1. 万用卡 The Pathophysiology of Respiratory Failure Department of pathophysiology Jianzhong Sheng MD PhD

2. O2O2 CO 2 External respiration circulation Internal respiration O2O2

3. Respiratory failure is a pathological process in which the external respiratory dysfunction leads to an abnormal decrease of arterial partial pressure of oxygen with or without carbon dioxide retention. What is respiratory failure

4. （ 1 ） PaO 2 < 8kpa （ 60mmHg ） （ 2 ） PaCO 2 > 6.6 kpa （ 50mmHg ） Classification of RF ： Hypoxemic (Group I, Type 1) RF—(1) Hypercapnic (Group I, Type 2) RF—(1) ＋ (2) How to judge respiratory failure

5. Etiology and pathogenesis of RF Ventilatory disorders Diffusion disorders Ventilation-perfusion imbalance Anatomic shunt

6. Etiology and Pathogenesis of RF (1) Ventilatory disorder 1. Restrictive ventilatory disorders 2. Obstructive ventilatory disorders

7. Restrictive ventilatory disorders 1.Paralysis of the respiratory muscles 2.Decreased compliance of chest wall 3.Decreased compliance of lungs 4.Hydrothorax or pneumothorax Etiology and pathogenesis of RF (1)

8. 1. Central airway obstruction 2. Peripheral airway obstruction Obstructive Ventilatory disorders

9. Central airway obstruction Peripheral airway obstruction Trachea Bronchia Iso-pressure

10. Extrathoracic variable obstruction expirationinspiration Iso-pressure

11. Intrathoracic variable obstruction expirationinspiration

12. Normal Chronic bronchitis emphysema ＋ 20 ＋ 30 ＋ 20 ＋ 35 0 ＋ 10 ＋ 20 0 ＋ 10 ＋ 20 ＋ 25 ＋ 20 Peripheral airway obstruction

13. Blood gas Low PaO 2 and High PaCO 2 Ventilatory disorders

14. Etiology and pathogenesis of RF (2) Area of alveolar- capillary membrane↓ Diffusion disorders Thickness of alveolar- capillary membrane ↑ Exchenge time ↓

15. O2 O2 CO 2 Alveolar-capillary membrane Surfactant Alveolar epithelium Capillary endothelial cells

16. Blood gas Low PaO 2 and Normal PaCO 2 Diffusion disorders

17. Etiology and Pathogenesis of RF (3) Local hypoventilation V A /Q ↓(Ventilation/perfusion) Functional shunt Local hypoperfusion V A /Q ↑ Dead space-like ventilation Ventilation- perfusion imbalance

18. Blood gas Low PaO 2 and Nomal or low or high PaCO 2 Ventilation-perfusion imbalance

19. Blood gas Ventilation-perfusion imbalance Functional shunt Damaged lung Normal lung Whole lung V/Q<0.8>0.8=0.8>0.8<0.8 PaO 2 ↓ ↑ ↓ CaO 2 ↓ ↑↓ PaCO 2 ↑ ↓ N↓↑ CaCO 2 ↑ ↓ N↓↑

20. Blood gas Ventilation-perfusion imbalance Dead space-like ventilation Damaged lung Normal lung Whole lung V/Q>0.8<0.8=0.8>0.8<0.8 PaO 2 ↑ ↓ ↓ CaO 2 ↑↓ ↓ PaCO 2 ↓ ↑ N↓↑ CaCO 2 ↓ ↑ N↓↑

21. Etiology and pathogenesis of RF (4) Anatomic shunt Abnormal anatomic shunt Be not ventilated at all Pulmonary arterio- venous fistulas Pulmonary edema Atelectasis

22. Functional shunt and Anatomic shunt Anatomic shunt No blood –gas exchange Applying O 2 can’t increase PaO 2 Functional shunt Blood –gas exchange decrease Applying O 2 can increase PaO 2

23. Blood gas Low PaO 2 Anatomic shunt

24. ARDS Adult/acute respiratory distress syndrome

25. What is ARDS? ARDS is a common form of acute respiratory failure in adult that is characterized by dyspnea, hypoxia.

26. History: Systemic or pulmonary insult Chest radiograph: Diffuse pulmonary infiltrates Respiratory distress: Labored breathing, tachypnea Severe hypoxemia: Refractory to treatment with supplement of oxygen Recognition of ARDS

27. Sequential development of ARDS

28. Trauma, shock, infection and other causative factors Pulmonary hypoperfusion and hypoxemia Damage to epithelium Hypoxemia Platelet aggregation Increased vascular permeability Release of vasoactive substances Mechanical obstruction Stagnation of blood Leakage of fluid and plasma into lungs Noncardiogenic pulmonary edema or hemorrhage Decreased surfactant Alveolar fillingAtelectasis

29. Pathogenesis of ARDS

30. Stimulus Complement activation Pulmonary edema Lysosomal proteinase Active oxygen Pulmonary vasoconstriction Arachidonic acid metabolites Epithelial and endothelial Cell damage C5 a Sequestration of neutrophils in lungs Increased pulmonary permeability Pulmonary hypertension

31. Pathophysiology of ARDS

32. Causative factors alveolar-capillary membrane damage inflammation Pulmonary edema Pulmonary vasoconstriction Microvascular thrombus Diffusion disorders Pulmonary shunt Dead space ventilation Atelectasis Bronchia constriction Hypoxemia

33. COPD Chronic obstructive pulmonary disease

34. What is COPD? COPD is a kind of chronic obstructive ventilatory disorders caused by chronic bronchitis and emphysema

35. Pathophysiology of RF in COPD

36. COPD Peripheral airway obstructed and convulsion surfactant ↓ respiratory muscles failure diffusion membrane↓ underventilated or poor perfusion Obstructive ventilatory disorders Restrictive ventilatory disorders Diffusion disorders Ventilation- Perfusion mismatching Respiratory Failure

37. Functional and Metabolic Alterations in Respiratory Failure (1) 1. Metabolic acidosis K ＋ ↑ 、 Cl － ↑ 2. Respiratory acidosis K ＋ ↑ 、 Cl － ↓or normal 3. Respiratory alkalosis K ＋ ↓ 、 Cl － ↑ Acid-base disturbance

38. Functional and Metabolic Alterations in Respiratory Failure (2) PaO 2 30mmHg PaCO 2 80mmHg Ventilation increase Ventilation depression 60mmHg 50mmHg 20mmHg 90mmHg medulla carotid Respiratory system 1 medulla

39. Functional and Metabolic Alterations in Respiratory Failure (2) Central depression PaCO 2 ↑ Cheyne-stokes respiration Central excitement PaCO 2 ↓ Respiratory system 2

40. Functional and Metabolic Alterations in Respiratory Failure (3) Pulmonary hypertension Hypoxia 、 Hypercapnia ↓ 【 H ＋ 】 ↑ Pulmonary embolism 、 Pulmonary arteriolitis Pulmonary arteriolosclerosis right ventricle Afterload ↑ polycythemia Blood viscidity ↑ Hypoxia acidosis Dyspnea Heart extrusion Cardiovascular system chronic Heart failure R

41. Functional and Metabolic Alterations in Respiratory Failure (4) Acidosis Hypoxia Cerebrovascular Vasodilation Damage endothelium ATP ↓ ↓ Na ＋ － K ＋ bump Activity of Glutamate decarboxylase ↑ Activity of phospholipase ↑ Membrane potential ↓ neurotransmitters↓ ATP ↓ Intracellular Ca 2 ＋ ↑ Cerebral vessels Neurons Nervous system

42. Principles of treatment of respiratory failure  Correcting the causes  Relieving the hypoxemia and hypercapnia

43. Quiz 1.What is respiratory failure? 2.What is ARDS? 3.What is V/Q?

44. Thanks