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This is done usingindicators specific to each compartment. A known quantity of thesubstance is infused into the bloodstream of the subject andallowed to disperse. A plasma sample is then obtained, and theamount of indicator determined. The compartment volume isthen calculated by the formula:Blood Volume = ( Plasma Volume ÷ [1 − hematocrit ])CompartmentTBWECFPlasma volumeIndicatorAntipyrine or tritiated water, because bothof these substances will diffuse through allcompartments.Inulin, which will diffuse throughout plasmaand ISF. Inulin is a large sugar (MW 500)that cannot cross cell membranes and isnot metabolized.Evans blue dye, which binds to plasmaproteins. The total blood volume iscomprised of the plasma and red bloodcells, and the hematocrit is the percentageof red blood cells (RBC) in the wholeblood.

Hematocrit is ~0.42 (42% RBC) innormal adult men, and ~0.38 in women.Total body water (TBW)amount of indicatorinjected ( mg )Volume ( in liters ) =final concentration ofindicator ( mg L )Extracellular fluid (ECF)IndicatorEvans blueInulinAntipyrine ortritiated H20PlasmavolumeInterstitialfluidIntracellularfluid (ICF)By extrapolation, the other compartments can be determined:Since TBW = ECF + ICF,ICF = TBW − ECFISF = ( ECF − Plasma Volume )Substances Used to Determine Fluid Compartment Size13Chapter2Membrane TransportCELLULAR TRANSPORT: PASSIVE ANDACTIVE MECHANISMSIons and solutes move through several different types ofcarrier proteins and channels that allow solute movementthrough the plasma membrane in several different ways.

Thecarriers and channels include:■■■■Ion channels and pores that allow diffusion of solutesbetween compartments.Uniporters, which are membrane transport proteinsthat recognize specific molecules, such as fructose.Symporters that transport a cation (or cations) down itsconcentration gradient with another molecule (eitheranother ion or a sugar, amino acid, or oligopeptide).Antiporters that transport an ion down its concentration gradient while another substance is transported inthe opposite direction. This type of transport is oftenassociated with Na+ transport, or may be dependenton gradients of other ions, as in the case of theHCO3−/Cl− exchanger.Transporters (or carrier proteins) can be energy dependent orindependent.

Movement through channels and uniportersfollows the concentration gradient of the molecule or theelectrochemical gradient established by movement of otherions. However, most movement in nonexcitable cells occursthough some expenditure of energy, either by primary orsecondary active transport.Passive TransportRegardless of the type of carrier or channel involved, if noenergy is expended in the transport process, it is consideredpassive transport. Passive transport can occur via simple orfacilitated diffusion.Where:■■■■■Thus, passive diffusion of a molecule across a membranewill be directly proportional to the surface area of themembrane and the difference in concentration of themolecule, and inversely proportional to the thickness of themembrane.Facilitated DiffusionFacilitated diffusion can occur through either gated channelsor carrier proteins in the membrane.

Gated channels are poresthat have “doors” that can open or close in response to external elements, regulating the flow of the solute (Fig. 2.2A).Examples include Ca2+, K+, and Na+. This type of gated transport into and out of the cell is critical to most membranepotentials, except the resting potential (see Chapter 3). Whenfacilitated diffusion of a substance involves a carrier protein,binding of the substance to the carrier results in a conformational change in the protein and translocation of the substanceto the other side of the membrane.Simple and facilitated diffusion do not require expenditureof energy, but do depend on the size and composition ofthe membrane and the concentration gradient for thesolute.

Key differences between these two types of diffusioninclude:■Simple DiffusionIf a substance is lipid soluble (a property of gases, some hormones, and cholesterol), it will move down its concentrationgradient through the cell membrane by simple diffusion (Fig.2.1). This movement is described by Fick’s law.Fick’s LawJi = Di × A (1 X ) × ( C1 − C 2 )Ji represents net fluxDi is the coefficient of diffusionA is the areaX is the distance through the membrane(C1 − C2) is the difference in concentration across themembrane■Simple diffusion occurs over all concentration ranges ata rate linearly related to the concentration gradient—asthe concentration gradient increases, the rate of diffusion from the compartment with high concentration tothe compartment with low concentration will increase.Facilitated diffusion is subject to a maximal rate ofuptake (Vmax).

The rate of facilitated diffusion is greaterthan that of passive diffusion at lower solute concentrations. However, at higher solute concentrations therate of facilitated uptake reaches its Vmax (carrier is14Cell Physiology, Fluid Homeostasis, and Membrane Transportsaturated), while the rate of passive diffusion is not ratelimited by a carrier. Another characteristic of facilitateddiffusion is that the Vmax can be increased by addingtransport proteins to the membrane—this is a key regulatory aspect of the transport process.Semipermeable membraneActive TransportPrimary Active TransportPrimary (1°) active transport involves the direct expenditureof energy in the form of adenosine triphosphate (ATP) totransport an ion into or out of the cell (Fig.

2.3). Althoughthe elements depicted in Figure 2.3 are important in manycells, the most ubiquitous is the Na+ pump (Na+/K+ ATPase).The Na+ pump uses ATP to drive Na+ out of the cells and K+into the cells, which establishes the essential intracellular andextracellular ion environments (Fig. 2.4). Because three molecules of Na+ are transported out of the cell in exchange fortwo molecules of K+ transported into the cell, this helps establish an electrical gradient (slightly negative inside the cell), inaddition to the effects of ion diffusion due to concentrationgradients (discussed in Chapter 3).

The ability of the Na+pump to maintain the internal and external cell Na+ and K+milieu is essential to cell function. If the Na+ pump is blocked(for example, by the drug ouabain), intracellular and extracellular Na+ and K+ would equilibrate, affecting membrane transport and electrical potentials (see Chapter 3).Secondary Active TransportΔxCACBΔC = CA – CBFigure 2.1 Diffusion through a Semipermeable Membrane Ifthe membrane is permeable to a solute, diffusion can occur down thesolute’s concentration gradient. The rate of diffusion is contingent uponthe solute gradient (ΔC) and the distance through the membrane (Δx).Many substances are transported into or out of the cell viasecondary active transport (2° AT, also known as cotransport) with Na+. The Na+ concentration gradient is maintainedby the active Na+/K+ pump, which results in diffusion of Na+into the cell down its concentration gradient through a specific symporter or antiporter (as described earlier), allowingsimultaneous transport of another molecule into or out of theChannelNa⫹ K⫹Cl⫺Ca2⫹ H2OFacilitated Transporter:Permease (Uniporter)D-hexoseUreaGateopenAGateclosedBFigure 2.2 Passive Membrane Transport Passive transport of substances through the membranecan occur via specific channels or transport proteins.

Channels (A) can be opened or closed depending onthe position of the “gate.” The conformational change to open and close gates can be stimulated by ligandbinding or changes in voltage. Specific transport proteins (B) bind substances, undergo conformationalchange, and release the substance on the other side of the membrane.Membrane TransportATPase transporter:Ion ATPase (ion pump)Na⫹/K⫹-ATPaseH⫹-ATPaseH⫹/K⫹-ATPaseCa2⫹-ATPaseⴙⴙⴙⴙⴙ15concentration gradient (e.g., Na+, Cl−, K+, Ca2+) (see Fig.

2.2A).Selectivity depends on the size of the ion, as well as its charge.Gated channels can open or close in response to differentstimuli. Stimuli such as sound, light, mechanical stretch,chemicals, and voltage changes can affect control of the ionflux by controlling the gating systems.Types of channels include the following:■ATPⴙ■ADPFigure 2.3 Primary (1°) Active Transport The proteins involvedin primary active transport require energy in the form of ATP to transportsubstances against their concentration gradients.Ouabain (or digoxin) is a cardiac glycoside derived fromleaves of the foxglove plant, and the plant extract hasbeen used in a variety of ways for hundreds of years.

It is anirreversible blocker of the Na+/K+ ATPase pump, which willallow equilibration of sodium and potassium across the membrane, effectively stopping Na+-dependent transport, and depolarizing the resting membrane potential. Digoxin is used in lowdoses to correct cardiac arrhythmias and in congestive heartfailure. The effective dose of digoxin is near the lethal dose, andexcess amounts can lead to death because of the wide-rangingeffects.