内科学教学课件：Pulmonary Tuberculosis

1、Pulmonary Tuberculosis,Introduction,Definition Tuberculosis is a chronic infection caused by Mycobacterium tuberculosis. All organs and tissue can be involved, lung is the most ; the major source of infection,Pulmonary TB ： 85%, a common disease and the most important form of tuberculosis. Extra-pul

2、monary TB ：15%, kidney, skeleton system, brain, intestine, reproduction system, lymph system, liver, eyes, ear,Introduction,TB ranked the 7th among ten leading causes of death. In some country, the epidemiology is a critical problem China： morbidity 8%, mortality 9%. but recently, morbidity risen. T

3、he characteristic in China:a. high sickness rate (523/100,000).b. high mortality is (20.9/100,000).c. high drug-resistant: primary drug-resistant (8.1%). acquired drug-resistant (41.1,Top ten leading causes of death,high-income countries: Heart disease Stroke Lung cancer Lower respiratory infections

4、 Chronic obstructive pulmonary disease (COPD) Colon and rectum cancers Alzheimers disease diabetes Breast cancer Stomach cancer,low- and middle-income countries: Heart disease Stroke Lower respiratory infections HIV/AIDS Fetus/newborn (perinatal) conditions Chronic obstructive pulmonary disease (COP

5、D) Diarrhea Tuberculosis Malaria Road traffic accidents,TB,Etiology and Pathogenesis,1. Causation organism : Mycobacteria TB (1) Biological feature a. acid-fast bacilli, Actinomycetales, Mycobacterium. b. growths slowly . c. The resistant strains produce easily d. Viability of tubercle bacilli1). su

6、rvive in the dark for 5 m or more . 2).highly susceptible to sunlight, direct kills in 5min . 3).rapidly destroyed by heat: 20 min , 60; 5 min, 70 ; 1 min , 100,Morphology and stain,Biology features,Mycobacteria TB,2) 4 types of M TB: human (90%), bovine, murine, avian. (3) Component : a. lipids: in

7、duce infiltration with monocytes, epithelioid and lymphatic cell forming tubercle. b. protein : induce allergy, neutrophil and monocytic infiltration. C. polysaccharides: induce certain immunoreactions,Component of the body and Antigenic structure,脂阿拉伯甘露聚糖,甘露磷酸肌醇,Lipid, Protein, polysaccharides （ara

8、binogalactan,mannophosphoinositide etc,4 groups of M TB (metabolic conditions,Group A: Metabolism is exuberant, located in caseous foci, easily killed by anti-TB drugs, the major source of infection. Group B (intracellular growth): In phagocytes and intracellular Mycobacteria, can be killed by the d

9、rug that can enter the phagocytes. Group C (intermittent growth): located in caseous material, intermittent, occasionally growth. Rifampin can kill it. Group D (dormant group): Metabolism is stopped, eliminated by phagocytes.Group B.C are also called persisters” , origin for relapse,2. Epidemiology,

10、1) Source of infection a. Sputum is positive on direct smear (1000million or more bacilli per day). b. The patient have cavity prior to diagnosis and initiation of treatment,Mainly route of transmission,2. Epidemiology,2) Route of transmission a. Respiratory spreading (main) inhaled aerosol droplets

11、 containing viable M tb. coughing, sneezing, shouting, any other way that will expel bacilli into the air b. Digestive tract (rare, milk) c. Others: skin, urogenital system (rare,2. Epidemiology,3) Susceptible population The persons have not immunological response for M TB, diabetes , HIV infection,

12、 infants, old ages,3. Immunologic response and allergy response,Immunity and allergy coexist . Immunity may play a role of protection for organism. Allergy may produce a severe response and hurt the tissues, but it is also a protective mechanism. The onset of TB is depending on: the amount of bacill

13、i inhaled, the virulence of bacilli, specific immunity and allergy,Coexist of immunity and allergy,免疫反应与变态反应,人体免疫力： 细胞免疫为主 非特异性免疫力 ：对任何病均有，较弱 特异性免疫力：具有特异性，较强 变态反应： 型（迟发型）48w 感染：受过感染而不发病，健康 患病：有明确组织病变,Primary and secondary TB,In primary the site of infection shows non-specific inflammation with devel

14、oping granulomas in nodes In secondary there are primed T cells which stimulate a localised granulomatous response,Kochs phenomenon,The organism has two different response to reinfection and primary infection of tubercle bacilli,guinea-pig,first time,infected TB,Foci lymph node blood disseminate to

15、whole body,die,No immunity No allergy,second time,ulceration, Caseous No blood dissemination No lymph node enlargement,immunity allergy,live,机体对结核菌再感染与初感染所表现出不同反应的现象 人体免疫力 变态反应 初感染与再感染,红肿、溃疡、坏死愈合,T.B,局部红肿溃疡、经久不愈,死亡,科赫（koch）现象,原发性肺结核与继发肺结核,III. Pathology,A. The basic pathological changes. 1.Exudative

16、 changes -congestion, edema, leukocytic infiltration; focus : TBb + ; main change : allergic. 2. Proliferative changesTubercle nodule formation. focus : TBb - ; main change : immunolgical response . 3. Degenerative changescoagulating or caseous necrosis, a cheesy, semisolid character. focus : TBb +

17、; main change : allergic,B. Evolution of foci 1.Resolution: -fibrosis, tubercle formation, calcification.-immunity predominant. 2.Exacerbation or pathological advance:-infiltration, liquefaction, cavity formation, dissemination-allergy predominant,III. Pathology,IV. TB infection and TB development,1

18、 Primary infection: the first infection of M TB cause pulmonary lesion. 2 Secondary infection: the persons had infected M TB , dormant or viable organisms reactivation,TB development -the nature course of TB,1.Primary infection a. primary complex b. heal spontaneously( dormant foci in various organs

19、). c. disseminated and miliary TB ; 2.Some TB latent period persist for long time until reactive or persist whole life without reactive. 3.dormant focus reactive secondary TB. 4. closely contact with TB patient who expel TBb,Bacteria coughed up in sputum,Inhalation of bacteria,Bacteria reach lungs,

20、enter macrophages,Bacteria reproduce in macrophages,Lesion begins to form (caseous necrosis,Activated macrophages,Bacteria cease to grow; lesion calcifies,Immune suppression,Reactivation,Lesion liquefies,Dead phagocytes, necrosis,M. tuberculosis,Phagocytes, T cells, and B cells trying to kill bacter

21、ia,Death,Spread to blood organs,Steps in the development of tuberculosis,Primary TB Ghon Focus,Secondary TB,Necrosis Fibrosis Cavitation T cell response: CD4 (helper) enhance killing. CD8 (cytotoxic) kill infected cells giving necrosis,Complications,Local spread (pleura, lung) Blood spread. Miliary

22、TB or “end-organ” disease (kidney, adrenal etc.) Swallowed - intestines,Clinical manifestation,1.Symptoms (1) The onset: usually insidious, sometime abrupt. (2) Systemic symptoms: low fever (afternoon-low grade-fever), fatigue, weight loss, anorexia, night sweats. (3) Respiratory symptoms: cough, sp

23、utum, breathlessness,1.Symptoms (4) Hemoptysis. It may be minimal with specking of the sputum and on occasions early in the disease.Bleeding from a large vessel and a cavity may cause a profuse or even fatal hemoptysis. (5) Occasionally, there may be no symptoms. 2. Physical findings The signs in th

24、e lung are minimal,Clinical manifestation,Laboratory examination,1. SputumThe diagnosis of TB is based on the finding of TBb in the sputum.Methods a. Smears with acid-stainedb. Collectionc. Cultured. PCR,2. X-ray examination,patchy infiltration located in the apical posterior area. character: multif

25、ormity a. Exudative lesion b. Increased density: caseation and productive lesions, small and nodular with sharply defined margins . c.Scar tissue: quite sharp margins and tends to contract. d.Healing exudative lesions: first smaller and less dense and then as scarring develops become more sharply de

26、fined,X-ray,Primary,involved,Blood diffused,CFC,effusion,3.Tuberculin test -OT or PPD (purified protein derivative,MethodIntracutaneous injection of 0.1ml of 1:2000 PPD is performed in the left forearm. After 48-72 hours, the induration may be palpated,5mm为“,15mm为“,Sclerosis diameter,Consequences fo

27、r PPD,1) Negative: induration 5mm in diameter a. No infection b. After infection and before the allergy raise within 4-8 weeks. c. severe febrile illness: miliary TB, measles or other acute infections disease. d. Hodgkins disease, sarcoidosis, lymphoma, leukemia. e. adrenal corticosteroid or other i

28、mmuno-suppressive drugs therapy f. others : malnutrition, old age. g. chronic renal failure ,virus infections.Patients with AIDS,Consequences for PPD,2) Positive: induation 5-10mm(+), 11-19mm(+): Suggest :the person had been infected tubercle bacilli, it does not designate the person suffering from

29、TB. (3)Strongly positiveinduration 20mm or blister and necrosis (+)Suggest: there is an active TB foci in the body. TB skin test significance : It identifies infected at some time with M TB, but does not distinguish between current disease and post infection,4.Fiberoptic bronchoscopy or bronchial wa

30、shing,Purpose (1) finding of tubercle bacilli in the lower respiratory secretions. (2) finding of endobronchial TB, lung cancer.Methoda.Lower respiratory secretions.b.Biopsy,VII. Classification of tuberculosis,I . Primary TB II. Hematogenous disseminated pulmonary TB III. Secondary pulmonary TB IV.

31、Tuberculous pleurisy V. Extra-pulmonary tuberculosis,I). Primary TB,Definition: The first infection with the TBb, mostly occur in the lung. Diagnosis 1. most common in young people, usually children. 2. symptomless, or symptoms mild. 3. chest physical signs -. 4. X-ray examinationprimary complexinfl

32、ammation in lung area, lymphangioitis and lymphadenitis. 5. Investigations PPD:,Primary TB X-ray,Evolution: 1.Cure spontaneously 2.Lymphadenectasis 3.Lympho-hematogenous dissemination 4.Local extension of the disease (uncommon): tuberculous pneumonia 5.Pleurisy,I). Primary TB,. Hematogenous dissemin

33、ative TB,Classification: acute, subacute, chronic miliary.1. Acute miliary TB Definition: acute diffuse dissemination of TBb via the blood stream.Clinical feature:(1) acute , high intermittent fever, night sweat , rigors. (2) 50% : with tuberculous meningitis.(3)physical signs is normal(4)The liver

34、and spleen may be enlargement.(5)X-ray: miliary shadows are of similar size, density and distribution from top to bottom in the lung,. Hematogenous disseminative TB,2. Subacute or chronic hematogenous TB Definition: When the immunity of organism is high, small amount of tubercle bacilli enter the lu

35、ng intermittently via blood stream. Clinical feature: (1) There arent overt symptoms of toxicity ,or there are weight loss, weakness, low-grade fever(2) X-ray: The spreading foci are not similar in size, distribution, dense, in the upper and middle part of lung,X-ray of Acute miliary TB,Secondary TB

36、 rapid death due to miliary disease,Miliary white foci blood spread to lower lobe,. Secondary pulmonary TB,1. Definition: It is major type in pulmonary tuberculosis.It is common type in adult TB. 2. Clinical features It is different according to character extent of the focus and response of the orga

37、nism. The person presents tuberculous toxic symptoms and respiratory symptoms, or asymptomatic,3. X-ray The foci located in upper lobe apical and posterior segment, or in the superior segments of the lower lobes. patch or nodular shadows and lineae bandlike, cavitary lesions, bronchogenic spreading.

38、 Including*infiltrative pulmonary TB*cavitary pulmonary TB*tuberculoma*caseous pneumonia*fibro-cavernous lung tuberculosis,. Secondary pulmonary TB,X-ray of secondary pulmonary TB involved,involved,involved,Tuberculous pleurisy,tuberculous dry pleurisy tuberculous serofibrinous pleurisy tuberculous

39、empyema,V) Extra-pulmonary tuberculosis,1 Bone tuberculosis 2 Tuberculous meningitis 3 Renal tuberculosis 4 Intestinal tuberculosis,VIII. Diagnosis,Pulmonary TB depend on: (1)Clinical manifestationsymptoms and signs: fatigue, weight loss, fever, night sweats and cough. (2)Sputumpositive for acid-fas

40、t bacilli will provide nearly conclusive evidence (3)X-ray: it is the most basis. (4)Positive tuberculin skin test reaction,Diagnostic formularecord method (1) zone and region of lesion (right, left, upper, middle, lower) (2) type (3) bacilli of sputum (4) history of chemotherapy (5) complication Re

41、cording secondary tuberculosis middle/(-) (no sputum) retreatment,VIII. Diagnosis,诊断,是否肺结核,有无活动性,分型,IX. Differential diagnosis,1.Pneumonia(1)acute attack, chill, fever, chest pain(2)response to anti-inflammatory drug well(3)involved segment, homogenous 2.Lung cancer(1)mostly affected in men above 40

42、 years(2)No toxic symptoms, there are irritable cough ,chest pain(3)peripheral lesion round focus no satellite,IX. Differential diagnosis,3.Chronic bronchitis(1)Seasonal cough with mucus-frosty sputum(2)X-ray: no patchy as TB with increased lung markings. 4. lung abscessdifferentiate from infiltrati

43、ve pulmonary tuberculosis.1) the onset is more abrupt ,with high fever2)The sputum is purulent and may have foul-smelling3) Tubercle bacilli in sputum are negative 4) Chest film shows a cavity with air-fluid level but no daughter focus,XI. Treatment,I) ChemotherapyA. Principle 1 early to start the t

44、reatment 2 combine to use the drugs 3 adequate dosage 4 regularity 5 full course,First-Line Treatment of TBfor Drug-Sensitive TB,ChemotherapyB. anti-TB drugs Isoniazid (H) Streptomycin (S) Rifampin (R) Ethambutol (E): Pyrazinamide (Z,bactericide , highly effective against actively metabolizing cells

45、 ,distributed all tissue , low toxicity and inexpensive (1) Dose adult : 300mg / day, or 5mg/ Kg / day. tuberculous meningitis and acute miliary tuberculosis: larger dose ( 600-900mg / day ). (2) Side effects_ uncommon 1)peripheral neuritis.2)transient elevation of SGPT and INH-related hepatitis may

46、 occur when larger than 300mg is used,Isoniazid (H,Streptomycin (S,semi-bactericidal drug, against mycobacteria , poor effect on intracellar tb poor effect in acidic condition. (1).Dose: intramuscularly ，1g /day during the first few months, but may be reduced to 1g 2-3 times/ week. 50 years old or w

47、ith impaired renal function : 0.75 gm. (2). side effect:excreted by kidneys , toxic levels develop when renal function poor.The toxic side effects are eight nerve toxicity (especially the vestibular branch). Rashes, fever, is rare,Rifampin (R,all bactericidal drug, older, effectiveness, low incidenc

48、e of toxicity and high degree of patients acceptance as H. (1)Dose 450-600mg/day administered by mouth. (2)Side effects:carefully used in liver disease.occasionally , cause transient hepatic dysfunction, SGPT elevation ,bilirubinemia,Ethambutol (E,bacteriostatic drug, the most useful oral companion drugs for H in original treatment cases. (1)Dose :25mg/kg/day, 15-18mg /kg : outpatient treatment for 2m. (2)side effect: uncommon.Disturbance of digestive tract .Optic neuritis ( loss of visual acuity, field constriction and loss of green color discrimination,Pyrazinam