呼吸系统（中英文）课件

病理学 Patholog y Respiratory system NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Anatomy 鼻 咽 喉 环状软骨 气管 支气管 肺 上呼吸道 下呼吸道 NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology v Rapid gas exchange Ventilation Perfusion Diffusion v Cleaning the air v Alveoli(300 million alveoli in two adult lungs, provide a surface area of some 160 meters square ) v Surporting structure Elastic recoil Structure and function General Considerations NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology (1) the conducting airways (dead air space) NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology (2) the gas exchange portions NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology 气 管 粘膜层 粘膜下层 外膜 上皮 ( 纤毛柱状 ) 固有膜 Ciliated cell Mucous cell sIgA 纤毛粘液排送系统 Mucous, serous and mixed glands Cartilaginous NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology 肺 导气部 ： 呼吸部 ： 肺内支气管Bronchiole Terminal bronchiole (软骨消失) Respiratory bronchiole （纤毛消失） Alveolar duct Alveolar sacAlveoli (SMC消失) 68 1518 Alveoli I 型 （90%） II 型Surfactant, repair I 肺间质、肺泡间隔 ：cap. , f, M Cohn 孔相互沟通 NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Histology of the Airways Mucosa Submucosa Cartilage Muscles l Components l Functions Bronchi are distinguished from bronchioles primarily by the presence of cartilage in their walls. Bronchioles also lack submucosal glands. NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Epithelium l Pseudostratified ciliated columnar cells l Mucous (goblet) cells NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Bronchial Submucosal Glands NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Histology of the Alveolar walls Alveoli Capillaries Pores of Kohn NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Simple squamous Stretchy Permeable to O2 and CO2 Easily injured Do not divide Reserve cells Cuboidal Produce and process surfactant Divide and differentiate to type I pneumocytes NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Section 1 Chronic obstructive pulmonary disease NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Chronic Obstructive Pulmonary Disease (COPD) u不可逆气道阻塞Irreversible airflow obstruction u慢支和肺气肿Chronic Bronchitis and Emphysema u常常伴发Frequently occur together u与空气污染和吸烟有关Strongly correlated with air pollution and smoking u男多于女More common in men than in women u社会经济影响Socioeconomic impact NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology COPD represents a growing global public health problem. vIn one population based study conducted at multiple international sites, approximately 10% of participants 40 years of age or older were found to have airflow obstruction of at least moderate severity according to spirometric criteria. ( Buist AS, McBurnie MA, Vollmer WM, et al. International variation in the prevalence of COPD (the BOLD Study): a population- based prevalence study. Lancet 2007;370:741-50. ) NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology 我国国家“十五”课题最新统计数据 （2005年公布）显示40岁以上人口COPD患 病率为8%。估计全国有2500万人罹患此病 ，每年因COPD死亡的人数达100万，致残人 数达5001000万，COPD居我国疾病负担的 首位。 NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology 一、慢支 Chronic bronchitis Clinical diagnostic criteria 慢性咳嗽、咳痰 每年个月 连续年 NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Chronic bronchitis Endoscopic image NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Pathogenesis 感染 吸烟气候空气污染等 NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology 大气道病变 Large airway disease v咳嗽、咳痰Cough and sputum production vHistological changes 杯状细胞数量增加 increased numbers of goblet cells in the epithelium 粘液腺数量增加 increased volume of the submucosal mucus glands 慢性炎症a component of chronic inflammation NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Reid index inner perichondrium basal lamina NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology 鳞化 Squamous metaplasia NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Chronic inflammation Hyperemia NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology 小气道病变 Small airway disease v呼气性呼吸困难 Decrease in maximum forced expiratory flow vHistological changes 杯状细胞数量增加 presence of goblet cells in the lining epithelium 慢性炎症 a component of chronic inflammation NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology luminal and mucus chronic inflammation NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Pathologic changes 起始于大支气管累及小 、细 支气管 粘膜上皮的损伤和修复 纤毛倒伏、脱失 上皮细胞变性、坏死脱落，可鳞化 上皮再生，杯状细胞大量增生 （ 4 5 ：1 2 ：1 ） 慢性非特异性炎 NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology 腺体变化 粘液腺肥大、增生 浆液腺化生为粘液腺 NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology 管壁病变 充血、水肿，炎细胞浸润 平滑肌束断裂，软骨变性萎缩 NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology v 小细支气管炎 晚期 病变向小支气管和细支 气管及管壁周围组织扩展 ，形成细支气管周围炎； 管壁增厚管腔闭塞 NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Clinical features 支气管粘膜炎症、粘液分泌旺盛咳痰 支气管痉挛，渗出物阻塞喘 NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology 晚期表现 Late stage menifestation u血氧饱和度低 insufficient oxygenation of blood (hypoxemia) u呼吸困难 labored breathing (hypoventilation) u右心衰 right-sided heart failure (cor pulmonale) Treatment u不能根治 No cure u控制症状 relieving symptoms u防止并发症 preventing complications NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology 二、肺气肿Pulmonary emphysema 呼吸性细支气管至肺泡的末梢肺组织因持续性含气量增 加而呈过度膨胀，伴有肺泡壁弹力组织破坏，间隔断裂致肺 泡互相融合，肺容积胀大的病理状态。 l Abnormal permanent enlargement of airspaces distal to the terminal bronchiole, accompanied by the destruction of their walls. (morphologically defined) NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology l Inadequate ventilation l Less perfusion l Narrowed bronchiole NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Pathogenesis u蛋白酶和抗蛋白酶水平失衡 Imbalance between proteases and anti-proteases (alpha-1 antitrypsin) in the lung uCigarette smoking u募集粒细胞和巨噬细胞 Recruits neutrophils and macrophages u氧自由基抑制抗胰蛋白酶 Oxidants and free radicals inhibit the alpha-1-antitrypsin circulating in the lung u慢支和反复感染 Chronic bronchitis and repeated infections u缺乏 Alpha-1 antitrypsin deficiency (1%) Who destroy the alveoli wall? NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology 肺气肿类型 Types of emphysema u中央性肺气肿 Centriacinar (centrilobular) emphysema u常见 u主要累及部位 respiratory bronchiole u上叶更常见 u见于吸烟者 NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology v全小叶性肺气肿Penacinar (panlobular) emphysema 累及整个腺泡 下叶常见 1/20 as common as centriacinar emphysema. Seen in alpha-1-antitrypsin deficiency 肺气肿类型 Types of emphysema NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology v隔旁肺气肿 Distal acinar (paraseptal) emphysema或小叶周 围性肺气肿 远端 The distal respiratory acinus is expanded 主要部位：上叶近胸膜或隔旁 肺气肿类型 Types of emphysema NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Centriacinar (centrilobular) emphysema NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Centrilobular emphysema in which there are “dirty holes“ that appear focally where the central portions of lung acini have lost lung parenchyma while collecting anthracotic pigment at the same time. This pattern is typical for smokers NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Centriacinar (centrilobular) emphysema NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Emphysema loss of alveolar walls NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology 镜下 ： 肺泡壁、肺泡间隔 萎缩、消失、破坏， 互相融合 NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology 其它 瘢痕旁肺气肿 Emphysema with irregular distribution related to scars (obstruction / traction) 代偿性肺气肿 Compensatory emphysema Caused by removal or collapse of adjacent pulmonary parenchyma 肺大泡 肺尖、胸膜下局灶性肺泡间隔破坏， 形成 2cm (D) 囊泡 间质性肺气肿 儿童多见 ，肺泡壁、细支气管壁急性破裂 ， 空气进入肺间质 NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Numerous large bullae apparent on the surface of the lungs in a patient dying with emphysema. NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology 临床病理联系 Late stage manifestation v气短 Short of breath, wheezling v咳嗽 Cough with or without mucous v疲劳 Fatigue vWeight loss v下肢水肿 Ankle feet leg swelling v肺感染 lung infections Complications l Respiratory infections l Respiratory failure l Cor pulmanale NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology 患者，女性，60岁。因反复咳嗽、咳痰11年 ，伴气促、心悸3年，下肢水肿2年，腹胀3月入 院。11年前感冒后发热、咳嗽、咳脓痰。以后每 逢冬春季常咳嗽、咳白色泡沫痰，有时为脓痰， 反复加重。3年来，在劳动或爬坡后常感心悸、 呼吸困难。2年前开始反复下肢凹陷性水肿。3月 前受凉后发热、咳嗽加重，咳脓痰，心悸气促加 剧并出现腹胀，不能平卧，急诊入院。 病例分析 NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology 体格检查： 体温37.4，脉搏98次/min，呼吸28次/min， 血压102/79mmHg。慢性病容，端坐呼吸，嗜睡 ，唇及皮肤明显发绀，颈静脉怒张，吸气时胸 骨及锁骨上窝明显凹陷，桶状胸，呼吸动度降 低，叩诊呈过清音，双肺散在干湿啰音。心率 98次/min，心律齐，心浊音界缩小。腹部膨隆 ，大量腹水征，肝在肋下7.5cm，较硬，双下 肢凹陷性水肿。 NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology 实验室检查： 血常规：血红蛋白98g/L，白细胞 6.7109/L，其中嗜中性粒细胞占0.89， 淋巴细胞0.11。入院后病人突然抽搐， 极度烦躁不安，继之神志不清，心率增 到156次/min，抢救无效死亡。 1根据主要临床表现作出诊断，并说明诊断依据 。 NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology 尸检摘要 左右胸腔积液各200m1，腹腔积液2000ml呈淡黄色 ，透明，比重1.012。双肺各重750g，体积增大， 极度充气膨胀，切面见双肺散在灶性实变，呈灰 白色，部分呈灰白与暗红相间，且以双肺下叶为 甚。镜下见双肺末稍肺组织过度充气、扩张，肺 泡壁变薄、部分壁断裂；灶性实变区见充血，肺 泡内及细支气管腔内有浆液、嗜中性粒细胞充填 ，部分上皮细胞坏死脱落； NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology 支气管黏膜上皮内杯状细胞增多，部分鳞状 上皮化生，个别管腔内见黏液或渗出物形成 的栓子，管壁黏液腺增多并肥大，管壁软骨 灶性钙化及纤维化，纤维组织增生，淋巴细 胞和少量嗜中性粒细胞浸润。心脏重300g， 右心室壁厚0.35cm，右心腔明显扩张，肉柱 及乳头肌增粗变扁，肺动脉圆锥膨隆，左心 及各瓣膜未见明显病变。心源性肝硬化。其 他脏器变性、淤血。 NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology 2说明该患者的疾病的发生发展过程。 3请用尸检发现解释患者的症状和体征。 咳嗽、咳痰，脓痰，劳动后心悸呼吸困难 ，下肢凹陷性水肿，腹胀 端坐呼吸，嗜睡，唇及皮肤发绀，颈静脉 怒张，吸气时胸骨及锁骨上窝凹陷，桶状 胸，双肺散在干湿啰音，大量腹水征， 肝 大、较硬 NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology vA 67-year-old man presents with a history of dyspnea, which has progressed for the past several years. He began smoking cigarettes at 15 years of age and continues to smoke one pack per day. Worsening breathlessness forced him to retire as a laborer, and he has sought emergency care for what he calls bronchitis twice in the past year. vHis physical examination is notable for diminished breath sounds on auscultation, with a prolonged expiratory phase. Spirometry reveals severe airflow obstruction NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology vThe sentinel clinical feature of severe chronic obstructive pulmonary disease (COPD) is dyspnea on exertion. Its onset is usually insidious, and it may progress to severe disability over a period of years or decades. Other common symptoms include cough, sputum production, wheezing, and chest congestion. NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology The principal pathophysiological features of COPD NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology vPatients with severe COPD often have exacerbations that result in medical visits and hospitalizations. Chronic hypoxemia and hypercapnia may cause pulmonary hypertension and cor pulmonale. vPatients with severe COPD are also at increased risk for other systemic diseases, including cardiovascular disease, osteoporosis, lung cancer, and depression. (Agust AG, Noguera A, Sauleda J, Sall a E, Pons J, Busquets X. Systemic effects of chronic obstructive pulmonary disease. Eur Respir J 2003;21:347-60.) NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Alpha1-Antitrypsin Deficiency vA 60-year-old white man presents for evaluation of progressive dyspnea. He is a former smoker with a 20 -pack-year smoking history and a 10-year history of diagnosed chronic obstructive pulmonary disease (COPD). There is no family history of COPD. vSevere airflow obstruction is seen on spirometry肺量 测定法, with a forced expiratory volume in 1 second (FEV1) that is 40% of the predicted value. Should the patient be evaluated for alpha1-antitrypsin (AAT) deficiency? If AAT deficiency is documented, how should his case be managed? NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology The Clinical Problem v AAT deficiency increases the risk of COPD, liver disease, and several other conditions. Although various definitions have been used, we define AAT deficiency as the inheritance of two severe deficiency alleles at the locus encoding AAT. AAT deficiency is relatively common in populations of European ancestry始祖, with an estimated prevalence of 1 case per 3000 to 5000 persons in the United States. The incidence of AAT deficiency in white newborns is similar to that of cystic fibrosis. v AAT is a serine protease inhibitor encoded by SERPINA1 (also known as PI). AAT is a highly effective inhibitor of neutrophil elastase; an imbalance between levels of AAT and this elastase increases the risk of emphysema (Fig. 1A). NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology v Figure 1. Pathogenesis of Alpha1-Antitrypsin (AAT) Deficiency. v Panel A shows a simplified representation of the mechanism for the development of emphysema in patients with AAT deficiency. Gross pathological examination often reveals basilar panacinar emphysema, with alveolar septal destruction and airspace enlargement seen on light microscopy. v Panel B provides an overview of liver disease in patients with AAT deficiency. The liver has hepatocytes containing cytoplasmic globules, which are made up of polymerized AAT molecules. The accumulation of these molecules appears to damage the liver, but there is no consensus regarding the specific mechanisms of this injury. NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology v Most persons with AAT deficiency inherit two copies of the PI*Z allele (Table 1). Persons who inherit one of the heterogeneous group of PI*Null alleles, which result in the absence of AAT production, and one PI*Z allele (i.e., PI ZNull) are not readily distinguished from those who are homozygous for the PI*Z allele on the basis of serum AAT levels or protein phenotyping. Therefore, patients with the PI ZZ and PI ZNull genotypes are often clustered together as having the Z protein phenotype. v The Z protein can form polymers that trap AAT within the rough endoplasmic reticulum of hepatocytes, the primary source of AAT synthesis, leading to reduced levels of circulating AAT in the bloodstream. Patients with the Z protein phenotype have approximately 15% of normal AAT levels. The accumulated AAT protein in hepatocytes appears to underlie the liver disease associated with AAT deficiency (Fig. 1B). v The genetic, biochemical, and pathogenetic features of AAT deficiency have been reviewed previously. NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology v The natural history of AAT deficiency in adulthood remains poorly understood. AAT deficiency is recognized in less than 10% of persons in whom a diagnosis would be expected on the basis of screening studies in the general population. v The diagnosis of AAT deficiency is generally made after the identification of COPD or liver disease or after the deficiency has been diagnosed in a family member. v The health status of patients with undiagnosed AAT deficiency is uncertain, but many patients may not be substantially impaired. Cigarette smoking greatly increases the risk of COPD in patients with the Z protein phenotype. Other risk factors for COPD in such patients are male sex and asthma. Genetic modifiers of lung and liver disease probably exist, although they remain largely undefined. NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology v The classic pulmonary presentation of AAT deficiency is severe, early-onset panacinar emphysema with a basilar predominance in adults (Fig. 1A and Fig. 2). However, emphysema may also occur in a diffuse distribution or predominantly in the upper lobes. Bronchiectasis, with or without concomitant伴发的emphysema, is less common. Dyspnea is generally the prominent symptom, but chronic cough or wheezing may also occur. v The majority of children with AAT deficiency with the Z protein phenotype who are identified through newborn screening have abnormal liver function tests at some point during their first year of life. v Approximately 10% of infants with the Z protein phenotype have prolonged obstructive jaundice, and about 2% present in childhood with liver failure requiring transplantation. As these children age, there is an increasing risk of liver disease, including cirrhosis and hepatocellular carcinoma. v A postmortem study in Sweden suggested that adults with the Z protein phenotype who died from causes unrelated to AAT deficiency often had asymptomatic cirrhosis, and this risk increased with age NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology v Figure 2. Variability of Radiographic Findings in Patients with Alpha1- Antitrypsin (AAT) Deficiency. v Computed tomography of the chest in patients with AAT deficiency shows a broad range of manifestations. AAT deficiency has classically been associated with the development of basilar- predominant panacinar emphysema (Panel A). v However, upper-lobe- predominant emphysema (Panel B) and bronchiectasis (Panel C) can also be observed, and sometimes the lungs are normal (Panel D). NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology vMost persons inherit two copies of the PI*M allele, which is associated with normal AAT levels. The PI*S allele is slightly more common than the PI*Z allele in most European populations and is associated with mildly reduced AAT levels. Available evidence suggests that patients with the PI MZ genotype may be at slightly increased risk for COPD and liver disease, but this association has not been proved. Patients with the PI SZ genotype are at increased risk for COPD, especially if they smoke, as compared with those with the PI MM genotype, but they have a lower risk than those with the Z protein phenotype. NMUNMU博学至精博学至精 明德至善明德至善 病理学病理学 PathologyPathology Strategies and Evidence v Diagnosis v AAT deficiency remains undiagnosed in many patients, and there are often long delays between the onset of respiratory symptoms and diagnosis. Approximately 1% of patients with COPD have AAT deficiency, and the condition is frequently not diagnosed. v In some cases, the underdiagnosis诊断不足of AAT deficiency may relate to perceived认知risks associated with testing for a genetic condition. It is recommended that patients be informed about risks of testing for AAT deficiency, including potential genetic discrimination, before testing is performed. v The lack of studies demonstrating that increased AAT detection leads to improved health