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1、Tuberculosis（结核）（结核） 病理系：刘颖 Mail: liu_ IntroductionA chronic infectious disease Mycobacterium Tuberculosis Pulmonary TB is the most common type. involve all organs (rare in thyroid, pancreas and myocardium)Characteristic changes: tuberculous granuloma+caseous necrosisEpidemiologyHistory Worldwide 1.
2、7 billion infected 8-10 million new cases 3 million deathsChina 0.55 billion infected 0.13 million deathsPredisposing factors social factors: poverty, crowding, aging chronic debilitating disease: diabetes mellitus, hodgkin disease, pulmonary silicosis, alcoholism, et al immunity deficiency: HIV Eti
3、ologyRobert Koch 24th, MarchPathogen species: M. hominis ( 人型） M. bovine (牛型） M. avium (鸟型） M. piscium (鱼型) M. murium (鼠型) humanHIV infected hostPathogenicity Lipid: mycolic acid（分枝菌酸） cord factor（索状因子） Wax D（蜡质D） phospholipid（磷脂） mycosides（分枝菌糖苷脂） Protein：结核菌素 GlycogenEtiologytransmissionRespirator
4、y tract (pulmonary T.B) : inhale the airborne organisms expose to contaminated secretionsDigestive tract (intestinal T.B): drinking infected milkSkin injury: Congenital BCG : non pathogenic, living T.B ,undergoing 230 passages,13yrs） motherplacentafetusPathogenesis infection disease Only a small fra
5、ction of those who contract an infection develop active disease. PathogenesisKoch phenomenon: cell mediated immunity (CMI) accompanied with delayed tissue hypersensitivity (DTH)PPD testPPD test false-negative false-positivePathogenesisCMI and DTH are different immunoreactions1.Different antigens2.Di
6、fferent T cell subtypes3.The amount of organisms or antigen and Th1/Th2 excursion 4.Different CKs5.Different methods to kill organismsPathological changesExudation dominant changes: happened in early stage of infection or deterioration of Dis. Predisposing factors: suppressed immunity, plenty of myc
7、obacterium T.B high virulence and strong DTH changes: serous inflammation, serous-fibrinous inflammation location: pleura, meninges, peritoneum Pathological changesExudation dominant changes: development: unstable absorbed without any changes change into proliferation dominant or necrosis dominant c
8、hanges easy to find organismsProliferation dominant change (Tubercle formation, granuloma) Predisposing conditions: strong immunity few mycobacterium low virulence Pathological changesProliferation dominant change (Tubercle formation, granuloma) Changes: Epithelioid cells Langhans giant cells Lympho
9、cytes difficult to find organismsPathological changesNecrosis dominant change Predisposing factors: weakened immunity, severe hypersensitivity large amount of mycobacterium T.B. high virulence Changes: caseous necrosis （干酪样坏死) Gross: granular, cheesy appearance( rich in lipid) LM: acidophilia granul
10、ar materials without structurePathological changesNecrosis dominant change easy to find organismsDevelopment: Exist for long timing bomb The amount of mycobacterium will increase sharply when the disease deteriorateFibrosis Pathological changesPathological changesexudation changesexudation changesgr
11、anuloma lesiongranuloma lesioncaseous necrosiscaseous necrosisConsequenceHealing exudative lesion: absorption proliferative lesion: fibrosis no organisms necrotic lesion: fibrosis and calcification (calcification foci may harbor viable bacilli for years)Deterioration 1. lesion enlarges, the disease
12、progresses granulomaexudation change exudation caseous necrosis caseous necrosis foci enlarge (infiltrative progressive stage)ConsequenceDeterioration 2. Cavitation and Dissemination caseous materials liquefy nature canal cavities formation in original sites mycobacterium disseminate to multiple sit
13、es open T.B lymphatic canal blood vessel (disseminated stage) ConsequencePulmonary TuberculosisPrimary pulmonary T.B. Secondary pulmonary T.B.Previously unexposedMost in children, aged or immunosuppressd persons (HIV)Exogenous organismPathological change: Ghon Complex （原发复合征) 1-1.5-cm area of gray-w
14、hite inflammatory consolidation (lower part of upper lobe or upper part of lower lobe) Tuberculous lymphatitis Regional node involvement, often with caseatePrimary Pulmonary TuberculosisGhon ComplexChief implications:1. It induces hypersensitivity and increased resistance 95% control2. The foci of s
15、carring may harbor viable bacilli for years nidus for reactivationPrimary Pulmonary TuberculosisPrimary Pulmonary TuberculosisDeterioration and Dissemination B. lymphaticsbronchial, tracheal LN、 subclavical LN、 mediastinal LN retroperitoneal LN C. bronchial spreading: uncommon in children. A. blood
16、circulation. acute miliary T.B. subacute or chronic miliary T.B. secondary or extrapulmonary T.B. (lie down)Acute Miliary T.B.Secondary Pulmonary T.B.Previously infectedAdult typePathogenesis 95% endogenous seedingSome special points1. Location: apex of lobe low arterial blood pressure, less M , les
17、s ventilation, high O2 pressure2. Changes: caseous necrosis - proliferation focus localization less lymphatic and vascular spreading more bronchial dissemination3. Long course of disease, complex changesPathological changes Focal lesion: (Focal lesion: (局灶型）局灶型）局灶型）局灶型） 1. location: 24 cm beneath ap
18、ex of lobe 2. pathological changes: less than 2cm in diameter single or multiple focuses proliferation dominant caseous necrosis in central and around fibrosis 3. development: healing by fibrosis or calcification few become infiltrative lesionPathological changes Infiltrative lesion Infiltrative les
19、ion （浸润型）（浸润型）（浸润型）（浸润型）: : 1. source: focal lesion 2. location: apex or subclavical area (subclavicular infiltration) 3. morphology: exudation dominant, caseous necrosis in central 4. clinical symptoms Pathological changes Infiltrative lesion Infiltrative lesion （浸润型）（浸润型）（浸润型）（浸润型）: : 5. developme
20、nt: healing by absorb, fibrosis，calcification disease progresses, acute cavitation may occur caseous pneumonia spontaneous pneumothorax tuberculous pyopneumothorax chronic fibro-cavitative type Chronic fibro-Chronic fibro-cavitativecavitative lesion( lesion(慢性纤维空洞型慢性纤维空洞型慢性纤维空洞型慢性纤维空洞型) ) 1. source:
21、 infiltrative type with acute cavity 2. Characters: single or multiple chronic cavities three layers-inner: caseous necrotic materials mid: tuberculous granulation tissue outer: fibrous scar diverse foci fibrosis (cirrhotic pulmonary tuberculosis)Pathological changes Chronic fibro-Chronic fibro-cavi
22、tativecavitative lesion( lesion(慢性纤维空洞型慢性纤维空洞型慢性纤维空洞型慢性纤维空洞型) ) 3. 3. clinicalclinical symptoms open T.B. (mycobacterium in sputum) emptysis, laryngeal T.B., Intestinal T.B., cor pulmonale 4. development healing : small cavity scar healing large cavity open healing Pathological changes CaseousCaseou
23、s Pneumonia( Pneumonia(干酪样肺炎）干酪样肺炎）干酪样肺炎）干酪样肺炎） 1. source: infiltrative lesion bronchial spreading of acute or chronic cavity 2. modality: lobular or lobar caseous pneumonia acute cavity ( local liquefaction). LM: caseous necrosis with serous-fibrinous exudate 3. Poor prognosis (百日痨 or 奔马痨)Pathologi
24、cal changes TuberculomaTuberculoma（结核球（结核球（结核球（结核球) ) 1. source: fibrosis of caseous necrosis in infiltrative type bronchia closure leads to caseous materials fill in the cavity combination of several tubercular 2. pathological changes: caseous lesion with fibrous capsule 2-5 cm in diameter 3. progn
25、osis: stable deteriorationPathological changesTuberculous pleuritis: wet and drywet type - Exudative pleuritis：Most in young peopleSource: mycobacteria dissemination from primary focus or hilar lymphnods DTH induced by protein of mycobacteria in pleuraPathological changes: serous-fibrinous inflammat
26、ionClinical symptomsPrognosis: 1. absorb 2. rich in fibrin may cause adhesion of pleuraPathological changesdry type - proliferative pleuritis：T.B. focus beneath pleura extend to pleuraMost in apex of lobe, local pleura adhesion and thickening Caseous pleuritis rare Pathological changesSecondary Pulm
27、onary T.B.Systemic symptoms response to T.B. “toxic” components Local manifestations: cough hemoptysis chest pain lower respiratory functionCPCmalaise, weary, night sweat, low fever in the afternoon, hectic rosy cheeks, loss of appetiteHematogenic tuberculosisResult from Primary tuberculosis or Seco
28、ndary tuberculosissystemic military tuberculosispulmonary military tuberculosis acute military tuberculosissubacute/chronic tuberculosis Primary P T.B Secondary P T.B Infection previously uninfected previously infectedPatient children adultsSpecial CMI and DTH occur in the course preexistPathologica
29、l changes Ghon complex various changes, localized, cavity Original focus lower part of upper lobe apex of lobe upper part of lower lobeDominant changes exudation, necrosis proliferation, necrosisDissemination lymphatic and vascular bronchialCourse of disease short, self-control long, fluctuant , cli
30、nical treatment ComparisonExtrapulmonary TuberculosisInvolve all organsReactivation of latent fociPathological changes and character of organs are correlative Intestinal TuberculosisSource of Mycobacterium primary: drinking infected milk secondary: swollen mycobacterium contained sputum Location : a
31、ny segment of intestine most common at ileocecal segment: 1. rich in lymph tissue, easy to invade 2. long time for food to stay in this segmentUlcerative intestinal T.B.Ulcerative intestinal T.B. Tubercles in lymph tissue fused necrosis ulceration Features of ulcer: Features of ulcer: 1. long axis o
32、f the ulcer is vertical to long axis of intestine, because of the circular lymphatics of intestine 2. irregular margin of the ulcer (rat-bite-like), caseous base and tubercular granulation tissue beneath, fibrin exudate and miliary tubercles in serosaIntestinal Tuberculosis Ulcerative intestinal T.B
33、.Ulcerative intestinal T.B.3. Intestinal straitness after ulcer healing Fibrosis leads to a adhesion among serosa and adjacent tissues Hemorrhage and perforation are uncommonClinical symptoms: Clinical symptoms: chronic abdominal pain, intermittent diarrhea and constipation, tubucular toxic symptoms
34、Intestinal Ulcerative T.B.Intestinal Ulcerative T.B.Proliferative intestinal T.B.Proliferative intestinal T.B. proliferative changes dominant, causing thickening of intestine, polyposis, leading to abdominal mass and/or ileus Intestinal T.B.Mesentery T.B.Tuberculous peritonitis wet typeperitoneal tu
35、bercle greenish yellow or hematic ascites dry typeperitoneal tubercle, fibrin exudation extensive adhesion and rubber-like consistency of abdomenIntestinal TuberculosisTubercular MeningitisSource of infection: Source of infection: systemic dissemination via blood cerebral T.B. spread to meningesChan
36、ges: exudation dominant changeChanges: exudation dominant changeThe exudation consists of serum, fibrin, lymphocytes and M gelatinous appearancecerebral infarction or softening Organization of exudate adhesion disturbance of CSF circulation hydrocephalusRenal TuberculosisSource of infection: Source
37、of infection: systemic dissemination via bloodChanges: Changes: begins from the border of cortex & medulla caseous foci enlarged and fused, cavity formed o one kidney bladder contralateral kidney ( (fibrosis and contraction of bladder ) ) destructive kidney CPC: CPC: hematuria, pyuria frequent urina
38、tion(尿频，尿急） Tuberculosis of Lymph NodesSource of infection: Source of infection: lymphatic disseminationLesions:Lesions: common in cervical or mesentery lymph nodes lymph nodes show enlarged, adhesive, caseous necrosis cervical lymph nodes may ulcerate and form sinus “瘰疬“Tuberculosis of Bone and Joi
39、ntsSource of infection:Source of infection: blood vessel dissemination, especially in teenagers (rich in blood supply)Changes:Changes: Lesions in bone and spine: caseous necrosis cold abscess and sinus formation spine T.B. destruction of vertebra humpback （T10-L2） Lesions in joints: tubercular granu
40、lation tissue and exudation joint mouse(关节鼠）, sinus 病例讨论病史摘要：患者，男，38岁，工人。咳嗽，消瘦1年多，加重1月入院。1年前患者出现咳嗽，多痰，数月后咳嗽加剧，并伴有大咯血约数百毫升，咯血后症状日渐加重。反复出现畏寒、低热及胸痛，至3个月前痰量明显增多，精神萎靡，体质明显减弱，并出现腹痛和间歇交替性腹泻和便秘。10年前其父因结核性脑膜炎死亡，患病期间同其父密切接触。体格检查：体温38.5，呈慢性病容，消瘦苍白，两肺布满湿性啰音，腹软腹部触之柔韧。胸片可见肺部有大小不等的透亮区及结节状阴影，痰液检出抗酸杆菌。入院后经积极抗结核治疗无效而
41、死亡 尸检摘要：尸检摘要：全身苍白，消瘦，肺与胸壁广泛粘连，胸腔、腹腔内均可见大量积液，喉头粘膜及声带粗糙。两肺胸膜增厚，右上肺一厚壁空洞，直径3.5cm，两肺各叶均见散在大小不一灰黄色干酪样坏死灶。镜下见结核结节及干酪样坏死区，并以细支气管为中心的化脓性炎。回肠下段见多处带状溃疡，镜下有结核病变。 思考题： 1、根据临床及尸检结果，请为该患者作出诊断并说明诊断依据。2、用病理知识，解释相应临床症状。3、请说明各种病变的关系。HomeworkWhat is the difference between primary tuberculosis and secondary tuberculosis? 谢 谢！
