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ALI/ARDS IN SEPSIS

ALI/ARDS IN SEPSIS. Dr Gül Gürsel Gazi University School of Medicine Department of Pulmonary Diseases. 60% of etiologies in ALI are sepsis Pulmonary source 46%, other source 33% 1. 1 NEJM 2005; 353:1685-93(King County Lung Injury Project-KCLIP) 2 Am J Respir Crit Care Med 1999; 159:1849-61

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ALI/ARDS IN SEPSIS

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  1. ALI/ARDS IN SEPSIS Dr Gül Gürsel Gazi University School of Medicine Department of Pulmonary Diseases

  2. 60% of etiologies in ALI are sepsisPulmonary source 46%, other source 33%1 1 NEJM 2005; 353:1685-93(King County Lung Injury Project-KCLIP) 2 Am J Respir Crit Care Med 1999; 159:1849-61 3 Am J Respir Crit Care Med 2000; 165:443-8

  3. The American-European consensus conference criteria for ALI and ARDS • ALI • Acute onset • PaO2/FiO2300 mmHg(regardless of PEEP level) • Bilateral infiltrates • PAOP 18 mmHg or no clinical evidence of left atrial hypertension • ARDS • Acute onset • PaO2/FiO2200 mmHg(regardless of PEEP level) • Bilateral infiltrates • PAOP 18 mmHg or no clinical evidence of left atrial hypertension Am J Resp Crit Care Med 1994;149:818-824

  4. Edema fluid to plasma protein concentrations <0.65transudate in hydrostatic pulmonary edema >0.65exudate in increased permeability pulmonary edema(ALI/ARDS) Matthay MA et al Physiol Rev 2002; 82:569-600

  5. Clinical disorders associated with the development of ALI and ARDS DİRECT LUNG INJURY (PULMONARY) • Aspiration of gastric contents • Pneumonia • Near drowning • Inhalational injuries • Pulmonary contusion • Pulmonary embolic disorders • Reperfusion injury • Thoracic radiotherapy INDIRECT LUNG INJURY (EXTRAPULMONARY) • Sepsis, SIRS • Severe trauma with shock • Acute pancreatitis • Transfusion of blood products • Drug overdose and toxins • Anaphylaxis • ECMO, CAGS • Decompression sickness

  6. Type I(90%), • Type II(10%) alveolar epitelial cells • Capillary endothelial cells • İnterstitium

  7. Problems in ALI ALI=edema+inflammation • Leukocyte recruitment and/or activation • Alveolar epitheal cell damage/alteration • Lung surfactant dysfunction/inactivation • Pulmonary interstitial injury • Inflammatory mediators/factors produced • Microvascular dysfunction • Airway injury • Coagulation abnormalities

  8. NEJM 2000 ;342 :1334-48

  9. Resident and Recruited Cells of The Lung Inflammatory Response

  10. Resident and Recruited Cells of The Lung Inflammatory Response

  11. Soluble mediators of inflammation

  12. Soluble Chemical Effectors of Inflammation

  13. The role of Toll-like receptors(TLRs) in pulmonary host response • TLR are the first to detect host invasion by pathogens, initiate immune responses and form the crucial link between the innate and adaptive immune systems

  14. The role of Toll-like receptors(TLRs) in pulmonary host response • TLR4 recognizes LPS of gram-negative bacteria and subsequently induces an inflammatory response • Gram-positive PAPMs are all ligans of TLR2 • Lipoteichoic acid • Lipoproteins • peptidoglycan SHOCK 2005; 24:12-18

  15. Role of Surfactant in ALI NEJM 2004; 351:853-855

  16. Endogenous compouns that inhibit lung surfactant activity • Biophysical inhibitors • Plasma en blood proteins(alb, Hb, fibrinogen) • Cell membrane lipids • Lysophospholipids • Fluid free fatty acids • Glycolipids and sphingolipids • Chemically acting inhibitors • Lytic enzymes(proteases, phospholipases) • Reactive oxygen and nitrogen species • Antibodies to surfactant proteins

  17. Am J Respir Cell Moll Biol 2005; 33:319-327

  18. Am J Respir Cell Moll Biol 2005; 33:319-327

  19. Apoptosis • Neutrophil apoptosis is inhibited early in ARDS and that the lifespan of neutrophils returns to normal as inflammation resolves • Apoptosis of alveolar epithelial cells by the Fas/Fas ligand system may also be of particular importance in the development of the permeability changes Critical Care 2003; 7: 355-8

  20. Am J Respir Cell Moll Biol 2005; 33:319-327 Mutlu G, Am J Respir Crit Care Med 2004;170:1270-1275

  21. The influence of preexisting inflammation • During severe inflammation such as sepsis immune response follows a biphasic pattern • Overwhelming proinflammatory response leads to tissue injury • Excessive activation of antiinflammatory pathways results in impaired pulmonary host defence • Dysfunctional mononuclear cells • Apoptosis of immune cells • Production of anti-inflammatory cytokines such as IL-10

  22. Local pulmonary host defense during respiratory tract infections is influenced by sepsis or sepsis like sydromes • J Immunol 1999; 162:392-399 • J Immunol 2000; 165:6496-6503 • Shock 2004; 21:415-425 Incidence of VAP in ARDS =60% • Am J Respir Crit Care Med 1997;156:1092-8

  23. JAMA 1999;282:54-61

  24. J Pathol 2004; 203:631-7

  25. Angiotensin-converting enzyme and ALI • Angiotensin-converting enzyme(ACE) has been identified as the functional receptor for SARS-CoV • Wenhui Li NATURE 2003; 426:450-454 • Mice deficient for ACE showed markedly improved disease and recombinant ACE2 can protect mice from severe acute lung injury • NATURE 2005;436:112-6 • ACE polymorfism is a significant prognostic factor for the outcome of ARDS • Crit Care Med 2006;34:1001-6

  26. Crit Care Med 2006;34:1001-6

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