1、上課名稱:心肺生理病理 阻塞性肺疾總論與慢性阻塞性肺疾(慢阻肺疾),高雄醫學大學 醫學院 呼吸治療學系 講師 附設中和紀念醫院 內科部 胸腔內科 主治醫師 王東衡 Phone: EXT. 5651 E-mail:。,時間地點:20120309 W1 1500-1650 CS601 對象:呼吸治療學系二年制在職專班3年級 課程:心肺病理生理學,Curriculum Title: Obstructive Pulmonary Diseases and Chronic Obstructive Pulmonary Diseases (COPD),上課名稱:心肺生理病理 阻塞性肺疾總論與慢性阻塞性肺疾(慢
2、阻肺疾),高雄醫學大學 醫學院 呼吸治療學系 講師 附設中和紀念醫院 內科部 胸腔內科 主治醫師 王東衡 Phone: EXT. 5651 E-mail:。,時間地點:20090313 W5 1300-1450 NB 116 對象:呼吸治療學系2年級 課程:心肺病理生理學,Curriculum Title: Obstructive Pulmonary Diseases and Chronic Obstructive Pulmonary Diseases (COPD),慢性阻塞性肺疾(慢阻肺疾) 症狀表徵 理學檢查 實驗室數據 影像學佐證 病理解剖實証 呼吸治療 肺量計檢查？ 支氣管擴張劑反應試
3、驗？,阻塞性肺疾總論：氣道阻塞 意義 種類 病理生理 呼吸治療的觀點,課程進度,學習目標study goals:,了解阻塞性肺疾與慢性阻塞性肺疾(慢阻肺疾)定義，介紹網路搜尋自學。了解阻塞性肺疾與慢性阻塞性肺疾(慢阻肺疾)病理解剖，病理生理變化。從構造層面了解阻塞性肺疾與慢性阻塞性肺疾(慢阻肺疾)病理解剖，病理生理變化。從發炎媒介質層面了解阻塞性肺疾與慢性阻塞性肺疾(慢阻肺疾)病理解剖，病理生理變化。從全身層面了解阻塞性肺疾與慢性阻塞性肺疾(慢阻肺疾)病理解剖，病理生理變化。鼓勵並回答提問，接受建議，當面溝通。,参考資料references:,CHAPTER 4: PATHOLOGY, PAT
4、HOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006) 2007年更新版慢性阻塞性肺病診治指引 台灣胸腔暨重症醫學會 Chronic obstructive pulmonary disease molecular and cellular mechanisms E
5、ur Respir J 2003 22 672 688 Airway dendritic cell phenotypes in inflammatory diseases of the human lung Eur Respir J 2007 30 878 886 Flow limitation and dynamic hyperinflation Eur Respir J 2005 25 186 199,KEY POINTS 1考試範圍:CHAPTER 4: PATHOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INITIATIVE FOR
6、CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006) 2007年更新版慢性阻塞性肺病診治指引 台灣胸腔暨重症醫學會,Pathological changes characteristic of COPD are found in the proximal airways, peripheral airways, lung parenchyma, and pulmon
7、ary vasculature. These changes include chronic inflammation, and structural changes resulting from repeated injury and repair. COPD的病理變化特徵為呼吸道、肺實質以及肺血管慢性發炎以及反覆受傷和修補所造成之結構改變。 Inhaled cigarette smoke and other noxious particles cause lung inflammation, a normal response which appears to be amplified i
8、n patients who develop COPD. COPD病人對吸入香菸和有毒微粒所引起之炎性反應比常人嚴重。,KEY POINTS 2考試範圍:CHAPTER 4: PATHOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006) 20
9、07年更新版慢性阻塞性肺病診治指引 台灣胸腔暨重症醫學會,There is a characteristic pattern of inflammation in the lungs of COPD patients, with increased numbers of neutrophils (in the airway lumen), macrophages (airway lumen, airway wall, and parenchyma), and CD8+ lymphocytes (airway wall and parenchyma). The pattern is differ
10、ent from that seen in asthma. COPD病人之炎性反應特徵是嗜中性球、巨噬細胞、CD8+淋巴球增加，其型態與哮喘不同。 Lung inflammation is further amplified by oxidative stress and an excess of proteases in the lung. 發炎氧化反應（oxidative stress）和過量蛋白酉每使肺部發炎更為嚴重。, Physiological changes characteristic of the disease include mucus hypersecretion, ai
11、rflow limitation and air trapping (leading to hyperinflation), gas exchange abnormalities, and cor pulmonale. COPD生理學變化特徵為黏液過度分泌、氣流受限、肺膨脹過度、氣體交換異常、肺心症(cor pulmonale)。 Systemic features of COPD, particularly in patients with severe disease, include cachexia, skeletal muscle wasting, increased risk of
12、 cardiovascular disease, anemia, osteoporosis, and depression. COPD之全身表現有惡體質（cachexia）、骨骼肌消耗、心血管疾病危險性增加、貧血、骨質疏鬆和憂鬱。 Exacerbations represent a further amplification of the inflammatory response in the airways of patients with COPD, and may be triggered by infection with bacteria or viruses or by envi
13、ronmental pollutants. COPD惡化可能由環境污染、細菌或病毒感染所引起，代表呼吸道發炎反應加劇。,KEY POINTS 3 考試範圍:CHAPTER 4: PATHOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006) 2
14、007年更新版慢性阻塞性肺病診治指引 台灣胸腔暨重症醫學會,網路搜尋自學,網路搜尋自學,網路搜尋自學,網路搜尋自學,Figure 4. Small airway obstruction (A) Normal small airway. (B) Small airway containing plug of mucus with relatively few cells, which could have been produced in the glands of the larger airways and aspirated into the smaller airways. (C) Ac
15、utely inflamed airway with thickened wall in which the lumen is partly filled with an inflammatory exudate of mucus and cells, which has probably been produced in the small airway. (D) Airway surrounded by connective tissue, which appears as if it might restrict normal enlargement of the lumen and u
16、nfolding of the epithelial lining that occurs with lung inflation.,Pathophysiology of airflow limitation in chronic obstructive pulmonary disease Lancet 2004; 364: 70921,GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OB
17、STRUCTIVE PULMONARY DISEASE (2006),GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006),GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT
18、, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006),GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006),CHAPTER 4: PATHOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INITIAT
19、IVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006),Chronic obstructive pulmonary disease molecular and cellularmechanisms Eur Respir J 2003 22 672 - 688,CHAPTER 4: PATHOLOGY, PATHOGENESIS, AND PATHOPH
20、YSIOLOGY GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006),1,CHAPTER 4: PATHOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATE
21、GY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006),2,CHAPTER 4: PATHOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMO
22、NARY DISEASE (2006),1,CHAPTER 4: PATHOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006),2,CHAPTER 4: PATHOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY
23、 GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006),CHAPTER 4: PATHOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE
24、 DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006),CHAPTER 4: PATHOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE
25、 (2006),CHAPTER 4: PATHOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006),CHAPTER 4: PATHOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INITIATI
26、VE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006),內容,COPD 定義與分類 病變的解剖位置 病理生理 GINA GOLD,區域 1 ：慢性支氣管炎，無氣流阻塞。 區域 2 ：肺氣腫，無氣流阻塞。 區域 3 ：慢性支氣管炎，併有氣流阻塞(COPD)。 區域 4 ：肺氣腫，併有氣流阻塞 (COPD)。 區域 5 ：慢性支氣管炎，併有肺氣腫及氣流阻塞
27、(COPD)。 區域 6 ：慢性支氣管炎，併有可部份恢復之氣流阻塞 (COPD)。,區域 7 ：肺氣腫，併有可部份恢復之氣流阻塞 (COPD)。 區域 8 ：慢性支氣管炎，併有肺氣腫及可部份恢復之氣流阻塞(COPD)。 區域 9 ：可完全恢復之氣流阻塞 (asthma)。 區域10：氣流阻塞，係肇因於已知病因或特殊病理變化，例如：支氣管擴張症，或阻塞性細支氣管炎。 區域11：慢性支氣管炎，併有肺氣腫，並無氣流阻塞。,http:/ emphysema,肺氣腫在病理學上可分為三類： 1.腺泡中央型肺氣腫(centriacinar emphysema)： 氣道擴大起自呼吸性細支氣管向周圍散佈，主犯上
28、肺野，好犯於吸菸者。 2.全腺泡型肺氣腫(panacinar emphysema)： 侵犯整個肺泡，主犯下肺野，好發於同基因型ATT缺乏症患者。 3.腺泡遠端型肺氣腫(distal acinar emphysema)： 病灶主要集中於肺小葉纖維中隔或肋膜旁，有時會造成氣胸,慢性支氣管炎之病理特徵為支氣管黏液腺肥大併腺體管道擴張，有時可見杯狀細胞增生與支氣管壁平滑肌肥大。,Hypothetical tracking curves of FEV1 for individuals throughout their lifespans. The normal pattern of growth and
29、 decline with age is shown by curve A. Significantly reduced FEV1 (65% of predicted value at age 20) can develop from a normal rate of decline after a reduced pulmonary function growth phase (curve B), early initiation of pulmonary function decline after normal growth (curve C), or accelerated decli
30、ne after normal growth (curve D). (From B Rijcken: Doctoral dissertation, p 133, University of Groningen, 1991; with permission.),Distributions of forced expiratory volume in 1 s (FEV1) values in a general population sample, stratified by pack-years of smoking. Means, medians, and 1 standard deviati
31、on of percent predicted FEV1 are shown for each smoking group. Although a dose-response relationship between smoking intensity and FEV1 was found, marked variability in pulmonary function was observed among subjects with similar smoking histories. (From Burrows et al, with permission.),Figure 2. Pro
32、posed mechanism of glucocorticoid resistance in COPD patients. Stimulation of normal alveolar macrophages activates nuclear factor kB (NF-kB) and other transcription factors to switch on histone acetyltransferase leading to histone acetylation and subsequently to transcription of genes encoding infl
33、ammatory proteins, such as tumor necrosis factor a (TNF-a) and interleukin 8 (IL-8). Glucocorticoids reverse this by binding to glucocorticoid receptors (GR) and recruiting histone deacetylase-2 (HDAC2). This reverses the histone acetylation induced by NF-kB and switches off the activated inflammato
34、ry genes. In COPD patients cigarette smoke activates macrophages, as in normal subjects, but oxidative stress (acting through the formation of peroxynitrite) impairs the activity of HDAC2. This amplifies the inflammatory response to NF-kB activation, but also reduces the anti-inflammatory effect of
35、glucocorticoids as HDAC2 is now unable to reverse histone acetylation.,Figure 1. Chromatin remodeling and gene expression. Gene activation and repression are regulated by acetylation of core histones. Histone acetylation is mediated by coactivators that have intrinsic histone acetyltransferase activ
36、ity opening up the chromatin structure to allow the binding of RNA polymerase II (PolII) and transcription factors. Gene repression is induced by histone deacetylases (HDACs) that reverse this acetylation.,致病機轉： Proteinase Antiproteinase Oxidative stress,病理生理學:,黏液過度分泌 纖毛運動變差 氣流受限 肺膨脹過度 氣體交換異常 肺動脈高壓
37、肺心症,上，下氣道 氣肺管，支氣管，肺,漏斗胸 雞胸 肋骨骨折 肋軟骨炎，肌肌膜炎 骨關節炎 脊柱前，後，側彎,胸廓 縱隔 內容臟器 橫膈 常見疾患：上縱膈前縱膈中縱膈後縱膈,總結Summary:,介紹了自我學習，終身學習，以網路搜尋關鍵字為例。介紹阻塞性肺疾與慢性阻塞性肺疾(慢阻肺疾)定義。介紹阻塞性肺疾與慢性阻塞性肺疾(慢阻肺疾)病理解剖，病理生理變化。從構造層面介紹阻塞性肺疾與慢性阻塞性肺疾(慢阻肺疾)病理解剖，病理生理變化。從發炎媒介質層面介紹阻塞性肺疾與慢性阻塞性肺疾(慢阻肺疾)病理解剖，病理生理變化。從全身層面介紹阻塞性肺疾與慢性阻塞性肺疾(慢阻肺疾)病理解剖，病理生理變化。再次鼓
38、勵並回答提問，接受建議，當面溝通。,Figure 1. Rate of decline in FEV1 with ageAdapted from references 2 and 8,Figure 1. Rate of decline in FEV1 with ageAdapted from references 2 and 8,Pathophysiology of airflow limitation in chronic obstructive pulmonary disease Lancet 2004; 364: 70921,Figure 2. Anatomical features o
39、f the innate and adaptive in flammatory immune responses,Pathophysiology of airflow limitation in chronic obstructive pulmonary disease Lancet 2004; 364: 70921,Figure 2. Anatomical features of the innate and adaptive in flammatory immune responses(A) Migration of inflammatory cells in the epithelial
40、 layer (white arrows) and entry into the surface mucous layer of a guineapig after exposure to cigarette smoke. (B) Histology of bronchial microvasculature. One capillary bed lies between the epithelium and muscle (single arrow) and a second lies in the adventitial compartment below outside the musc
41、le (double arrow). These two capillary beds are joined by connecting vessels (arrow head) that pass between the muscle bundles. (C) Lymphoid follicle in BALT with a germinal centre (GC). The follicle is covered by a specialised epithelium containing M cells (between the arrows), which transport anti
42、gens from the lumen into the subepithelial tissue. (D) Diagram of a regional lymph node, which differs from BALT in that it has afferent lymphatic vessels that penetrate a capsule surrounding the node and an efferent lymphatic vessel that leaves at the hilum. The blood supply to the follicle forms a
43、 network around the outer edge of the follicles in both lymph nodes and BALT. The vessels that form this network around the follicles located in BALT arise from the outer vascular plexus shown in (B).,Pathophysiology of airflow limitation in chronic obstructive pulmonary disease Lancet 2004; 364: 70
44、921,Figure 3. Key lesions in chronic bronchitis(A) Histology of bronchus with epithelial lining that extends from lumen into gland duct and gland. (B) Enlarged glands from a patient with chronic bronchitis. (C) One of these gland at higher magnification showing inflammatory cells (arrow and arrowhea
45、d). Reproduced from reference 2 with permission.,Pathophysiology of airflow limitation in chronic obstructive pulmonary disease Lancet 2004; 364: 70921,Figure 4. Small airway obstruction (A) Normal small airway. (B) Small airway containing plug of mucus with relatively few cells, which could have be
46、en produced in the glands of the larger airways and aspirated into the smaller airways. (C) Acutely inflamed airway with thickened wall in which the lumen is partly filled with an inflammatory exudate of mucus and cells, which has probably been produced in the small airway. (D) Airway surrounded by connective tissue, which appears as if it might restrict normal enlargement of the lumen and unfolding of the epithelial lining that occurs with lung inflation.,Pathophysiology of airflow limitation in chronic obstructive pulmonary disease Lancet 2004; 364: 70921,
