The Pathophysiology of Respiratory Failure

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

2. O2 CO2 O2 CO2 External respiration circulation Internal respiration

3. What is respiratory failure 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.

4. How to judge respiratory failure （1）PaO2< 8kpa（60mmHg） （2）PaCO2> 6.6 kpa（50mmHg） Classification of RF： Hypoxemic (Group I, Type 1) RF—(1) Hypercapnic (Group I, Type 2) RF—(1)＋(2)

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

8. Etiology and pathogenesis of RF (1) Obstructive Ventilatory disorders 1. Central airway obstruction 2. Peripheral airway obstruction

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

10. Extrathoracic variable obstruction Iso-pressure expiration inspiration

11. Intrathoracic variable obstruction expiration inspiration

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

13. Ventilatory disorders Blood gas LowPaO2 andHigh PaCO2

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

15. Alveolar-capillary membrane Surfactant O2 CO2 Alveolar epithelium Capillary endothelial cells

16. Diffusion disorders Blood gas LowPaO2 andNormal PaCO2

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

18. Ventilation-perfusion imbalance Blood gas LowPaO2 and Nomal or low or high PaCO2

19. Ventilation-perfusion imbalance Functional shunt Blood gas

20. Ventilation-perfusion imbalance Dead space-like ventilation Blood gas

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

22. Anatomic shunt No blood –gas exchange Applying O2can’t increase PaO2 Functional shunt Blood –gas exchange decrease Applying O2 can increase PaO2 Functional shunt andAnatomic shunt

23. Anatomic shunt Blood gas LowPaO2

24. ARDS Adult/acute respiratory distress syndrome

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

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

27. Sequential development of ARDS

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

29. Pathogenesis of ARDS

30. Stimulus Complement activation C5a Sequestration of neutrophils in lungs Arachidonic acid metabolites Lysosomal proteinase Active oxygen Epithelial and endothelial Cell damage Pulmonary vasoconstriction Increased pulmonary permeability Pulmonary hypertension Pulmonary edema

31. Pathophysiology of ARDS

32. Causative factors alveolar-capillary membranedamage inflammation Pulmonary edema Bronchia constriction Atelectasis Pulmonary vasoconstriction Microvascular thrombus Diffusion disorders Dead space ventilation Pulmonary shunt 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 surfactant ↓ respiratory muscles failure Peripheral airway obstructed and convulsion diffusion membrane↓ underventilated or poor perfusion Obstructive ventilatory disorders Ventilation-Perfusion mismatching Restrictive ventilatory disorders Diffusion disorders 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) Ventilation increase 60mmHg 50mmHg medulla carotid PaCO2 80mmHg PaO2 30mmHg medulla medulla 90mmHg Ventilation depression 20mmHg Respiratory system 1

39. Functional and Metabolic Alterations in Respiratory Failure (2) Cheyne-stokes respiration PaCO2↑ Central depression Central excitement PaCO2↓ Respiratory system 2

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

41. Functional and Metabolic Alterations in Respiratory Failure (4) Neurons Cerebral vessels Activity of Glutamate decarboxylase↑ Activity of phospholipase↑ Acidosis Cerebrovascular Vasodilation Damage endothelium Membrane potential↓ neurotransmitters↓ ATP ↓ IntracellularCa2＋ ↑ Hypoxia ATP ↓ ↓ Na＋－K＋bump Nervous system

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

43. Quiz • What is respiratory failure? • What is ARDS? • What is V/Q?

44. Thanks