Acute and Chronic Renal Failure.........

Acute and Chronic Renal Failure (ARF and CRF)

1. Renal Pathophysiology
Acute and Chronic Renal Failure
Dr. Vishal Balakrushna Jadhav
Assistant Professor (Pharmacology)
School of Pharmaceutical Sciences (SOPS), SUN
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2. Content
Definition
a.AcuteRenalFailure(ARF)
b.ChronicRenalFailure(CRF)
EtiopathogenesisofCOPD
Pathologicalchanges
Clinicalfeatures
Illustration-COPDandMicroscopicchanges
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3. Acute Renal Failure (ARF)
Definition
Asyndromecharacterizedbyrapidonsetofrenaldysfunction,
chieflyoliguriaoranuria,andsuddenincreaseinmetabolic
wasteproducts(ureaandcreatinine)inthebloodwith
consequentdevelopmentofuraemia.
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4. Etiopathogenesis of ARF
Pre-renal,Intra-renalandPost-renalCauses.
a)Pre-renalCauses-
Pre-renaldiseasesarethosewhichcausessuddendecreaseinthebloodsupply
tothenephron.Renalischaemiaresultsinthefunctionaldisordersor
depressionofGFRorboth.Thecausesincludesaninadequatecardiacoutput
andhypovolaemiaorvasculardiseasecausingreducedrenalperfusion.
b)Intra-renalcauses-
Intra-renaldiseaseischaracterizedbythediseaseofrenaltissueitself.This
includesthevasculardiseaseofthearteriesandarterioles.Withinthekidney,
diseasesoftheglomeruli,acutetubularnecrosisduetoischaemiaortheeffect
ofthenephrotoxin,acutetubulo-interstitialnephritisandpyelonephritis.
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5. Etiopathogenesis of ARF
c)Post-renalcauses-
Post-renaldiseaseischaracterizedbyurinaryflowobstructionanywherealong
therenaltractdistaltoopeningofthecollectingducts.
Thismaybecausedbyamasswithinthelumenorfromwalloftractorfrom
externalcompressionanywherealongthelowerurinarytract-ureter,bladder
neckorurethra.
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6. Clinical features of ARF
DependsontheunderlyingcauseofARFandonthestageofdiseaseatwhich
thepatientpresent-
A)Syndromeofacutenephritis-
Associatedwithacutepost-streptococcalglomerulonephritisandrapidlyprogressive
glomerulonephritis.
Thecharacteristicfeaturesofacutenephritissyndromeare-
Proteinuria,
Haematuria,
Edema,
Mildhypertension,
FluidretentionduetodiminishedGFRandincreasedsaltandwaterreabsorptionin
thedistalnephron
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7. Clinical features of ARF
B)Syndromeaccompanyingtubularpathology-
WhenARFiscausedbythedestructionoftubularcellsofthenephron,thedisease
typicallyprogressesthrough3characteristicstagesfromoliguriatodiuresisto
recovery.
Oliguricphase-
Lastingonanaveragefrom7to10days
characterizedbyurinaryoutputlessthan400mlperday.
Oligurialeadstotheaccumulationofwasteproductsofproteinmetabolisminthe
bloodandresultantazotaemia,metabolicacidosis,hyperkalaemia,hypernatraemia
andhypervolaemiaduetosecondaryeffectofcirculatoryoverloadandpulmonary
edema.
Thespecificgravityoftheurineislow,buttheconcentrationofsodiuminurinetends
tobeelevated.
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8. Clinical features of ARF
B)Syndromeaccompanyingtubularpathology-
Diureticphase-
Theurinaryoutputisimprovedwiththeonsetofhealingoftubulesduetodrawingof
waterandsodiumbypreceedinghighlevelsofcreatinineandurea.Sincethetubular
cellshavenotregainednormalfunctionalcapacity,theurineisofloworfixedspecific
gravity.
c)Phaseofrecovery-
Inabout50%ofthepatients,fullrecoverywithhealingoftubularepithelialcellsis
observedwhilerestterminatesindeath.
Theprocessofhealingmaytakeuptooneyearwithrestorationofnormaltubular
function.
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9. Clinical features of ARF
C)Pre-renalsyndrome-
ItresultsduetoARFoccurssecondarytodisordersinwhichneithertheglomeruli
northetubulesaredamaged.
Typicallythispatternisseeninmarginalischaemiacausedbyrenalarteriolar
obstruction,hypovolaemia,hypotensionorcardiacinsufficiency.
Duetodecreasedrenalbloodflow,GFRisalsoreducedandcausingazotaemia
(elevationofBUNandcreatinine),oliguriaandpossiblefluidretentionandedema.
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10. B) Chronic Renal Failure (CRF)
Definition
Asyndromecharacterizedbyprogressiveandirreversibledeteriorationofrenal
functionduetoslowdestructionofrenalparenchyma,eventuallyterminatingin
deathwhensufficientnumbersofnephronhavebeendamaged.
AcidosisisthemajorprobleminCRFwithdevelopmentofbiochemical
azotaemiaandclinicaluraemiasyndrome.
Etiopathogenesis-AllchronicnephropathiescanleadstoCRF.Thediseases
leadingtothedevelopmentofCRFareclassifiedintotwomajorgroups-
1)Thosecausingglomerularpathology,and
2)Thosecausingtubulo-interstitialpathology.
InthefinalstageofCRF,allthepartsofnephronareinvolved.

11. 1)Diseasescausingglomerularpathology-
Glomerulardestructionresultsinthechangesinfiltrationprocessandleads
tothedevelopmentofnephroticsyndromecharacterizedbyproteinuria,
hypoalbuminaemiaandedema.
Theimportantchronicglomerulardiseasesare-
a)Chronicglomerulonephritis,
b)Certainconditionsoriginatesoutsidetherenalsystembutinducesthe
changesinnephronsecondarilysuchassystemiclupuserythematosus
(SLE),serumsicknessnephritisanddiabeticnephropathy.

12. 2)Diseasescausingtubulo-interstitialpathology-
Damagetothetubulo-interstitialtissueresultsinalterationsin
reabsorptionandsecretionofimportantconstituentsleadingto
excretionoflargevolumeofdiluteurine.Tubulo-interstitialdiseases
categorizedaccordingtoinitiatingetiologyintothefollowinggroups-
a)Vascularcauses-
Longlastingprimaryoressentialhypertensionproducescharacteristic
changesintherenalarteriesandarteriolesreferredasnephrosclerosis.
Nephrosclerosiscausesprogressiverenalvascularocclusionterminatingin
ischaemiaandrenaltissuenecrosis.

13. b)Infectiouscauses-Chronicpyelonephritisisanexampleofchronic
renalinfectioncausingCRF.Theprogressofchronicrenalinfection
causesincreaseinthedamageofnephronsleadstoCRF.
c)Toxiccauses-Sometoxicsubstancesinduceslowtubularinjury,
eventuallycausesCRF.Themostcommonexamplesare-
1)intakeofhighdosesofanalgesicssuchasphenacetin,aspirinand
acetaminophen(paracetamol)-causeschronicanalgesicnephritis.
2)prolongedexposureoflead,cadmiumanduraniumalsocausesCRF.
d)Obstructivecauses-Chronicobstructionintheurinarytractleadsto
progressivedamagetothenephronduetobackfluidpressure.The
examplesofthistypeofchronicinjuryarestones,bloodclots,
tumours,stricturesandenlargedprostate.

14. Regardlessoftheinitiatingcause,CRFevolvesprogressivelythroughthe
fourstages-
i)Decreasedrenalreserve-Atthisstage,damagetorenalparenchymais
marginalandthekidneysremainsfunctional.TheGFRisabout50%
ofnormal,BUNandcreatininevaluesarenormalandthepatients
areusuallyasymptomaticexceptattimesofstress.
ii)Renalinsufficiency-Atthisstageabout75%offunctionalrenal
parenchymahasbeendestroyed.TheGFRisabout25%ofthe
normal,accompaniedbytheelevationofBUNandserumcreatinine.
Polyuriaandnocturiaoccursduetotubulo-interstitialdamage.
Suddenstressmayprecipitatesuraemicsyndrome.

15. iii)Renalfailure-Atthisstage,about90%offunctionalrenaltissue
hasbeendestroyed.TheGFRisapproximately10%ofnormal.
Tubularcellsareessentiallynon-functional.Asaresult,sodium
andwaterregulationislostresultinginedema,metabolic
acidosis,hypokalaemia,andsignsandsymptomsofuraemia.
iv)End-stagekidney-TheGFRatthisstageislessthan5%of
normalandresultsincomplexclinicalpicturesofuraemic
syndromewithprogressiveprimary(renal)andsecondary
systemic(extra-renal)symptoms.

16. Clinicalfeatures-
ClinicalmanifestationsofCRFresultinginuraemicsyndromeare
describedundertwomainheadings-
1)Primaryuraemic(renal)manifestations-
Primarysymptomsofuraemiadevelopswhenthereisslowand
progressivedeteriorationofrenalfunction.Theresultingimbalance
causesthefollowingmanifestations-
Metabolicacidosis,
Hyperkalaemia,
Sodiumandwaterimbalance,
Hyperuricaemia,
Azotaemia

17. 2)Secondaryuraemic(extra-renal)manifestations-
Numberofsecondaryextra-renalsystemicmanifestationsdevelops
secondarilyfollowingthefluid-electrolyteandacid-baseimbalances.
Theseincludesthefollowings-
Anaemia,
Integumentarysystemrelatedsymptoms,
CVSrelatedsymptoms,
Respiratorysystemrelatedsymptoms,
Digestivesystemrelatedsymptoms,
Skeletalsystemrelatedsymptoms.

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