PathRenalOutline

KranesCategorizationofDisease+AlotofExtras

KidneyDisease

AcuteRenalFailure

IntrinsicKidneyDisease

PreRenal

RenalIntrinsic

SodiumExcretion<1%
SodiumExcretion<1%
BUN/Creatinine>20

CHF,Cirrhosis,Edema

AcuteTubular
Necrosis

SodiumExcretion>2%
BUN/Creatinine<10

AcuteInterstitial
Nephritis

DirtyBrownCasts

SodiumExcretion>2%

PostRenal
Labsarentthatuseful

Acute
Glomerulonephritis

InabilitytoconcentrateUrine
Inabilitytosecreteacid
Edema
Leukocytes
FocalTubularNecrosis

RBCCasts

GlomerularDisease

TubulointerstitialDisease

Urinalysis:Proteinuria+Hematuria
SpotTestRatio>1.5,
24Urinecontains>2.0g/24hrs

NephroticSyndrome
>3.5gprotein/24hrs(hugeproteinuria)
Hypoalbuminemia
Hypercholesterolemia
Edema

BenignProteinuria
SpotTestRatio<1.5,
24Urinecontains<1.0g/24hrs

NephriticSyndrome
HematuriaandProteinuria(<3.5)
RBCCasts
SaltandWaterRetention=HTN
ReducedGFR

Pyelonephritis
AllergicInterstitialNephritis
AnalgesicNephropathy
MultipleMyeloma

Minimalchangedisease
MembranousGlomerulopathy
FocalsegmentalGlomerulosclerosis

MelegSmithsHematuriaBreakDown

MembranoproliferativeGlomerulonephritis
(MPGN)Type1andType2

AcuteProliferativeGlomerulonephritis
Goodpastures(aformofRPGN)
RapidlyProgressiveGlomerulonephritis
PostStreptococcalGlomerulonephritis
IgAnephropathy
Alports

Hematuria

RBCsOnly

Tumor

RBC+Crystals

RBC+WBC

RBC+Protein

Lithiasis(Stones)

Infection

RenalSyndrome

ChemicalAnalysis

Culture

RenalBiopsy

Imaging

ElderlySmokers=RenalCellCarcinoma

Babies+Kids=WilmsTumor
Infection=UrothelialCarcinoma

CastsinUrine

CalciumOxalatemostcommon
MagnesiumPhosphate=Struvite
UricAcidcrystals=radiolucent
CystineCrystals=Cystinuria
AcidicUrineincreasesstone

WhiteCellCasts=Pyelonephritis
WBCwithoutCasts=Cystitis
EColimostcommonagent

RedCellCasts

Glomerulonephritis

WhiteCellCasts

Pyelonephritis

MuddyBrownCasts

|T 2 R e v i e w S h e e t s

SeeKranesChart,Above

AcuteTubularNecrosis
1 of 41

PathRenalOutline

CongenitalAnomalies

AgenesisOftheKidneys
o BilateralAgenesisisincompatiblewithlifefoundinstillborninfants.Withoutkidneys,
amnioticfluidisnotmade,andthebabygetscrushed.Thisiscalledpotterssequence
o UnilateralAgenesisiscompatiblewithlifewithoutotherabnormalities.Thegoodkidney
willbecomeenlargedwithhypertrophy,somedevelopsclerosisandrenalfailure
Hypoplasia
o Failureofthekidneystodeveloptoanormalsize
o Bilateralisextremelyrare,Unilateralisstillrare
o Conditionmaybeindistinguishablefromanacquiredatrophickidney
o Truehypoplastickidneyhasreducedlobesandpyramids(<6)andnosignsofscarring
EctopicKidneys
o Definitivemesonephrosdevelopsatectopicfoci,usuallyonpelvicbrimorwithinpelvis
o Theectopickidneysareusuallysmallandasymptomatic
o Maycausetorsionorobstructionorureter,predisposingforinfection(Pyelonephritis)
HorseshoeKidneys
o FusionoftheKidneysproducesahorseshoeshapedstructurecontinuousacrossthe

anterioroftheaortaandinferiorvenacava,getcaughtbyinferiormesentericartery
HorseshoeKidney
o Most(90%)arelowerpolefusion,whileonly10%areupperpolefusion
connectedatlowerpole
o Riskforstoneformation
CysticDiseases

CysticRenalDysplasia
o Abnormalityinmetanephroticdifferentiation
o Characterizedhistologicallybythepersistenceinthekidneyofabnormalstructures
(cartilage,undifferentiatedmesenchyme,andimmaturecollectingducts)andby
abnormallobarorganization.Largecystssurroundedbymesenchyme
o
Ongross,thereareuniorbilateralcysts,withextremelyenlargedkidneys

Massivecystsonthiskidney.
o Ifunilateral,thereisagreatprognosisiftheaffectedkidneyisremoved;poorprognosis
Youknowitskidneybecause
forbilateralinvolvement
oftheureter

CysticdiseasesarepresentedoutoforderfromRobbinsso
thateachdiseasedoesnotgoontothenextpage(reduces
flippingbackandforth)

Cystssurroundedbymesenchyme

Acquired(DialysisAssociated)CysticDisease
o Causedbyendstagekidneydiseasewithprolongeddialysis
o Cortical+Medullarycyststhatcontainclearfluidormaybleed(hematuria)
o Majorcomplication=renalcellcarcinomafromthewallsofcysts

|T 2 R e v i e w S h e e t s

2 of 41

PathRenalOutline

AutosomalDominantPolycysticDisease=AdultformofPolycysticKidneyDisease
o Pathogenesis
AutosomalDominantInheritancePattern
PolycysticKidneyDiseaseGenes(PKD1andPKD2)onchromosome16and14,
respectively,areimplicatedinthegenerationofcystsviapolcycystinprotein
abnormalityleadingtoproliferationofdifferentregionsofthetubules
Exactmechanismunknown
o Morphology

Bilaterallyenlargedkidneysreachingenormoussizes(4kg/kidneyreported)
Kidneysurfaceisentirelycysts
Surfaceappearsentirelycysticthoughhistologyrevealsfunctionalparenchyma
Arisefromdifferentregionsofthetubulessocystsexpressvariableepithelia
o Clinical
Maybeasymptomaticuntilrenalinsufficiencyannouncespresence
Hemorrhagemaycauseflankpain(bleedingintocysts)orinsightsinvestigation
(hematuria)foundespeciallywithlargepalpableabdominalmasses.
ExtrarenalCystscanbefound

Cutsurfaceshowsinternalcysts
40%occurintheliverfrombiliaryepitheliumandareasymptomatic
Someoccurinthelungsorspleen;mitralvalveprolapseinheart
IntracranialBerryAneurysmsaccountfor10%ofdeathsinthesepts

Cysts(Dark)Kidney(Light)
AutosomalRecessivePolycysticDisease=ChildhoodformofPolycysticKidneyDisease
o Pathogenesis
GenePHKD1codesforfibrocystinexpressedinadult/fetalkidneys
liver/pancreas
Mutationsscrewupthecollectingtubule+biliaryepitheliumdifferentiation
o
Morphology
Withouthistory,thiscanbe
eitherRecessive(kids)or
Enlarged,smoothsurfaced,tinyelongatedcystsalongtheinterior(cortexand
Dominant(Adults)
medulla),perpendiculartothecorticalsurface.
Linedbycuboidalcellsbecauseallcystscomefromthecollectingtubules
InvariablyBilateral
o Clinical
Highlyfatalininfancy,obviousrenalfailureinallcases
4subcategoriesformedbasedononset(perinatal,neonatal,infantile,juvenile)
Childhoodform
showssmallercysts
Survivorsdevelopcongenitalhepaticfibrosis(biliaryepitheliuminorigin)with
atrightanglesto
HTNandSplenomegaly
corticalsurface

Simple(Localized)RenalCysts
o Thesegetmistakenfortumorsbecausetheycreateawkwardradiographicshadows
o Theyaretranslucent,grey,glistening,andlinedbyasinglelayeredmembrane
o Maybleedintothem,causingpainanddistention
o Areusuallysmallandcortical

|T 2 R e v i e w S h e e t s

3 of 41

PathRenalOutline

MedullarySpongeKidney=innocuousmedullarycysticdisease
o Occursinadultswithunknownpathogenesis
o Foundincidentallyonradiograph;increasedriskofstones,hematuria,infection
o Cystsconsistofcuboidalepitheliumfromcollectingtubules

NephronophthisisMedullaryCysticDiseaseComplex=maliciousmedullarycysticdisease
o Pathogenesis
Juvenile=NPHgenesmakenephrocystinwithoutaknownpathogenesisthough
thereareautosomaldominantandautosomalrecessiveforms
Adult=MCKD1,littleisknown
Inducescystsatthecorticomedullaryjunctionandinterstitialfibrosis
o Morphology

MedullaryCystsconcentratedtothecorticomedullaryjunctionthoughsmall
Largecystsatthecorticomedullary
junction
corticalcystsmayexist
Cystsarelinedbyflattenedcuboidalepitheliumwithinflammationorfibrosis
surroundingit
o Clinical
Affectskids,suspectedinunexplainedrenalfailurewithFamilialHistory
Firstpolyuriaandpolydypsiareflectinginabilitytoconcentrateurine
Renalfailureoccursin510years
Cystsmaybetoosmalltoseeonradiograph
ClinicalFeaturesor
Complications
RenalFailure

CysticRenal
Dysplasia
Adultpolycystic
kidneydisease

Inheritance
None

PathologicFeatures
LargeCystsonKidney

Autosomal
dominant

Childhood
polycystickidney
disease
Medullary
spongeKidney
Familialjuvenile
nephronophthisis
Simplecysts

Autosomal
recessive

Largemulticystickidneys,
livercysts,berry
aneurysms
Enlarged,cystickidneysat
birth

Hematuria,flankpain,urinary
tractinfection,renalstones,
hypertension
Hepaticfibrosis

Hematuria,urinarytract
infection,recurrentrenalstones
Saltwasting,polyuria,growth
retardation,anemia
Microscopichematuria

Benign

Acquiredrenal
cysticdisease

None

Medullarycystson
excretoryurography
Corticomedullarycysts,
shrunkenkidneys
Singleormultiplecystsin
normalsizedkidneys
Cysticdegenerationinend
stagekidneydisease

Hemorrhage,erythrocytosis,
neoplasia

Dependenceondialysis

None
Autosomal
recessive
None

TypicalOutcome
Ifunilateral+nephrectomy
prognosisisgood
Chronicrenalfailure
beginningatage4060yr
Variable,deathininfancyor
childhood

Progressiverenalfailure
beginninginchildhood
Benign

|T 2 R e v i e w S h e e t s

4 of 41

PathRenalOutline

GLOMERULARDISEASES(thisisamonstersectionthatlastsfor7pages)

Initiation
o Somethinghastoinitiatetheinflammatorydamagesthatinduceglomerulonephritis
o Eventsareanycombinationofthefollowing
AntibodyAntigenDeposition=TypeIIIHypersensitivity,circulatingAgAb
GranularImmunofluorescence
AntibodyBasementMembrane=TypeIIhypersensitivity,Goodpastures
LinearImmunoFluorescence
AntibodyAntigenPlanted=TypeIIHypersensitivity,Agstuckinglomerulus
GranularImmunofluorescence
TCellDamage=TypeIVHypersensitivity,reactiontoAginendothelium
NoImmunofluorescence,NoimmuneDeposition
o Pathogenesis
ShortterminjuryisclearedbyMacrophagesandtheitisislimited
Longterminjury(Lupus)causespersistentdamagethatbecomeschronic
DifferentinjuriesoccuratdifferentratesuntilGFR=3050%,thentheyprogress
Progression
o OnceGFRgetsdownbetween3050%,progressionisbasicallyconstant,irrelevantof
theseverityortimecourseoftheunderlyinginsultthatcausedit
o Targetfortherapy,sincealldiseasesmustfunneltoonefinalprogressionmechanism
o FocalSegmentalGlomerulosclerosis(FSGS)
Leadstoproteinuriaandhematuriaeveniftheinitialinsultwasnonglomerular
Stemsfromalossofrenalmassfromwhatevercause(ischemia/infarction,
immunemediatedfibrosis,etc.)andisaresultofadaptivechanges
Lossofrenalmassresultsinhypertrophyofremainingglomeruli
Podocytescannotgrowwiththeglomeruli,losingfiltrationbarrier
Proteinsandcellsareallowedtoleakout,resultinginmacrophage
inducedfibrosis,causingareductioninrenalmass
CycleRepeats
TreatedwithReninAngiotensinSystemInhibitors
o TubulointerstitialFibrosis
Literallyfibrosisofthetubulesandinterstitum,opposedtotheglomerulus
Thereisastrongercorrelationbetweenthedeclineofrenalfunctionandthe
amountoftubulointerstitialfibrosisthanwiththeoriginalinsult
Resultsfromtwomechanisms
Infarctionoftubules,possiblyfromalterationsofhemodynamicsinthe
abovecondition(FSGS)
Activationoftubulecellseitherfromproteinuriaorothercytokines.
Activatedtubulecellsexpressadhesionmoleculesandelute
inflammatorycellsthatleadtofibrosis

|T 2 R e v i e w S h e e t s

5 of 41

PathRenalOutline

NEPHRITICSYNDROME=AcuteGlomerulonephritis

AcuteProliferativeGlomerulonephritis/PostStreptococcalGlomerulonephritis
o Definition
Diffuseproliferationofglomerularcellswiththepresenceofleukocytes
o Pathogenesis
PoststreptococcalABetaHemolyticPharyngitisORSkinInfection
FormationofAntibodyagainstMproteinAntigen(ASOtiterelevated)resultsin
immunecomplexformationanddeposition
Enlargedandhypercellular
Immuneresponseresultsinanacutenephriticsyndrome
(noticeallthepurpledots)
o Morphology
LM=EnlargedandHypercellularglomeruli;TubulesoftencontainRedCell
Casts;LMisnotentirelyspecific,useIFandEM
IF=showsgranulardepositsofIgM,IgG,andC3
EM=discrete,amorphous,electrondensedepositonthesubepithelialside
(whichistheimmunecomplex),oftentermedlumpybumpy
EMshowingtheimmune
o ClinicalCourse
complexonepithelialside
Youngchild(610yearsold)withmalaise,fever,nauseaandhematuria(cocoa
urine)12weeksafteraStrepAinfection,showingelevatedASOtiters
95%recoverwellasAgAbisclearedwithFluid/Electrolytetherapy
1%developrapidlyprogressiveglomerulonephritis(Seebelow)
ProlongedandpersistentProteinuria/AbnormalGFRmarksapoorprognosis
o Notes
ThiscanhappenfromotherinfectionsthanStrepA,andarebacterial(Strep
PneumoPneumonia),Viral(HepB,HepC,HIV),orparasite(Toxo,Malaria)
RapidlyProgressive(Crescentic)Glomerulonephritis
NormalkidneyCrescents
o Definition
Severeglomerularinjuryassociatedwiththeformationofcrescentsinmost
glomeruliandisnotnecessarilyassociatedwithonesyndrome
o Pathogenesis
Itisimmunologicallymediated,subdividedbasedonimmunologicalfindings
TypeI=AntiGBMAntibodiesasinGoodpastures;AntiCollageTypeIV
Darkpurpleproliferationswith
theobliterationofBowmans
TypeII=ImmuneComplexasinpostinfectious,SLE,orHenolchSchloen
Space.AlltypesofCresentic.
TypeIII=PauciImmuneakaotherwithoutassociationtoAntiGBMor
immunecomplex,butisassociatedwithANCA(pandc),asinWegners
o Morphology
Histo=Crescents=proliferationparietalcells,macrophages,PMNs,andfibrin
strandsbetweencells,allcontainedwithinbowmansspace
EM=wrinkledandrupturedbasementmembranes
IF=variablepatterndependingontype:1=Linear,2=Granular,3=None
Gross=EnlargedandpalekidneyswithcorticalPetechialhemorrhage.
Smoothlinearpatternof
o
ClinicalCourse
immunofluorescencethatis
Alltypes:hematuria,redcellcasts,proteinuriaapproachingnephroticranges
pathognomonicfor
Goodpastures.Comparethisto
Rapidlyprogressivediseasewithlossofrenalfunction
membranousonpage8
Treatmentisplasmaphoresis(Type2),otherwisesteroidsandcytotoxicdrugs
(antiinflammation)isthewaytogo;prognosisisterrible
|T 2 R e v i e w S h e e t s

ForGoodpasturesseetheInflammationLectureonHypersensitivityforcompletedetailand
immunofluorescentpattern.KaplanseparatesCresenticfromGoodpastures;Dr.Krane
6 of 41
assumesGoodpastures=Cresentic;RobbinssaysGoodpasturesisjustonetypeofcresentic

PathRenalOutline

IgANephropathy(BergerDisease)
o Definition
PrimaryRenaldiseasewhereIgAdepositsarefoundinthemesangium
detectedbyimmunofluorescence
SystemicDiseases,discussedlater,cancauseIgAdepositioninthe
kidneys(HenochSchonleinPurpura)
o Pathogenesis
AssociatedwithaoneparticularformofIgA(IgA1)
AntigenrecognitioninmucosalmembranesresultsinformationofIgAandIgA
complexesthatcirculateintheblood;incitingantigenisunclear
LiverdecomposespolymericIgA(usuallyexistsasadimerinmucosallumen)
LiverdiseasecanpresentwithIgAdepositionandglomerulonephritis
SomeIgAbecometrappedinglomerulusleadingtocomplementactivationand
MesangialProliferationwithinglomerulus
(thedarkregions)
glomerularinjury.
o Morphology
Microscopicchangesarevariable,butmesangialproliferationorovertcresentic
glomerulonephritismayoccur
DiagnosisisbasedonimmunofluorescentstainsforcomplementorIgAinthe
characteristicpatternshowntotheleft(granularmesangialpattern).
o ClinicalCourse

Mostcommonnephropathyworldwide
ImmunofluorescenceshowsIgAin
mesangium;diagnosticofBergers
Fairlybenigngross,brightredbleedinginurineusuallyfollowinganUpper
RespiratoryTractinfection(IgAmediatedimmunity IgAdeposition)
Prolongedprogressiontoeventualrenalfailure

MembranoproliferativeGlomerulonephritis
o Clinical
AdolescentsandChildren
Lowlevelsofserumcompliment
SecondarytoHepBorHepC,orcanbeaprimarydisease(poorprognosis)
NephriticorNephrotic Ifyoucanttellwhichitis,pickthisone
o Pathogenesis
Immunecomplexdepositionand/orC3complementactivation
Silverstainshowscapillaries
C3willbelowinplasmaserumbecauseitgetsusedup
surroundedbyadoublelayered
BM
Thereismesangialproliferation(theprolifverativepart)withinvolvementof
thebasementmembrane(membranopart)
o Morphology
LM=Hypercellularity+Basementmembranethickening&splitting=tramtrack
Lookforsilverstaintogiveyouabetterpictureofsplitting
Arrowheadis
IF=IgG,IgMandC3inagranularpatternpushedtotheperiphery
extraBMlayer
EM=SubendothelialDeposits(capillarylumenside,withtheRBCs)
RBC

|T 2 R e v i e w S h e e t s

SubendothelialElectron

DenseDeposits

7 of 41

PathRenalOutline

NEPHROTICSyndrome

DefinitionandpathogenesisofNephroticSyndrome
o Aninitialeventcausesaderangementofglomerularcapillarieswithincreased
permeabilitytoprotein,withresultantproteinuria
o Albuminleaksoutalongwiththeproteinurialeadingtodecreasedcolloidpressure
o Edema(periorbital+peripheral)resultfromthelossofcolloidpressurewithsubsequent
ADH/aldosteronefluidretention(becauseallfluidisintheinterstitum,itlookslike
thereisfluiddepletion)exacerbatingtheedema
o
Hyperlipidemia/cholesteremiahasacomplexgenesis,butexistsinnephroticsyndrome
LinearbutGranularoutlineof
theBM(likegoodpastures)but o Patientsareatanincreasedriskofinfection
itsdotted(notassmooth).This
Lipiduria (maltese cross)
isMembranous
MembranousGlomerulonephropathy
o CriticalConcepts
Mostcommoncauseofnephroticsyndromeinadults
Eitherisidiopathicorissecondarytoanimmunedisease
Doesnotrespondwelltocorticosteroids
o Definition
Diffusethickeningoftheglomerularcapillarywallwithaccumulationofelectron
denseimmunoglobulinswithdepositsontheSubepithelialsideoftheBM
o
Pathogenesis
Thickeningofcapillarywalls
ChronicImmuneComplexDepositionDisease

Idiopathic=MHCsusceptibility+anunknownnephritogenicantigen
Spikesprotrudingoutintothe
Secondary=LSE,drugs(penicillamine),tumors,metals(drugs/mercury),or
electrondensematerial(lightgrey
infections(HepC,HepB,shistosomiasis,malaria)
intothedarkgrey)
o Morphology
LM=Uniformdiffusethickeningofbasementmembrane,thickcapillaryloops
EM=densedepositsinsubepithelialside,withtheBMformingspikesinto
thedeposit.Spikeswillgrowoutandencompassthedepositformingdomes
IF=Immunoglobulinsandcomplimentinalinearbutgranularpattern String of Pearls
o ClinicalCourse
Usuallyinsidiousonsetofnephroticsyndrome
ElectronDenseMaterialshownby
Proteinuriaisnonselectiveanddoesnotrespondtocorticosteroids
thearrow(domesnotpresent)
EventualsclerosisofglomerulileadstoelevatedBUN,Creatinine,andHTN

MinimalChangeDisease
o CriticalConcepts
Mostcommoncauseofnephroticsyndromeinchildren.
CharacterizedbyeffacedfootprocessesonEMwithanormalLMglomerulus
Enormouslyresponsivetocorticosteroidsandremitsafterpuberty
o Definition
Achildhoodnephroticsyndromethatischaracterizedbyeffacedfootprocesses
Normal,happylookingGlomerulus
onEMresultinginmassiveproteinuriawithanormalglomerulusonLM
ofminimalchangedisease.There

isNOvisiblepathology
|T 2 R e v i e w S h e e t s

8 of 41

PathRenalOutline

Pathogenesis
Unknown,butthereissomelinktoautoimmuneorpostinfection,eventhough
thesechangescanbeseenintheabsenceofimmunedepositionorinfection
o Morphology
LightMicroscopyshowsanormalglomeruluswithoutanychanges
ElectronMicroscopyshowseffacedfootprocesses,vacuoles,andfused
podocytes,whichareactuallyjustflattenedepithelium
IFshowsnothing;thereisoftennoimmunedeposition
o ClinicalCourse
Effaced(fused)podocytes.You
Primarytargetischildren,thoughadolescentsandyoung20saffected
shouldseelittlefeetextending
out(youcanseeremnantson
Despitemassiveproteinuria,thereisapreservationofrenalfunctionwithout
thecapsideonthebottomof
hematuriaorhypertension
theimage).
Effectivelytreatedbycorticosteroids,andalthoughresistanceordependence
maydevelop,diseaseremitsafterpuberty.
FocalSegmentalGlomerulosclerosis(FSGS)nowthedisease,insteadofprogression.
o Definition
Sclerosisofsome,butnotall(i.e.focal)glomeruliaffectingonlypartofeach
affectedglomeruli(i.e.segmental)withnephroticsyndrome
o Pathogenesis
Possiblyaprogressionfromminimalchangediseasewithsimilareffacementof
NormalPart
podocytesbutwiththeextraepithelialdamageandsclerosisunderLM
Nephringenescodeforcelladhesioninteractionsatthediaphragmand
mutationsinnephringenescauseacollapseofthefiltrationbarrier
Proteinuriaresultswithsubsequententrapmentofplasmaproteins,resultingin
hyalinosisandsclerosisofaffectedsegments

NormalGlomeruliScleroticPart
o Morphology
LM=partsofsomeglomeruliareeosinophilic(pink)withsclerosis***
EM=EffacementofpodocytesasinMinimalChangeDisease(above,thispage)
Sclerosedpart
Normalpart
IF=IgMandC3inscleroticareas
o ClinicalCourse
Affectsadultsandkids,usuallyblacks,associatedwithHIV,HepB,HepC
Doesnotrespondtocorticosteroidsanddoesnotremitspontaneously
Somewillendwithrapidonsetrenalfailure(2years)whilesomemaylastas
longas10;renaltransplantationordialysisisinevitable
Zoomedinonadifferent
glomerulus
o Notes
Thereisamorphologicaldistinctvariantthatalsoinvolvescompleteglomerular
collapseandsclerosiswiththefocalsegmentalchangesofFSGSinHIVpositive
patients,calledcollapsingglomerulosclerosis.
TheRenalAblationFSGSthatoccursaftertheremovalofadiseasedorhealthy
nephroticsegmentcausedbyhypertrophyoftheremainingsegmentwas
discussedabove,thefirsttimeweencounteredFSGSasaprogression.
|T 2 R e v i e w S h e e t s

9 of 41

PathRenalOutline

HereditarySyndromesofIsolatedHematuriageneticGlomerulonephropathies

Alports=Nephritic
o Definition
Xlinkeddisorderinvolvingcollagenformationcharacterizedbyrenalfailure,
auditorydisturbances,andeyeproblems(cornealatrophy,lensdislocation)
o Pathogenesis
DefectiveglomerularbasementmembraneasaresultofadefectintypeIV
collagensynthesis
LackofalphachainsrendersthesepatientimmunetoGoodpastures,

sincetheylackthealpha3antigen
Defectisinparticularofthealpha5chainofcollagentypeIV
o Morphology
A AisforAlports
EMrevealschanges;geneticscreeningdeterminesdisease
L LPisarecord,thatyoulistento;
FullblowndiseaseisshownonEMasalternatingthickeningandthinning
remindsyouofdeafness
P
glomerularbasementmembranewithlaminationofthelaminadensa
o ClinicalCourse
O Oisforocular
Diseaseonsetisatbirth;symptomstonotoccuruntillaterinlife
R RRenalfailure
AssociatedwithVisionAbnormalitiesandAuditoryProblems
T TThickeningofBMand
TypeIVCollagen
Earliestsigns(microscopichematuria)detectedbetween520years
OvertKidneyFailureoccursbetween2050years.

ThinBasementMembraneDiseaselikealports,butnot
o Benignfamilialhematuriadiscoveredbyroutineurinalysis
Ineveronceencountered
thisonanyQbankor
o DiagnosisconfirmedbyEMdemonstratingthinningofGlomerularBasement
practiceexam.Itshere
Membrane
becauseitwasinRobbins
o CausedbyadefectinTypeIVcollagenformation(alpha3,maybealpha4)
o 5TypeIVcollagenpresentandtherearenoocularorauditorylesions(notAlports)
andthereisnoIgAimmunedepositioninthemesangium(notIgANephropathy)
o Prognosisisexcellentwithamaintenanceofnormalrenalfunctionthroughoutlife
ChronicGlomerulonephritistheendpointofallNephroticandNephriticSyndromes

Endpointofalldiseasesdiscussedhere,occurringatvaryingratesdependentonprimarydisease
Histologymaydemonstratepathologyoftheoriginaldisease,thoughchronic
glomerulonephritisischaracterizedbyextensivehyalinizationandfibrosisoftheglomeruli,
demonstratedbylargeamountofcollagenonatrichromestain
Becausehypertensionisoftenconcomitantwithchronicrenalfailure,arterialsclerosismaybe
presentaswell
Inevitably,chronicrenalfailureleadstouremiawithcharacteristicchanges(pericarditis/
secondaryhyperparathyroid)Courseisprogressiverenalfailure,oftenwithhypertension,
eventualedema,and,withoutdialysisorrenaltransplant,death.OthersignsofCKD(edema)
maybepresent.

|T 2 R e v i e w S h e e t s

10 of 41

PathRenalOutline

Disease
Poststreptococcal
glomerulonephritis

Presents
Nephritic

Clinical
95%Recover
1%RenalFailure

Pathogenesis
Antibodymediated;
circulatingantigen(ASO
titer)TypeIIIhypersens

GoodpastureSyndrome Nephritic Plasmaphoresis& AntiGBMCOL4 A3antigen

(TypeICresentic)
Steroids.95% (collagentypeIV,alpha3)
RenalFailure
IdiopathicRPGN
(TypeIIICresentic)

Nephritic

IgAnephropathy

Nephritic

Painless
Hematuria,
Recurs

Alports

Nephritic

ANCAassociated;no
circulatingimmune
depositionorantiGBM
antibody.
Unknown;maybeassociated
withsystemicIgAdiseaseor
Virus.

HearingLoss, Xlinkeddisorder oftypeIV

Visionproblems, collagenalpha5(geneCOL4
Nephritic
A5)

LightMicroscopy
Immunofluorescence
Diffuseproliferation;
Granular IgGandC3in
leukocytic(PMNs)infiltration GBMandmesangium.
LumpyBumpy
Crescents

Crescents

SmoothLinear IgGand
C3,neonsignpattern

ElectronMicroscopy
Subepithelialhumps

Nodeposits;GBMdisruptions;fibrin

Linear orGranular,not Samething,notveryuseful,because

veryuseful.
therecanbedeposits,canbe
anywhere,ornotbethereatall.

Focalproliferative
glomerulonephritis;
mesangialwidening

Granulardepositionof
IgAinmesangium

Mesangialandparamesangialdense
deposits.Basically,youwontuseit.

Notlisted

Notlisted

Alternatingthickeningandthinningof
thebasementmembrane

Membranous
glomerulopathy

NephrOtic Mostcommonin
adults.

AntibodyMediated,
penicillamine,Lupus,Hep
B/C,gold/mercury,schisto

Thickeningofthebasement
membrane

GranularIgGandC3;
diffuse

Subepithelial deposits;
SpikeandDomebasement
membrane

MinimalChange
(LipoidNephrosis)

NephrOtic Kids,Steroids=
GreatPrognosis

Unknown,podocytes
effacement

Normal

Normal

Lossoffootprocesses;
Podocytefusion/effacement

Focalsegmental
glomerulosclerosis

NephrOtic Adults,evenwith Unknown.Mostcommonin Focal(onlysomeglomeruli)

steroids=poor AfricanAmericans.Lossor andsegmental(onlypartof
prognosis
renaltissue,SickleCell,
eachglomerulusaffected)
Heroin,AIDS,obesity.
sclerosisandhyalinosis.

Membranoproliferative

glomerulonephritis NephrOtic
(MPGNTypeI)
or
Nephritic
Densedepositdisease

(MPGNTypeII)
Chronic
glomerulonephritis

CKD

Dialysisand
Transplant

|T 2 R e v i e w S h e e t s

Nonspecific

Immunecomplex deposition
(I)IgG+C3;C3levelsare
andactivationofIgGand
MesangialProliferation,
lowerinbloodfrom
complement
Basementmembranesplitting complementactivation
TramTrackAppearance
Autoantibody:alternative
(II)C3 levelslow;C3

complementpathway
nephriticfactor
Endstageofeverydisease Hyalinized/Fibrotic glomeruli
listedabove
thathidesprimarydisease

Nonspecific

Lossoffootprocesses,
SubendothelialDeposits

(I)Subendothelialdeposits

(II)Densedeposits
Notuseful

TakenfromBigRobbins,Modifiedtobeeasiertouse(Kaplanhelpedabit). KaplansMedEssentialsincludes
someotherclinicalcluesandprognosis.ItjustdidntfitwiththeinformationRobbinsandKranewantedyou
toknow.RPGN=rapidlyprogressiveglomerulonephritis
11 of 41

PathRenalOutline

Disease
Poststreptococcal
glomerulonephritis

Serum
Presents Complement
Nephritic
Lowered

LM
Hypercellular

EM
Subepithelialdeposits
describedaslumpy
bumpy

IF
GranularIgGC3

Patho/Prognosis
ChildrenfollowinganinfectionofgroupABeta
HemolyticStrepwithelevatedASOTiters.Patients
dowellwithconservativetreatment.95%recover,
1%goesontorenalfailure.

Goodpasture
Syndrome

Nephritic

Nochange

Crescents

Nonspecific

LinearBM
NeonSignPattern

AntiGBMautoantibodyagainstcollagenTypeIV
alpha5.Presentswithhemoptysisandhematuria,
malesintheir20sor30s.Horribleprognosis
thoughplasmaphoresisandtransplantaretried

RapidlyProgressive
Glomerulonephritis

Nephritic

Nochange

Crescents

Nonspecific

Nonspecific

Thereisarapidprogressiontorenalfailure,usually
followingGoodpastures.itcanresultfromStrepA
infections,butmostofthemrecover

IgAnephropathy

Nephritic

Nochange

MesangialProliferation

Nonspecific

GranularIgAin
mesangium

Itisthemostcommonnephriticsyndromeworld
wide.Comesonafteranupperrespiratory
infection.HenochSchloneinPurpurapresent.

Low
Low
Low

Tramtracking of
basementmembrane

Nonspecific,typeIIhas
densedeposits

GranularC3pattern

Slowlyprogressivedisorderthatisrefractoryto
treatment.TypeIIhasacirculatingnephriticfactor
thatbindstoanddestabilizesC3.

Nonspecific

ThickeningandThinning
ofBM

Nonspecific

Presentswithblindness,deafness,hematuriain
kids.ItisadefectincollagentypeIValpha5.Itisa
progressivediseaserefractorytotreatment

Membranoproliferativ Nephriticor
(I)=ImmuneComplex Nephrotic
(II)=DenseDeposit
Alports

Nephritic

NoChange

Membranous
glomerulopathy

NephrOtic

NoChange BMthickening,Silverstain
showsspikes

MinimalChange
(LipoidNephrosis)

NephrOtic

NoChange

Normal

Focalsegmental
glomerulosclerosis

NephrOtic

NoChange

Someglomeruli(focal)
wherenotallofthe
glomerulusiseffected
(segmental)

Nonspecific

Nonspecific

Associatedwithheroin,AIDS/HIV,RenalAblation.
Thereisapoorresponsetosteroidsanditrecursin
transplants.Mostcommonnephroticsyndromein
AfricanAmericans.

Chronic
glomerulonephritis

CKD

Nochange

Hyalinized/Fibrotic
glomerulithathides
primarydisease

Nonspecific

Nonspecific

Endstageofalldiseasesthatarelistedabove.
Anemia,Uremia,elevatedBUN,elevated
creatinine,proteinuriaandHTN.Death.

|T 2 R e v i e w S h e e t s

SpikeandDomes,
subepithelialdeposits
withBMextending
PodocyteEffacement

GranularLinear (looks Variableprognosis.AssociatedwithHepB/HepC,

likeGoodpastures heavymetals(goldmercury),drugs(penicillamine),
dotted)
andsicklecelldisease
Nothing
Mostcommoninkids.Greatresponsetosteroids
withawonderfulprognosis!

Doneagaininahowtoanswerthequestionformat.ThiswascreatedfromlisteningtoKaplansLectures.I
thinkitsgotlessthantheothertable,butIendedupmakingthisonetohelpgetthroughLippincottsReview
12 of 41
questions.Thingsinboldaretheuniqueorbuzzwordassociation.

PathRenalOutline

GlomerularLesionsAssociatedwithSystemicDiseases

Lupus
o LupusformsAntibodyAntigencomplexesthatdepositintheglomerularfiltration
barrier.
o Macrophageactivationleadstoinjuryandeventualfibrosisoftheglomerulusandeven
somevasculitidies.
o RenalFailureisoneofthemostseverecomplicationsinthekidney,givingriseto
hematuria,acutenephritis,nephroticsyndrome,andhypertension
HenochSchonleinPurpura
o ProbablyaspectrumofdiseaserelatedtoIgAnephropathy(Bergers)
IgAisdepositedintherenalmesangium,sometimesC3
HenochSchonleinisalsosystemicwhileBergersislocalizedtokidney
o PresentswithPuriticskinrashesonextensorsurfacesofarmsandlegs
SkinlesionscontainnecrotizingVasculitiswithmicrohemorrhage
o Onsetof38yearswithexcellentprognosisunlessominousclinicalsignsarepresent
(crescentsorsevereprolongednephroticsyndrome)
Amyloidosis(AssociatedwithMultipleMyeloma)
o CongoRedPositiveandapplegreenbirefringentpatterns
o Amyloid,usuallythelightchain(AL)isdepositedinareasoflargebloodflow:glomerular
capillariesandmesangium
o Progressestoworseningrenalfailurewitheventualterminationfromuremia
o SeenunderEMasmassivebasementmembranewithoutdeposits
o Urinalysisshowsheavyproteinuria(largeUprotein/Ucreatinineratio)withonlytrace
proteinondipstick
Dipstickpicksupalbumenonly,Uprotein/Ucreatinineshowsallprotein

LightChainsarenotalbumen,butareprotein!
Thishugechunkdoesnotlook
likeanythingelse
FibrillaryGlomerulonephritis
o Lookslikeamyloidonhisto,butwithoutCongoRedorAppleGreenPolarizedLight
o DoeshaveIgGandC3onImmunofluorescence
o Unknownetiology
EssentialMixedCryoglobulinemia
o IgGIgMcomplexesinduceVasculitisandmembranousglomerulonephritis
o AssociatedwithHepC
PlasmaCellDyscarias
o MultipleMyelomaproduceslotsofmonoclonalimmunoglobulins
o LesionslooklikeamyloidwithoutCongoRedorAppleGreenPolarizedLight
o Calledlightchainormonoclonalimmunedeposition
BacterialEndocarditis
o Particularlyoccurringwithrheumaticfever,circulatingantigenscauseimmune
depositionandnephritis
Discussionofdiabeticnephropathybeginsonthenextpage
|T 2 R e v i e w S h e e t s

13 of 41

PathRenalOutline

DiabeticGlomerulosclerosis/Nephropathy
o Definition
Termappliedtothearrayofvascularandrenallesionsthatoccurconcomitantly
inthekidney(hyalinizedarteriosclerosis,glomerularfibrosis,etc.)
o Pathogenesis
Discussedintheendocrinesection,themaincauseofthedamageisthesame
fordiabeticangiopathy,withsalientpointsrelatedhere
MetabolicDefect
DecreasedInsulin=IncreasedGlucose
IncreasedGlucose=ProliferationofTypeIVcollagen(sclerosis)
IncreasedGlucose=AdvancedGlycosylationEndProducts
HemodynamicDefect
IncreasedglucoseleadstoincreasedfiltrationandGFR
GlomerularHypertrophyensues
Hypertrophyleadstosclerosisandlossofrenalmasswithresultant
compensatoryhypertrophy,leadingtomoresclerosis,etc.
o Morphology
CapillaryBasementMembraneThickening
Nodular,AcellularLesionsinthe
periphery
Partofthediabeticangiopathy

Concomitantlywithtubularbasementmembranethickening
DeterminedonlybyEMstudies
DiffuseMesangialSclerosis
Mesangiumproliferates,becomesthickened,thensclerotic
Occursdiffuselythroughouttheglomerulus
NodularGlomerulosclerosis
KnownisKimmelstielWilsondisease

Allthedarkpinkstuff(PASpositive)is
MesangialSclerosisbecomesnodularandacellular
themesangialsclerosis.Robbinsdidnt
Nodulesmayimpingeoncapillariesleadingtoischemia,deformationof
haveapictureofBasementMembrane
theglomerulartuft,andtubularnecrosis.
thickeningofDM
o ClinicalCourse
EarlyfindingsaresubtlemicroalbuminuriaandanelevatedGFR
Soonafter,overtproteinuriadevelops,witheventualdeclineofGFRintoend
stagerenalfailure
SystemicHypertensionmayoccurpriortoproteinuriaormicroalbuminuria.
Thehypertensionmayleadtothedisease,mayoccurfrom,orsimply
exacerbate
Pancreatictransplantationcanreversetheglomerulopathyassociatedwith
Type1DM

|T 2 R e v i e w S h e e t s

14 of 41

PathRenalOutline

INTERSTITIALANDTUBULARDISEASES
Disease
TipOff
AcuteTubular
DirtyBrowncastsinUrine,
Necrosis
usuallyfollowsIschemia
Tubulointerstitial Eosinophilia,Rash,Fever
Fibrosis
AcuteTubularNecrosis

Pathogenesis
IschemiaorToxins
Inflammation

Definition
DamagetoTubularEpithelialCells
AcuteDiminishedRenalFunction
Eosinophilia

Definition
o Clinicopathologicfindingcharacterizedmorphologicallybydamagetotubularepithelial
cellsandclinicallybyaacutelydiminishedrenalfunction
o Mostcommonformofacuterenalfailure
o OccursaseitherIschemicATN(trauma,sepsis,shock)orNephrotoxicATN(seecauses)
Pathogenesis
o IschemicATNcausedbyanacute,severelossofbloodfloworobstruction,usually
associatedwithtrauma;canalsobecausedbytoxins
o TubularEpithelialCellshavehighmetabolicdemands(constantmassiveresorptionand
Na/KATPase)
o Ischemic/PoisonedcellslosecellpolarityinsertingNa/KATPaseontheluminalaspect,
increasingdistalsodiumdelivery,inducingvasoconstrictionviatubuloglomerular
feedback
o Ischemiccellsdetachfromthebasementmembrane,obstructlumen,increase
bowmanshydrostaticpressure,decreasingGFR
o VasoconstrictionfurtherdecreasesGFRbyconstrictingafferentarteriole
Morphology
o IschemicATNshowsfocaltubularepithelialcellnecrosisandbasementmembrane
eruptionwithlargespacesofunaffectedtubuleinbetween
o ToxicATNshowsfocal,nonspecificnecrosisparticularlyattheproximaltubule
o Inbothcasesmoresubtlefindingsarepossible
LossofBrushBorder

Simplificationofcellarchitecture
CellVacuolizationandEnlargement
Causes(Toxic)
o Rhabdomyolysisfollowingcrushinjuriesoranyotherconditionthatbreaksdown
muscle(cocaine,statins,cyclosporine,alcoholism).Myoglobinisreleasedandisdirectly
Mostcommonlythisis
nephrotoxic
causedbyischemic
o Aminoglycosidesaredirectlynephrotoxicandcauseacuterenalfailurein1520%of
conditions(renaltubules
hatehypoxia).Secondly,
patients.Thesearereservedforlifethreateninggramnegativesepsis
thiscanbecausedbydrugs
o CisplatinumandCyclosporine,amongstotherchemotherapeuticagents
o ContrastDyeishyperosmolarand,especiallyinthedehydratedstate,canleadto
neprhotoxicityinapatientwithalreadydiminishedkidneyfunction(diabetics)
o Crystaldepositionfromeithertumorlysissyndrome(lymphoma/leukemia)orfromthe
ingestionofethyleneglycol(whichformsoxalate calciumoxalatestones)
|T 2 R e v i e w S h e e t s

15 of 41

PathRenalOutline

ClinicalCourse
o Becauseofthepatchynatureoftheischemia,andthetendencytomaintainbasement
membraneattachmentoftheunaffectedcells,repairandresolutionislikelygiven
supportivecare.
Batuman,atTulane,
o Phases(disparitybetweenBatumans4stagesvsRobbins3stages)
organizesthisas
EvolutionPhase=ashortperiodduringwhichthenephrotoxicinsulthasnotyet

causedacuterenalfailure.ThereisaslightriseinBUN.
(1)Evolution
MaintenancePhase=sustaineddecreasesinBUNandurineoutput(oliguria),a
(2)Oliguria
GFR~0,andtheinabilitytotoleratewaterloads.Electrolytedisturbancesare
(3)Polyuric
common(hyperK).Withpropermanagement,thepatientwillpushthroughthis
(4)FunctionalRecovery

RecoveryPhase.Renalfunctionbeginstoimproverapidlywithresolutionina
Robbinscombines
fewweeks.Thereisaninitialpolyuriaaswaterbalanceisrestored(excessfluid
PolyuricandFunctional
thatgotjammedupisnowallowedtoexit).BewarehypoK
recovery
o Dialysis,thoughperformed,doesnotincreasesurvivalorprognosis.
o DirtyBrownGranularCasts,alsocalledrenalfailurecastsarediagnosticforATN
PyelonephritisandUTI(theycauseTubulointerstitialDisease)

Definition
o Infectionoftheuretersandrenalpelvisresultingintubules,interstitium,andpelvis
beingaffectedbyinfection;kidneys=nephritis,pyramids=pyelo,bladder=cystitis
o Canbedividedintoacuteandchronicpyelonephritis
CommonEtiologyandPathogenesis
o Bacteria
Gramnegativebacteriaviaendogenousspread=EColi,Proteus,Klebsiella,

Cartoondemonstrating
Enterobactercomefromfecalflora,thoughStaphandothersarepossible
possibleroutes
Canbespreadhematogenously(rare)orthroughascendinginfectionfroma
lowerurinarytractinfection(common)
o AscendingInfection
Beginswithcolonizationoftheurethra
Entrancetothebladderisachievedviacatheterization(males)orfromascent
throughasmallurethra(females)
VesiculouretalRefluxallowsbacteriatogainaccesstoureters.

Congenital=malformedorincompetentvalve
Thebladder,ureters
Acquired=Atonyofthebladder
(dilated)andthekidneys
alllightupduringvoiding.
IntrarenalRefluxoccurswitheachcontractionofthebladder,urineexitingthe
Onlybladdershouldbelit
urethraandtheureters,pushinginfectionup(especiallywithoutflow
obstruction)
o ThisistheintroductiontoPyelonephritisinRobbins,whichthendivergesintochronic
andacutepyelonephritis

|T 2 R e v i e w S h e e t s

16 of 41

PathRenalOutline

AcutePyelonephritis

Definition
o Infectionofthekidneyintheacutesetting
Pathogenesis
Neutrophilsintubule
o Invariablyascendinginfectionthoughhematogenousspreadispossible.
o Descriptionofvesiculouretalrefluxonlastpagedescribedpathogenesis
AcutePyelonephritisMorphology
o Hallmark=patchyinterstitialsupparativeinflammation,intratubularWBCaggregates

(WBCcastsonurinalysis)andtubularnecrosis
Interstitialandtubularinfiltrateof
o Affectstheupperandlowerpolesmorethanthemiddle
neutrophils
o Abscessesarepossibleingrossoronthescope
o Papillarynecrosisisseenindiabeticswithdistalpyramidnecrosis
o Pyonephrosisissevereinfectionthattotallyoccludesthelumenandoutflow
o Healingbringsvariablescarstotheaffectscortexbutalwaysshowsfibrosisofthe
underlyingrenalpelvisandcalyces
AcutePyelonephritisClinical
o Males<1and>40aremorecommon.Whenunder1yo=congenitaldefects)andover
40yo=catheterizationandprostateobstruction
o Womenmorecommoninadultagesbecauseofashorterurethra
o Dysuria/Frequencywithsuddenonsetofpaininthecostovertebralangle(FlankPain)
o Cultureshowsbugs,urineshowsWBCs(whitecellcasts)

Papillarynecrosis
o Patientscomeinandtheyaresick.Realsick.Fever,Malaise,etc.
confinedtopyramids
o Treatwithantibioticsagainsttheculturedbug
ChronicPyelonephritis

Definition
o Tubulointerstitialinflammationcausesdiscrete,corticomedullaryscarsoverlyingdilated,
blunted,anddeformedcalyces.
Pathogenesis
o AscendingInfectionsthatconstantlyrecurcancausechronicPyelonephritis.The
pathogenesisisthesameasforacute,buttheyhappenoverandoveragain,worsening
destructionofkidneys
o ObstructiveUropathypreventstheflowofurine,givingbacteriaaplacetogrow.If
thereisonlyoneinfection,butitsallowedtogrowandgocrazybecauseofan

obstruction,youcangetthesamechronicchanges.
LumpyBumpyscarring
dilatedbluntedcalyces
o Xanthogranulomatous(rare)maymimicrenalcellcarcinomaingrossandhisto
Dilatedcalycesandpelvis
Morphology
o Corticomedullaryscaringoverlyingdilated,blunted,ordeformedcalyx
o Sclerosisofarteriesinaffectedregions
o Dilated,flattenedepitheliumfilledwiththyroidcastsonhisto

Clinical
o Withreflux,therecanbeaninsidiousonsetwithoutsymptoms
|T 2 R e v i e w S h e e t s

17 of 41

PathRenalOutline

FSGSispossiblewithincreasedscaring;proteinuriaisapoorprognosticfinding

TubulointerstitialNephritiscausedbyDrugs(AllergicNephritis)

Definition
o Immunemediatedreaction(HypersensitivityTypeIandIV)toavariablenumberof
drugsresultingintubulitisandacuterenalfailure
Pathogenesis
o Itisnotdoserelated
o Drugsactsasahaptenuntilconcentratedinthetubulesforexcretioninurinewhereby
activationofIgEandT/B/Plasmacellsinthelocalizedarea
Morphology
o Pronouncededemaintheinterstitum
o Eosinophils/Neutrophilsarepresentinlargenumbers
o Granulomasmaybepresent;variousstagesofnecrosisandhealing
Clinical
o Fever,Rash,Eosinophilia,andAcuteRenalFailure(increasedSrCrandoliguria)240
(average15)daysafterexposuretooffendingagent
NSAIDs,SyntheticPenicillins,others(Allopurinol)
o RemovalofDrugsleadstorecoveryandhealing

AnalgesicNephropathy

NecroticPapilla
MedullaryFibrosis

Definition
o ChronicRenalDiseasecausedbyexcessiveanalgesicmixturesresultinginchronic
tubulointerstitialnephritisandrenalpapillarynecrosis
Pathogenesis
o Phenacetinanditsmetaboliteacetaminopheninjurescellbybothcovalentbindingand
oxidativedamage
o AspirincausedownregulationofPGI2,vasoconstriction,papillaryischemia(pyramids)
o VolumeDepletionexacerbatesboth

o Papillarynecrosisoccursfirst,followedbycorticaltubulointerstitialnephritis
Morphology
o Depressedareasofcortexoverliepapillarynecrosis
o Patchy(early)andtotal(late)necrosisofpapillaonhisto
o Medullashowsinterstitialfibrosisandinflammation,aproductofobstructioncausedby
papillarysloughingintotubulelumen
Clinical
o Peoplewithheadachesormusclepains(analgesicusers/abusers)
o Papillarydamage=inabilitytodiluteurine/secreteacid=metabolicacidosis
o Drugwithdrawl=reversalandhealing
o Increasedriskfortransitionalcellcarcinomaoftherenalpelvis

|T 2 R e v i e w S h e e t s

18 of 41

PathRenalOutline

DISEASESOFTHEBLOODVESSELS
BenignNephrosclerosis

FibrousThickening
associatedwith
hypertension.

DefinitionandPathogenesis
o SclerosisoftherenalarteriolesandsmallarteriesassociatedwithagingandHTN
o Sclerosisfrommedialandintimalthickening
o HyalineDepositionfromextravazationofplasmaproteinsthroughinjuredepithelium
Morphology
o HyalinizedArterioleswithtypicalarteriolarchangesinHTNseenincardioblock
o Kidneysarenormaltosmallwithaleatheryappearanceingross
Clinical
o Usuallyinconspicuousbutproteinuria,decreasedGFR,andanincreasedrisktowards
chronicrenalfailuredoexist

MalignantHypertensionNephrosclerosis

OnionSkinning

Definition
o Renaldiseasewithtypicalarterialchangesassociatedwithmalignanthypertension
Pathogenesis
o ExtremeBP=endothelialcelldamage,increasepermeability,plateletactivation,fibrin
extravazation,andnecrosis,allsummingupintofibrinoidnecrosis
o HyperplasticChanges(onionskinning)resultsfromcompensatorychanges
o Thekidneybecomesischemic
o IschemiaresultsinactivationoftheReninAngiotensinAxis,activationofANGIIandan
exacerbationofHTN
o Resultisaviscouscycleleadingtomalignantarteriosclerosis
Morphology
o FibrinoidNecrosis=eosinophilic,fibrin+necrosiswithoutinflammatorycells
o OnionSkinning=concentricduplicationofthebasementmembrane
Clinical
o DiastolicBP>130mmHg,renalfailure,papilledema,retinopathy
o Proteinuria,maybehematuria,presentsatonsetwithpreservationofrenalfunction
o Chronicconditionresultsintotalrenalfailureanduremicdeath

UnilateralRenalArteryStenosis

Isuncommon,butishistoricallysignificant(animalmodelsofconstrictedrenalarteries
producedincreasesinbloodpressureinproportiontotheamountofstenosis)
Resultsfromcardiovascularchanges(atheromatousplaques)thatleadtoadecreasedRBF,
elaboratingANGIIviatheRAS

ThesepatientstoverywellwithACEIorARBandsurgeryisdefinitivetherapy
Yellowshowsmedialthickening
andstenosedlumen.Darkbands
stainingelastin |T 2 R e v

iewSheets
19 of 41

PathRenalOutline

ThromboticMicroangiopathies=HUS/TTP

Groupofoverlappingclinicalmanifestations
o TTP=pentad=thrombocytopenia,Microangiopathichemolyticanemia,thrombosis,
o HUS=TTPwithouttheneurologicsymptomsbutwithrenalfailure
Despitebeingpathogeneticallydistinct,HUS/TTPisconsideredonesyndrome
Pathogenesisiseitherfromendothelialinjuryandactivationorfromplatletteaggregation
o vWFelaborationleadstoclots
o DecreasedNOorPGI2increasesvasoconstrictionandpermitsclots
o Denudationoftheendotheliumresultsinexposuretothrombogeneticbasement
membrane
Types
o Classic(Childhood)HUS
Causes
E.ColiHamburgers(O157:H7)containingshiggaliketoxin
ToxincausesdenudationofepitheliumanddecreasedNOsynthesis
Clinical
Suddenonsethematemesisandmelenafollowingaflulikeprodrome
Oliguria/Hematuria/HemolyticAnemiamayfollow
Managedbydialysis,acutesettingresolvesitself,thoughlongterm

Stainforfibrinshowsplateletfibrinclots
prognosisispoor
(theredstuff)intheglomerularcapillaries
Morphology
(thegreenbluestuff)
Fibrinoidnecrosisoflobulararteries
Intermesangialhemorrhage
IntimalHyperplasiaandThrombosis
o AdultHUS
LSE/AntiphospholipidAntibodies=HUSwithoutimmunedeposition
Infection
Complicationofpregnancy=uncomplicateddeliveryresultsinspontaneous
renalfailureadayto3monthslater.
VascularRenalDiseases=Wegners,scleroderma,HTN
Chemotherapy=cyclosporine,bleomycin,cisplatin
o FamilialHUS
Thereisadefectincomplementregulatoryproteins
ResultsinComplement(C3)activation,thrombosis,andcapillarydestruction
o Idiopathic
LinkedtoplateletaggregationADAMTSgene
Itsidiopathic

|T 2 R e v i e w S h e e t s

20 of 41

PathRenalOutline

OtherVascularDisorders

Whitecortex(infarct)

AtheroscleroticIschemicRenalDisease
o OccurringespeciallyinadultsBilateralrenalarterystenosiscausesrenalischemia
o HTNmayactuallybeabsent,butwithbilateralstenosis,ANGIIisusuallyelevated
o AvoidACEIandARBssincethedecreaseinANGIIwilldilatetheefferentarteriole
resultinginanincreasedRBFbutadecreasedGFR=acuterenalfailure.
AtheroembolicRenalDisease
o Embolifromatheromatousplaquesproximaltorenalartery(aorta,coronary
angiography)
o Causesnoproblemsinhealthykidneys,butinfarctsleadtoARFindiseaseskidneys
SickleCellNephropathy
o Sicklinginthevasarectadecreasesconcentratingabilityandincreasesthrombosis
o Characteristicsarehematuria,diluteurine,andproteinuria
DiffuseCorticalNecrosis
o FollowsmalignantHTN,ObstetricEmergencies,SepticShock,andExtensiveSurgery
o Ischemiaandnecrosisislimitedtocortex,withwhiteinfarcts
o Thrombosisofglomerulusandrenalartery;hemorrhagemaybepresent
Infarcts
o Kidneyisandendorganwithlittlecollateralcirculation
o Infarctsarewhiteandwedgeshaped.

PinkCenter(normal)

Disease
BenignNephrosclerosis

Image
Hyalinizedarterioles
(fibrousthickening)

Presentation
Onlyafteryearstodecadesof
HTN

MalignantHypertension
Nephrosclerosis

OnionSkinning
(hyperplasticchanges)

UnilateralRenalArtery
Stenosis

Usuallyshownonarteriogram
withdilatedarteryproximal
tostenosis
Hypoplastic/Smallkidneyson
CTorXray.Stenosedlumen
withmedialthickening
Plateletfibrinclotswithin
glomerularcapillaries

DiastolicBP>130+other
changes(ocular)fromCardio
block
Otherkidneycompensates,
treatwithACEIorARB

BilateralRenalArtery
Stenosis
ChildhoodHUS

AdultHUS

Causedbyavarietyofthings

AtheroembolicRenal
disease

Swollenbluefeet

|T 2 R e v i e w S h e e t s

Pathophys
MedialandIntimalthickeningofarterioles,
compensatoryresponsetoprotective
vasoconstrictionagainstHTN.
ExtremeHTNinducesfibrinoidnecrosisand
ischemiawhichleadstoANGIIrelease,
increasingbloodpressure(viscouscircle)
Medialthickeningandstenosisofthelarger
renalartery/musculararteries.

SevereHTN,highlevelsof
PatientsarereliantonANGIItomaintain
ANGII,Aldosterone,and
theirGFR(increasesresistanceonefferent
Renin
arteriole);DONOTGIVEACEIorARB
Childrenwhohaveaflulike
EnterohemorrhagicEColi(0157:H7)
prodromewithhematemesis, ingestioncontainsshiggaliketoxin
melena,andhematuria
Hematuria+UremiainaSyndromethatfollowsinfection,lupus,vascular
renaldiseases(Wegners),orevenanormalpregnancy
Swollenpurplishfeetafter
Manipulationofatheroscleroticaorta
somesortofaorticrepairor
proximaltorenalarteriesproduces
coronarycatherization
cholesterolembolithatlodgeinkidneys

21 of 41

PathRenalOutline

MetabolicAcidosis(10PageHandoutfromSimon)

TBL/PBLStuffnotfoundinRobbins,takenfromselected
handouts(Na,K,BodyWater,Prostate,Acid/Base).It
wasanadditional~40pagesofreading.Thisdoesnot
includesummariesofTBLjournalarticles.

Causes
o LossofHCO3
DiarrheacauseslossfromtheGItract
ProximalTubularAcidosisortreatmentwithCarbonicAnhydraseinhibitor
o DecreasedH+Excretion
Occursduringearlyrenalfailure(proximaltubuleandcollectingducts)
Renaltubularacidosiscreatesaelectrochemicalbarrierresistanttoexcretion
Aldosteroneinhibition
o AcidLoadingexceedingrenalhandlingcapacity
Requiresalargeamountofacidconsumption(toxicityfromSalicylates,methanol,
ethyleneglycol)orendogenousproduction(lacticacidosis,diabeticKetoacidosis)
AnionGap
o UsefulfordifferentiatingMetabolicAcidosisintotwoforms,definedbythefollowingformula

AnionGap=[Na] [Cl] [HCO3]normalis1012

o HighAnionGap=additionoforganicacids(notH+)suchaslacticacidorketoacidsthat
consumethebicarbwithoutaffectingthechlorideconcentration
SevereRenalFailure
LacticAcidosisfromhypoxiaproduceslactate
Ketoacidosisseenindiabeticsandmalnourishedalcoholics
PoisoningssuchasSalicylates,methanol,andethyleneglycol
RememberedbythemnemonicMUDPILES(Methanol,Uremia,DKA,Paraldehyde,
Isoniazid,Lactic,Ethanol,Salicylates)
o NormalAnionGap=additionofvolatileacids(HCl)thatcombinewithHCO3decreasingHCO3
levelsbutreciprocallyincreasingthechloridelevels,effectivelyleavingtheaniongap
unchanged
DiarrheacausesalossofHCO3inthestool
RenalTubuleAcidosis
TypeI=DistalDefect.ThereisnolossofHCO3butinsteadthereisaninabilityto
acidifytheurine(intercalatedcellsofdistaltubulecannotsecreteH+andmake
HCO3).Theurineisthereforeneverlessthan6.UrinepH>6
Seepage21for
TypeII=ProximalDefect.Theproximaltubulenormallyreabsorbsallthefiltered
breakdownofall
bicarbonate.Infanconissyndrometheproximaltubuleisbunk,andcannotresorb
acidosis,alkalosis,and
bicarbonate.Thedistaltubulehaslimitedcapacitytoresorb,sobicarbislostinthe
whichlabvaluesto
urineuntilaserumlevellowenoughtobereabsorbedbytheproximaltubuleis
reached,UrinepH<5.5.AlsoassociatedwithMultipleMyeloma.
lookat
TypeIV=AldosteroneDefect.ItisthemostcommonRTAassociatedwith
hyperkalemia.Itiscommonindiabeticnephropathy,ACEIadministration,and
|T 2 R e v i e w S h e e t s

22 of 41

PathRenalOutline

urinaryobstruction.ThingsthatreduceReninAngiotensinAxis,blocktheeffectsof
ANGII,decreaserenalsensitivitytoANGIIorreducealdosteroneactivity.
MetabolicAlkalosis

Cause
o MaintenanceProcess+GeneratingProcess
Normally,analkaliload(additionofbicarborlossofacid)iseasilyaccommodatedby
thekidneys.Itrequiresaconcomitantmaintenanceprocess(volumedepletionismost
common,renalfailureisanother)andageneratingprocess(alkaliload)toinducea
metabolicalkalosis
Types
o ChlorideResponsive(urinechloride<10)
GeneratingProcess=Vomiting,NGSuction,orDiureticLossofNaCl
MaintenanceProcess=VolumeDepletion
VolumedepletioncausesresorptionofBicarb,releaseofAldosterone(whichcauses
hydrogensecretion),andadecreasedGFR.CombinethatwithalossofacidfromtheGI
tractandalossoffluidfromdiuretics,andyouvegotmetabolicalkalosis
o ChlorideResistant,associatedwithexcessmineralcorticoids(urinechloride>20)
Mineralcorticoidexcesseitherfromaprimaryissue(hyperaldosteronism/Cushings)or
fromasecondaryissue(renalarterystenosiscauseincreasedReninAngiotensinAxis)
resultsinincreasedsecretionofacid
o PostHypercapneicMetabolicAcidosis
COPDersarechronicCO2retainers.Thiscausesarespiratoryacidosisthatisoffsetbya
metabolicalkalosis(increasedbicarbfromthekidneys).Ifthedoctorthen
hyperventilatestheCOPDpatientinordertofixanoxygenationproblem,thepatient
willblowoffCO2(nomoreacidosis)andbeleftwithalotofbicarb(creatingarelative
alkalosis)becauseCO2changesfasterthanHCO3does.
o MilkAlkaliSyndrome
Consumingmilkandantacids(antacidsasinbicarb)leadstoprecipitationofbicarbin
thekidneys

RespiratoryAcidosisandAlkalosis

Essentially,changesinrespiratoryratesorairwayobstructioncausechangesinCO2levels.
ChangesinCO2levelshappenfasterthanbicarbcompensation,soyouareleftwithonlyCO2
alterations.
Acidosisoccurswithhypoventilation(central,airwayobstructionCOPD,neuromuscular)
Alkalosisoccurswithhyperventilation(CNSsystem,Pregnancy)

|T 2 R e v i e w S h e e t s

23 of 41

PathRenalOutline

PossibleDerangements

MetabolicAcidosis
MetabolicAlkalosis
RespiratoryAcidosis
RespiratoryAlkalosis

pH
PCO2
[HCO3]
CompensatoryResponse

Hyperventilation

Hypoventilation

RenalHCO3Reabsorption

RenalHCO3Secretion
HendersonHasselbalchEquation:pH=pKa+Log[HCO3/(PCO2*0.03)]
PrimaryDisturbanceCompensatoryResponse

Whencompensated,thepHisnormal,butCO2andbicarbaredifferent.Whenuncompensated,pHis
deranged,oftenwithonlyachangeineitherCO2orBicarb.ThisisdependentontheHenderson
Hasselbalchequation,below.Thepointisthatifonethingchanges(HCO3orCO2)theothermustchange
inthesameamountinorderforthepHtoremainconstant.Theonlyvariables,then,arebicarbandCO2,
everythingelseisconstant.Thisiswhatyouwereaskedtodoinphysio.
Whenbicarbchanges,pCO2mustchangethesameamountin
ordertokeepthepHconstant.Theoppositeistrueaswell.

ChlorideResponsive ChlorideInsensitive
UrineChloride<10
Vomiting,NGSuction,
Diuretics

UrineChloride>20

HTN

TypeIRTA

DistalTubuleProblem
CannotSecreteH+
pH>6

TypeIIRTA
ProximalTubuleProblem
pH<5.5
MultipleMyeloma
CannotreabsorbBicarbonate

TypeIVRTA
AldosteroneDefect
MostCommonRTA
Diabetics,ACEI,UrinaryObstruction
AssociatedwithHyperkalemia

Garters
Gitelmans

ExcessMineralcorticoids
fromeitheraprimary
tumororsecondary
activationofRAS

HandlingAcidBasequestionsisharderinPaththanitwasinPhysio.ThepH,bicarb,andCO2pointyouin
therightdirection.Nowyouhavetousetheaniongap(serumchloride),urinechloride,potassiumand
urinepHtodeterminewhatdiseaseprocessisgoingon.Thenyouhavetoknowsomethingaboutit.
|T 2 R e v i e w S h e e t s

NoHTN

24 of 41

PathRenalOutline

NaandWater(20pagehandoutfromSimon)

NormalPhysio
o Segmentsofthekidney:
PCT=Isoosmotic,tAL/TAL=Diluting,DCT=Diluting,CD=variable
o ADHregulateswhethertheCDiswaterpermeableorimpermeable
ADHisapolypeptidethatis9aainlength,madebythehypothalamusand
storedattheposteriorpituitary
OsmoticStimuli@thehypothalamusinduceADHrelease
BaroreceptorsdetectdropsinvascularfluidvolumeandinduceADHrelease.
Baroreceptorscanhaveastrongereffectunderextremestimuli,butOsmotic
Receptorsaremoresensitiveintheminutetominutechanges
Green=releaseofADHinresponseto
ReleaseofADHleadstoactivationofV2(vasopressin)receptors,cAMPand
changesinosmolarity;smallbutsensitive
insertionofAquaporinChannels
Red=releaseofADHinresponseto
changesinvolume;largebutinsensitive

ProblemsofUrinaryDilution(fluidretentionbecauseyoucannotgetridofwater)
o GeneralPathogenesis
Decreaseddeliveryofurinetodilutingsegments
DependentonRBF(shock)andGFR(renalfunction)
Iftheamountfilteredisless,ortheamountreabsorbedintheproximal
tubuleisless,thenthereislesswatertobeexcretedattheCD
DecreasedNaReabsorption
Askdude
IncreasedPermeabilityofCollectingDucts
ItissupposedtobecontrolledbyADH,soaberrantADHproduction,or
oversensitivitytoADHwillproduceaconcentratedurine
Alternatively,decreasedurineflowallowsforthesmallamountof
permeabilitythereistoact,reabsorbingthewater
o SpecificPathologies
VolumeDepletion
Lossofisotonicvolume(hemorrhage)causesaRBF=GFR= Proximal
TubulereabsorptionresultingindeliveryofeverythingtoCD
Unlesswateristakenon(thirstviaANGII)therewillbenochangeinNa
concentration;ifwateristakenon,thentherewillbehyponatremia
CHF/Cirrhosis/NephroticSyndrome
Alltheseconditionscausesomesortofedemasuchthattotalbody
waterandtotalbodysodiumarenormal,buttheeffectivecirculating
volumeislow.
ThiscausesnonosmolarADHreleaseaswellasadecreaseddeliveryof
urinetodilutingsegmentsfromRBFandGFR

|T 2 R e v i e w S h e e t s

25 of 41

PathRenalOutline

ChronicRenalFailure
IfyouhavecrapGFRbecauseofchronicrenalfailure,youcannotget
wateroutofyourbody
Leadstofluidretentionandhyponatremia
Hypothyroidism
Controversialpathogenesis,thoughaCOmimicsCHFpathogenesis
AdrenalInsufficiency
Aldosteroneisresponsibleforsodiumreabsorptionatthecostof
potassiumintheCD.Deficiencyresultsinvolumedepletiondiuresis
GlucocorticoidsplayaroleinCO,sowithoutthemthereisBP
TogethertheyinduceanonosmolarADHrelease
Diuretics
Includedinthissectionbecausetheyinducehyponatremia
LoopsblockNaattheTAL,ThiazidesattheDCT,resultinginvolume
depletionandhyponatremiaalongwithhypokalemia
SyndromeofInappropriateADH(SIADH)
ADHsecretingtumors,CNSabnormalities,orpulmonarydisease
PatientsreleasetomuchADH,arethereforefluidoverloadedwithout
edemawithmildorundetectablehyponatremia
o

Clinical

Hyponatremia=Hypotonicityinmostcases
Hypotonicityresultsinedema(waterentersthemorehypertoniccompartment)
resultingincerebraledemathataccountsforsymptoms
Symptoms=lethargy,agitation,anorexia,seizures,etc.
Treatment=isotonicsalinereplacement.HypertonicSaline+Lasixisa
dangeroustreatmentusedforsevere,acutehyponatremia
ProblemsofUrinaryConcentration(youcannotconcentrateitsoyoupeeitout)
o GeneralPathogenicMechanisms
Increasedurinedelivery
Oppositeofproblemsofurinarydilution.
Iftoomuchfluidisdelivered,reabsorptionmaybeinadequate
Includesincreasedflowratesaswellasincreasedvolume
InhibitionofSodiumReabsorptioninTAL
Requiredforcountercurrentexachangeandmedullaryhypertonicity
Contributestowashout
WaterReabsorptionproblems
ToolittleADH,orafailuretorespondtoADHmeansnowater
reabsorption
MedullaryWashout
Countercurrenteffectmaybeabolishedbyrapidflowratesorinhibited
countercurrentexchangeintheLoopofHenle

|T 2 R e v i e w S h e e t s

26 of 41

PathRenalOutline

SpecificPathologies
CentralDiabetesInsipidus
Abnormallylow[ADH]causesdiuresisrequiringpolydypsia
Causedbymanythings,thoughisoftenidiopathicorsurgical,but
alwaysoriginatingfromtheCNS/Pituitary
NephrogenicDiabetesInsipidous
NormalADHbutwitharesponsivenessoftherenaltubule
XLinkedDefectoftheV2(vasopressin)receptorpossible
Morelikelytobedamagetotubules(suchasinATN)
OsmoticDiuresis
SubstanceisfilteredthroughtheglomerulusbutnotreabsorbedinPCT
Obligateswatertoremaininlumeninordertobalanceosmoles
Increasesurineflowrates(washout)andlimitsreabsorption
AssociatedwithMannitol,ContrastDye,andDiabeticGlycosuria
ProteinMalnutrition/Cirrhosis
Concentrationofurinereliesonurea
Ureaismadebytheliver,inresponsetoproteinmetabolism
PsychogenicPolydypsia
Abnormalthirstreflexcausesconsumptionofaberrantvolumesoffluids
leadingtoincreasedfluiddeliveryandtheinabilitytoconcentrate.
Renalresponseisappropriate(gettingridofexcessfluid)butmayrisk
electrolytedisturbances
o DifferentialDiagnosisandTreatments
SerumOsmolarity
DecreasedinPsychogenicPolydypsia
IncreasedinCentralandNephrogenicDiabetesInsipidous
WaterDeprivationTest
Restrictfluidsfor24hrs,measuringBP,VitalSigns,andweightregularly
Onceurineosmolalityhasplateaued,giveadoseofADH
o UrineOsmolalityresultsinCentralDiabetesInsipidus
o NochangeinPsychogenicorNephrogenic
Dangerousbecausepatientswhoarevolumedepleted(diabetes
insipidus)canbecomehypovolemicrapidlywithwaterdeprivation
Disease
Tests
Treatment
CentralDiabetesInsipidous SerumOsmolalityfromWaterLoss
AdministrationofADHanalogs
IncreasedUrineOsmolalitywithADH
NeprhogenicDiabetes
SerumOsmolalityfromWaterLoss
Notverygood;givediureticstogetrid
Insipidous
IncreasedUrineOsmolalitywithADH ofsalt,dietchangestorestrictsalt
PsychogenicPolydypsia
SerumOsmolalityfromWaterintake Restrictfluids(consciousrestriction)
IncreasedUrineOsmolalitywithADH

|T 2 R e v i e w S h e e t s

27 of 41

PathRenalOutline

Clinical
Hyperosmolar=Hypernatremia(exceptionisDiabeticKetoacidosis)
Symptomsarethesameasforhyponatremia,butareduetowaterlossfrom
cellsintheCNS,notedema.
Ifyoucannotconcentrateyoururine,youlosewaterthroughthekidneys.You
canalsolosewaterthroughtheGIandthroughsweat.
Ifyoucannottakethewaterbackon,sodiumisreabsorbed,butwaterisnot,
youbecomehypernatremic

Potassium(10pagehandoutfromSimon)

ExtrarenalHandling
o DietaryconsumptionwithoutExtrarenalmechanismswouldleadtoextracellular
concentrationsofpotassiumthatarerapidlyfatalevenafteronemeal
o Certainmechanismsareactivatedthatadjustextracellularpotassiumthatmaintain
homeostasisthatdoesnotrequirerenalhandling
Insulingoestheuptakeofglucoseandpotassium
BetaAdrenergicStimulation(epi)notonlyisadditivetotheglucose
metabolismofinsulin,butalsotothecellularuptakeofpotassium
Aldosterone(apparentlyinadditiontotherenaleffects)increasesuptake
RenalHandling
o Sincepotassiumreallyisntconsumed,whatcomesinthroughthediet,mustpassout
throughurineandfeces.
o Themainactionofpotassiumhandlinginthekidneyoccursintheprincipalcellsofthe
collectingtubules
BasalNa/KATPasebringspotassiumintothecellandsodiumoutofthecell
ApicalNachannelsallowleakintothecell,whicharepumpedoutthebasalside
ApicalKchannelsallowleakintothelumen
Overalleffectisonesodiumresorbedforonepotassiumlost

o Aldosteroneisthedrivingforcetoimproveallelectrolytechannelsoftheprincipalcells
IncreasestheApicalNa+leakchannels
IncreasetheApicalK+leakchannels
IncreasestheNa/KATPasechannels
o UrineFlowRatealsoplaysaroleinrenalexcretion
Higherflowratesresultinincreasedlossinpotassium=washouteffect
Decreaseflowratesresultindecreasedlossinpotassium
Hypokalemia
o Rarelyaconsequenceofdecreaseddietaryintake
o TranscellularPotassiumShiftscanoccurwiththeadministrationofsomediuretics,or
evenmoresowiththeadministrationorreleaseofinsulinandepinephrine
o TruePotassiumDefects
Diarrhea.GIlossthroughloosestoolcanaccountforlossofbothdietaryand
extracellularpotassium,upto80mEq/L

|T 2 R e v i e w S h e e t s

28 of 41

PathRenalOutline

Vomiting.PotassiumisNOTLOSTinthevomitus,butdehydrationfromfluidloss
stimulatesaldosteronewhichcausesanexcessofpotassiumloss.Theeffectof
increasebicarbonatecreatesamorenegativelumentodrawK+out(minor)
Diureticsarethemostcommoncauseofhypokalemia.Theyincreaseurineflow
rates,clearingmorepotassium.Some(loopdiuretics)directlyinhibit
reabsorptionofpotassiuminthethickascendingloopofhenle.Finally,volume
depletioncanleadtoaldosteronerelease
RenalArteryStenosiscausesadecreasedflowthroughthekidney,elevatedJGA
activationwithReninAngiotensinAldosteroneactivation
o EffectsofHypokalemia
Muscleweaknessandintestinalileusat2.5mEq/Lorless
CardiacConductivityalterations=heartblock,afib,vfib,Vtach
Hypokalemiapotentiatessideeffectsofdigitalis
Metabolicalkalosismaybeperpetuatedbyhypokalemia
o Treatment
Givethemoralpotassium,butmonitorsoyoudontovershoot.
Hyperkalemia
o Causes
IncreasedIngestionorIntravenousInfusionusuallycauseatransientandmild
hyperkalemia(unlessyouaretryingtokillsomeonewithpotassium)
UncontrolledDiabeticshavedecreasedinsulinproductionaswellasosmolar
gradientsthatshiftelectrolytesoutofthecell.Theymostoftenhavesome
dilemmawithrenalhandlingfromdiabeticnephropathyorosmolarchanges
RenalExcretionProblemsisthemaincauseofsignificanthyperkalemia.
ReducedGFRresultsinincreasedpotassiumexcretionuntilGFRissolowthat
potassiumcanbesufficientlysecreted(akaIneedDialysis)
SeverelydecreasedECFVolumecausesareducedGFRandurineflowrates.This
isnotthe17yearoldgirlwhoisvomiting,butthe34yearoldmanlostinthe
desertforaweek
***ACEInhibitorscausehyperkalemia***alongwithpotassiumsparing
diureticssuchasSpironolactone.
Pseudohyperkalemiaoccurswhenyousqueezeyourmuscles(depolarization
resultsinpotassiumreleaseforrepolarizationorRBChemolysisreleasesK)and
thenurseisdrawingyourbloodwhileyousqueeze(localizedhyperkalemia)
o EffectsofHyperkalemia
Usuallyasymptomatic,evenathighlevels(ashighas7)
PeakedTwavesthenwidenedQRSonECGisominousforfatalarrhythmias
o Treatment
Dependsonlevelofhyperkalemiaandpathophysiologythatbroughtiton
Forourcase,diabeticsrequireinsulinandfluids(dilutionandfluidshifts)

|T 2 R e v i e w S h e e t s

29 of 41

PathRenalOutline

PROSTATE
Normalandinfo

Prostateweighs20gramsandisdividedinto5zones
Tubularglandsseparatedbyfibromuscularstromasurroundedbyacapsule
Glandsarelinedby2layersofepithelialcells
NormalgrowthiscontrolledbyDihydrotestosterone(DHT)ametaboliteofTestosterone,made
viatheLeydigCellsandanenzymecalled5alphareductase.

InflammationofProstate

AcuteBacterialProstatitis
o CausedbyE.ColiandsometimesStaphorEnterococcusfromalowerUTI(cystitis)
o Dysuria,Fever,Chills,Perianalpain;theprostateistenderandsoft
o ProstaticSecretionsshowgreaterthan9neutrophilsperhighpowerview
ChronicBacterialProstatitis
o FrequentboutsofUTI frequentprostaticinfection
o Dysuria,PelvicDiscomfortandLowerBackPain
o Infiltratesofplasmacells,lymphocytes,andmacrophages
NonbacterialChronicProstatitis
o Mostcommonprostatitisoccurringinallagegroupsofsexuallyactivemen
o Showsnegativecultures,butlikelytobeanatypicalbug(mycoplasma/Chlamydia)
GranulomatousProstatitis
o Diagnosedhistologicallywhichmaybenecrotizingornonnecrotizing
o Itmaymimicprostaticcarcinomaclinically,grossly,andhistologically
o Itisoftensecondarytosurgicalmanipulation(biopsy/TURP)orstromalinfiltrationof
prostaticfluid.

BPH=NodularHyperplasia

Definition
o Commondisorderdefinedasenlargementofprostateduetoproliferationofglandular
andstromaresultinginoutflowobstructionfrombladder
Pathogenesis
o Withage,testosteronedecreases,estrogenincreases,andDHTstaysthesame
EstrogensincreasesensitivityfortheDHTreceptorsinprostate
Testosteronereallydoesntplayanyrole
DHT(fromLeydigcells)hasanincreasedselectivityonepithelialnuclear
androgenreceptorsthatinduceglandularandstromalproliferation

|T 2 R e v i e w S h e e t s

30 of 41

PathRenalOutline

Morphology
o Enlargementbeginsinthetransitionalandperiurethralzones
Causescompressionandobstructionofurethra
o Gross=largefirmgreywhitetanwithnarrowcentralurethraandpotentialprostatic

caliculi(stoneswithintheprostate)
o Histo=glandularhyperplasia(withadoublelayerofepithelialcells)mixedwitha

hyperplasticstroma.
Clinical
o Menstartingintheir50s,90%haveitbythe80s,blacks>whites,25%asymptomatic
o Presentswithnocturia,urgency,hesitancy,inabilitytostop/dribbling
o Rectalexam=firmrubberymass
o Completeobstructionresultsinacuteurinaryretentionpredisposingforbladder
hypertrophy,cystitis,andhydroureter/hydronephrosis
o Itisnotpremalignant
o Treatment=5alphareductase(testosterone DHT)inhibitororsurgery(oldertx)

Adenocarcinoma

Pathogenesis
o Idiopathic,multifactorial,acombinationofenvironmentandgenes
o Androgensplayaroleinactivationofgrowthsignals
o Susceptibilitymutationofunknowntumorsuppressormappedto1q2425
PredisposingFactors(allincreaserisk)
o Sexatanearlyage,withmultiplepartnersplusSTD
o MechanicalManipulation(vasectomy)
o DietshighinfatwhichmayinhibitVitaminAabsorption
o UrbanDwellinghaveincreasedriskofcontractionanddeathduetopotentialexposure
o Cadmiumisametalassociatedwithcarcinomaofprostate
o SincenorthernEuropeandescentandcountriesgetitmoreoften,theremustbe
Dontmistakethesesinglecell
somethingtodowithVitaminDorSunlight
layeredtubulesforrenal
o Smokingisnotlinkeddespitebeingthe#1cancerinmen
tubules!
Clinical
o ObstructionoftheurinarytractpresentinglikeBPH
o Firm,DiscreteNodulesonrectalexam
o MetastaticDisease(anemia,bonepain,hypercalemia)
o ParaneoplasticSyndromes=DVT,DIC,NonbacterialThromboticEndocarditis
o PSAandPAPlevelsareelevatedinbothBPHandAdenocarcinoma;%FreePSAis
elevatedinBPH,lowincarcinoma.PSAandPAPareusedasscreens
o Beginscreeningforwhitesat50,blacksat40
o Doublingtimeisslow(~24years)meaningitmayremainasymptomaticforalongtime,

withanexcellent10yearsurvivalrate(dependingonstage)
Enormouspurplenuclei
o Tx=surgery,radiotherapy,hormonalmanipulation(antiDHT)
surroundingtubuleswith
concretions.Thisisahighgrade
o ProstaticIntraepithelialNeoplasia(PIN)isaprecursorformalignancy
(79)Adenocarcinoma
|T 2 R e v i e w S h e e t s

31 of 41

PathRenalOutline

Morphology
o Foundinperipheralzoneswithonlyasinglelayerofepithelialcells
o Maybedifficulttoseeongross,butpalpableonrectalexam
o Histoshowsprominentnucleoli,bluemucin,andperineuralinvasion
o GradingbasedontheGleasonGradingsystemwhichisdeterminedbycellular
architecturewhilestagingisdeterminedbasedoninvasionandmetastasis.
Taketwosamples,gradethem,thenaddthescoretogether
Benign=2(1+1),Malignantis10(5+5)
o Stagingisdependentoncapsularormetastaticinvolvement

IV

GleasonGradingSystem
Differentiation
10yearsurvival
VeryWellDifferentiated
94%
WellDifferentiated
Somewherein
between.The
ModeratelyDifferentiated
pointisgood
survival
PoorlyDifferentiated

VeryPoorlyDifferentiated

I
II
III

Stage
I
II
III
IV

Staging
Description
Almostnothing(5%)
Tumorconfinedtoprostate
CapsularInvolvementorInvasionto
SeminalVesicle
Tissueinvasionandmetastasis(lymph
node)

54%

Disease
BPH

EpithelialLayer
DoubleCellLayer

PSA/PAP
<10

Adenocarcinoma

SingleCelllayer

>10

Feel
Rubberyand
Nodular
DiscreteFirm
Masses

Zone
Periurethral,
Transitional
Peripheral

Androgens
ElevatedEstrogen
Pathogenic
ElevatedEstrogen
Protective

OtherMalignanciesoftheUrinaryTract

Carcinomaisthemostcommonofallcancersandhassomeinterestingvariantsyoushouldjust
recognizebyname(mucinousandendometroid)
Rhabdomyosarcomaisthemostcommonsarcomaacrosstheboard
Leiomyosarcomaoccursmostofteninchildrenlessthan20
UrothelialCarcinomacanoccurinanywherethereistransitionalepithelium
o RenalPelvis,Urethra,BladderWall
o AssociatedwithSchistosomiasisinfection(sqaumouscellcarcinoma)
o Associatedwithsmokingandoldage(transitionalcellcarcinoma)
o Canleadtooutflowobstruction,pyleonephritis,hydronephrosis
BabieswithamassisusuallyWilmstumor.However,ifthereiselevatedVMAtheyhavea
neuroblastoma.Thiswasntinanythingwelearned,butcameupinthreedifferentQbanks.
GoodbonuspearltoknowincaseitsonSteporaBonusQuestionontheexam.

|T 2 R e v i e w S h e e t s

32 of 41

PathRenalOutlinePa t

UrinaryTractObstruction

DilatedRenalPelvis

CysticMedulla
(thereare3cysts)

Definition
o Uhmduh?Itcanbeunilateral,bilateral,complete,incomplete,intrinsictothekidney,
oranextrinsicthingcompressingtheureters.
Causes
o UrinaryCaliculi=KidneyStones(usuallyunilateral),ureterorrenalpelvis
o NormalPregnancy=theparasite/tumor(thebaby)compressestheureters
o BenignProstaticHypertrophy=cutsoffflowattheurethra(seeBPHsectionatend)
o Tumors=prostate,bladder,uterus
o Others,lessimportant,listedonpage1012ofRobbins
Pathogenesis
o Generationofobstructionisdependentonthetypeofobstruction
o Hydronephrosis=dilationandatrophyofthekidneyassociatedwithdecreasedoutflow
Evenwithcompleteobstruction,GFRdoesnotsufferasthefluidissimply
reabsorbedintointerstitumandperirenalspace=severedilation
Highpressuresfromthedilationresultsinrenalatrophy
Vascularcomplicationsarereversible;theinitialinjuryistothetubules
o Obstructionleadstoaninflammatoryreactionwithsubsequentfibrosis
Morphology
o WithcompleteobstructionthereisnoGFRandmilddilationofrenalpelvis
o Withincompleteobstructionthereisconstantfiltrationandmassivedilation
o Earlymorphologicalchangesaredistendedcalycesandpelvis;latersignsarethe
formationofthinwalledcysticpockets
o Interstitialfibrosisonhistologicpreparationisseenalongwithtubularnecrosis
ClinicalCourse
o AcuteObstructionprovokespainfromrapiddilationofareaimmediatelyproximal;
stonescausecolicfromureter/capsuledistension,prostatecausesbladdersymptoms
o UnilateralorIncompleteObstructionmayremainasymptomaticleadingto
hydronephrosis,atrophy,andlossofrenalfunctionthatcouldotherwisehavebeen
preventedwithintervention.Ultrasonographyiscriticaltoidentifybeforedamage
o BilateralPartialObstructionpresentswiththeinabilitytoconcentrateurine,reflected
bypolyuriaandnocturia.Thisresultsfromtubularatrophyandscarringassociatedwith
tubularinterstitialnephritis
o CompleteBilateralObstructionresultsintheinabilitytoproduceurine(anuriaor
oliguria).Whentheobstructionisremoved,massivesaltconcentrateddiuresisoccurs.

|O w l C l u b R e v i e w S h e e t s

33 of 41

PathRenalOutlinePa t

Urolithiasis,RenalCaliculi,Stones
Type
CalciumOxalate

Incidence
75%

Struvite(Magnesium
AmmoniumPhosphate)
UricAcid

1525%

Cystine

2%

510%

Cause
Hypercalcemia=highcalciumblood
Hypercalciuria=highcalciumurine
Hyperoxaluria=highoxalateurine
Hypocitriuria=lowcitrateurine
Theyjusthappensometimes,too
InfectionbyUreaSplittingBacteria such
asProteus
Hyperuricosuria=highuricacidurine
Hyperuricemia=highuricacidblood
AssociatedwithLeukemiaGout
50%NoMetabolicAbnormalities
GeneticDiseasesthatprevent
reabsorptionofaminoacids(Cystinuria)

Opacity
Radioopaque

Radioopaque
Radiolucent

Radiolucent

Definition
o TheformationofsolidcrystalsintheGUtract,mostforminginthekidney,asaresultof
increasedconcentrationofparticlesthatprecipitateout
Causes
o Themostimportantdeterminantisanincreasedurinaryconcentrationofthestones
constituentssuchthatitexceedstheirsolubilityinurine(supersaturation)
o AcidificationoftheurineandLowurineflowratesmayalsocontribute
o Absenceofinhibitors,whichhasalongtheoreticallist,mustalsooccur,sincenotallpatients
withhighstoneconcentrationsandlowurineratesgetstones.
TypesandPathogenesis
o CalciumOxalateStones,madeofcalciumandoxalate
SmallStones(twoblackdots)
Mostcommontypeofstone,75%incidence

LargeStone(black)
Associatedwithhypercalciuriawithorwithouthypercalcemia
Whenbotharepresent,itisaresultofhyperparathyroidism,whichcanbearesult
ofprogressivekidneyfailure(seeCa/P,ChronicKidney)
Renalimpairmentofcalciumreabsorptionorahyperabsorpativeintestinaltract
canleadtohypercalciuriawithouthypercalcemia
Kidneyhasbeencutand
Agoodchunk(20%)areassociatedwithUricAcidSecretion
openedlikeabook.Distal
Mayoccurwithorwithouthypercalciuria
stonecausesmassive
obstructionwhichcanleadto
Involvesnucleationofthecrystalinthecollectingducts
hydronephrosis
Some(10%)areassociatedwithhyperoxaluria
Primary,orgeneticformislesscommon
Overabsorptionfromdiet(enterichyperoxaluria)occurseveninvegetarianswho
haveadietrichinoxalates.
Hypocitriuria
Seenindiarrheaandmetabolicacidosismayalsoleadtocalciumstones
1520%havenoknownmetabolicderangement

|O w l C l u b R e v i e w S h e e t s

34 of 41

PathRenalOutlinePa t

StruviteStones,madeofMagnesiumPhosphate
Causedbyureasplittingbacteria,aka,aninfection
Increasedammoniafromureadegradationinthetubulescausesanalkalationof
theurine,favoringMagnesiumAmmoniumPhosphateSalts
Formsthelargestkidneystones
StaghornCaliculioccupyingrenalpelvisarecausedbyinfectionandareStruvite
o UricAcidStones
Commoninpatientswhohaveconditionspredisposingtohyperuricemia,suchasgoutor
anyleukemias,formingatalowurinarypH
MorethanhalfofpatientswithUricAcidStoneshavenometabolicderangement
Theseareradiolucent
o CystineStones
Formedwithgeneticdiseasesthatpreventreabsorptionofproteinsfromthelumen
Ex.Cystinuria(welearnedaboutitinphysio,lastsemester)
FormatlowUrinarypH
Morphology
o Mostoccurunilaterallyattherenalpelvisorthebladder
o Varyinsize,<5mmsmall,57mmintermediate,>7mmlarge
o Theymaybesmoothorjagged
o StaghornCaliculiarelarge,formingoffasmallstoneinthepelvis,growingupwards,forminga
castofthepelvisandcalyces
ClinicalCourse
o Thesecauserenalcolicwhichisintermittent,sharpflankpainthatmayradiatetogroin
o Hematuriamaybepresentasthestonepassesandshredstheureter
o Largestonesdonotpassandstayinpelvis,causingobstruction
o Predispositionforinfection

Stone

ThisCTshowsakidneywithabrightdotinthe
center.Offtothetopright,isanotherbrightdot.
Thisslicehappenstoshowthekidneyandthe
ureter,bothwithsomethingradioopaquein
them.Stone.

Weseeadilatedtubulewithinterstitial
inflammation(giantcell)withcompressedtubules.
Whenunderpolarizedlight,youwillseethatthereis
morethancalcium.

|O w l C l u b R e v i e w S h e e t s

35 of 41

PathRenalOutlinePa t

TUMORS
BenignTumors

RenalPapillaryAdenoma
o Small(<5cm),pale,yellowgray,wellcircumscribednoduleswithinthecortex
o Ultrastructurally(EM)appearaslowgradepapillaryrenalcellcarcinoma
o Haspapillomatousstructureswithnumerouscomplexfolds
Theonlyusefulassociation
fromBenignTumors
RenalFibromaorHamartoma
o Tiny(<2cm)Nonmalignant,greywhitefirmnodulesfoundwithinthepyramids
o AssociatedwithTuberousSclerosiswherethetumoriscalledaangiomyolipoma
Oncocytoma
o Epithelialtumorcomposedoflarge,eosinophiliccellswithbenignlookingnucleiandmonster
nucleoli
o EMrevealsmassiveamountsofmitochondria
o Whilebenign,itcangetprettybig(12cm)andcausecompressionsyndromes
o Tumorsareyellowtobrown,wellcircumscribed

MalignantTumors

RenalCellCarcinoma
o Pathogenesis
Mostcancersareidiopathic,thoughsomefamilialdatahasgivenrisetoanunderstanding
ofrenalcarcinomagenesis.Goodnews,youdonthavetoknowit
Theaged(after40butespeciallyin60+)whosmokeareatgreatestrisk
Exposuretoasbestos,petroleum,heavymetalshasbeenimplicatedaswell
o TypeandMorphology
ClearCellCarcinoma(byfarthemostimportantofthethreetypes)
CausedbyamutationintheVHLgenethatcausesvonHippelLindaudisease
Causesmultiple,bilateraltumorsifVHL
Formfromproximaltubularepitheliumpresentingwithlargeclearcells
UsuallyUnilateral
Massesareyellowbecauseofthefoamlikefatcellspresentinthetumor

Marginsareilldefined,thoughitisoftencontainedwithintherenalcapsule
PapillaryCarcinoma
Bilateralinmostcases
Thecancerassociatedwithdialysisassociatedcysticdisease
Tumorsareoftenhemorrhagicandcystic

Cuboidalorcolumnarepitheliumarrangedinpapillarypattern
Largeclearcellswithsmall
Chromophobe
nuclei(Clearcell
carcinoma).Thisisthemost
Eosinophilccytoplasm,perinuclearhalo,localizedtovasculature
commonandmost
Growfrominterstitialcells(likeoncocytoma)
importantvariantofRenal
CellCarcinoma
|O w l C l u b R e v i e w S h e e t s

36 of 41

PathRenalOutlinePa t

ClinicalCourse
Oftenasymptomatic,discoveredbyCTscanorMRIforanonrenalcause
Mayreachmassivesizes(10cm)beforesymptomssetin
ClassicTriadofSymptoms=hematuria(whichisthemostreliable),flankpain,andmass
25%oftumorshavemetastasizedpriortodiscovery
ParaneoplasticSyndromesarehugeinRenalCell
Polycythemia(Epo),Hypercalcemia(PTH),Hypertension(Aldo,Renin),Cushings
(ACTH),andFeminization(Androgens)
Openedlikeabookdownthe
Stagingisdependentonlocalinvolvement
center
Stage
Involvement
5yearsurvival
StageI
Kidney
6080%
StageII
Kidney+Fat
15%
StageIII
Kidney+RenalVeinorLymph
<10%
o Treatment

Totalnephrectomyisusuallycurativewithoutmetastasis,butpartialnephrectomyto
preserverenalfunctionhasbeendone,andhasbeensuccessful

WilmsTumor(Nephroblastoma)
Commonchildhoodmalignancywithpeakageof2yearsold
CausesbyalossofaTumorSuppressorGene(WT1orWT2)WilmsTumor
Symptoms=abdominalmass+HTN/Nausea/Heamturia
Gross=verylarge,demarcatedmass,mostareunilateral
Micro=embryonicglomerularandtubularstructures(blastema)surroundedby
Massivewhite/tantumor
mesenchymalspindlecells.
Prognosisofaunilateraltumorisgood(90%survival)becausewecandeterminehow
anaplasticthetissueis
Thosethatarelargelyanaplasticgetchemoandsurgery
Thosethataremildlyanaplasticdontgetchemoanddomuchbetter

Tumor
RenalCell
Carcinoma

Pathogenesis
VHLgene,smoking,age

Wilms

Blastemaoffetalkidney,
abnormalwtgene

RENALTUMORS
AgeRange
Elderly

Babies/Kids

Pearl
ClearCellmostcommon,presents
withhematuria,thoughmostare
asymptomatic
Enormousmassinaninfant;
FetalComponentsinchildkidney

|O w l C l u b R e v i e w S h e e t s

37 of 41

PathRenalOutlinePa t

CONGENITALANOMALIES
Disease
AgenesisofKidneys

HorseshoeKidneys

EctopicKidneys

Hypoplasia

Character
Ifunilateraliscompatiblewithlife,thenormalkidneywillhypertrophy toaccommodateload
Ifbilateral,itisincompatiblewithlifepresentingwithpotterssequence(oligohydramnios
indicativeof amnioticfluidandacrushedfetus,withasmallheadandparrotbeakdeformity)
Fusionofthekidneyseitherattheupperpole (10%)orthelowerpole(90%)
Astheyascendtheygetcaughtontheinferiormesentericartery
Normalfunctionofkidneys,butmayleadtoincreasedriskofstoneformation
Normal=Thekidneysdevelopinthepelvis,thenascendtotheirlocation
Ectopic=Failuretoascenddevelopingusuallywithinthepelvisoratthepelvicbrim
Tortuousureterscauseincreaseriskoftorsionandobstruction Pyelonephritis
Atrulyhypoplastickidney,thatis,onethatdidnotfullydevelopwillbesmall,havefewerthan6
pyramidsandnosignsofscarringvsanormalkidneythatshrankfromfibrosisorHTN

Disease
Autosomal
RecessivePolycystic
KidneyDisease
Autosomal
DominantPolycystic
KidneyDisease
MedullaryCystic
DialysisAssociated
CysticRenal
Dysplasia

CYSTICDISEASES
Character
Becauseitisrecessiveyouwillseeitinkids atbirth;causedbyamutationofPHKD1
BilateralInvolvementwheretheentirekidneyismadeofelongatedcystsperpendiculartocapsule
Thereisobviousrenalfailurewhichisfatal;survivorsdevelopliver/biliaryfibrosis
Becauseitisdominantyouwillseeitinadultsatvaryingages;mutationofPKD1orPKD2
BilateralInvolvementwheretheentirekidneyismadeofcircularnonuniformcysts
Areasymptomaticuntilrenalfailuresetsin,maybeprecededwithflankpainfromhemorrhage
ExtrarenalCystsarepresentinLiverorinthebrain=fatalBerryAneurysms(subarachnoidbleed)
Typicallyabenignoutcomewithanidiopathiccause
Riskforstonesandinfections
ProlongedDialysiscausescorticalandmedullarycysts
This riskofRenalcellCarcinoma
Presentswithmassivecystscausedbyanabnormalityinmetanephroticdifferentiation
Persistenceofmesenchymesurroundinglargecysts
ifunilateralremovalofdiseasedkidney=greatprognosis;ifbilateral=terribleprognosis
Veryfew,verylargecystsdifferentiatesthisfromthePolycsticKidneyDiseases(many,smallcysts)

NEPHRITICVERSUSNEPHROTIC
Nephritic
Nephrotic
Hematuria
Hypoalbuminemia(<3g/dL)
Hypertension
GeneralizedEdema
Azotemia
Hyperlipidemia
Oliguria
Lipiduria
MildProteinuria(<3g/day)
SevereProteinuria(>4g/day)
BloodinurineandhighBUN Proteininurineandedema
orCreatinine
withlossofprotein

|O w l C l u b R e v i e w S h e e t s

38 of 41

PathRenalOutlinePa t

NEPHROTICSYNDROMES
Disease
Character
MinimalChange
OccursinchildrenwithedemaandanasarcabutwhohavenoLMorIFchanges
Disease
TheonlythingthatchangesiseffacementofpodocytesrequiringEMtovisualize
Membranous
Thisisaimmunecomplexdepositiondiseasethatiscommonlyidiopathic
ThereisagranularbutlineardepositionofIgGandC3(comparedtoGoodpastures)
NoteaspikeanddomeappearanceonEMwithsubepithelialdeposits
LightMicroscopywillshowacapillaryloopthickening
FocalSegmental
CommoninAfricanAmericans,AIDSpatients,andIVdrugusers
Glomerulosclerosis
Somepartsof(Segmental)onlySomeGlomeruli(focal)areeffected
NephroticSyndromeischaracterizedbyHypoalbuminemia(<3g/dL),GeneralizedEdema,Hyperlipidemia,Lipiduria,Severe
Proteinuria(>4g/day).LookforProteininurineandedemawithlossofserumproteinintheurine.

NEPHRITICSYNDROMES
Character
ProducedbyantibasementmembraneantibodiesdirectedatColagen3chainofType4Collagen
PresentsasasmoothlinearpatternofIgGandC3
PresentswithHematuriaandHemoptysis,ultimatelyresultsinCresenticglomerulonephritis
RapidlyProgressive
Rapidandprogressivediseasethatresultsintotalrenalfailureinmonths
Cresentic
Characterizedbycrescentswithintheglomerulus,crushingthevasculature
Hasmanycauses(Type1=Goodpastures,Type2=Lupus,Type3=PauciImmune)
TerriblePrognosis
Membranoproliferative Diseasewithmultipletypes(neverhavebeenaskedtodistinguishthetypes)
Producesasubendothelialdepositwithtramtrackingofthebasementmembrane
TheMembranethickens(fromtramtracking)whilethemesangiumproliferates.
Lookforsubendothelialdeposits,tramtracking,andlowC3inthequestionstem
Alports
AutosomalRecessivediseasecausedbyamutationoftheColagen 5chain
AlternatingthickeningandthinningofbasementmembraneonEM
AssociatedwithVisualandAuditoryDeficienciesinaChild
NephriticSyndromeischaracterizedby:Hematuria,Hypertension,Azotemia,Oliguria,MildProteinuria(<3g/day).Youshould
lookforBloodinurineandhighBUNorCreatinineinthevignette
Disease
Goodpastures

Disease
AcuteTubularNecrosis

AllergicNephritis

AnalgesicNephropathy

TUBULOINTERSTITIALDISEASES
Character
Causedbyischemiaortoxins(Myoglobin,CancerDrugs,Aminoglycosides,EthelyeneGlycol)
Lookforwaxycastsintheurineandnecrosisofthetubulesonbiopsy
Withdeathoftubules,unabletoreabsorbsodium= Naexcretion=>2%offilteredload
PresentswithEvolution(slight BUN) Maintenance(Oliguria,GFR=0) Recovery(Polyuria)
Administrationofdrugdoesnothinguntilconcentratedintubulesleadingtoimmunogenicity
Immunereaction(TypeIVandI)occurwith eosinophilsandneutrophils
SeeaninterstitialnephritiscommonlycausedbyNSAIDs,Penicillins,andAllopurinol
AssociatedwithAspirin,butmainlylookforPhenacetin(partofAcetominophenpreparations)
Causespapillarynecrosisinpeoplewhohavechronicpain(backache,headache,abusers)
Increasesriskfortransitionalcellcarcinomaoftherenalpelvis

|O w l C l u b R e v i e w S h e e t s

39 of 41

PathRenalOutlinePa t

PYELONEPHRITIS
Disease
Character
AcutePyelonephritis
Morecommoninmaleswhenreallyyoung(congenitaldefects)orreallyold(prostateobstruction)
Morecommoninfemalesingeneralbecauseofashorturethra
Isanacuteinfection=neutrophilswithinthepelvis(pyelo)andtubules(nephritis)
Lookforlotsofneutrophils,gramnegativeorganisms,andWBCcastsintheurine
Patientpresentswithcostovertebraltendernessandtheneedtopeealot(Dysuria/frequency)
ChronicPyelonephritis CorticomedullaryScaringOverlyingDilatedBluntedCalyces
CausedbyrepeatedboutsofacutePyelonephritis
Pyelonephritisispredisposedbythreethings:(1)ShortUrethra(women)becausebacteriausuallyascendtheurinarysystem.
(2)VesiculourethralReflux(bacteriahavetogooutofthebladderandintotheureters,goingthewrongway)and
(3)Obstruction.Iftherightwayoutisblockedanywherealongthetract,theonlywayforfluidandbacteriatogoisbackup
intothekidneys,leadingtonotonlyPyelonephritis,butalsohydroureter.CommonlycausedbyNormalGutFlora,butmay
includeE.Coli,Klebsiella,andProteus.

KIDNEYSTONES
Cause
Opacity
Hypercalcemia=highcalciumblood
Radioopaque
Hypercalciuria=highcalciumurine
Hyperoxaluria=highoxalateurine
Hypocitriuria=lowcitrateurine
Struvite(Magnesium
1525%
InfectionbyUreaSplittingBacteria suchasProteus
Radioopaque
AmmoniumPhosphate)
AlsocalledaStaghornCaliculithatpermeatestheentirepelvis
UricAcid
510%
Hyperuricosuria=highuricacidurine
Radiolucent
Hyperuricemia=highuricacidblood
AssociatedwithLeukemia(cellturnover)andGout
50%NoMetabolicAbnormalities
Cystine
2%
GeneticDiseasesthatpreventreabsorptionofneutralamino
Radiolucent
acids(Cystinuria)
Regardlessoftheircause,kidneystonesarepainful.Theycauseflankpainthatradiatestothegroinandcostovertebralangle
tenderness.Theremaybeaslighthematuria.Thestoneisbeingmovedalonganarrowmuscularureter,whichcontractsto
movethestone.Thepresenceofthestonecancauseobstructionanddistention,increasingriskofinfectionandhydroureter
Type
CalciumOxalate

Incidence
75%

CANCER
Disease
Angiomyolipoma
CorticalAdenoma
RenalCellCarcinoma

WilmsTumor

Character
HamartomaswithininthekidneythatiscausedbyTuberusSclerosis
Benign,tinytumorthatdoesntreallydoanything
BiggestriskfactorisSmoking,abuseofPhenacetin,orVonHippelLindau
UnlessyouhaveVHL,theyaresingularlargeyellowtumors
Tendtoinvade(highlymalignant),withhematogenousspreadintotherenalvein
Mostcommonlyaclearcellcarcinoma(lookslikealargewhitefatcell)
Demonstrateswiththeclassictriad=Hematuria,Flankpain,MassandParaneoplasticSyndromes
(thisisaNeuroendocrinetumor)=Polycthemia(Epo),Cushings(ACTH),
Atumorofthekidneysinchildrenwithpeakageof2years,amutationofWT1onchromosome11
Hugemassonatinykidneythatiseasilypalpableabdominally
3Components=ImmatureEpithelium,Blastema(DarkBlueCells),andStromalComponent
Excellentprognosiswiththeinterventionofsurgery,radiation,andchemo

|O w l C l u b R e v i e w S h e e t s

40 of 41

PathRenalOutlinePa t

PROSTATE
Disease
Character
BenignProstatic
Histologicallydemonstratesadoublecelllayerandisanormalconsequenceofaging
Hypertrophy
Presentsasarubbery,nodularmassinthePeriurethralzoneleadingtourinarytractobstruction
(isactuallyHyperplasia) Despitename,isNOThypertrophybutIShyperplasia
EstrogensincreaseDHTReceptorswhileDHTstimulatesgrowth
Relieveurinarysymptomswithblockers,shrinkprostatewithFinesteride
Adenocarcinomaof
Histologicallydemonstratesasinglecelllayerduct
Prostate
PresentsasaDiscreteFirmMassinthePeripheralZoneleadingtohemeoccultbloodinstool
CausedbyaPSAlevelgreaterthan10(donotrelyonlyonthisfordiagnosis)
MustbeabletointerpretGleesonGrade(2=lowest,benign,10=highest,malignant)
GrowthisinducedbyDHT(removingsourceoftestosterone[castration])isrecommended
Alternatively,canusepharmacologicalcastrationwithFinesterideorLeupralide
CommonlyspreadstotheSpineasametastasis
Prostatitis
Inflammationoftheprostateaccompanyinganascendinginfectionoftheurethra
CommonorganismsaregutflorasuchasE.ColiorEnteroccocus
PyogenicProstatisis=BacterialInfection=>9Neutrophilsperhighpowerfield
Nonbacterialprostatitis=Viralinfection=lymphocytesandmacrophages

Disease
BPH

EpithelialLayer
DoubleCellLayer

Adenocarcinoma

SingleCelllayer

BPHVSADENOCARCINOMA
PSA/PAP
Feel
Elevated<10
Rubbery,Nodular
Elevated >10

DiscreteFirm
Masses

Zone
Periurethral,
Transitional
Peripheral

Androgens
ElevatedEstrogen
Pathogenic
ElevatedEstrogen
Protective

URINARYCONCENTRATIONDISEASES
Character
NotenoughADHissecreted,sothekidneyslosewater=diluteurine,concentratedblood
Withholdingwaterjustdehydratespatients=diluteurine,moreconcentratedblood
AdministrationofexogenousADH=concentratedurine,dilutingblood
EnoughADHissecreted,butkidneysdonotrespond=diluteurine,concentratedblood
Withholdingwaterjustdehydratespatients=diluteurine,moreconcentratedblood
AdministrationofexogenousADHdoesntwork=diluteurine,concentratedblood
Thepersoniswackoandjustdrinkingtoomuchsothebodyeliminatesit=diluteurine
Withholdingwaterfixestheproblemandshewillpeeless=concentrateurine,diluteblood
AdministrationofADHisunnecessary,butifshekeptdrinking,youwouldinducean
exogenoussyndromeofinappropriateADH=concentrateurine,diluteblood
Syndromeof CausedbyaNeuroendocrinetumorsecretingADH
Inappropriate ExcessADHcausesunusualreabsorptionofwaterfromthecollectingtubuleregardlessoffluid
ADH
andosmolarstatus.Holdingontowater=dilutionofblood=hypoOsmandhypoNawith
cerebraledema
Disease
Central
Diabetes
Insipidous
Nephrogenic
Diabetes
Insipidous
Psychogenic
Polydypsia

Osmoles
U= P=
U= P=
U= P=
U= P=
U= P=
U= P=
U= P=N
U= P=N
U= P=

U= P=

Checkoutpage24fortheSelfStudyTBLAcidosis/Alkalosisstuff.ThisisinFirstAidAswell.Therejust
wasnotenoughaboutthetubulardiseasesandNa/KhandlinginourBoardStudyingtobuildatablefor
it.ItsALOTofstuff,butcountsforonlyONETBL.

|O w l C l u b R e v i e w S h e e t s

41 of 41