Respiratory Failure

1. Respiratory Failure Zhihua Gao Zhejiang University

2. Outline • Review • Respiration • Respiratory system • Lung function • Respiratory failure • Definition • Classification • Etiology • Mechanism • Changes in the body • Prevention and therapy

3. Respiration-a process of gas exchange 1. O2 intake External respiration 2. Hb carrying O2 3. O2 transport in circulation 4. O2 utilization in the tissue

4. Respiratory System • Consists of three parts: • Pumpimg part • respiratory muscles • respiratory control system • Conductive part • the complete trachea system • Gas exchange part • Alveoli in the lung VENTILATION • GAS EXCHANGE

5. Lung function respiratory function • Ventilation • O2 inspiration &CO2 expiration • Gas exchange • Oxygenation of the blood

6. Lung function • Non-respiratory function • Defense • Filtration • Metabolism Endothelial cell Pulmonary surfactant (PS, 肺泡表面活性物质) Metabolism of arachidonic acid ---prostaglandin and leukotrienes APUD cell (amine precursor uptake and decarboxylation cell) ---VIP血管活性肠肽,P,CCK胆囊收缩素, somatostatin生长抑素

7. Ventilation The driving force (动力): contraction of respiratory muscles

8. Ventilation The resistance : elastic and airway resistance 顺应性=1/弹性阻力 Pulmonary surfactant (PS, 肺泡表面活性物质) Ventilation Elastic resistance Airway resistance

9. 8Lη R= πr4 Airway resistance Influence factors: airway diameter, length and shape, rate of air flow 气道内径，长度，形态，气流速度，形式等 大气道阻力：直径>2mm，有软骨环支撑，不易塌陷， 80% 小气道阻力：直径<2mm，无软骨环支撑，易扭曲闭合， 20% 气道阻力与气道长度成正比，与气道半径的四次方成反比

10. Gas exchange (oxygenation) Influence factors: • The difference of partial pressure cross the aveolar membrane • Molecular weight and solubility of the gas • The areaand thicknessof alveolar membrane • The contact time between alveoli and blood. • 肺泡膜两侧的气体分压差 • 气体的分子量与溶解度 • 肺泡膜的面积与厚度 • 血液与肺泡接触时间

11. Respiratory failure Concept A pathologic process caused by severe external respiratory dysfunction that results in decrease of PaO2with or without retention of CO2 Diagnostic criteria Respiratory failure is defined as PaO2 <60 mmHg with or without PaCO2 >50 mmHg.

12. Classification

13. Classification • PaO2 ↓ • Is PaCO2 ↑? • no PaCO2↑--type I (hypoxemic, 低氧血症型)， failure of gas exhcange • PaCO2↑--type II (hypercapnic， 高碳酸血症型) , failure of ventilation

14. Respiratory System External respiration dysfunction • Consists of three parts: • Pump • respiratory muscles • respiratory control system • Conductive part • the complete trachea system • Gas exchange part • Alveoli in the lung VENTILATION • GAS EXCHANGE Respiratory failure

15. Etiology and Pathophysiology Dysfunction of external respiration • Ventilation failure (通气障碍) • Restrictive hypoventilation (限制性通气不足 ) • Obstructive hypoventilation (阻塞通气不足 ) • Gas-exchange failure (换气障碍) • Diffusion disorder (弥散障碍) • VA/Q mismatch (通气/血流比值失调) • Increased anatomical shunt (解剖分流增加)

16. Ventilation failure • Hypoventilation (通气不足 ) • Driving force ↓ • Resistance ↑ Ventilation Elastic resistance↑ Airway resistance↑ Driving force ↓

17. Ventilation failure • Hypoventilation (通气不足 ) • Driving force ↓ • Resistance ↑ • Restrictive hypoventilation (限制性通气不足 ) • Driving force ↓or elastic resistance ↑ • Limited alveolar distension (肺泡扩张受限) • Obstructive hypoventilation (阻塞通气不足 ) • Airway resistance ↑ due to obstruction

18. Restrictive hypoventilation (限制性通气不足) Caused by diseases that affect either the distensibility (扩展性) of the lungs or chest wall. Inspiration-an active process—mostly affected in restrictive hypoventilation Expiration-an passive process

19. Restrictive hypoventilation (限制性通气不足) • Paralysis of respiratory muscle • Disorders of central or peripheral nerve • Inhibition of respiratory center • Intrinsic diseases of respiratory muscle • Decreased compliance of chest wall • Severe chest deformity • Multiple rib fracture • Pleura (胸膜)fibrosis; • Decreased compliance of lung • Disorders of lung (diffuse fibrosis, edema); • Lack of alveolar surfactant (as seen in ARDS) • Pneumothorax 气胸or hydrothorax 胸腔积水

20. Obstructive hypoventilation (阻塞性通气不足) • 管壁收缩或增厚: • 支气管哮喘、慢支→支气管痉挛 • 炎症→支气管粘膜下充血、水肿、纤维增生 • 管腔阻塞： • 支气管哮喘、慢支→粘液↑ • 纤毛损伤、肿瘤、异物 • 管壁受压：肿瘤、肿大淋巴结 • 肺组织对小气道管壁的牵拉作用减弱 Airway obstruction/narrowing→Airway resistance ↑ →obstructive hypoventilation Central airway obstruction Peripheral airway obstruction

21. Obstructive hypoventilation (阻塞性通气不足) Central airway obstruction- obstruction above the rachea crotch (气管分叉以上的阻塞) outside the thorax →inspiratory dyspnea吸气困难 阻塞位于胸外：声带麻痹、喉炎、喉头水肿，喉癌，白喉 • in the airway inside →expiratory dyspnea呼气困难 • 阻塞位于胸内：气管，大支气管的狭窄和阻塞如气管肿瘤，气管异物，气管外肿物压迫（甲状腺，纵隔肿瘤）

22. Central airway obstruction Extrathoracic obstruction Intrathoracic obstruction Inspiratory dyspnea Expiratory dyspnea

23. 中央气道胸外段阻塞无呼气困难

24. 中央气道胸外段阻塞吸气困难

25. 中央气道胸内段阻塞呼气困难

26. 中央气道胸内段阻塞无吸气困难

27. Central airway obstruction Extrathoracic obstruction Intrathoracic obstruction Inspiratory dyspnea Expiratory dyspnea 大气压 (Patm)，气管内压 (Ptr)，胸内压 (PpI)三者之间的关系决定呼吸困难的形式

28. Peripheral airway obstruction The peripheral airway is usual referred to as the smaller airways (diameter<2 mm). 直径<2mm，无软骨环支撑，易扭曲闭合 specific chemical mediatorssuch as histamine, prostaglandins, leukotrients, released during inflammatory and allergic responses Abnormal neural regulation of airway smooth muscle tone Edema of mucosa and secretions in the lumen all contribute to the narrowing of airway. Expiratory dyspnea (呼气性呼吸困难)

29. Isobaric Point等压点 +35 +25 Expiratory dyspnea (呼气性呼吸困难) Mechanism +20 +20 Emphysema Normal COPD Emphysema

30. Blood gas measurements upon ventilation failure PAO2, PACO2 PaO2, PaCO2  The ratio between the decreased PaO2 and increased PaCO2 is equal to the respiratory quotient (0.8) PA: pressure in the alveoli; Pa: pressure in the arterial PAO2= PiO2 - PACO2 / R(PiO2 = PO2 of inspired gas) PaCO2 (PACO2) is optimal parameter reflecting the total volume of alveolar ventilation: PaCO2=PACO2= 0.863×VCO2 / VA (VCO2 = CO2 production /min in vivo, VA = volume of alveolar ventilation /min)

31. Blood gas measurements upon ventilation failure PAO2↓ PaO2↓ Hypoventilation PACO2↑ PaCO2↑ d PaCO2↑ d PaO2↓ = R Hypoventilation d: differences Hypoventilation→ Type II respiratory failure

32. Etiology and Pathophysiology Dysfunction of external respiration • Ventilation failure (通气障碍) • Restrictive hypoventilation (限制性通气不足 ) • Obstructive hypoventilation (阻塞通气不足 ) • Gas-exchange failure (换气障碍) • Diffusion disorder (弥散障碍) • VA/Q mismatch (通气/血流比值失调) • Increased anatomical shunt (解剖分流增加)

33. Gas-exchange failure (换气障碍) • Diffusion disorder (弥散障碍) generally characterized by the disruption in the exchange of O2，CO2 or both across the alveolar-capillary membrane. Influence factors: • The difference of partial pressure cross the aveolar membrane • Molecular weight and solubility of the gas • The areaand thicknessof alveolar membrane • The contact time between alveoli and blood

34. Causes of diffusion disorder • Reduction of the alveolar membrane surface area (normal: 80 m2， only 35-40 m2 is involved at rest) • Atelectasis (肺不张), emphysema (肺气肿),pneumonectomy （肺叶切除） • Increased thickness of alveolar membrane (normal: 1~5µm) • Pulmonary edema, fibrosis, hyaline membrane (透明膜形成）formation, pulmonary capillary extension • Shortened diffusion time (normal 0.75s) • Usually only need 0.25s, the PaO2 can increase to PAO2 • Increased cardiac outputincreases，faster blood flow

35. PO2 PCO2 (mmHg) PaO2 100 PvCO2 80 46 60 PvO2 40 20 40 PaCO2 0 0.25 0.50 0.75 s Blood gas measurements in diffusion disorder At rest Blood gas normal In labor PaO2  , PaCO2 normal

36. Etiology and Pathophysiology Dysfunction of external respiration • Ventilation failure (通气障碍) • Restrictive hypoventilation (限制性通气不足 ) • Obstructive hypoventilation (阻塞通气不足 ) • Gas-exchange failure (换气障碍) • Diffusion disorder (弥散障碍) • VA/Q mismatch (通气/血流比值失调) • Increased anatomical shunt (解剖分流增加)

37. 4L VA 正常 = = 0.8 Q 5L VA/Q mismatch (通气/血流比值失调) the most common mechanism of respiratory failure caused by pulmonary diseases. differences ranged 3.0~0.6 from the top to the bottom of the lung

38. VA/Q mismatch (通气/血流比值失调) Hypoventilation in some alveoli →VA / Q↓ Reduced ventilation with normal blood flow Functional shunt ( venous admixture) (功能性分流) Normally, only account for ~3 % of total pulmonary blood flow Similar to A-V shunt (functional shunt) While in chronic bronchitis and obstructive emphysema, it is markedly increased up to 30-50 %. Chronic bronchitis, asthma, COPD

39. VA/Q mismatch (通气/血流比值失调) Reduced blood flow in some alveoli →VA / Q  Reduced blood flow with normal ventilation DIC, pulmonary arteritis,pulmonary artery embolization, pulmonary vasoconstriction, may be increased up to 60-70 %. Similar to dead space ventilation dead space-like ventilation (死腔样通气) Normally, the physiological dead space account for about 30 % of tidal volume.

40. Blood gas measurements in VA/Qmismatch Functional Shunt VA/Q↓ Dead Space-like Ventilation VA/Q↑ COPD Emphysema DIC, pulmonary arteritis PaO2  PaCO2 N (,)

41. Blood gas measurements in QA/V mismatch Functional Shunt Diseased Normal Total V/Q <0.8 >0.8 ≈0.8 PaO2  CaO2 PaCO2  N  CaCO2 N 

42. Blood gas measurements in QA/Vmismatch Dead Space-like Ventilation Diseased Normal Total V/Q >0.8 <0.8 ≈0.8 PaO2  CaO2 PaCO2  N  CaCO2 N 

43. Etiology and Pathophysiology Dysfunction of external respiration • Ventilation failure (通气障碍) • Restrictive hypoventilation (限制性通气不足 ) • Obstructive hypoventilation (阻塞通气不足 ) • Gas-exchange failure (换气障碍) • Diffusion disorder (弥散障碍) • VA/Q mismatch (通气/血流比值失调) • Increased anatomical shunt (解剖分流增加)

44. Increased anatomical shunts True shunt-abnormal anatomic pathway In normal persons: 2-3 % of the cardiac output. Bronchiectasis (支气管扩张) bronchogenic carcinoma pulmonary arterio-venous fistulas (瘘管) In most pulmonary edema, atelectasis (肺不张)and pneumonia, the alveoli are filled by fluid or closed. There is perfusion but no ventilation at all. Blood disturbances: PaO2 , PaCO2 N (,)

45. Differential diagnosis • Functional shunts v.s. True shunts • 功能性分流与真性分流的鉴别诊断 • Pure O2 intake for 30 min can correct functional but not real shunts. PaO2 ↑ PaCO2 N Compensatory hyperventilation Gas exchange disorder Type Irespiratory failure

46. Acute Respiratory Distress Syndrome （ARDS) 急性呼吸窘迫综合征 致病因子 激活中性粒细胞/单核巨噬细胞/血小板/内皮细胞 微血栓形成 释放体液介质 肺泡-毛细血管膜损伤 和通透性增高 • ARDS病理改变：肺出血、水肿、肺不张、微血栓、肺泡透明膜形成

47. 肺水肿 透明膜形成 弥散障碍 • ARDS引起呼衰的机制 PaO2↓ PaCO2 N或↓ 肺不张 支气管阻塞 支气管痉挛 功能性分流 VA/Q mismatch Ⅰ型呼衰 微血栓形成 肺血管收缩 死腔样通气

48. Chronic obstructive pulmonary disease (COPD) Chronic obstructive pulmonary disease (COPD) is chronic airway obstruction caused by chronic bronchitis and emphysema.

49. COPD Pathogenesis: Congestion,swelling, spasm, blockage of bronchi wall Upward shift of Isobaric point Decreased alveolar surfactant Respiratory muscle failure Decreased alveolar surface area Low ventilation in part of alveoli Low blood flow in part of alveoli ? Obstructive Ventilatory inadequacy Restrictive ? Ventilatory inadequacy Diffusion disorder ? Ventilation-perfusion mismatching ?

50. Changes in the body • Alteration of blood gas • Acid-base and electrolyte disturbances • Disorders of vital organ systems