Understanding Chronic Bronchitis: Etiology, Pathogenesis, and Clinical Features

1. The Lung-2 1.Pneumonia 2.COPD 3.Pneumoconiosis 4.Chronic cor pulmonale 5. Lung cancer Keqing Zhu 竺可青 Pathology Department Zhejiang University School of Medicine 2015-1-6

2. 2. COPD • Chronic bronchitis • Pulmonary emphysema • Bronchial asthma • Bronchiectasis

3. Chronic obstructive pulmonary disease A group of conditions that share a major symptom dyspnea and are accompanied by chronic or recurrent obstruction to airflow within the lung

4. 2.1 Chronic bronchitis • Chronic bronchitis, so common among habitual smokers and inhabitants of smog-laden cities, is not nearly as trivial as was once thought. • When persistent for years, it may • (1) progress to chronic obstructive airway disease, • (2) lead to cor pulmonale and heart failure, • (3) cause atypical metaplasia and dysplasia of the respiratory epithelium, providing a rich soil for cancerous transformation.

5. A persistent productive cough for • at least 3 consecutive months in at least 2 consecutive years Etiology • 1. Infection • virus/ bacteria • 2. Physical chemical factors • （1）smoking （2）air pollution（3）cold（4）others: neuroendocrine, nutrition

6. Pathogenesis • Hypersecretion of mucus beginning in the large airways • Irritants---hypersecretion of the bronchial mucous glands---hypertrophy of mucous glands---metaplastic formation of mucin-secreting goblet cells in the surface epithelium of bronchi.

7. Chronic bronchitis per se is defined clinically. It is present in any patient who has persistent cough with sputum production for at least 3 months in at least 2 consecutive years, in the absence of any other identifiable cause. • In simple chronic bronchitis, patients have a productive cough but no physiologic evidence of airflow obstruction. • Some individuals may demonstrate hyperreactive airways with intermittent bronchospasm and wheezing. This condition is called chronic asthmatic bronchitis. • Finally, some patients, especially heavy smokers, develop chronic airflow obstruction, usually with evidence of associated emphysema, and are classified as showing obstructive chronic bronchitis.

8. Morphology • Grossly, there may be hyperemia, swelling, and edema of the mucous membranes, frequently accompanied by excessive mucinous to mucopurulent secretions layering the epithelial surfaces. • The characteristic histologic features of chronic bronchitis are chronic inflammation of the airways (predominantly lymphocytes) and enlargement of the mucus-secreting glands of the trachea and bronchi.

9. This increase can be assessed by the ratio of the thickness of the mucous gland layer to the thickness of the wall between the epithelium and the cartilage (Reid index). • The Reid index (normally 0.4) is increased in chronic bronchitis, usually in proportion to the severity and duration of the disease. • The bronchial epithelium may exhibit squamous metaplasia and dysplasia. There is marked narrowing of bronchioles caused by goblet cell metaplasia, mucus plugging, inflammation, and fibrosis.

10. Pathological changes • Gross • the mucosal lining of the larger airways is hyperemic and swollen by edema fluid, covered by a layer of mucinous or mucopurulent secretions • the smaller bronchi and bronchioles filled with similar secretions

11. LM • injury/ repair of respiratory epithelium • cilia epithelium injured: adhere, detachment, degeneration, squamous metaplasia • hyperplasia and hypertrophy of the mucous cells and an increased proportion of mucous to serous cells • mucosa and submucosa inflammation • asthematic type: SMC increase, stenosis, calcification

12. Clinical Features • The cardinal symptom of chronic bronchitis is a persistent cough productive of sputum. For many years, no other respiratory functional impairment is present, but eventually, dyspnea on exertion develops. • With the passage of time, and usually with continued smoking, other elements of COPD may appear, including hypercapnia 高碳酸血症, hypoxemia, and mild cyanosis. • Differentiation of pure chronic bronchitis from that associated with emphysema can be made in the classic case, but, as has been mentioned, many patients with COPD have both conditions. • Long-standing severe chronic bronchitis commonly leads to cor pulmonale with cardiac failure.

13. 慢性支气管炎(chronic bronchitis) • 慢性支气管炎(chronic bronchitis)定义：指气管、支气管粘膜及其周围组织的慢性非特异性炎症。临床上表现为咳、痰或伴喘，反复发作，每年持续３个月，连续两年以上。

14. 一、病因与发病机制多因素长期综合作用所致。一、病因与发病机制多因素长期综合作用所致。 １．理化因素：如吸烟、空气污染、天气寒冷等引致腺体分泌增加和支气管上皮损伤。 ２．过敏因素：与气道防御功能下降有关。 ３．感染因素：如病毒、细菌反复感染，与慢性支气管炎的发生和复发密切相关。

15. 二、病理变化 • 各级支气管慢性非特异性炎症。 • １．粘液-纤毛系统受损，粘膜上皮损伤，鳞化。 • ２．腺体分泌亢进，浆液腺发生粘液化生。 • ３．管壁充血，慢性炎细胞浸润。 • ４．严重者，平滑肌束断裂，软骨破坏。 • 三、临床病理联系 • 支气管粘膜炎症，分泌物增多→咳，痰（白色粘液泡沫痰或脓性痰）。 • 支气管痉挛（气喘型），分泌物阻塞→喘，哮鸣音。 • 小气管阻塞致阻塞性通气障碍→肺呼吸功能不全。 • 四、并发症 • 肺气肿 • 肺心病 • 支气管扩张

16. 2.2 Pulmonary emphysema • Emphysema is a condition of the lung characterized by abnormal permanent enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls and without obvious fibrosis. • In contrast, the enlargement of airspaces unaccompanied by destruction is termed "overinflation," for example, the distention of airspaces that occurs in the remaining lung after unilateral pneumonectomy.

17. Types of Emphysema • Although the term "emphysema" is sometimes loosely applied to diverse conditions, there are four major types: • (1) centriacinar, (2) panacinar, (3) paraseptal, and (4) irregular. • Only the first two cause clinically significant airflow obstruction. • Centriacinar emphysema is far more common than the panacinar form, constituting more than 95% of cases.

18. Pathologic changes gross：voluminous with round margin, pale/gray-white, soft LM： • thinning and destruction of alveolar walls • abnormal enlargement of alveoli---alveolar loss • alveolar capillaries diminished • destruction of septal wall

19. 预 后 • 肺部代偿能力较大，其预后与FEV1值相关 • FEV1<1.2L生存年限为10年，FEV1<1.0L生存年限为5年，<700ml生存年限为2年

20. Predominant Bronchitis Predominant Emphysema • Age (yr) 40-45 50-75 • Dyspnea Mild; late Severe; early • Cough Early; copious sputum Late; scanty sputum • Infections Common Occasional • Respiratory insufficiency Repeated Terminal • Cor pulmonale Common Rare; terminal • Airway resistance Increased Normal or slightly increased • Chest radiograph Prominent vessels; large heart Hyperinflation; small heart

21. 肺气肿 (pulmonary emphysema) • 定义：指呼吸细支气管以远的末梢肺组织因残气量增多而呈持久性扩张，并伴有肺泡间隔破坏，以致肺组织弹性减弱，容积增大的一种病理状态。

22. 一、病因和发病机制 １．慢性阻塞性肺气肿（继发性肺气肿） • （1）慢性细支气管炎→阻塞性通气障碍→肺排气能力下降→肺泡内残气量增多→末梢肺组织扩张→肺泡壁破坏 • （2）细支气管周围炎时，中性粒细胞，单核细胞→释放弹性蛋白酶，生成氧自由基抑制α1－抗胰蛋白酶→肺泡壁破坏 ２．原发性肺气肿 • 遗传性α1－抗胰蛋白酶缺乏症（常染色体显性遗传）→抑制弹性蛋白酶及胶原酶活性的作用减弱→使较轻的慢性炎症也会引起肺泡壁破坏

23. 二、类型及其病变特点 １．肺泡性肺气肿：指病变发生在肺腺泡内的肺气肿。 • （1）弥漫性：腺泡中央型、腺泡周围型、全腺泡型肺气肿 • （2）局限性：不规则型肺气肿（瘢痕旁肺气肿）、肺大泡（气肿囊腔泡>2cm） ２．间质性肺气肿：指空气进入肺间质如肺膜下、肺小叶间隔等部位内的肺气肿。

24. 2.3 Bronchial asthma • Asthma is a chronic inflammatory disorder of the airways that causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and/or in the early morning. • It is thought that inflammation causes an increase in airway responsiveness (bronchospasm) to a variety of stimuli. • Many cells play a role in the inflammatory response, in particular eosinophils, mast cells, macrophages, T lymphocytes, neutrophils, and epithelial cells.

25. 2.4 Various forms of atelectasis in adults

26. 2.5 Bronchiectasis支气管扩张 • Bronchiectasis is a disease characterized by permanent dilation of bronchi and bronchioles caused by destruction of the muscle and elastic tissue, resulting from or associated with chronic necrotizing infections. • To be considered bronchiectasis, the dilation should be permanent; reversible bronchial dilation often accompanies viral and bacterial pneumonia.

27. Morphology • Bronchiectasis usually affects the lower lobes bilaterally, particularly air passages that are vertical, and is most severe in the more distal bronchi and bronchioles. • The airways are dilated,sometimes up to four times normal size. • These dilations may produce long, tubelike enlargements (cylindrical bronchiectasis), • in other cases, may cause fusiform • Or even sharply saccular distention (saccular bronchiectasis).

28. CPC • severe persistent cough and expectoration of copious amounts of purulent sputum, fetid sputum or hemoptysis • dyspnea • hypoxemia, hypercapnia, cor pulmonale • lung abscess • clubbing fingers • metastatic brain abscesses and reactive amyloidosis

29. Clinical Course • Bronchiectasis causes severe, persistent cough; expectoration of foul-smelling, sometimes bloody sputum; dyspnea and orthopnea in severe cases; and occasional life-threatening hemoptysis. • In the full-blown case, the cough is paroxysmal in nature. Such paroxysms are particularly frequent when the patient rises in the morning, and changes in position lead to drainage into the bronchi of the collected pools of pus. • Obstructive ventilatory insufficiency can lead to marked dyspnea and cyanosis. Cor pulmonale, metastatic brain abscesses, and amyloidosis are less frequent complications of bronchiectasis.

30. 支气管扩张症 (bronchiectasis) • 定义：指肺内支气管管腔持久不可复性扩张伴管壁纤维性增厚的慢性化脓性疾病。 病因和发病机制 • （１）支气管反复感染→慢性化脓性炎症→管壁破坏,弹性减弱。 • （２）支气管不完全阻塞、咳嗽→阻塞下方管腔内压增大，管壁扩张。 • （３）支气管周围炎症纤维化牵拉→管腔扩张。

31. 病理变化 • （１）特点：支气管的慢性化脓性炎症 • （２）大体：单侧或双侧，范围不一，各级支气管受累，主要在肺段支气管（直径>2mm），多见于左下叶。病变呈圆柱状或囊状扩张，管壁纤维增厚，管腔内脓性分泌物。 • （３）镜下：管壁及周围组织慢性化脓性炎症，粘膜上皮脱落、鳞状化生，平滑肌和软骨萎缩等。

32. 临床病理联系 • 多为成年男性，但大多起于儿童时的支气管炎。 • 表现：长期咳嗽，大量脓痰，反复咯血。 并发症 • 感染→肺炎、肺脓肿、脓胸。 • 肺组织破坏严重→肺气肿、肺心病。

33. Disorders Associated with Airflow Obstruction: The Spectrum of Chronic Obstructive Pulmonary Disease Clinical Term Anatomic Site Major Pathologic Changes Etiology Signs/Symptoms Chronic bronchitis Bronchus Mucous gland hyperplasia, hypersecretion Tobacco smoke, air pollutants /Cough, sputum Bronchiectasis Bronchus Airway dilation and scarring Persistent or severe infections /Cough, purulent sputum, fever Asthma Bronchus Smooth muscle hyperplasia, excess mucus, inflammation Immunologic or undefined causes Episodic wheezing, cough, dyspnea Emphysema Acinus Airspace enlargement; wall destruction Tobacco smoke/Dyspnea

34. 复习题 • 1. Emphysema, Reid index, Bronchiectasis, Chronic cor pulmonale • 2. In lobar pneumonia, four stages of the inflammatory response have classically been described: • 3. Complications of pneumonia ？ • 4. Chronic bronchitis is defined clinically? • 5. The characteristic histologic features of chronic bronchitis? • 6. There are four major type emphysemas? • 7. Various forms of atelectasis in adults? • 8. Comparison of bronchopneumonia and lobar pneumonia? • 9. What is the difference among Chronic bronchitis , Bronchiectasis , Asthma, Emphysema ?