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1、Acute Renal Failure(ARF)Chengwu Liu2012Company Logo 1.Review of renal structure and physiology2.Definition of ARF3.Causes and classification4.Pathogenesis(acute tubular necrosis，ATN)5.Alterations of metabolism and function6.Prevention and treatmentoutline2Company Logo vTo excrete urine and waste pro
2、ductsvTo regulate the balance of water and electrolytes vTo regulate the BPvTo involve in endocrine regulation:-Renin -Erythropoietin(EPO)-Vitamin D3 -Prostaglandin(PG)reviewThe main functions of kidney1.review3Company Logo Abdominal aortaAdrenal glandUreterInferior vena cavareviewThe renal structur
3、e4Company Logo review5review6review CortexMedula7reviewNephroticsyndrome:EdemaProteinuria HyperlipidemiaHypoproteinemia The Structure ofthe Glomerulus8Sympathetic nerve fiberJuxtaglomerular cellsAfferent arterioleMacula densaSmooth muscle cellsDistal tubuleMesangial cellsEfferent arteriolePodocytesT
4、he Juxtaglomerular Apparatusreview9Company Logo review10Net Filtration PressureBlood hydrostatic pressure(BHP)60 mmHg outColloid osmotic pressure(COP)-25 mmHg inCapsular pressure(CP)-10 mmHg inNet filtration pressure(NFP)25 mmHg outNFPBHP60 outCOP25 inCP25 out10 inreview11review12adrenal gland corte
5、xJuxtaglomerular apparatus,cellreninangiotensinogenangiotensin angiotensin liverlungACEVessel constriction aldosterone H2O,Na+reabsorptionBPEndocrine function of kidney:Activation of RAASBP,Na+,sympathetic N(+)review13Company Logo v 2.definitionAcute Renal Failure(ARF)：an acute and severe syndrome w
6、hich shows a abrupt and sustained decline in kidneys ability to clear toxic substances in blood,leading to an accumulation of metabolic waste,manifesting azotemia,hyperkalemia,metabolic acidosis,and often accompanied by oliguria or anuria.definition14Company Logo Characters：(1)Abrupt sustained decli
7、ne in GFR(2)Rising serum urea and creatinine(3)Loss of water and salt homeostasis(4)Life threatening metabolic changecharacters15Company Logo Characters：(5)Occurs over hours or days(6)Incidence about 140 ppm per year(7)High mortalitycharacters16classification:vprerenal ARF vintrarenal ARFvpostrenal
8、ARFbladderureterkidney3.cause and classification17Company Logo Pre-renal ARF(1)Causes of prerenal ARFhypovolemiahaemorrhage,burns,fluid loss，hypotension,cardiogenic shock,sepsisrenal hypoperfusionrenal vasoconstriction,drugs,liver diseases,renal vascular diseases(thrombosis,DIC)feature:reversibility
9、 causes and classification18renal angiographystraitnesscauses and classification19Company Logo (2)Causes of intrarenal ARFvDiseases of the renal parenchyma ATNprolonged ischaemia(50%),direct toxicity(35%):fish gallbladder,aminoglycoside(Gentamycin),mercury,arsenic(As),myoglobin,sepsis vascular disea
10、sevasculitis,infarctioncauses and classification20Company Logo diseases of glomerulus or arteriolesRPGN(rapidly progressive glomerulonephritis)HUS(haemolytic uraemic syndrome)SLE(systemic lupus erythematosus)vasculitis tubule-interstitial nephritisDrug relatedparaneoplasticcauses and classification2
11、1Immune complex glomerulonephritiscauses and classification22 The thickened basement membrane stains black,and forms spike-like projections around immune complex deposits,which are unstained.rapidly progressive glomerulonephritiscauses and classification23Immune complex deposition in the glomerulus(
12、B).B,immunofluorescence micrograph stained with fluorescent anti-IgG from a patient with diffuse proliferative lupus nephritis.causes and classification24Company Logo (3)Causes of postrenal ARFvuretercalculi,carcinoma,fibrosis,straitnessvbladderprostatic hypertrophy or malignancy,carcinoma,calculica
13、uses and classification25 type causes clinical featuresprerenalintrarenal postrenal renal hypoperfusion:early stage of shockoliguria or anuria,azotemia,urineNa+kidneys organic changes:prolonged renal ischemia nephrotoxinoliguric:nonoliguric:obstruction of ureter and urethra by calculus or carcinomaa
14、brupt anuria,aggravation of azotemiacauses and classificationsummary26Company Logo (1)Change of renal hemodynamics：v Renal hypoperfusion:the progressive stage of shock4.Pathogenesis of ARF:(ATN)27Company Logo Renal vasoconstriction：The activation of Renin-Angiotensin System(RAS)Catecholamine:adrenal
15、ine,noradrenaline Unbalance of prostaglandin/TXA2 Endothelin(ET)Others:NO,TNF,ADH,PAF(platelet activating factor)28Swelling of epithelial cellsNecrosis of epithelial cellsIschemia,hypoxiaPoisonous agents:Mercury,Plumbum,GentamycinOliguria,anuria,waste accumulation(+)Hypoperfusion(2)Injury of renal t
16、ubules:Constriction ofafferent arterioleEffective filtratingpressure GFR Na+reabsorptionNa+load in macula densaRAS(+)Backflow of ultrafiltrateObstruction of tubulespathogenesis29efferent arterioletubular epithelialcellsultrafiltrateoliguria,anuriaThe mechanism of backflow of ultrafiltrateinterstitia
17、ledemadebris,necrotic cellsoppress effectless filtration30urine flowdenudedtubularmembraneinjuredtubularcellsobstructionfrom debris andnecrotic cellspathogenesis31ATN and interstitial edemapathogenesis32pathogenesis33Acute tubular necrosis in the allograftpathogenesis34Company Logo (3)renal cell inj
18、ury:endothelial cell,mesangial cellATP,ion pump impaired:ischemia,shockOFR:ischemia/reperfusionGlutathione clean FRpathogenesis35Company Logo phospholipases hydrolyze phospholipid activate neutrophils and inflammatory responsecell apoptosispathogenesis36Company Logo oliguric ARFnonoliguric ARFoligur
19、ic phasediuretic phaserecovery phaseAFR5.Alterations of metabolism and function37Company Logo (1)Oliguric ARF1)oliguric phasevThe most dangerous phasev7-14days,If 1 month bad prognosisoliguric phase38Company Logo vurine volume:oliguria(400ml/24h)or anuria(40mmol/L)vurine specific gravity:(1.010-1.02
20、0)or isosthenuria alteration of urineoliguric phase39Company Logo vblood urea nitrogen(BUN):normal value：3.577.14 mmol/L 30%nephrons can maintain BUN in normal valuevserum creatinine(Scr):normal value：53106 mol/L;azotemiaoliguric phase40Company Logo disturbance of body fluidvH2O retention hyponatrur
21、ia,intracellular edema hyperkalemiavthe most dangerous change and common cause of deatholiguric phase41Company Logo metobolic acidosisvacid producevacid excludedysfunction of other systemoliguric phase42The comparison of organic and functional ARFFunctional(hypovolaemia)organic(ATN)urine microscopic
22、al testalmost normal more cast(protein,RBC,WBC,EC)urine protein(-)or traceurine Na+(mmol/L)400(700mmol/L)1.02040/130(40)+oliguric phase43Company Logo 2)Diuretic phasevurine400ml/24h,indicating the regeneration of tubulesv14daysDiuretic phase44Company Logo The mechanisms of diuresis GFR restore gradu
23、ally；Obstruction are released gradually；Tubular epithelial cells begin to regenerate,but its concentrated functions are still very weak；Urea blocked in oliguric phase begin to be exclude，causing osmotic diuresis；Diuretic phase45Company Logo still in dangerous situation:v filtration failure still exi
24、sts；v might have dehydration,hyponatremia,hypokalemia,etc；v the function of epithelium is not completely recovery.Diuretic phase46Company Logo (3)recovery phasevSeveral weeks to 1 year.vUrine volume and NPN return to normalvDisturbance of water,electrolyte and base-acid balance and their symptoms di
25、sappear.rescovery phase47Company Logo vUrine volume:400-1000ml/24hvmilder symptom,shorter course,less complication,light pathological injury.(2)Nonoliguric ARFNonoliguric ARF48Company Logo vMainly caused by the dysfunction of tubular concentration,so urine volume is within normal range although seru
26、m NPN is high.vUrine special gravity(1.020),less hyperkalemiaNonoliguric ARF49relation between GFR and urine volumeNormal GFRTFVUVUV/TFVOliguric phaseDiruetic phaseNonoliguric AFR1208141801.51261500150-3001200-2400600-1200110-2010-2010-20TFV:total filtrating volume;UV:urine volume50Company Logo The
27、nature of nonoliguric AFR is the same as oliguric AFR,the only difference is that their degree and course of illness51Company Logo (1)PreventionvIdentify at risk patientspre-existing CRF,diabetes,jaundice,myelomavOptimise renal perfusioni.v.fluids,vMaintain adequate diuresisMannitol,frusemide,NOT do
28、paminevAvoid nephrotoxic agentsACE inhibitors,radiological contrast,aminoglycosides6.Prevention and Treatment52Company Logo (2)TreatmentvCorrect renal perfusionoptimise volume statusvRemove nephrotoxinsvRelieve obstructionbladder catheternephrostomy53Company Logo vMake the patient safetyhyperkalaemi
29、avolume overloaduraemiaacidosisvSpecific treatmentsantibiotics,steroidsvDialysishaemodialysisperitoneal dialysis54peritoneal dialysis55haemodialysis56Company Logo OutcomevFull recoveryvPartial recoveryvNo recovery:progress to ESRF(end-stage renal failure)vDeath57Company Logo summaryvARF is a life-threatening disease vMany cases can be avoided vEarly diagnosis and expert treatment is associated with a better outcomevARF requiring specific treatment,especially urinary tract obstruction and RPGN must not be missedvUrgent treatment is needed for life-threatening complications58