1、Acute Renal Failure(ARF)Chengwu Liu201521.Review of renal structure and physiology1.Review of renal structure and physiology2.Definition of ARF2.Definition of ARF3.Causes and classification3.Causes and classification4.Pathogenesis(4.Pathogenesis(a acute cute t tubular ubular n necrosisecrosis，ATN)AT
2、N)5.Alterations of metabolism and function5.Alterations of metabolism and function6.Prevention and treatment6.Prevention and treatmentoutline3vTo excrete urine and waste productsvTo regulate the balance of water and electrolytes vTo regulate the BPvTo involve in endocrine regulation:-Renin -Erythrop
3、oietin(EPO)-Vitamin D3 -Prostaglandin(PG)reviewThe main functions of kidney1.review4Abdominal aortaAdrenal glandUreterInferior vena cavareviewThe renal structure5review6review7review CortexMedula8reviewNephroticNephroticsyndrome:syndrome:EdemaEdemaProteinuriaProteinuria HyperlipidemiaHyperlipidemiaH
4、ypoproteinemia Hypoproteinemia The Structure ofThe Structure ofthe Glomerulusthe Glomerulus9Sympathetic nerve fiberSympathetic nerve fiberJuxtaglomerular cellsJuxtaglomerular cellsAfferent arterioleAfferent arterioleMaculaMacula densadensaSmooth muscle cellsSmooth muscle cellsDistal tubuleDistal tub
5、uleMesangial cellsMesangial cellsEfferent arterioleEfferent arteriolePodocytesPodocytesThe Juxtaglomerular Apparatusreview10review11Net Filtration PressureBlood hydrostatic pressure(BHP)60 mmHg outBlood hydrostatic pressure(BHP)60 mmHg outColloid osmotic pressure(COP)-25 mmHg inColloid osmotic press
6、ure(COP)-25 mmHg inCapsular pressure(CP)-10 mmHg inCapsular pressure(CP)-10 mmHg inNet filtration pressure(NFP)25 mmHg outNet filtration pressure(NFP)25 mmHg outNFPNFPBHPBHP60 out60 outCOPCOP25 in25 inCPCP25 out25 out10 in10 inreview12review13adrenal gland cortexadrenal gland cortexJuxtaglomerular J
7、uxtaglomerular apparatus,apparatus,cellcellreninreninangiotensinogenangiotensinogenangiotensin angiotensin angiotensin angiotensin liverliverlunglungACEACEVessel Vessel constriction constriction aldosterone aldosterone HH2 2O,NaO,Na+reabsorptionreabsorptionBPBPEndocrine function of kidney:Endocrine
8、function of kidney:Activation of RAASActivation of RAASBP,Na+,BP,Na+,sympathetic N(+)sympathetic N(+)review14So,every part of the renal system should be intact in structure,otherwise,it is hard to ensure its function,including original urine producing,diluting and concentrating,endocrine regulatory
9、function etc.review152.definition2.definitionAcute Renal Failure Acute Renal Failure(ARF)(ARF)：an an acute and and severe syndrome which syndrome which shows a abrupt and sustained shows a abrupt and sustained decline indecline in kidneys ability to clear toxic substances kidneys ability to clear to
10、xic substances in blood,in blood,leading toleading to an accumulation of metabolic an accumulation of metabolic waste,waste,manifestingmanifesting azotemia,hyperkalemia,metabolic acidosis,and often accompanied and often accompanied by by oliguria or or anuria.definition16CharacteristicsCharacteristi
11、cs：(1)(1)Abrupt sustained decline in GFRAbrupt sustained decline in GFR (2)(2)Rising serum urea and creatinineRising serum urea and creatinine(3)(3)Loss of water and salt homeostasisLoss of water and salt homeostasis (4)(4)Life threatening metabolic changeLife threatening metabolic change(5)(5)Occur
12、s over hours or daysOccurs over hours or days(6)(6)Incidence about 140 ppm per yearIncidence about 140 ppm per year(7 7)High mortality High mortalitycharacters17classification:classification:vprerenal ARF prerenal ARF vintrarenal ARFintrarenal ARFvpostrenal ARFpostrenal ARFbladderbladderureterureter
13、kidneykidney3.cause and classification18Pre-renal ARF(1)Causes of prerenal ARF(1)Causes of prerenal ARF hypovolemiahypovolemia haemorrhage,burns,fluid losshaemorrhage,burns,fluid loss，hypotension,hypotension,cardiogenic shock,sepsis cardiogenic shock,sepsis renal hypoperfusionrenal hypoperfusion ren
14、al vasoconstriction,drugs,liver diseases,renal vasoconstriction,drugs,liver diseases,renal vascular diseases(thrombosis,DIC)renal vascular diseases(thrombosis,DIC)feature:reversibilityfeature:reversibility causes and classification19renal angiographyrenal angiographystraitnessstraitnesscauses and cl
15、assification20(2)Causes of intrarenal ARF(2)Causes of intrarenal ARFvDiseases of the renal parenchymaDiseases of the renal parenchyma ATN ATN（acute tubular necrosisacute tubular necrosis）prolonged ischaemia(50%),prolonged ischaemia(50%),direct toxicity(35%):fish gall,direct toxicity(35%):fish gall,a
16、minoglycoside(Gentamycin),mercury,aminoglycoside(Gentamycin),mercury,arsenic(As),myoglobin,sepsisarsenic(As),myoglobin,sepsis vascular disease vascular diseasevasculitis,infarctionvasculitis,infarctioncauses and classification21 diseases of glomerulus or arterioles diseases of glomerulus or arteriol
17、esRPGN(RPGN(rapidly progressive glomerulonephritisrapidly progressive glomerulonephritis)HUS(HUS(haemolytic uraemic syndromehaemolytic uraemic syndrome)SLE(systemic lupus SLE(systemic lupus erythematosuserythematosus)vasculitisvasculitis tubule-interstitial nephritis tubule-interstitial nephritisDru
18、g relatedDrug relatedparaneoplasticparaneoplasticcauses and classification22Immune complex glomerulonephritisImmune complex glomerulonephritiscauses and classification23Immune complex deposition in the glomerulusImmune complex deposition in the glomerulus(B).(B).B B,immunofluorescence micrograph sta
19、ined,immunofluorescence micrograph stained with fluorescent anti-IgG from a patient with with fluorescent anti-IgG from a patient with diffuse proliferative lupus nephritis.diffuse proliferative lupus nephritis.causes and classification24(3)Causes of postrenal ARF(3)Causes of postrenal ARFvureterure
20、ter calculi,carcinoma,fibrosis,calculi,carcinoma,fibrosis,straitnessstraitnessvbladderbladder prostatic hypertrophy or prostatic hypertrophy or malignancy,carcinoma,malignancy,carcinoma,calculicalculicauses and classification25 type type causes clinical featurescauses clinical featuresprerenalpreren
21、alintrarenal intrarenal postrenalpostrenal renal hypoperfusion:renal hypoperfusion:early stage of shockearly stage of shockoliguria or anuria,oliguria or anuria,azotemia,urineNaazotemia,urineNa+kidneys organickidneys organic changes:prolonged changes:prolonged renal ischemia renal ischemia nephrotox
22、innephrotoxinoliguric:oliguric:nonoliguric:nonoliguric:obstruction of ureter obstruction of ureter and urethra by calculus and urethra by calculus or carcinomaor carcinomaabrupt anuria,abrupt anuria,aggravation of aggravation of azotemiaazotemiacauses and classificationsummarysummary26(1)Change of r
23、enal hemodynamics(1)Change of renal hemodynamics：v Renal hypoperfusion:the progressive stage of shock4.Pathogenesis of ARF4.Pathogenesis of ARF:(ATN)(ATN)27Renal vasoconstrictionRenal vasoconstriction：The activation of Renin-Angiotensin The activation of Renin-Angiotensin System(RAS)System(RAS)Catec
24、holamine:adrenaline,noradrenaline Catecholamine:adrenaline,noradrenaline Unbalance of prostaglandin/TXA Unbalance of prostaglandin/TXA2 2 Endothelin(ET)Endothelin(ET)Others:NO,TNF,ADH,PAF(platelet Others:NO,TNF,ADH,PAF(platelet activating factor)activating factor)28Swelling of epithelial cellsNecros
25、is of epithelial cellsIschemia,hypoxiaPoisonous agents:Mercury,Plumbum,GentamycinOliguria,anuria,waste accumulation(+)Hypoperfusion(2)Injury of renal tubules:Constriction ofafferent arterioleEffective filtratingpressure GFR Na+reabsorptionNa+load in macula densaRAS(+)Backflow of ultrafiltrateObstruc
26、tion of tubulespathogenesis29efferent efferent arteriolearterioletubular tubular epithelialepithelialcellscellsultrafiltrateultrafiltrateoliguria,anuriaoliguria,anuriaThe mechanism of backflow of ultrafiltrateThe mechanism of backflow of ultrafiltrateinterstitialinterstitialedemaedemadebris,debris,n
27、ecrotic cellsnecrotic cellsoppress oppress effectless effectless filtrationfiltration30urine flowurine flowdenudeddenudedtubulartubularmembranemembraneinjuredinjuredtubulartubularcellscellsobstructionobstructionfrom debris andfrom debris andnecrotic cellsnecrotic cellspathogenesis31ATN and interstit
28、ial edemaATN and interstitial edemapathogenesis32pathogenesis33Acute tubular necrosis in the allograftAcute tubular necrosis in the allograftpathogenesis34(3)renal cell injury:endothelial cell,(3)renal cell injury:endothelial cell,mesangial cell mesangial cell ATPATP,ion pump impaired,ion pump impai
29、red:ischemia,shock ischemia,shock OFR OFR :ischemia/reperfusion:ischemia/reperfusion GlutathioneGlutathione clean FR clean FR pathogenesis35 phospholipases phospholipases hydrolyze phospholipid hydrolyze phospholipid activate neutrophils andactivate neutrophils and inflammatory response inflammatory
30、 response cell apoptosiscell apoptosispathogenesis36oliguric ARFoliguric ARFnonoliguric ARFnonoliguric ARFoliguric phaseoliguric phasediuretic phasediuretic phaserecovery phaserecovery phaseAFRAFR5.Alterations of metabolism 5.Alterations of metabolism and function and function37(1)Oliguric ARF(1)Oli
31、guric ARF1)oliguric phasevThe most dangerous phaseThe most dangerous phasev7 7-14-14days,If 1 monthdays,If 1 month bad prognosis bad prognosisoliguric phase38vurine volume:urine volume:oliguriaoliguria(400400ml/24h)or ml/24h)or anuriaanuria(100ml/24h);(4040mmol/L)mmol/L)vurine specific gravity:urine
32、 specific gravity:(1.010-1.01.010-1.020)or 20)or isosthenuriaisosthenuria alteration of urinealteration of urineoliguric phase39vblood urea nitrogen(blood urea nitrogen(BUN):BUN):normal value normal value：3.577.14 mmol/L 30%nephrons can maintain BUN 30%nephrons can maintain BUN in normal value.in no
33、rmal value.vserum creatinine(Scr)serum creatinine(Scr):normal valuenormal value：5353106 mol/L;azotemiaazotemiaoliguric phase40 disturbance of body fluiddisturbance of body fluidvH2O retention hyponatruria,intracellular edema hyperkalemiahyperkalemiavthe most dangerous change and common cause of deat
34、holiguric phase41metabolic acidosismetabolic acidosisvacid produceacid producevacid excludeacid excludedysfunction of other systemdysfunction of other systemoliguric phase42The comparison of organic and functional ARFFunctional(Functional(hypovolaemiahypovolaemia)organic(ATN)organic(ATN)urine micros
35、copical testurine microscopical testalmost normalalmost normalmore cast(protein,more cast(protein,RBC,WBC,EC)RBC,WBC,EC)urine proteinurine protein(-)or trace(-)or traceurine Naurine Na+(mmol/L)(mmol/L)20400(700mmol/L)400(700mmol/L)3501.0201.0201.01540/140/110/130(40)30(40)+oliguric phase432)Diuretic
36、 phasevurineurine400400ml/24h,indicating ml/24h,indicating the regeneration of tubulesthe regeneration of tubulesv14days14daysDiuretic phase44 The mechanisms of diuresisThe mechanisms of diuresis GFR restore graduallyGFR restore gradually；Obstruction are released gradually Obstruction are released g
37、radually；Tubular epithelial cells begin to regenerate,Tubular epithelial cells begin to regenerate,but its but its concentrated functions are still very concentrated functions are still very weakweak；Urea blocked in oliguric phase begin to be Urea blocked in oliguric phase begin to be excludeexclude
38、，causing osmotic diuresiscausing osmotic diuresis；Diuretic phase45still in dangerous situation:still in dangerous situation:v filtration failure still exists filtration failure still exists；v might have dehydration,might have dehydration,h hyponatremia,yponatremia,hypokalemia,etc hypokalemia,etc；v t
39、he functions of epithelium are not the functions of epithelium are not completely pletely recovery.Diuretic phase46(3)recovery phasevSeveral weeks to 1 year.Several weeks to 1 year.vUrine volume and NPN return to Urine volume and NPN return to normalnormalvDisturbance of water,electrolyte and Distur
40、bance of water,electrolyte and base-acid balance and their symptoms base-acid balance and their symptoms disappear.disappear.rescovery phase47vUrine volume:Urine volume:400-1000ml/24h400-1000ml/24hvmilder symptom,shorter course,milder symptom,shorter course,less complication,light pathological less
41、complication,light pathological injury.injury.(2)Nonoliguric ARFNonoliguric ARF48v Mainly caused by the dysfunction of Mainly caused by the dysfunction of tubular concentration,so urine volume is tubular concentration,so urine volume is within normal range although serum within normal range although
42、 serum NPN is high.NPN is high.v Urine special gravity Urine special gravity (1.020),less(1.020),less hyperkalemia hyperkalemiaNonoliguric ARF49 The nature of nonoliguric The nature of nonoliguric AFR is the same as oliguric AFR is the same as oliguric AFR,the only difference is AFR,the only differe
43、nce is that their degree and course that their degree and course of illness.of illness.50relation between GFR and urine volumerelation between GFR and urine volumeNormal Normal GFRGFRTFVTFVUVUVUV/TFVUV/TFVOliguric phaseOliguric phaseDiruetic phaseDiruetic phaseNonoliguric AFRNonoliguric AFR1201208 8
44、1 14 41801801.51.512126 615001500150-300150-3001200-24001200-2400600-1200600-12001110-2010-2010-2010-2010-2010-20TFV:total filtrating volume;UV:urine volumeTFV:total filtrating volume;UV:urine volume51(1)Prevention(1)PreventionvIdentify at risk patientsIdentify at risk patients pre-existing CRF,diab
45、etes,jaundice,pre-existing CRF,diabetes,jaundice,myelomamyelomavOptimise renal perfusionOptimise renal perfusion i.v.fluids,i.v.fluids,vMaintain adequate diuresisMaintain adequate diuresis Mannitol,frusemide,NOT dopamineMannitol,frusemide,NOT dopaminevAvoid nephrotoxic agentsAvoid nephrotoxic agents
46、 ACE inhibitors,radiological contrast,ACE inhibitors,radiological contrast,aminoglycosidesaminoglycosides6.Prevention and Treatment6.Prevention and Treatment52(2)Treatment(2)TreatmentvCorrect renal perfusionCorrect renal perfusion optimise volume statusoptimise volume statusvRemove nephrotoxinsRemov
47、e nephrotoxinsvRelieve obstructionRelieve obstruction bladder catheterbladder catheter nephrostomynephrostomy53vMake the patient safetyMake the patient safety hyperkalaemiahyperkalaemia volume overloadvolume overload uraemiauraemia acidosisacidosisvSpecific treatmentsSpecific treatments antibiotics,
48、steroidsantibiotics,steroidsvDialysisDialysis haemodialysishaemodialysis peritoneal dialysisperitoneal dialysis54peritoneal dialysisperitoneal dialysis55haemodialysishaemodialysis56OutcomeOutcomevFull recoveryFull recoveryvPartial recoveryPartial recoveryvNo recovery:progress to No recovery:progress
49、 to ESRF(end-stage renal failure)ESRF(end-stage renal failure)vDeathDeath57summaryvARF is a life-threatening disease.vMany cases can be avoided.vEarly diagnosis and expert treatment is associated with a better outcome.vARF requiring specific treatment,especially urinary tract obstruction and RPGN must not be missed.vUrgent treatment is needed for life-threatening complications.
