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These G proteins interact with other membranebound proteins that activate second messenger systems. The second messengers represented (cAMP andIP3) activate the effector proteins PK-A (A) and PK-C (B), respectively.Nuclear protein receptorHormoneFigure 2.9 Nuclear Protein Receptors Several lipophilic hormones do not bind to the cell membrane, but instead diffuse through themembrane and are translocated through the cytosol to the nucleus. Inthe nucleus, they bind to receptors associated with the DNA and regulateRNA synthesis.

Because this involves transcription and translation ofproteins, the process takes time to produce the end effect.NucleusEffectDNAProteinsynthesismRNAReceptor tyrosine kinaseGrowthfactorGuanylate cyclaseAdapterproteinNitric oxidesynthasePPPArgNOSGTPNONOAPPPSGCSolubleguanylatecyclasecGMPMAP-kinaseNucleusEffectMonomericG proteinDNATranscriptionfactorsEffectmRNABFigure 2.10 Simple and Complex Transduction Systems A, Some transduction pathways haveimmediate effects, such as those observed with guanylate cyclase activation of cGMP. B, Other pathwaysare far more complex, involving multiple effectors and nuclear transcription, which prolongs the time for thefinal effect.Proteinsynthesis20Cell Physiology, Fluid Homeostasis, and Membrane TransportCLINICAL CORRELATECystic FibrosisThe importance of membrane transporters can be illustrated incystic fibrosis, the most common lethal genetic disease affectingCaucasians (1 in ∼2000 live births).

Cystic fibrosis is caused by adefect in the cystic fibrosis transmembrane regulator (CFTR) genethat regulates specific apical (luminal) electrogenic chloride channels (see Fig. 2.2A). The defect has profound effects on ion andfluid transport, primarily in the lungs and pancreas. In thesetissues, it is critical for Cl− to be secreted into the lumen of theconducting airways and pancreatic acini and ducts, drawing Na+and water. In cystic fibrosis, the CFTR proteins are significantlyreduced, decreasing Cl− secretion and resulting in thick secretions.In the lungs, the thick, dry mucus layer contributes to increasedinfections; in the pancreas, the ducts from the acini are cloggedwith mucus and unable to secrete proper amounts of the buffersand enzymes necessary for proper digestion. The pancreatic insufficiency can result in GI complications such as meconium ileus innewborns and maldigestion, malabsorption, and weight loss as thechild grows older.Cystic Fibrosis Foundation).

Though antibiotics are used to treatthe frequent lung infections, there is currently no cure for thedisease. Treatment includes physical therapy in which the patient’schest and back are pounded to loosen and expel the mucus. Thereare new methods to simulate the percussive action on the mucus,such as the intrapulmonary percussive ventilator and biphasiccuirass ventilation. As lung disease worsens, patients may need touse bilevel positive airway pressure (BiPAP) to assist in the ventilation of clogged airways.In addition to the lung pathology, the effects on the GI tractcaused by pancreatic dysfunction can necessitate surgical removalof areas of the small intestine that are amotile and usually requiressupplementation of pancreatic enzymes that are reduced. In addition, reduction in endocrine pancreas function (insulin, glucagon,somatostatin) can increase the incidence of diabetes in patientswith cystic fibrosis.In all, morbidity is high and lifespan is considerably shortened.

Ifthe patient does not succumb to lung infection, the progressivedecrease in lung function and exercise intolerance usually leads tolung transplant.Cystic fibrosis is usually diagnosed by age 2, and recently the meanage of survival was determined to be 37 years (as cited by theClinical Features of Cystic FibrosisInfancyMeconium ileusMeconium peritonitisJaundiceBeyond infancy Failure to thriveChildhoodSteatorrheaRecurrent bronchopulmonaryinfectionsIntestinal obstructionsAdultHepatic steatosisGallstonesBiliary strictureCBD obstructionPancreatitisFibrosis,cystic dilatationof pancreaticacini, lamellarsecretionPancreasslightly hyperemic,granular, exaggeratedlobulation, roundededgesBronchiectasisBronchopneumoniaMeconiumileusCongenital Cystic Fibrosis CBD, common bile duct.Review Questions21Review QuestionsCHAPTER 1: THE CELL AND FLUIDHOMEOSTASISCHAPTER 2: MEMBRANE TRANSPORT4.

Select the TRUE statement about cell transport processes:1. Antipyrine and inulin are injected into a 60-kg man. Afterequilibrium, blood is drawn, and the concentrations of thesubstances are determined.AntipyrineInulinAmount ofindicator injected50 mg20 mgConcentrationin blood1.39 mg/L1.67 mg/LUsing the values above, select the best answer:A.B.C.D.E.The intracellular fluid volume is 28 L.The interstitial fluid volume is 8 L.The plasma volume is 5 L.The total body water is 42 L.The extracellular fluid volume is 28 L.2. Determine the pressure and direction of fluid movement(in or out of capillary) given the following Starling forces ina capillary bed where σ is approximately 1:HPc = 30 mm Hg HPi = 3 mm Hgπc = 28 mm Hg πi = 8 mm HgA.B.C.D.E.3 mm Hg, into capillary3 mm Hg, out of capillary7 mm Hg, into capillary7 mm Hg, out of capillary19 mm Hg, out of capillary3.

Addition of pure water to the extracellular fluid (ECF) willhave what effect on intracellular fluid (ICF) and ECF compartment volume and osmolarity after steady state is achieved?Assume no excretion of water, and an original plasma osmolarity of 300 mosm/L.A.B.C.D.E.ICF volume decreases, ECF volume increasesICF osmolarity decreases, ECF osmolarity increasesICF osmolarity increases, ECF osmolarity increasesICF volume increases, ECF volume increasesICF volume and osmolarity decreaseA. Simple (passive) diffusion of a molecule is not dependenton the thickness of the cell membrane.B.

Ion channels are relatively nonselective and allow movement of multiple electrolytes through a single channel.C. Voltage-gated channels are ion-specific and open inresponse to a change in membrane voltage.D. Secondary active transport directly uses ATP to move substances in and out of cells.E. Facilitated diffusion requires energy to move substancesin and out of cells.5. The membrane transporter directly responsible for maintenance of low intracellular sodium concentration is the:A.B.C.D.E.basolateral Na+/H+ antiporter.basolateral Na+/Ca2+ antiporter.apical Na+/H+ antiporter.basolateral Na+/K+ ATPase.apical Na+/K+ ATPase.6. Ouabain (digoxin) works by:A.B.C.D.E.stimulating cGMP.blocking Na+/K+ ATPase.stimulating Na+/K+ ATPase.blocking cGMP.stimulating H+/K+ ATPase.This page intentionally left blankSection2THE NERVOUS SYSTEMAND MUSCLEIn complex organisms such as humans, homeostasis requires communicationbetween distant parts of the body; continuous monitoring of changing internaland external conditions; and coordinated, often complex, responses to theseconditions.

This is accomplished in an integrated manner by highlydifferentiated tissues, organs, and systems. This demanding set of tasks isorchestrated in large part by the nervous system, along with various motorsystems that receive its input.Chapter 3Nerve and Muscle PhysiologyChapter 4Organization and General Functions of the NervousSystemChapter 5Sensory PhysiologyChapter 6The Somatic Motor SystemChapter 7The Autonomic Nervous SystemReview Questions23This page intentionally left blank25Chapter3Nerve and Muscle PhysiologyTo understand the physiology of the nervous system andmuscle, it is necessary to examine function in terms ofrelatively simple cellular processes, as well as more complicated interactions between parts of the central nervoussystem, peripheral nerves and receptors, and muscle. In thischapter, basic principles of neuronal and muscular functionare discussed.

The role of the central nervous system in integrating neural and muscular function is considered inChapter 4.RESTING MEMBRANE POTENTIALSCommunication through the nervous system requires generation and transmission of electrical impulses, which in turn aredependent upon the ability of cells to maintain resting membrane potentials. The term resting membrane potential issynonymous with steady state potential. A resting membranepotential is created by passive diffusion of ions through aselectively permeable membrane, producing charge separation. An example using a hypothetical cell is illustrated inFigure 3.1.In the simplest theoretical case, if a cell membrane is permeable to only one ion and that ion is present in higher concentration inside the cell compared with outside, that ion willdiffuse out of the cell until sufficient membrane potential isestablished to oppose further net flux of the ion.

For example,if the membrane is permeable only to K+, and intracellular K+concentration is higher than extracellular concentration, thenoutward net flux of K+ will occur, resulting in a negativemembrane potential, in which the intracellular compartmentis electrically negative relative to the outside of the cell.Only a minute fraction of the ions will diffuse out of the cell,with no appreciable change in ion concentration in the compartments, before the established electrical gradient will besufficient to oppose further outward net flux of the ion. Atthis point, a resting membrane potential will be established.Due to the difference in potential between the two compartments (inside vs.

outside), the excess positive charges remainclose to the membrane in the extracellular compartment,while negative charges line up along the inside of themembrane.Nernst EquationThe electrical potential difference between the inside and theoutside of a cell (EX) can be predicted if the membrane is permeable to only one ion, using the Nernst equation (see Fig. 3.1):E X = ( RT ZF ) ln ([ X ]o [ X ]i )Where:■■■■■■Ex is the Nernst potential or equilibrium potentialln([X]o/[X]i) is the natural log of the ratio of the concentration of ion X outside compartment ([X]o) to theconcentration of the ion inside the compartment ([X]i)R is the ideal gas constantT is absolute temperatureZ is the charge of the ionF is Faraday’s numberIn biological systems at 37°C, this equation can be simplified to:E X = ( 61mV Z ) log ([ X ]o [ X ]i )Thus, in a simple hypothetical situation in which a single,monovalent cation is permeable and its concentration insidethe cell is 10-fold higher than outside (see Fig.