医学课件大全阻塞性肺疾總論與慢性阻塞性肺疾病(慢阻肺)(86p)

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) 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

2、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) 2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驗？3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4課程進度

3、5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。6参考資料references:CHAPTER 4: PATHOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INI

4、TIATIVE 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 Eur Respir J 2003 22 672 688Airway dendritic

5、 cell phenotypes in inflammatory diseases of the human lung Eur Respir J 2007 30 878 886Flow limitation and dynamic hyperinflation Eur Respir J 2005 25 186 1997KEY POINTS 1考試範圍:CHAPTER 4: PATHOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRAT

6、EGY 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 pulmonary vasculature. These changes include chronic

7、 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 in patients who develop COPD. COPD病人對吸入香菸和有毒微粒所引

8、起之炎性反應比常人嚴重。8KEY 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) 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There is a characte

9、ristic 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 different from that seen in asthma. COPD病人之炎性反應特徵是嗜中性球

10、、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。9 Physiological changes characteristic of the disease include mucus hypersecretion, airflow limitation and air trapping (leading to hyp

11、erinflation), 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 cardiovascular disease, anemia, osteoporosis, an

12、d 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 environmental pollutants. COPD惡化可能由環境污染、細菌或病毒感染所引起，代表

13、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) 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10網路搜尋自學11網路搜尋自學12網路搜

14、尋自學13網路搜尋自學1415Figure 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) Acutely inflamed airway with thickened wall in

15、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

16、 with lung inflation.Pathophysiology of airflow limitation in chronic obstructivepulmonary disease Lancet 2004; 364: 709211617 GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006)18 GLOBAL

17、 INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006)19 GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE

18、 PULMONARY DISEASE (2006)20 GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006)21CHAPTER 4: PATHOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DIS

19、EASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006)22Chronic obstructive pulmonary disease molecular and cellularmechanisms Eur Respir J 2003 22 672 - 68823CHAPTER 4: PATHOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INITIATIVE FOR CHR

20、ONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006)124CHAPTER 4: PATHOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT,

21、AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006)225CHAPTER 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)126CHAPTER 4: P

22、ATHOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006)227CHAPTER 4: PATHOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INITIATIVE FOR CHRONIC OBS

23、TRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006)28CHAPTER 4: PATHOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVE

24、NTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006)29CHAPTER 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)30CHAPTER 4: PATHOLOGY, P

25、ATHOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006)31CHAPTER 4: PATHOLOGY, PATHOGENESIS, AND PATHOPHYSIOLOGY GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUN

26、G DISEASE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (2006)323334內容COPD定義與分類病變的解剖位置病理生理GINA GOLD35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 (COPD)。區域 6 ：慢性支氣管炎，併有可部份恢復之氣流阻塞

27、(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。3637383940centriacinar 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，主犯上肺野，好犯於吸菸者。2.全腺泡型肺氣腫(panacin

28、ar 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。4142434445464748Hypothetical tracking curves of FEV1 for individuals throughout their lifespans. The normal pattern of growth and decline with ag

29、e is shown by curve A. Significantly reduced FEV1 (Part 9. Disorders of the Respiratory SystemSection 2. Diseases of the Respiratory SystemChapter 242. Chronic Obstructive Pulmonary DiseasePathogenesis52Figure 2. Proposed mechanism of glucocorticoid resistance in COPD patients. Stimulation of normal

30、 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 inflammatory proteins, such as tumor necrosis factor a (TNF-a) and interleukin 8 (IL-8).

31、 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 inflammatory genes. In COPD patients cigarette smoke activates macrophages, as in normal subje

32、cts, 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 glucocorticoids as HDAC2 is now unable to reverse histone acetylation. 53Figure 1.Ch

33、romatin 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 activity opening up the chromatin structure to allow the binding of RNA polymerase II (P

34、olII) and transcription factors. Gene repression is induced by histone deacetylases (HDACs) that reverse this acetylation. 54致病機轉：Proteinase AntiproteinaseOxidative stress解剖構造：發炎的位置組織細胞：發炎的細胞媒介物質：發炎的物質氣道巨噬細胞Leukotriene B4肺實質淋巴球Interleukin-8肺血管嗜中性球Tumor necrosis factor55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

35、換異常肺動脈高壓肺心症5657585960上，下氣道氣肺管，支氣管，肺6162636465666768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69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70717273747576777879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。

36、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。再次鼓勵並回答提問，接受建議，當面溝通。80Figure 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 obstructivepulmonary disease Lancet 2004; 364

37、: 7092181Figure 2.Anatomical features of the innate and adaptive in flammatory immune responses Pathophysiology of airflow limitation in chronic obstructivepulmonary disease Lancet 2004; 364: 7092182Figure 2. Anatomical features of the innate and adaptive in flammatory immune responses(A) Migration

38、of inflammatory cells in the epithelial 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 adventi

39、tial compartment below outside the muscle (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 (be

40、tween the arrows), which transport antigens 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 network around the outer edge of the follicles in both lymph nodes and BALT. The vessels that form this networ