290 mOsm/kg = 17400 mOsm

Initial ICF osmoles = 40 kg x 290 mOsm/kg = 11600 mOsm

Initial ECF osmoles = 20 kg x 290 mOsm/kg = 5800 mOsm

Final conditions:

Question indicates water absorbed but not excreted. Water will be addedto ECF, then equilibration of water between ECF and ICF will take place.Assume solutes do not move between compartments.Final TBW = 60 L +5 L = 65 LNew osmolality = 17400 mOsm/65 kg water = 267.7 mOsm/kgwater in ECF and ICF

ECF Volume = (ECF osmoles)/(new ECF osmolality)


ICF Volume = (ICF osmoles)/(new ICF osmolality)


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As a check, note that 21.7L + 43.3L = 65 L Note also, that the new water isproportioned in the same 1/3, 2/3 ratio as existed originally, since the ratio ofmilliosmoles is 1/3, 2/3 and does not change when pure water is added.

8. In the patient in 7... The new plasma osmolality would be the same as theosmolality of the other fluids, 267.7 mOsm/kg water.

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