Renal Pathophysiology: The Essentials

394 Pages·2009·11.264 MB·English

by  Helmut G. Rennke MD, Bradley M. Denker MD

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RENAL
Pathophysiology
The Essentials
THIRD EDITION
HELMUT G. RENNKE, M.D.
ProfessorofPathology
HarvardMedicalSchooland
Harvard–MITDivisionofHealthSciencesandTechnology
DepartmentofPathology
Brigham&Women’sHospital
Boston,Massachusetts
BRADLEY M. DENKER, M.D.
AssociateProfessorofMedicine
HarvardMedicalSchool
RenalDivision,DepartmentofMedicine
Brigham&Women’sHospital
ChiefofNephrology
Harvard–VanguardMedicalAssociates
Boston,Massachusetts
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Rennke,HelmutG.
Renalpathophysiology:theessentials/HelmutG.Rennke,BradleyM.Denker.—3rded.
p.;cm.
Includesbibliographicalreferencesandindex.
ISBN978-0-7817-9995-9
1.Kidneys—Pathophysiology. I.Denker,BradleyM. II.Title.
[DNLM:1.KidneyDiseases—physiopathology. 2.Kidney—physiopathology.WJ300
R416r2010]
RC903.9.R6722010
616.6(cid:2)107—dc22
2009013471
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Toourfamilies,
StephanieandChristianne
Mary,Brendan,Jennifer,andMackenzie
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Preface
InthisthirdeditionofRenalPathophysiology:TheEssentials,wehave
maintained the general principles that guided us in the design and ap-
proach of the last two versions of the book. Over these last 15 years,
we have received many comments and suggestions not only from our
second-yearmedicalstudents,butalsofromhousestaff,nephrologyfel-
lows,andcolleagues;wearemostgratefulfortheirfeedbackandencour-
agingwords.Asaconsequenceofthesesuggestions,wehaveexpanded
thesectionsonmolecularaspectsofthemechanismsthatresultinkid-
neydysfunctionandthemorphologicexpressionofthemajordiseases
thataffectthekidney.Theschematicillustrationsareintwocolorsand
thelistofsuggestedreadingshasbeenupdated.Wehavealsoaddedsome
colorimagesthatdepictthehistopathologychangesofthemajordisease
processes that affect the kidney. The core and the principal aim of the
bookremainunchanged:toprovidethestudentwithasolidunderstand-
ingofthemechanismsthatresultinkidneydysfunctionanddiseaseand
to serve as the basic reading material and text for a course in kidney
pathophysiology.
HGRandBMD
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Contents
Preface iv
CHAPTER
1 ReviewofRenalPhysiology 1
CHAPTER
2 RegulationofSaltandWaterBalance 32
CHAPTER DisordersofWaterBalance:Hyponatremia,
3
Hypernatremia,andPolyuria 69
CHAPTER
4 EdematousStatesandtheUseofDiuretics 99
CHAPTER Acid–BasePhysiologyandMetabolic
5
Alkalosis 126
CHAPTER
6 MetabolicAcidosis 156
CHAPTER
7 DisordersofPotassiumBalance 175
CHAPTER UrinalysisandApproachtothePatient
8
WithRenalDisease 199
CHAPTER PathogenesisofMajorGlomerularand
9
VascularDiseases 219
CHAPTER
10 TubulointerstitialDiseases 269
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vi Contents
CHAPTER
11 AcuteRenalFailure 296
CHAPTER
12 ProgressionofChronicRenalFailure 317
CHAPTER SignsandSymptomsofChronic
13
RenalFailure 342
FigureCredits 367
Index 369
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1
REVIEW OF RENAL
PHYSIOLOGY
OBJECTIVES
Bytheendofthischapter,youshouldhaveanunderstanding
ofeachofthefollowingissues:
■ Thegeneralmechanismsbywhichsolutereabsorptionandsecretion
occurinthedifferentnephronsegments.
■ Thefactorsregulatingtheglomerularfiltrationrate.
■ Themechanismsbywhichtheglomerularfiltrationrateismeasuredin
patients.
Introduction
Althoughreadersofthisbookshouldhavealreadycompletedacourseon
normalrenalphysiology,abriefreviewofthebasicprinciplesinvolvedis
helpfulinunderstandingthemechanismsbywhichdiseasemightoccur.
Tubularfunctionswillbediscussedwithamajoremphasisonsodiumand
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2 RenalPathophysiology:TheEssentials
waterreabsorption.Theglomerularfiltrationrateincludingitsregulation
andhowitisestimatedintheclinicalsettingwillalsobereviewed.
Thekidneyperformstwomajorfunctions:
■ Itparticipatesinthemaintenanceofarelativelyconstantextracellular
environmentthatisnecessaryforthecells(andorganism)tofunction
normally. This is achieved by excretion of some waste products of
metabolism(suchasurea,creatinine,anduricacid)andofwaterand
electrolytes that are derived primarily from dietary intake. Balance
or steady state is a key principle in understanding renal functions.
Balance is maintained by keeping the rate of excretion equal to the
sumofnetintakeplusendogenousproduction:
Excretion= Intake+Endogenousproduction
■ Aswillbeseen,thekidneyisabletoindividuallyregulatetheexcre-
tionofwaterandsolutes(suchassodium,potassium,andhydrogen)
largelybychangesintubularreabsorptionorsecretion.If,forexam-
ple, sodium intake is increased, the excess sodium can be excreted
withoutrequiringalterationsintheexcretionofwaterorotherelec-
trolytes.
■ It secretes hormones that participate in the regulation of systemic
andrenalhemodynamics(renin,angiotensinII,andprostaglandins),
red cell production (erythropoietin), and mineral metabolism [cal-
citriol,(1,25-OHdihydroxyvitaminD),themajoractivemetaboliteof
vitaminD].
Thekidneyalsoperformsanumberofmiscellaneousfunctionssuch
as the catabolism of peptide hormones and the synthesis of glucose
(gluconeogenesis)underfastingconditions.
Relation between Filtration and
Excretion
Thenormalglomerularfiltrationrate(GFR)rangesfrom130to145L/day
(90 to 100 mL/min) in women and from 165 to 180 L/day (115 to 125
mL/min) in men. This represents a volume that is more than 10 times
that of extracellular fluid and approximately 60 times that of plasma;
as a result, survival requires that virtually all of the filtered solutes
and water be returned to the systemic circulation by tubular reabsorp-
tion.
Preventingexcessiveurinarysodiumlossisessentialtomaintenance
oftheextracellularandplasmavolumes(seeChapter2).Figure1.1shows
the organization of the nephron, and Table 1.1 lists the relative contri-
butionofthedifferentnephronsegmentstothereabsorptionoffiltered
sodiumandtheneurohumoralfactorsinvolvedinregulatingtransportat