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

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 GAS EXCHANGE VENTILATION

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

6. 6 –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 Lung function

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

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

9. 9 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% R= 8Lη πr 4 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 area and thickness of 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. 11 Concept A pathologic process caused by severe external respiratory dysfunction that results in decrease of PaO 2 with or without retention of CO 2 Respiratory failure Diagnostic criteria Respiratory failure is defined as PaO 2 50 mmHg.

12. 12 Classification PaCO2MECHANISMPATHOGENIC SITE COURSE Type IGas-exchangeCentralAcute Type IIVentilationPeripheralChronic

13. Classification PaO 2 ↓ Is PaCO 2 ↑? –no PaCO 2 ↑--type I (hypoxemic, 低氧血症 型 ) ， failure of gas exhcange –PaCO 2 ↑--type II (hypercapnic ， 高碳酸血 症型 ), failure of ventilation

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

15. 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 ) –V A /Q mismatch ( 通气 / 血流比值失调 ) –Increased anatomical shunt ( 解剖分流增加 ) Etiology and Pathophysiology Dysfunction of external respiration

16. Airway resistance↑ Ventilation Elastic resistance↑ Ventilation failure Hypoventilation ( 通气不足 ) –Driving force ↓ –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. 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. 19  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 Restrictive hypoventilation ( 限制性通气不足 )

20. Obstructive hypoventilation ( 阻塞性通气不足 ) Airway obstruction/narrowing→Airway resistance ↑ →obstructive hypoventilation Central airway obstruction Peripheral airway obstruction 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

21. 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） 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 )

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

23. 23 中央气道胸外段阻塞无呼气困难

24. 24 中央气道胸外段阻塞吸气困难

25. 25 中央气道胸内段阻塞呼气困难

26. 26 中央气道胸内段阻塞无吸气困难

27. Extrathoracic obstruction Intrathoracic obstruction Expiratory dyspnea Inspiratory dyspnea Central airway obstruction 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. 28 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 mediators such 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. Peripheral airway obstruction Expiratory dyspnea ( 呼气性呼吸困难 )

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

30. 30 P A O 2 , P A CO 2   P a O 2 , P a CO 2  The ratio between the decreased P a O 2 and increased P a CO 2 is equal to the respiratory quotient (0.8) P A : pressure in the alveoli; P a : pressure in the arterial P A O 2 = PiO 2 - P A CO 2 / R (PiO 2 = PO 2 of inspired gas) PaCO 2 (P A CO 2 ) is optimal parameter reflecting the total volume of alveolar ventilation: PaCO 2 = P A CO 2 = 0.863×VCO 2 / V A (VCO 2 = CO 2 production /min in vivo, V A = volume of alveolar ventilation /min) Blood gas measurements upon ventilation failure

31. Hypoventilation PAO2↓PAO2↓PAO2↓PAO2↓ PaO 2 ↓ P A CO 2 ↑ PaCO 2 ↑ Hypoventilation→ Type II respiratory failure Hypoventilation d PaCO 2 ↑ d PaO 2 ↓ = R Blood gas measurements upon ventilation failure d: differences

32. 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 ) –V A /Q mismatch ( 通气 / 血流比值失调 ) –Increased anatomical shunt ( 解剖分流增加 ) Etiology and Pathophysiology Dysfunction of external respiration

33. Gas-exchange failure ( 换气障碍 ) generally characterized by the disruption in the exchange of O 2 ， CO 2 or both across the alveolar- capillary membrane. Diffusion disorder ( 弥散障碍 ) Influence factors: The difference of partial pressure cross the aveolar membrane Molecular weight and solubility of the gas The area and thickness of alveolar membrane The contact time between alveoli and blood

34. 34  Reduction of the alveolar membrane surface area (normal: 80 m 2 ， only 35-40 m 2 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 PaO 2 can increase to P A O 2  Increased cardiac output increases ， faster blood flow Causes of diffusion disorder

35. At rest Blood gas normal In labor P a O 2 , P a CO 2 normal Blood gas measurements in diffusion disorder PvO2 PvO2 PaO2PaO2 P a CO 2 P v CO 2 46 40 PO 2 PCO 2 (mmHg) 100 80 60 40 20 0 0.25 0.50 0.75 s

36. 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 ) –V A /Q mismatch ( 通气 / 血流比值失调 ) –Increased anatomical shunt ( 解剖分流增加 ) Etiology and Pathophysiology Dysfunction of external respiration

37. 37 = = 正常 VAVA Q 4L 5L 0.8 V A /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. Hypoventilation in some alveoli →V A / Q↓ While in chronic bronchitis and obstructive emphysema, it is markedly increased up to 30-50 %. Similar to A-V shunt (functional shunt) Functional shunt ( venous admixture) ( 功能性分流 ) Normally, only account for ~3 % of total pulmonary blood flow Reduced ventilation with normal blood flow V A /Q mismatch ( 通气 / 血流比值失调 ) Chronic bronchitis, asthma, COPD

39. DIC, pulmonary arteritis, pulmonary artery embolization, pulmonary vasoconstriction, may be increased up to 60-70 %. Reduced blood flow in some alveoli →V A / Q  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. Reduced blood flow with normal ventilation V A /Q mismatch ( 通气 / 血流比值失调 )

40. 40 Blood gas measurements in V A /Q mismatch Functional Shunt V A /Q ↓ Dead Space-like Ventilation V A /Q↑ PaO 2  PaCO 2 N ( ,  ) COPD Emphysema DIC, pulmonary arteritis

41. 41 Diseased Normal Total V/Q 0.8 ≈0.8 PaO 2    CaO 2    PaCO 2   N  CaCO 2   N  Functional Shunt Blood gas measurements in Q A /V mismatch

42. 42 Dead Space-like Ventilation Diseased Normal Total V/Q >0.8 <0.8 ≈0.8 PaO 2    CaO 2    PaCO 2   N  CaCO 2   N  Blood gas measurements in Q A /V mismatch

43. 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 ) –V A /Q mismatch ( 通气 / 血流比值失调 ) –Increased anatomical shunt ( 解剖分流增加 ) Etiology and Pathophysiology Dysfunction of external respiration

44. 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: P a O 2 , P a CO 2 N ( ,  )

45. 45 Functional shunts v.s. True shunts 功能性分流与真性分流的鉴别诊断 Pure O 2 intake for 30 min can correct functional but not real shunts. Differential diagnosis Gas exchange disorder Compensatory hyperventilation P a O 2 ↑ P a CO 2 N Type I respiratory failure

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

47. 47 ARDS 引起呼衰的机制 肺水肿透明膜形成 肺不张支气管阻塞支气管痉挛 微血栓形成肺血管收缩 弥散障碍 功能性分流 死腔样通气 PaO 2 ↓ PaCO 2 N 或 ↓ Ⅰ型呼衰 V A /Q mismatch

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

49. 49 ? ? ? ? COPD Pathogenesis : Ventilatory inadequacy Ventilation-perfusion mismatching Diffusion disorder Ventilatory inadequacy Obstructive Restrictive 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

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

51. 51 Disorders of acid-base balance and electrolyte metabolism (l) RF type II→H 2 CO 3 ↑ → H + — K + exchange (cells) Cl – — HCO 3 – exchange (RBC) excreted (NH 4 Cl, NaCl) by kidney (2) Hypoxia→ acid product↑ Renal insufficiency ( excreting acid / reserving base↓) anion gap normal, Cl － ↑ (3) RF type I → hyperventilation → pCO 2 ↓ K + ↑ Cl – N → Respiratory alkalosis→ K↓,Cl － ↑ Metabolic acidosis Respiratory acidosis K + ↑ Cl － ↓

52. 52 Alterations in respiratory system Alterations caused by hypoxia and hypercapnia PCR RC Total effect PaO <60 <30 PaCO >50,<80 >80 (PCR: peripheral chemical receptor; RC: respiratory center) － ＋ ＋ ＋ < － － － ＋ > － ＋ O 2 therapy for chronic Type II RF: low concentration, low flow rate, continuous O 2 supply, maintain P a O 2 ~60 mmHg

53. 53 Alterations in circulatory system (1) Mild PaO 2 , PaCO 2   excitation (reflex): Cardiac Output  Blood redistribution (peripheral constriction, coronary & cerebral artery dilation) (2) Severe PaO 2 , PaCO 2   inhibition (direct): BP  Cardiac contractility , arrhythmia (3) Chronic lung disease  right-heart failure Pulmonary Heart Disease (PHD)

54. 54 Hypoxia, Hypercapnia, Overload Disorder of electrolyte metabolism Myocardial injury Resistance ↑ PaO 2 , PaCO 2  →constriction of pulmonary arteriole Primary disease →thickening and sclerosis of vessel wall, Narrowing of vessel lumen Persistent hypoxia→ RBC↑, blood volume↑, viscosity↑ PHDPHD → Pulmonary artery hypertension

55. 55 Alterations in central nervous system Respiratory failure  dysfunction of brain Pulmonary encephalopathy 肺性脑病

56. 56 Dilation, permeability↑ →vasogenic brain edema ATP  → Na-K-ATPase  →cytoxic brain edema Cerebral blood vessels Cerebral cells Glutamate decarboxylase↑ →GABA↑→CNS inhibition Phospholipase↑→release lisozyme→ injury of brain cells Intracranial Pressure↑ Hypoxia Acidosis Pulmonary encephalopathy Respiratory failure Pulmonary encephalopathy

57. 57 Hypoxia and acidosis → sympathetic stimulation → renal vasoconstriction → decreased renal blood flow →functional renal failure Alterations in kidney

58. 58 Alterations in gastrointestine Severe hypoxia → vasoconstriction in stomach wall → mucosa damage → loss of barrier function mucosa ulcer bleeding and necrosis Severe retention of CO 2 → active carbonic anhydrase → increased secretion of HCl

59. 59 Principles of prevention and treatment 1. Prevention and correction of the causes 2. Oxygen administration to enhance PaO 2 3. Improving pulmonary ventilation to decrease PaCO 2 ( relieving blockage, enhancing motive force, artificial ventilation, supplying nutrition) 4. Improving internal environment (electrolytes & acid- base balance) and the functions of vital organs.

60. 60 Respiratory failure is a pathological process in which the external respiratory dysfunction leads to an abnormal decrease of PaO 2 (60mmHg or less) with or without retention of PaCO 2 (50mmHg or more) Summary Definition

61. 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 ) –V A /Q mismatch ( 通气 / 血流比值失调 ) –Increased anatomical shunt ( 解剖分流增加 ) Summary Etiology and Pathophysiology Dysfunction of external respiration

62. 学习目标与要求 掌握： 呼吸衰竭定义与分类 病因与发病机制 通气不足与换气障碍引起呼吸衰竭的机制 限制性通气不足与阻塞性通气不足原理与病因 中枢性与外周性阻塞导致呼吸困难的机制 弥散障碍致呼吸衰竭机制 通气 / 血流比值失常致呼吸衰竭机制 功能性分流，死腔样通气，真性分流特征 I 型与 II 型呼吸衰竭血气分析特征 ARDS 与 COPD 致呼吸衰竭的主要发病机制 慢性 II 型呼吸衰竭氧疗注意事项 肺源性心脏病与肺性脑病的发病机制

63. Thanks! Have a good summer holiday!

64. 64 Driving force ↓ Respiratory center  respiratory muscle Resistance ↑ Elastic resistance of chest wall or lung Airway Resistance for gas flow respiratory amplitude respiratory velocity Restrictive hypoventilation Obstructive hypoventilation Inadequate driving force or excessive elastic resistance may restrict respiratory amplitude Increased resistance of air way may lower respiratory velocity