1. Pathophysiology Multiple Organ Dysfunction Syndrome Pathophysiology Department, Tongji Medical College, HUST

2. World War One Circulatory failure, hypovolemic shock World War Two Korean War Post-traumatic acute renal insufficiency Viet Nam War Post-traumatic acute respiratory insufficiency Seventy’s 70’s syndrome 1991 Multiple organ dysfunction syndrome

3. Left leg open trauma Day 2: Shortness of breath, Oliguria Day 4: ↑ T 39.5 ℃ ↑WBC (18×10 9 /L) ↑ R 35 /m, cyanosis, PaO 2 <60mmHg Urine <100ml/d Creatinine ↑↑ BUN ↑↑ Renal failure Respiratory failure Day 6: Death Case report

4. Pathophysiology Multiple Organ Dysfunction Syndrome (MODS) is dysfunction of two or more organs (initially uninvolved developing within a short period of time. short period two or more organs initially Definition uninvolved Cor pulmonale?

5. Multiple system organ failure. The role of uncontrolled infection.  They studied multiple parameters in 553 consecutive emergency surgical patients.  MSOF is primarily due to infection.  MSOF is the most common fatal expression of uncontrolled infection. 1980,115(2):136-140. Causes

6. Pathophysiology Why did anti-biotic strategies fail in some of the patients with MODS? Why did anti-biotic strategies fail in some of the patients with MODS?

7. MODS Biliary tract infection Shock Pancreatitis Burn Intra-abdominal infection Infective diseases Non-infective diseases Multiple trauma

8. Pathophysiology MODS Biliary tract infection Shock Pancreatitis Burn Intra-abdominal infection Infective diseases Non-infective diseases Multiple trauma

9. Pathophysiology Bacterial translocation The viable bacili locomote from the gastrointestinal tract to the other organs.

10. Pathophysiology Intestinal flora imbalance Immune dysfunction Intestinal mucosal ischemia Causes for the translocation

11. Pathophysiology What exactly is "leaky gut" or "increased intestinal permeability"? To understand the importance of increased intestinal permeability, you must first understand the basic concepts that: 1) the intestines are supposed to absorb nutrients, and 2) the intestines are supposed to exclude (not absorb) potentially harmful substances like bacteria, toxins, food proteins (which cause food allergy). Therefore, when we talk about "leaky gut" and "increased intestinal permeability" we are describing a condition where in these basic functions are failing. The intestines are failing in the ability to absorb nutrients, and the intestines are absorbing too many toxins.

12. Pathophysiology Infective diseases Non-infective diseases MODS

13. Pathophysiology  Ischemia/reperfusion injury Mechanism UUncontrolled inflammatory response  Microcirculatory hypo-perfusion

14. Pathophysiology Causes MODS Uncontrolled inflammatory response Q1Q2

15. Pathophysiology Inflammation Inflammatory cells Inflammatory cytokines

16. Pathophysiology Pro-inflammatory reaction TNF-a, IL-1, IL-6, IFN TXA 2, PAF Cell activation Anti-inflammatory reaction IL-10, IL-4, TGF-β IL-1ra,Lipoxin Cell elimination

17. Pathophysiology MODS is the failure of the balance Uncontrolled inflammatory response

18. Pathophysiology Systemic Inflammatory Response Syndrome (SIRS)  An uncontrolled inflammation process  Pro-inflammatory signals exceed its normal domain or degree  Result in end-organ damage and multi-system failure. 【 Definition 】 Anti-inflammatory reaction IL-10, IL-4, TGF-β IL-1ra,Lipoxin Cell eliminate Pro-inflammatory reaction TNF-a, IL-1, IL-6, IFN TXA 2, PAF Cell activation

19. Infection/ injury Local inflammatory cell activated ,PMN,VEC,) (M ,PMN,VEC,) Pro-inflammatory mediators released Inflammatory stimulator Tissue injury Systemic inflammatory cell activated ,PMN,VEC,) (M ,PMN,VEC,)

20. Pathophysiology 【 SIRS Clinical manifestations 】  Body temperature above 38 ℃ or less than 36 ℃.  Heart rate >90 beat/min.  Respiration rate >20/min or PaCO 2 <32 mmHg.  WBC >12,000/mm 3 or 10% immature cells. above 38 ℃ >20/min >12,000/mm 3

21. Pathophysiology SIRS Renal failure Respiratory failure Left leg open trauma Case review

22. Pathophysiology Compensatory Anti-inflammatory Response Syndrome( CARS)  An uncontrolled anti-inflammation process  Anti-inflammatory signals exceed its normal domain or degree  Result in end-organ damage and multi-system failure. 【 Definition 】 Immune paralysis Anti-inflammatory reaction IL-10, IL-4, TGF-β IL-1ra,Lipoxin Cell eliminate Pro-inflammatory reaction TNF-a, IL-1, IL-6, IFN TXA 2, PAF Cell activation

23. Pathophysiology SIRSCARS MODS Uncontrolled inflammatory response Infection/Injury Controlled inflammatory response Infection/injury controlled

24. Pathophysiology Infection/Injury Host response SIRSCARS MODS Uncontrolled inflammatory response Excessive Adequate Death Inadequate Infection/injury controlled Summary

25. Pathophysiology Alternations in Functions and Mechanism in different organs

26. Pathophysiology Respiratory system Alveolar epithelial cell swelling lack of surfactant WBC assembling phagocytosis

27. Pathophysiology Respiratory circulation Systemic circulation superior vena cavainferior vena cava Mechanism Highest incidence earliest occurring

28. Pathophysiology WBC Leukotriene Permeability Neutrophils adhesion WBC assembling Main manifestation Pulmonary edema pulmonary hemorrhage Dyspnea death

29. Pathophysiology Urinary system Acute renal failure Mechanism Acute necrosis of tubular cells Decreased perfusion of kidney

30. Pathophysiology Hepatic changes Trauma,infection Hepatic dysfunctionBody injury Icterus Hepatic failure ① Elimination of ET ② Production of energy

31. Pathophysiology“No great discovery was ever made without a bold guess.” Isaac Newton (1642-1727)

32. Pathophysiology THANK YOU!