病理学ppt课件

1、1Ischemia-reperfusion Injury Pathophysiology Department, Tongji Medical College, HUST2Concepts: Ischemia-reperfusion (I-R) injury, oxygen/calcium/pH paradox, calcium overload, no-flow phenomenonCauses and conditions of I-R injuryMechanisms of I-R injuryMetabolic and functional alterationsPrevention

2、and treatment principleContents3Aggravated ischemic injury during reperfusion Reperfusion Injury4Ischemia Components560 hrReperfusionIschemic Injury of Neurons1 hr2 hr7IschemiaTimeInjuryDeathInjury WindowsReperfusionOxygen paradox, calcium paradox, pH paradox8Causes and Conditions of Reperfusion Inj

3、uryCausesConditionsRecover from cardiac arrestOrgan transplantationLysing thrombiIschemia timeBranch circulationOxygen consumptionTemperature, Na+, pH, Ca2+9Case PresentationA 50-year-old man was admitted to the hospital with severe chest pain of 5 hours duration. Mental confusion and in acute dyspn

4、ea. HR: 110 beats/min, sinus rhythm;BP: 75/50 mmHg;ECG: ST segment elevation, V1-V6LVEF: 31% Improvement in breathBP: 100/70 mmHgLVEF: 38%Temporary ventricular tachycardiaDiuretic, tissue plasminogen activatorBalloon angioplasty?10Mechanisms of Reperfusion InjuryFree radicalsCa2+iNeutrophil activati

5、on and Others11Free radicalAny atom or molecule possessing unpaired electronsSuperoxide anion (O2.-)Hydroxyl radical (OH.)Nitric oxide (NO.)Peroxynitrite （ONOO- )( 过氧亚硝酸盐）Lipid peroxide radical (LOO.)Oxygen free radicalsReactive oxygen species (ROS) Oxygen free radicalsHydrogen peroxide Others121. M

6、itochondria2. Activated inflammatory cells3. Nitric oxide4. Ionizing radiationFormation of ROS13Reperfusion Ca2+iROSMechanism 1O214 Xanthine oxideseReperfusionIschemiaATPCa2+iXanthine dehydrogenaseHypoxanthinexanthineO2Uric acid AMPO2O2.- H2O2Endothelial cellMechanism 215IschemiaReperfusionO2Pro-inf

7、lammatory mediators(e.g. cytokines)NOONOO-O2- (Respiration burst)Mechanism 316Biochemical Impacts of ROS1718Calcium OverloadThe abnormal increase of intracellular calcium which causes cell injury 19Mechanism 1ReperfusionIschemia ATP Membrane depolarizationCa2+Na+Na/Ca exchanger20 Ca2+Na+ReperfusionH

8、+H+ Na+IschemiaCa2+Na+Mechanism 2H+Na/H exchanger21ReperfusionCa2+Na+H+Na+a1NAPLCPIDGPKCIP3SRCa2+Mechanism 322Mechanism 4ReperfusionMitochondriaERSRCa2+2324Na+i Gene activation Neutrophil activation Neutrophil Activation and Others25Neutrophil activation ROSInflammatorymediatorsInjury of Micro-vesse

9、ls No-reflow phenomenonCell injuryRole of NeutrophilReperfusion 26Structural and Functional Changes Reperfusion arrhythmiaMyocardial stunningHeart:Brain:EdemaCell death2728Electrocardiographic Alterations Associated with the Three Zones of Myocardial Infarction29Heart InjuryIschemia-reperfusion injuryCalcium overload Free radical Destroy of contractile protein Myocardial stunningCa+ K+ Na+ArrhythmiaCell death30Brain Injury3132Principles of Prevention and Treatment Control of reperfusion conditionsRemoval of