Multiple Organ Dysfunction Syndrome (MODS)Jianzhong Sheng MD, PhDDepartment of PathophysiologySchool of MedicineZhejiang UniversityDefinition Dysfunction or failure of multiple organ or system happened simultaneously or sequentially due to various etiological factors.EtiologyInfection: Gram positive/negative bacteria, fungal, Virus Shock :hemorrhage, etc.Allergy Burns Trauma Severe acute pancreatitisClassification of MODSnImmediate Type (Primary)：Dysfunction are happened simultaneously in two or more organs due to primary disease. nDelayed type (Secondary）：）：Dysfunction happened in a organ, other organs sequentially happened dysfunction or failure.nAccumulation type：Dysfunction leaded by chronic disease.AttentionImmediate TypeNot related to SIRSCoup injury with chemical or physical factorsNo time interval from diseaseARDS+ARF or ARDS+ARF+DIC+LFDelayed typeNot the direct outcome from injuryRelating to SIRS（systemic inflammatory response syndrome）Time interval existed from primary diseaseAccumulation typeAccumulation typeAccumulationAccumulationIrreversibleIrreversibleARDS: acute respiratory distress syndromeARF: acute renal failureLF: liver failureMechanism Inflammatory mediators priming SIRS leading to MODS Vascular permeability PMN chemotaxisMono / Macrophage PMN elastase PLA2 PLA2 oxygen free radicals TNF IL TNF IL8 8 IL IL1 1 IL IL6 6 Liver： acute phase Remote organ injuryRemote organ injuryTissue injury EndotheliumInjuryfactors PMNPAFPAFAdhensive moleculesDICpolymorphonucleocyte PAF, platelet activating factorCommon Manifestations of MODS OrganSymptomsHeartAcute heart failurePeripheral circulationShockLungALI /ARDSKidney ARFGastro-intestineStress ulcer/enteroparalysisLiver Acute hepatic failureBrain CNS failure Coagulation DICDiagnosis of CriteriaOrgan/ system dysfunction and failureGLASGOW SCORETreatments of MODSnCombined therapyCorrection of ischemia: fluid resuscitation, mechanical ventilation Prevention of infection：drainage, antibiotics Interruption of pathological reaction：hemofiltrationStabilization of internal environment：water, electrolyte, acid-base imbalance Regulation of immunity：cellular and humor nSupport of organ functionVentilator Artificial kidneyArtificial liverProtection of enteral mucosaDrugs of protection of heart Thanks!Acute Renal Failure (ARF)Definition Characterized by ineffective filtration across glomeruli in short time. Such as azotemia, imbalance of water, electrolyte and acid-base.Etiology and classificationnPrerenal Proximal to kidney Decrease in renovascular flow1.Hypovolemia, severe cardiac dysfunction, loss of vascular tone, drugs (renal vasoconstriction), renal artery occlusion2.Abdominal Compartment Syndrome (ACS)3.50% of the ARFPostrenalDistal to kidney. Obstruction of urinary flow1.Collecting system2.Ureters: tumor, stone, etc.3.Bladder outlet (strictures, prostatism)Intrinsic renal Renal parenchyma injury (glomerular filtration ) Renal tubular dysfunction Both1. Acute glomerulonephritis2. ATN : renal ischemia（hemorrhage,septic,shock,serum anaphylaxis）; nephrotoxins (aminoglycosides, radiocontrast dye, pigments, biotoxins, polymyxin)3. Acute interstitial nephritisMechanismnOliguria and anuria stage（400ml/24h or 100ml/24h）Renal ischemia1.Decrease in glomeruli filtration（systolic blood pressure 800ml/24h ）Glomerular filtrate not concentrated：un-recovery from resorption and concentrated function of renal tubulus re-epitheliaOsmotic diuresis: large amount of BUN accumulated in body during anuria stage.Water diuresis：much electrolyte and water excess during anuria stage aggravate uresis.Clinical ManifestationnAnuria stage：（：（714 days，the longest is more than one month）Urine : （hypobaric and fixed; albuminuria; red cells and cast）Imbalance of water, electrolyte and acid-base. Three increase ：blood phosphorus, potassium, magnesium Three decrease: blood calcium, sodium, chloride Two intoxication：metabolic acidosis, water toxicationAccumulation of metabolic products-uremia（azotemia, phenol, guanidine, etc.）：）：Nausea , vomitingHeadache , restless, weakness, unconsciousness, comaHemorrhagic tendency（decrease in platelet function, increase in capillary fragility, hepatic dysfunction, DIC ）：）：Subcutaneous hemorrhageOral mucosa and gingiva bleedingGastrointestinal bleedingWounds bleeding nUrorrhagia stage(14 days）：）：Mode of urine recovery Increase Abruptly： usually in 57th day，urine output increases to 1500ml/24h abruptly.Increase gradually：Usually in 714th day， urine output increases to 200500ml/24hIncrease tardily：When urine output increases to 500700ml/24h，stopping increasing. Prognosis is poor. Imbalance of water, electrolyte; and azotemia still exist.Complicating with infection easilynStage of recovery（several months）：）：anemiaweaknessWasting DiagnosisnHistory and physical examination Etiology Whether prerenal factors exist Whether postrenal factors existExamination of urine Record urine output per hour Acid urine, specific gravity stabilizes at the range of 1.010-1.014 Microscopic examination1.More red cells and renal tubulus epithelia（cortex and medulla necrosis)2.Lenity brown cast（renal failure cast） 3.Acidophilic cell increase（interstitial nephritis）4.Red cell cast（glomerular nephritis）5.Non apparent abnormality（early stage with prerenal or postrenal failure）nExamination of renal functionUrine BUN decrease, less than 180mmol/24h usually.Urine sodium increase, more than 175mmol/24h.Fractional excretion of filtrated sodium is more than .5 FE Na（%）=（U Na/P Na）（P Cr /U Cr）100Urine osmolalityLess than 350 mOsm/L in ARFMore than 500mOsm/L in prerenal failure or glomerular nephritisSerum BUN, Cr：elevating for 3.89.4 mmol/L/dPlasma/urine Cr20Renal failure index (RFI) RFI U Na（ P Cr / U Cr ） RFI.5: ARF RFI: Prerenal oliguriaRenal and prerenal oliguria Renal and postrenal1.Renal ultrasound（nephrauxe, ureter expansion）2.Plain abdominal X-ray（calcification, stone or obstruction）3.intravenously pyelography ( IVP)4.Retrograde pyelographyTreatmentnOliguria or anuria stage Control fluid input: body weight is decreased 0.5kg daily.Output is input, less input is better than the moreFluid amount dailydominance lossnon-dominance loss endogeny water Nutrition Less protein, high calorie, high vitamin dietProtein synthesis hormone: GH, testosterone Corection of electrolyte imbalance(hyperkalemia, hyponatremia, hypocalcemia, acidosis） Antibiotics:harmful to kidneyBlood purification1.hemodialysis：artificial kidney. High clearance rate for small molecules; hemodynamics unstable2.peritonealdialysis：small molecular substances; infection; low clearance rate3.hemofiltration：high clearance rate for middle molecules; hemodynamics stable nUrorrhagia stage Infuse optimal fluid，avoiding loss of extra cellular fluidFluid infusion is 1/31/2 fluid output equivalently.Correction of electrolyteInfuse sodium and potassium according to determination of electrolyte daily.Increase amount protein.Treat infection actively Prophylaxis nTo diagnose volume deficient timelyPerform fluid test first when oliguria existedTo treat according to fluid deficientnTo correct water and electrolyte imbalance in patients with trauma and pre-operationnManagement of xenotype blood infusionTo rise pH values in urine for alkaliMannitol for diuresisnRestrict inotropic agents Norepinephrine pressor agentnTreatments of DICHeparinAcute Respiratory Distress Syndrome (ARDS)Definition Acute pulmonary dysfunction originating from diffuse infiltrate and pulmonary compliance decreased leading to severe hypoxia.ARDS is an inflammatory processNot a accumulation of edema fluidBoth lungsPredisposing conditionsInjury Lung injury：lung contusion, smoke, aspiration of gastric contents, toxic gas, drowning, oxygen Extra-lung injury: fractures, trauma, burns, massive transfusion, amniotic fluid thrombosis, transplantation Operation: cardiopulmonary bypass, major operation Infection: sepsis/septic shockShock and DICMechanism lInitial stagePulmonary capillary permeability lung parenchyma edema. Erythrocytes exudates Leukocytes infiltrate deterioration of cellular damages Pulmonary vasoconstriction, thrombosis, A-V shunt.Alveoli Edema DPL Hyaline and bloody fluid Hyaline and bloody fluid in bronchia flake atelectasislAdvanced stagePulmonary parenchyma inflammation aggravated Complicating with infectionlFinal stagePulmonary fibrosis Capillary vessels occlusion Afterload rise, hypoxiaClinical Manifestation 1. Initial stage Tachypnea, refractory to supplemental oxygen Progressive hypoxemia No rales Unrevealing in chest X-ray 2. Advanced stage Prominent dyspnea and cyanosis Need mechanical ventilation Rales; bronchi secretion rise Chest X-ray: bilateral infiltrates Conscious disturbance Temperature and leukocytes rise3. Final stage Arrhythmia bradycardia cardiac arrest Deep comaDiagnosisnPredisposing conditionsAcute injurySystemic infection RR30 Dyspnea Transplantation Exclude other conditionsDiagnostic Criteria FiO2(%)=4oxygen inflow(L/min) + 21Therapy & TreatmentnCorrection of hypoxemia quicklynMechanical ventilation earliernOptimal PEEP, recovery of alveolar function and functional residual capacity nOpen lung nRecovery of circulation and prevention of pulmonary interstitial edema nOptimal colloid and crystal fluid rationOptimal diureticsnOptimal negative fluid balance （To evaluate by CVP/PAWP, urine and rales）Treatment of infection: -sputum drainage; antibioticsBlock SIRSGlucocorticosteroid earlierInflammatory mediators inhibitor：Ibuprofen, oxpentifylline, TNF Ab.Heparin Hemofiltration nMechanical ventilation Ventilatory mode: positive ventilationPEEP: the optimal Prevention of hypovolemia: prevention of imbalance of V/Q Barotrauma: PIP 50cmH2O Thanks！