Acute Respiratory Distress Syndrome ARDS or Cardiogenic Pulmonary Edema

1. Acute Respiratory Distress Syndrome (ARDS) or Cardiogenic Pulmonary Edema?

2. Cardiogenic Pulmonary Edema increased pulmonary venous pressure without left ventricular failure (eg. Mitral Stenosis) increased pulmonary venous pressure secondary to left ventricular failure increased pulmonary capillary pressure secondary to increased pulmonary arterial pressure

3. Non-cardiogenic Pulmonary Edema Decreased plasma oncotic pressure Increased negativity of interstitial pressure Altered alveolar-capillary membrance permeability(ARDS) lymphatic insufficiency others: high-altitude, neurogenic, narcotic overdose

4. ARDS

5. Definition of ARDS acute onset bilateral infiltrates on chest radiography pulmonary-artery wedge pressure <= 18mmHgor absence of clinical evidence of left atrial hypertension acute lung injury: PaO2:FiO2 <= 300 ARDS: PaO2:FiO2 <= 200 (definition recommended by American-European Consensus Conference Committee)

6. Clinical Features of ARDS rapid onset severe dyspnea severe tachypnea arterial hypoxemia refractory to O2 therapy decreased pulmonary compliance

7. Radiographic Features

8. in hydrostatic pulmonary edema interstitial edema (15-25 mmHg) mild enlargement of peribronchovascular spaces appearance of Kerley lines alveolar flooding (>25 mmHg) sudden extension of edema into alveolar spaces, creating tiny nodular or acinar areas of increased opacity

9. in ARDS Exudative stage interstitial edema, followed rapidly by perihilar areas of increased opacity Proliferative stage organization of the fibrinous exudate inhomogeneous pattern of ground-glass areas of increased opacity Fibrotic stage subpleural and intrapulmonary cystic lesion be observed

10. Compared with cardiogenic Alveolar edema in ARDS has more patchy and peripheral distribution No cardiomegaly, apical vascular redistribution, Kerley lines

11. Hydrostatic versus increased permeability pulmonary edema: diagnosis based on radiographic criteria in critically ill patients 87% with hydrostatic edema identifiedonly 60% with increased permeability edema identified Patchy, peripheral distribution of edema: 13% of patients with hydrostatic edema50% of increased permeability edema more typical of hydrostatic edema widened vascular pedicle (56%)pleural effusion (36%)peribronchial cuffs (72%)septal lines (40%)

12. Echocardiography Valve problems left ventricular ejection rate presence of cardiac chamber enlargement

13. Swan-Ganz catheters Pulmonary-artery wedge pressure: cardiogenic: high, > 18 mmHgnon-cardiogenic: normal or low, <=18 mmHg monitoring cardiac output

14. Pathogenesis of ARDS

16. Endothelial and Epithelial Injury alveolar-capillary barrier: microvascular endothelium and alveolar epithelium influx of protein-rich edema fluid into air spaces epithelial injury: alveolar flooding normal epithelial fluid transport disrupted, impairing the removal of edema reduced production and turnover of surfactant septic shock with bacterial pneumonia disorganized or insufficient repair lead to fibrosis

17. Neutrophil-Dependent Lung Injury neutrophil predominate in the pulmonary edema fluid and bronchoalveolar lavage fluid adhering to the injured capillary endothelium and marginating through the interstitium into the air space releasing oxidants, proteases, leukotrienes, proinflammatory molecules cause or result? In patients with severe pneumonia received GCSF, no increase in incidence or severity in lung injury

18. Other proinflammatory mechanisms(I) Cytokines initiate and amplify the inflammatory response produced locally by inflammatory cells, lung epithelial cells, or fibroblasts macrophage inhibitory factor: increases production of IL-8, TNF-alpha inhibitor of proinflammatory cytokines:IL-1 receptor antagonist, soluble TNF receptor, autoantibodies against IL-8, anti-inflammatory cytolines IL-10 and IL-11

19. Other proinflammatory mechanisms(II) Ventilator-Induced Lung Injury high volumes and pressures can injury the lung cyclic opening and closing of atelectatic alveoli cause lung injury alveolar overdistention coupled with repeated collapse and reopening: intiate a cascade of proinflammatory cytokines protective ventilation could reduce pulmonary and systemic cytokine response

20. Other proinflammatory mechanisms(III) abnormalities of the coagulation system platelet-fibrin thrombi in small vessels impaired fibrinolysis within the distal air space abnormalities in the production, composition, and function of surfactant contribute to alveolar collapse and gas-exchange abnormalities

21. Fibrosing Alveolitis alveolar space becomes filled with mesenchymal cells and their products, along with new blood vessels begins early in the course of the disorder and may be promoted by early proinflammatory mediators such as IL-1 procollagen III peptide: precusor of collagen synthesis

23. Resolution Alveolar edema is resolved by the active transport of sodium and chloride clearance occur early within the first few hours after intubation removal of soluble protein: diffusion removal of insoluble protein: endocytosis and transcytosis by alveolar epithelial cells and by phagocytosis by macrophages epithelial cells type II: reepithelialization

24. Biologic Markersassociated with alveolar epithelial function

25. Airspace Protein Hydrostatic/Permeability pulmonary edema:<65% / >75% of plasma protein concentration Edema fluid should be obtained soon after the edema developed, or edema fluid cleared higher mortality in patients without fluid clearance than with fluid clearance sequential measurements of the albumin to total protein ratio

26. Surfactant(I) Composed of phospholipids and apoproteins synthesized by type II cells Phospholipids: dipalmitoyl phosphatidylcholine(vital for reducing surface tension) phosphatidylglycerol Apoproteins: surfactant proteins A through D facilitate the re-organizing into surface-active lining material, accelerating formation of phospholipid film

27. Surfactant(II) increase in the minimum surface tension and alteration of lipid composition in ARDS patients total BAL phospholipids and SP-A were significantly decreased in at-risk patients and ARDS patients(lowest level) sera apoprotein levels: ARDS > cardiogenic pulmonary edema > controls serum SP-A level: also a prognostic factor SP-A and SP-B: good permeability monitor

28. Keratinocyte Growth Factor (KGF)Hepatocyte Growth Factor(HGF) Growth factors of alveolar type II cells HGF in pulmonary edema fluid:21.4 (8.3~41.3) ng/ml in acute lung injury6.6 (4.8~11.4) ng/ml in hydrostatic edema KGF: was low in both groups Edema fluid stimulated proliferation of rat type II cells higher HGF, higher mortality in acute lung injury

29. Parathyroid hormone-related protein PTHrP: produced by type II cells Patients undergoing pulmonary thrombo-endarterectomy(PTE) with cardiopulmonary bypass, reperfusion injury after lung reperfusion, prebypass PTHrP level:  severe injury: 21 (21-30) pg/ml no injury : 34 (21-41) pg/ml

30. Type I Cell Markers HT156: an integral membrance protein specific to human alveolar type I cells in pulmonary edema fluid:levels in patients with acute lung injury / with hydrostatic pulmonary edema = 4.5 in plasma:levels in patients with acute lung injury / with hydrostatic pulmonary edema = 1.6