1625915643-5d53d156c9525bd62bd0d3434ecdc231 (Netters - Essential Physiology (на английском)), страница 3

This is especially relevant for drug dosages. Because fat solubility varieswith the type of drug, body water composition (relative tobody fat) can affect the effective concentration of the drug(Fig. 1.5).Intracellular and Extracellular CompartmentsThe intracellular and extracellular compartments are separated by the cell membrane. Within the ECF, the plasma andinterstitial fluid are separated by the endothelium and basement membranes of the capillaries. The ISF surrounds thecells and is in close contact with both the cells and theplasma.The ICF has different solute concentrations than the ECF,primarily due to the Na+ pump, which maintains an ECF highin Na+, and an ICF high in K+ (Fig.

1.6). The maintenance ofdifferent solute concentrations is also highly dependent on theselective permeability of cell membranes separating the extracellular and intracellular spaces. The cations and anions in ourbody are in balance, with the number of positive charges ineach compartment equaling the number of negative charges(see Fig. 1.6). Because the ion flow across the membrane isresponsive to both the electrical charge and the solute gradient, the overall environment is controlled by maintenance ofthis electrochemical equilibrium.The osmolarity (total concentration of solutes) of fluids in ourbodies is ~290 milliosmoles (mosm)/L (generally rounded to300 mosm/L for calculations). This is true for all of the fluidcompartments (see Fig.

1.6). The basolateral sodium ATPasepumps (seen on cell membranes) are instrumental in establishing and maintaining the intracellular and extracellularThe Cell and Fluid Homeostasis5Lungs:Exchangeof gasesGasexchangeO2Kidney:Regulationof water,salt, andacid levelsSkin:Emission ofheat, water,and saltCO2H2OReception and processingof signals; regulationIngestionDigestive tract:Uptake ofnutrients,water, saltsDigestionIntracellularenvironmentWaterbalanceHeatexchangeCirculatory system:DistributionMotilityDigestive tract:Excretion of solidwaste and toxinsMuscle and bone:Movement,support, andprotectionExcretionKidney:Excretion of excess water,salts, acids; excretion ofwaste and toxinsFigure 1.2 Buffering the External Environment In multicellular organisms, the basic homeostaticmechanisms of single-celled organisms are mirrored by integration of specialized organ systems to createa stable environment for the cells.

This allows specialization of cellular functions and a layer of protectionfor the systems.environments. Intracellular Na+ is maintained at a low concentration (which drives the Na+-dependent transport intothe cells) compared with the high Na+ in ECF. The extracellular sodium (and the small amount of other positive ions) isbalanced by chloride and bicarbonate anions and anionic proteins. For the most part, the concentration of solutes betweenplasma and ISF is similar, with the exception of proteins (indicated as A−), which remain in the vascular space (undernormal conditions, they cannot pass through the capillarymembranes). The high ECF Na+ concentration drives Na+leakage into cells, as well as many other transport processes.The primary intracellular cation is potassium ion, which isbalanced by phosphates, proteins, and small amounts of othermiscellaneous anions.

Because of the high concentration gradients for sodium, potassium, and chloride, there is passiveleakage of these ions down their gradients. The leakage ofpotassium out of the cell through specific K+ channels is thekey factor contributing to the resting membrane potential.The differential sodium, potassium, and chloride concentrations across the cell membrane are crucial for the generationof electrical potentials (see Chapter 3).OSMOSIS, STARLING FORCES,AND FLUID HOMEOSTASISOsmosisMembranes are selectively permeable (semipermeable),meaning they allow some, but not all, molecules to passthrough. Membranes of tissues vary in their permeability tospecific solutes. This tissue specificity is critical to function, asseen in the variation in cell solute permeability through a renalnephron (see Chapters 17 and 18). On either side of the membrane, there are factors that oppose and facilitate movementof water and solutes out of the compartments.

These factorsinclude:■■■Concentration of specific solutes. Higher concentrationof a solute on one side of the membrane will favor movement of that solute to the other by diffusion.Overall concentration of solutes. Higher osmolarity onone side provides osmotic pressure “pulling” water intothat space (diffusion of water).Concentration of proteins.

Because the membraneis impermeable to proteins, protein concentration6Cell Physiology, Fluid Homeostasis, and Membrane TransportHydrophilic(polar) regionPhospholipidGlycolipid(e.g., phosphatidylcholine) (e.g., galactosylceramide)AlcoholCholesterolSugar (e.g.,galactose)PhosphateOH groupHydrophobic(nonpolar) regionSteroidregionFattyacid“tails”Fattyacid“tail”CollagenLigandAntibodyIonIntegralproteinPeripheralproteinsIonchannel1SurfaceantigenReceptor23Adhesionmolecule4CytoskeletonFigure 1.3 The Eukaryotic Plasma Membrane The plasma membrane is a lipid bilayer, withhydrophobic ends oriented inward and hydrophilic ends oriented outward.

Primary constituents of themembrane are phospholipids, glycolipids, and cholesterol. There are a wide variety of proteins associatedwith the membrane, including (1) ion channels, (2) surface antigens, (3) receptors, and (4) adhesionmolecules.■establishes an oncotic pressure “pulling” water into thespace with higher concentration.Hydrostatic pressure, which is the force “pushing” waterout of the space, for example, from capillaries to ISF(when capillary hydrostatic pressure exceeds ISF hydrostatic pressure).If the membrane is permeable to a solute, diffusion of thesolute will occur down the concentration gradient (see Chapter2). However, if the membrane is not permeable to the solute,the solvent (in this case water) will be “pulled” across themembrane toward the compartment with higher solute concentration, until the concentration reaches equilibrium acrossthe membrane.

The movement of water across the membraneby diffusion is termed osmosis, and the permeability of themembrane determines whether diffusion of solute or osmosis(water movement) occurs. The concentration of the impermeable solute will determine how much water will movethrough the membrane to achieve osmolar equilibrationbetween ECF and ICF.The Cell and Fluid Homeostasis2/3Bodyx 0.6weightTotalbodywater(TBW)70 kgIntracellularfluid (ICF)28 LCell membrane42 L1/3Extracellularfluid (ECF)14 L3/41/4ISF(75% ECF)ICF2/3 TBW7Interstitialfluid (ISF) ~10.5 LCapillary wallPlasma ~3.5 LPlasma(25% ECF)ECF1/3 TBWFigure 1.4 Body Fluid Compartments Under normal conditions the total volume of water in thehuman body (TBW) is about 60% of the body weight.

Of TBW, most (2/3) is intracellular fluid (ICF), and 1/3is extracellular fluid (ECF). The extracellular fluid is made up of plasma and interstitial fluid (ISF).1.00Ratio of TBW/body weight0.750.60.50InfantMen WomenYoung0.5Men0.45WomenOldFigure 1.5 Total Body Water as Function of Body Weight Under normal conditions, total body water is most affected by the amountof body fat, and there is more body water as a percentage of body weightin infants and women (because of estrogens). Aging also decreases theratio because of reduced muscle mass.Osmosis occurs when osmotic pressure is present. This isequivalent to the hydrostatic pressure necessary to preventmovement of fluid through a semipermeable membrane byosmosis.

The idea can be illustrated using a U-shaped tubewith different concentrations of solute on either side of anideal semipermeable membrane (where the membrane is permeable to water but is impermeable to solute) (Fig. 1.7A).Because of the unequal solute concentrations, fluid will moveto the side with the higher solute concentration (right side oftube), against the gravitational force (hydrostatic pressure)that opposes it, until the hydrostatic pressure generated isequal to the osmotic pressure. In the example, at equilibrium,solute concentration is nearly equal and water level is unequal,and the displacement of water is due to osmotic pressure(Fig. 1.7B).In the plasma, the presence of proteins also produces a significant oncotic pressure, which opposes hydrostatic pressure(filtration out of the compartment) and is considered theeffective osmotic pressure of the capillary.8Cell Physiology, Fluid Homeostasis, and Membrane TransportExtracellular FluidPlasmaIntracellular FluidInterstitial fluidATP200CationsCationsCationsAnionsAnionsMisc./phosphates80Cell membranesCapillaries150100Anions500Figure 1.6 Electrolyte Concentration in Extracellular and Intracellular Fluid The primaryextracellular fluid (ECF) cation is sodium, and the primary interstitial fluid (ICF) cation is potassium.

This difference is maintained by the basolateral Na+/K+ ATPases, which transport three Na+ molecules out of thecell in exchange for two K+ molecules transported into the cell. A balance of positive and negative chargesis maintained in each compartment, but by different ions. (Values are approximate.)Starling ForcesThe oncotic and hydrostatic pressures are key components ofthe Starling forces. Starling forces are the pressures thatcontrol fluid movement across the capillary wall. Net movement of water out of the capillaries is filtration, and net movement into the capillaries is absorption.

As seen in Figure 1.8,there are four forces controlling fluid movement:■■■■HPc , the capillary hydrostatic pressure, favors movement out of the capillaries and is dependent on botharterial and venous blood pressures (generated by theheart).πc , the capillary oncotic pressure, opposes filtration outof the capillaries and is dependent on the protein concentration in the blood. The only effective oncotic agentin capillaries is protein, which is ordinarily impermeableacross the vascular wall.Pi , the interstitial hydrostatic pressure, opposes filtration out of capillaries, but normally this pressure islow.πi , the interstitial oncotic pressure, favors movementout of the capillaries, but under normal conditions,there is little loss of protein out of the capillaries, andthis value is near zero.Movement of fluid through capillary beds can differ due tophysical factors particular to the capillary wall (e.g., pore size,fenestration) and its relative permeability to protein, but ingeneral these factors are considered constant for mosttissues.These forces are used to describe net filtration using the Starling Equation,Net filtration = K f [( HPc − Pi ) − σ ( πc − πi )]in which the constant, Kf , accounts for the physical factorsaffecting permeability of the capillary wall, and s describes thepermeability of the membrane to proteins (where 0 < σ < 1).The liver capillaries (sinusoids) are highly permeable to proteins, and σ = 0.