病理学第十章传染病

传染病结核病Tuberculosis•概述: 结核病是由结核杆菌引起的一种慢性传染病。

•病变特点–组织内形成肉芽肿性病变，即结核结节，伴干酪样坏死。

•临床表现–低热、盗汗、食欲不振、消瘦、血沉加快等病因•病原菌–结核分枝杆菌人型和牛型。

–致病力与菌体成分有关•脂质、蛋白质和多糖类•传播途径–主要经呼吸道传染;少数经消化道发病机制•以细胞免疫为主。

•在感染局部由巨噬细胞聚集而形成的肉芽肿—结核结节•人体感染结核杆菌2—6周后出现细胞免疫反应，同时也发生变态反应，后者造成广泛的组织坏死。

•免疫反应和变态反应同时贯穿在结核病的发生发展过程中结核病的基本病变•特殊性炎症，肉芽肿性病变–结核结节（tubercle）渗出性病变•发生条件–结核病早期或免疫力低下，菌量多或变态反应明显时•病理表现–浆液、纤维素性炎–早期有中性粒细胞浸润，很快被巨噬细胞取代渗出性病变•部位–好发于肺、浆膜、滑膜、脑膜等（与组织特性有一定关系）•转归–完全吸收—增生为主–变态反应剧烈—变质坏死为主增生性病变•发生条件–菌量少，毒力低，免疫力强•病理变化–形成结核结节结核结节tubercle•镜下–结节中央可见干酪样坏死–周围有巨噬细胞、放射状排列的上皮样细胞、郎罕（Langhans）巨细胞–外周的淋巴细胞，少量成纤维细胞结核结节•肉眼–灰白色、粟粒大小，境界清楚，干酪样坏死多时呈淡黄色。

•转归–进一步好转，上皮样细胞→成纤维细胞，结核结节纤维化Note the rounded, focal nature of these granulomas at low power magnification.Elongated epithelioid cells, which are transformed from macrophages, as well as a Langhans giant cell (a committee of macrophages with the nuclei arranged at the periphery) are shown here.坏死为主的病变•发生条件–细菌数量多，毒力强，免疫力低或变态反应强•病理表现：干酪样坏死caseous necrosis–肉眼—淡黄色，均匀细腻，质地较实，状似奶酪–镜下—红染无结构颗粒状物Note the pink, amorphous region in the center of this granuloma at the upper right, and ringedby epithelioid cells at the left and lower areas of this photomicrograph. This is the microscopic appearance of caseous necrosis.结核病基本病变的转化规律•1 转向愈复•（1）吸收消散•（2）纤维化、纤维包裹、钙化•2 转向恶化•（1）病灶扩大，浸润进展•（2）溶解播散肺结核病原发性肺结核病•机体第一次感染结核杆菌引起的肺结核病•又称儿童型肺结核病病变特点•肺的原发病灶、引流淋巴管炎、肺门淋巴结结核三者合称为原发综合征(primary complex) •X—ray 呈哑铃状阴影•临床表现：症状轻微而短暂发展和结局•（1）自然痊愈–纤维化和钙化•（2）恶化进展–支气管淋巴结结核–肺内或全身粟粒性结核✧淋巴道播散：淋巴结结核•镜下：淋巴结结核结节形成，干酪样坏死•肉眼：淋巴结肿大，粘连，干酪样坏死✧支气管播散•→形成空洞。

引言概述：传染病是一类由病原体引起的具有传染性的疾病，其具有高发性、广泛性和可传播性的特点。

病原体可以是细菌、病毒、真菌、寄生虫等微生物，通过直接接触、空气飞沫、水源等途径传播给其他人。

因其具有较强的传染性和危害性，传染病对人类的健康和社会稳定造成了重大威胁。

研究传染病的病理学对于预防、控制和治疗传染病具有重要意义。

正文内容：一、传染病的基本概念与分类1.1传染病的定义和特点1.2传染病的分类与病原体特征1.3传染病的传播途径和机制1.4传染病的发展过程和临床表现1.5传染病的流行病学特征和防控策略二、传染病的病理学变化2.1病原体感染和侵入宿主的过程2.2宿主免疫系统的应答与免疫损伤2.3传染病引起的病理学变化2.4细菌、病毒、真菌、寄生虫感染的特点比较2.5传染病的病理诊断和鉴别诊断三、典型传染病的病理学特点与机制3.1疟疾的病理学特点和致病机制3.2肺结核的病理学变化和发展过程3.3流行性感冒的病理学特征和临床表现3.4急性病毒性肝炎的病理学变化和临床意义3.5艾滋病的病理学特点和免疫损伤机制四、传染病的病理检测和防控措施4.1传染病的病理检测方法和意义4.2传染病的传播途径控制和个人防护4.3传染病的筛查、检测和监测体系的建立4.4传染病的疫苗研发和机制研究4.5传染病的药物治疗和传播阻断措施五、传染病的病理学研究进展与展望5.1传染病病理学研究的现状和问题5.2传染病病理学新技术和方法的应用5.3传染病病理学研究对疫情预测和防控的作用5.4传染病病理学研究的未来发展方向5.5传染病病理学研究的意义和应用前景总结：病理学作为传染病研究的重要分支，对于传染病的预防、控制和治疗具有重要意义。

本文分别从传染病的基本概念与分类、病理学变化、典型传染病的病理学特点与机制、病理检测和防控措施以及病理学研究进展与展望五个大点进行了详细阐述。

传染病的病理学研究可以帮助我们揭示病原体感染和宿主免疫应答的机制，进一步完善传染病的预防、控制和治疗策略，为保障人类的健康和社会稳定做出更大的贡献。

Infectious DiseasesInfectious disease➢Infectious diseases are a group of diseases caused by pathogenic organisms and can be epidemic among certain population.➢Necessary factors for transmission of infectious disease❿Source of transmission❿Routes of transmission❿Susceptible hostRoutes of entry and dissemination of microbes➢Epidemiology: infectious disease is a public condition associated with the socioeconomic conditions.➢The organisms producing diseases in human are various.➢Major histologic patterns of tissue reaction in infections⏹suppurative inflammation⏹mononuclear and granulomatous inflammation⏹necrotizing inflammation⏹chronic inflammation and scarringPneumococcal pneumonia. Note the intra-alveolar polymorphonuclear exudateand intact alveolar septaSchistosoma haematobium infection of the bladder with numerous calcified eggsand extensive scarringTuberculosisThis is the chronic,communicable disease caused by mycobacterium tuberculosis.Tuberculosis is estimated to affect1.7billion individuals worldwide,with8to10million new cases and1.7million deaths each year.After HIV,tuberculosis is the leading infectious cause of death in the world.Infection with HIV makes people susceptible to rapidly progressive tuberculosis;over50million people are infected with both HIV and M.tuberculosis.1.Etiology and pathogenesis:The common human strain infects only humans.Patients with pulmonary tuberculosis who cough up bacilli in the sputum are the source of transmitted infections.The bovine strain of M.tuberculosis infected dairy,causing human infection via contaminated milk.Bovine tuberculosis typically involved the oropharynx or intestine because the organism was ingested in milk.Components of the M.tuberculosis cell wall(such as cold factor,wax D,complement,heat-shock protein,etc)and host response(immune response and delayed hypersensitivity) contribute to its pathogenicity.Inhalation of virulent Mycobacterium tuberculosis organisms and culminating with the development of cell-mediated immunity to the organism.2. Basic pathological changes➢Exudative changes dominate—Early infections, numerous mycobecteria, high bacteria virulence, low host immunity and pronouned hypersensitivity.—Serous membrane, synovium, meninx and lung.—Serous or sero-fibrinous inflammation.➢Proliferative changes dominate—Few organisms,low virulence and high host immunity.—The tubercle-the most characteristic changes in tuberculosis.Typical tubercle(tuberculous granuloma)consists of caseous necrosis in the center,surrounding it by the epithelioid and some Langhan’s giant cells,with a peripheral aggregation of small Lymphocytes and fibroblasts.The tubercle can be isolated or fuse to a large one.TubercleTubercle➢Necrotic changes dominate—Numerous organisms, high bacteria virulence, low host immunity and strange hypersensitivity reaction.—Extensive caseous necrosisGross : pale yellowish or creamy-white in color,soft and friable, similar to dry cheese.Microscopically: red strained homogeneous amorphic material withcell debris sometimes or slightly granular material Caseous necrosis is equal diagnostic importance in TB.Large areas of caseous necrosis are a sign of TB progression.TubercleTubercle3. Conclusion :—The lesions of tuberculous infection depends on the interaction between the organism and the host(the infecting host,virulence of the organism,the degree of immunity or resistance,and hypersensitivity of the host) .—These three basic pathological changes can also interchange according to host conditions. Hence the disease may be manifest different.4. Fate of the tuberculosis➢Healing of tuberculosis lesion—Absorption and resolution.—Fibrosis, fibrous encapsulation and calcification of lesions.➢Exacerbation of tuberculous lesions —Infiltration and progression.—Dissolution and dissemination.5. Pulmonary tuberculosisThe lungs are the most commonly affected by tuber-culosis than any other organs.The pattern of host response depends on whether the infection represents a primary first exposure to the organism or secondary reaction in an already sensitized host.The natural history and spectrum of tuberculosis.Ⅰ.Primary pulmonary tuberculosisThis form occurs when child who has not been previously exposed to tuberculous bacillus or immunised by BCG.So called the childhood type TB,but primary lesion may also occurs in adult at a low rate of the tuberculosis.➢PathologyPrimary complex (the Ghon complex).The lesion consists of three components—Primary lesion (Ghon focus).—Tuberculous lymphangitis.—Tuberculous lymphadenitis (in the hilar lymph nodes).Primary pulmonary tuberculosis, Ghon complex.➢Clinical featuresPrimary pulmonary tuberculosis is usually asymptomatic or manifested as a mild flu-like illness.➢The fate of primary pulmonary TB—In 95% of cases, immunity stops disease progression and healing occurs. The lesions heal by fibrosis and may calcify.—In 5% of cases, rapidly progressive pulmonary disease causing extensive caseous consolidation of the lung, usually occurs only in malnourished or immunodeficient children.Ⅱ. Acute pulmonary milliary tuberculosisCaseous necrosis in the hilar lymphadenopathy escape into a systemic vein,either directly or by involvement of the thoracic duct,and via right heart,pulmonary artery, disseminating to the lung.Miliary pulmonary tuberculosisⅢ. Acute systemic miliary tuberculosis Hematogenous disseminated lesions of pulmonary TB ➢Large numbers of mycobacteria enter usually one of the pulmonary veins,via left heart,into the arterial systemic circulation and spreading to the general various organs.➢Gross:multiple,scattered,too small(approximate1-2mm in diameter),fairly uniform size,round,gray white well demarcated nodules.➢Microscopically:proliferative changes dominate(formation tubercle,often without giant cells,but with central necrosis.➢Clinical symptoms:high fever,night sweats,loss of appetite, failure,hepatomegaly and splenomegaly.Miliary tuberculosis of the spleen.Ⅳ、Second pulmonary tuberculosis➢Secondary pulmonary TB is occurrence of the disease in a patient who has a prior primary infection.It usually occurs in an adult as a result either of reinfection or reactivation,with the latter more common.➢Secondary tuberculosis,however,tends to produce more damage to the lungs than does primary tuberculosis.➢The subsequent course of the secondary lesions is variable.Secondary pulmonary tuberculosis.①Focal pulmonary tuberculosis➢The earliest lesions.➢The most common site is the lung apex, one or more small focus of consolidation.➢Small epithelioid cell granulemas characterized by caseous necrosis and fibrosis.➢Usually asymptomatic.They either may heal spontaneously or with therapy,resulting in a fibrocalcific nodule, or may progress along the many pathways, discussed next.②Infiltrative pulmonary tuberculosis➢This is a most common form in the second pulmonary tuberculosis and usually transformed from focal pulmonary TB.➢This is a activity pulmonary TB.➢The heavy exudation and caseous necrosis continue to appear at the periphery focal tuberculous lesion and to cause the lesion enlargement.➢Complication: irregular acute cavities.spontaneous pneumothorax.tuberculosis pyopneumothorax.➢Clinic features: tuberculous toxic symptoms and chronic cough,frequently with hemoptysis.③Chronic fibro-cavitative pulmonary TB➢This is a most common form of chronic pulmonary TB in an adult. ➢Pathological changes :•It may affect one, many or all lobes of both lungs.•The upper lobes of lung contains multiple variant sizes, thick-walled chronic cavities.•The wall of cavity is lined by a yellow-green caseous material, tuberculous granulation tissue and fibrous tissue successively.•There may be coexisting bronchial disseminated many tuberculous lesions and diffuse fibrosis in the pulmonary tissues.•Later period, the lung becomes small, indurated,with pleural extensive adhesion, the function of the lung may be severely damaged.④Caseous pneumonia➢May occur in debilitated immunodeficient or highly sensitized patients.➢Dissemination large numbers of organisms in the focus via the bronchial tree,and spreading rapidly throughout large areas of lung parenchyma and producing a diffuse bronchopneumonia or lobar exudative consolidation (“galloping consumption”).⑤Tuberculoma➢The caseous necrosis coalescence to form a large solid and spherical mass (usually 2-5cm in diameter), well-demarcated margin, surrounded by fibrous tissue.⑥Tuberculosis pleuritisAccording affected feature divide into:➢Moist tuberculous pleuritis (exudative tuberculous pleuritis)•This is a exudative inflammation dominate(serious or serofibrinous).•Heave serious liquid→hydrothorax.heavy fibrin formation→thoracalgia.➢Dry tuberculous pleuritis (proliferative tuberculous pleuritis)•This is a proliferative lesion dominate.•Localized tubercles may form in the visceral pleura, and this may be followed by an tuberculous focus beneath pleura.6. The extrapulmonary tuberculosis➢A relatively small number of mycobacteria gain entrance the bloodstream(capillary vessel of primary focus)and may be formed latent lesion in the extrapulmonary organs, causing extrapulmonary tuberculosis such as meningitis and tuberculomas of brain,vertebral tuberculosis,renal tuberculosis, intestinal tuberculosis.Intestinal tuberculosisVertebral tuberculosisTyphoid feverTyphoid fever is an acute infectious disease caused by salmonella typhi with hyperplasia of mononuclear-macrophages in the reticuloendothelium of all over the body (intestinal and the mesenteric lymph nodes,liver,spleen and bone marrow,etc)and corresponding clinic features.1.Etiology and pathogenesis➢Pathogen•S typhi is a facultative intracellular organism and infects only humans. endotoxin(strong pathogenicity).without exotoxin.•Somatic antigen(“o”antigen).•Flagellar antigen(“H” antigen)→serum agglutination.•Surface antigen (“V1“ antigen) test(wildal’s test).➢Source of infection—patients and healthful carriers.➢Routes of infection—fecal-oral transmission.The infection results from contamination of food and water with feces from a symptomatic case or a symptomatic carrier of typhoid.The files are important vectors.➢Pathogenesis1.The ingested bacillus invades the small intestinal mucosa,where it is taken up by macrophages and transported to regional lymph nodes and multiplies in the intestinal lymphoid tissue during the ten days incubation period.2.At the end of the incubation period,the bacilli enter the bloodstream(endotoxaemia and bacteremic phase,in the first week), resulting in fever headache and muscle aches.Many tissues may be infested during this phase,blood culture is positive in95%of case.3.S typhi reenters the intestinal lumen by way of biliary excretion. The organism reinfects lymphoid tissue in the small intestine causing acute inflammation,necrosis and ulceration(organism direct invasion, endotoxin released by the bacillus,together with delayed hypersensitivity).Stool and urine culture is positive at this stage blood culture is still positive in about60%of pationts widal’s test is positive.4.Healing usually begins’about the end of the third week and is complete by the fifth week in uncomplicated cases.2.Pathology and clinical features➢Acute hyperplastic inflammation(hyperplasia of the mononuclear-macrophages).The hyperplastic mactophages ingest bacteria,red cells and nuclear debris tend to form a small nodule in lymphoid tissue,such nodule is caused typhoid granuloma and the macrophage is called typhoid cells.Typhoid granuloma (typhoid nodule)Typhoid granuloma (typhoid nodule)Ⅰ.Intestinal lesion*Location—terminal ileum and caecum.*Lymphoid tissue in intestine tract—usually most marked in the Peyer’s patches of the distal ileum and solitary lymphoid follicles of the caecum.。

病理学：第一单元细胞、组织的适应、损伤和修复适应性改变：萎缩：体积变小和数量减少。

肥大：体积的增大，细胞内线粒体、内质网、核糖体及溶酶体增多。

（三体一网）。

增生：实质细胞数量增多。

化生：一种分化成熟的细胞因受刺激因素的作用转化为另一种分化成熟细胞的过程。

鳞状耐磨。

结缔组织间叶骨化。

损伤：细胞水肿：细胞膜及细胞内线粒体等结构受损。

轻度水肿实为肿胀的线粒体和扩张的内质网。

病毒性肝炎时，肝细胞重度水肿，整个细胞变圆如气球，故称气球样变。

脂肪沉积：常见于肝，也可见于心、肾等器官。

脂滴可被苏丹Ⅲ染成橘红色。

严重贫血时，心内膜下和乳头肌部分心肌细胞发生脂肪变性呈黄色、未发生脂肪变性的心肌呈红色，二者相同排列形成虎皮斑纹状故称虎斑心。

玻璃样变性的概念：1.结缔组织玻璃样变：常见于纤维瘢痕组织、纤维化的肾小球以及动脉粥样硬化的纤维性斑块等。

2.血管壁玻璃样变：常见于高血压病时的肾、脑、脾和视网膜的细动脉。

3.细胞内玻璃样变：慢性肾小球肾炎时，合成玻璃样小滴；病毒性肝炎时，嗜酸性小滴。

坏死：活体。

1.坏死的病理变化：1）细胞核的改变：核浓缩，核碎裂，核溶解。

2）细胞质的改变：如肝细胞坏死出现的嗜酸性小体。

3）间质的改变。

2.坏死的类型：（1）凝固性坏死：蛋白质凝固，如肾、脾的贫血性梗死。

（2）液化性坏死：酶性水解而液化，脑、胰腺。

凝固性坏死的特殊类型：①干酪样坏死：主要是结核杆菌引起的坏死。

如：肺干酪性结核。

②坏疽：干性坏疽：由于动脉受阻而静脉仍通畅，水分少，多见于四肢末端，原因有下肢动脉粥样硬化、血栓闭塞性脉管炎等；湿性坏疽：肢体或与外界相通的脏器（肠、子宫、肺）。

因动脉闭塞而静脉回流受阻。

气性坏疽：因深部肌肉，按之有捻发音。

结局 1.溶解吸收2.分离排出：残留的空腔称空洞。

3.机化：毛细血管和成纤维细胞等组成的肉芽组织长入坏死区，最后成为瘢痕组织。

4.纤维包裹、钙化。

凋亡的概念：是生理过程。

修复：再生能力：永久性细胞：包括神经细胞、骨骼肌及心肌细胞。