Pulmonary Tuberculosis课件.ppt

1、2nd Respiratory Department liu yaxin,Case,A fifty years old man presented to a hospital: 1)Chief complaint: hemoptysis,a productive cough, night sweats and weight loss over the previous one month. 2)He had been seen in a community health center for persistent productive cough and unexpl

2、ained weight loss 10 days before, but was treated with antibiotics for a presumed upper respiratory infection. 3)Past medical history: diabetes.,4)Physical examination: thin, a temperature of 38.9 ; heart rate 116/min, respiratory rate 32/min, there was inspiratory crackles and expiratory rhonchi in

3、 the right upper and middle lobes. 5)His chest x-ray revealed a right upper lobe cavitary infiltrate and a sputum smear was positive for acid fast bacilli.,What is the possible diagnosis of the patient? If you are his doctor, what will you do next?,Pulmonary Tuberculosis,A general outline,Introducti

4、on Etiology agent and Epidemiology Pathogenesis and Immunity Clinical patterns of tuberculosis Clinical Manifestations Diagnosis Differential Diagnosis Treatment,Tuberculosis is a chronic infection, potentially of lifelong duration, caused by bacteria belonging to the Mycobacteria tuberculosis compl

5、ex. M.tuberculosis is commom, and, rarely, M.bovis. It was isolated by Robert Koch in 1882.,Introduction,The lungs are primarily involved, but the infection can spread to other organs. It is characterized by the development of granular tumors(nodes) in the infected tissues. If properly treated, tube

6、rclosis caused by drug-susceptible strains is curable in virtually all cases.If untreated, the disease may be fatal within 5years in more than half of cases.,Introduction,Etiology agent,The tubercle bacillus (M.Tuberculosis) is a rod-shaped, aerobic, non-motile,non-spore-forming, high in lipid conte

7、nt, and acid and alcohol-fast (AFB). It grows slowly . It cant tolerate heat, but It can live in humid or dry or cold surroundings.,AFB - Ziehl-Neelson stain,Acid-fast staining techniques,A, Ziehl-Neelson staining of Mycobacterium tuberculosis from sputum. The red rods are M. tuberculosis. B, A fluo

8、rescent acid-fast stain of M. tuberculosis from sputum.,According to the World Health Organization (WHO) 2008 report, a third of the worlds population is infected by TB. In 2006, WHO estimated that 9.2 million new cases of TB occurred,90% of them from developing countries. population -over crowding,

9、 malnutrition Since 1985 incidence is increasing in west The number of AIDS, Diabetes, Immunosuppressed patients increased.,Epidemiology,Epidemiology,The key link of epidemic The source of contagious The route of spread Peoples of easily affected,Tuberculosis is transmitted by airborne droplet nucle

10、i (containing tubercle bacilli ), which are aerosolized by coughing, sneezing, or speaking. TB may spread through gastrointestinal tract, skin, and placenta.,Many droplet nuclei are capable of floating in the immediate environment for several hours. Large particles may be inhaled by a person breathi

11、ng the same air and impact on the trachea or wall of the upper airway.,The transmission is determined,The probability of contact with a case of TB The intimacy and duration of that contact The degree of infectious of case The shared environment of the contact,From exposure to infection,From infectio

12、n to disease,endogenous factors,exogenous factors,Pathogenesis and Immunity,tubercle bacillus,Human immunity,Death,Survival,or,Human Immunity after infected tubercle bacillus and tuberculin hypersensitivity,The natural immunity of human to TB is nonspecific After infected or given BCG vaccine, human

13、 will obtain specific immunity The immunity of tubercle bacillus is cellmediated immunity,Two types of cells are essential in the formation of TB,Macrophages: directly phagocytize TB and processing and presenting antigens to T lymphocytes T lymphocytes(CD4+): induce protection through producting lym

14、phokines,T lymphocytes(CD4+),Many lymphokines are involved in tuberculosis, the interplay of these cytokines determine the hosts response， for example Interleukin-1 is related to fever IL-6 is related to hyperglobulinemia TNF is related to the killing of mycobacteria formation of granolomas other cy

15、tokines including IL-4,IL-5,IL-10 can promote humoral immunity,Genetic factors play a key role in innate nonimmune resistance to infection with M. Tuberculosis These genes may have a role in determi-ning susceptibility to tuberculosis,During the course of TB, there are three basic pathologic changes

16、 infiltration hyperplasia ulceration or calcification These changes happen in different stage of tuberculosis,When host defense is destroyed and there is much more bacterias, caseating ulceration will exist Otherwise, when host defense is predominant and there is less bacteria, perhaps hyperplasia a

17、nd calcification will happen,Koch phenomenon,It refers that there is different reaction to TB infection between primary and secondary infection,second time（36w）,2-3d,Local swelling, ulceration, spread to the whole body, death,first time,+,+,10-14d,Local swelling, superficial ulceration, and healing

18、scab,The result of the tuberculosis after infection,Absorption Fibrosis Calcification Deterioration: enlargement of infected aeras and appear newer infiltrated regions or spreading.,Clinical patterns of tuberculosis,1. Primary pulmonary tuberculosis (Primary Complex and Bronchial Lymphnod-Tuberculos

19、is) 2. Miliary Tuberculosis (acute, subacute and chronic hematogenous pulmonary tuberculosis) 3. Secondary pulmonary tuberculosis(Infiltrative pulmonary tuberculosis, Chronic fibrocavenous pulmonary tuberculosis) 4.Tuberculous pleuritis 5.Extrapulmonary tuberculosis,Follows the patients rst exposure

20、 to the TB the inhaled bacilli implant in the alveoli. As the bacilli multiply over a 3- to 4-week period, the initial response of the lungs is an inammatory reaction similar to any acute pneumonia.,Primary Tuberculosis,the lung tissue that surrounds the infected area slowly produces a protective ce

21、ll wall called a tubercle, or granuloma. On a chest radiograph, these initial lung lesions are called Ghon nodules. As the disease progresses, the combination of tubercles and the involvement of the lymph nodes in the hilar region is known as the Ghon complex or primary complex.,Primary or Ghons Com

22、plex,Primary tuberculosis is the pattern seen with initial infection with tuberculosis in children. Reactivation, or secondary tuberculosis, is more typically seen in adults.,Ghon nodules,Clinically, this phase of TB coincides with a positive tuberculin reaction a positive purified protein derivativ

23、e (PPD) skin test result (later in this chapter),The central core of the tubercle has the potential to break down, especially in a patient with a depressed immune system. When this happens, the center of the tubercle lls with necrotic tissue that resembles dry cottage cheese. During this stage the t

24、ubercle is called a caseous lesion or caseous granuloma,In Non Immunized individuals (Children) Primary Tuberculosis: Self Limited disease Ghons complex or Primary complex. Primary Progressive TB： 10% of adults, Immunosuppressed individuals Common in malnourished children Miliary TB and Meningitis.,

25、Primary Tuberculosis(Summary),Secondary Tuberculosis,Also called reactivation TB, reinfection TB, or postprimary TB. The reactivation of TB after the initial infection has been controlled. A positive tuberculin reaction generally persists even after the primary infection stage has been controlled. A

26、t any time, TB may become reactivated, especially in patients with depressed immune systems.,Risk factors:,Malnourished individuals People in institutional housing (e.g., nursing homes, prisons, homeless shelters) People living in overcrowded conditions Immunosuppressed patients (e.g., organ transpl

27、ant patients, cancer patients) Human immunodeciency virus (HIV) infected patients (TB is a leading cause of death in HIV patients) Alcoholism,Results from endogenous reactivation of latent infection Located apical, posterior segment of the upper lobes and superior segments of the lower lobes. Involv

28、ed lung parenchymal variously, cavity formation, satellite lesions, tuberculous pneumonia, fibrotic, calcify.,Cavitary Tuberculosis,When soft, necrotic center drain out leave behind a cavity. Cavitation is typical for large granulomas. Cavitation is more common in the reactivation tuberculosis seen

29、in upper lobes.,cavity,satellite lesions,Secondary Tuberculosis(Summary),In immunized individuals Reactivation or Reinfection Apical, posterior lobes or upper part of lower lobes Caseation, cavity - soft granuloma Discharge tubercle bacilli into the environment - infectivity.,Miliary Tuberculosis,Ex

30、tensive infection Hematogenous spread Low immunity Pulmonary or Systemic types.,Tuberculous pleuritis,Dry pleurisy Fibrinous pleurisy Young adults Tuberculosis poisoning symptoms,Pleural effusion,Extrapulmonary tuberculosis,TB bacilli usually gather and multiply in position of high oxygen tension Re

31、gional lymph nodes, kidneys, spine, long bones, genital tract, brain, and meninges, joint.,Clinical Manifestations,Systemic symptoms: fatigue, weight loss, anorexia, low-grade fever, night sweats Pulmonary symptoms: dry cough, bloody sputum or later productive of purulent sputum, chest pain, tachype

32、nea or no symptoms. Physical signs: nonspecific. Rhonchi, amphoric breath sounds.,Diagnosis,Chest X-ray Sputum examination Tuberculin test PCR test to detect TB TB antibody test Detection of T lymphocyte after TB infection Additional methods,Chest radiography,Patchy or nodular shadows (usually in th

33、e upper lobe) Hilar and paratracheal lymph node enlargement (Ghon complex） Cavity formation, sometimes containing an air-fluid level Pleural effusion Segmental atelectasis Calcication and brosis,Primary complex,Lung lesions, Hilar lymph node, and lymph gland. Like a dumbbell,Miliary tuberculosis,Acu

34、te Miliary tuberculosis: widespread; uniformly distributed; ne nodulation,Secondary pulmonary tuberculosis,infiltration,Chronic fibro-cavitary pulmonary tuberculosis,When combined with infection containing an air-fluid level,Tuberculous effusion,Pleural effusion often appears in pleural tuberculosis

35、. It can be seen when 300ml of fluid is present on a chest radiograph. Usually unilatera.,Sputum examination,There are direct smear, concentrated-digested, and culture. Direct smear examination is only positive when large numbers of bacilli(5x103104/ml) begin to be excreted. In order to increase the

36、 positive rate, concentrated-digested sputum specimens as a screening method.,Methods for obtaining sputum samples,Three consecutive morning sputum. Rinse the mouth before getting the sputum. Sputum induction: patients who cannot voluntarily produce satisfactory specimens.,The frequently used Ziehl-

37、Neelsen stain reveals bright red acid-fast bacilli against a blue background.,Another popular technique involves a fluorescent acid-fast stain that reveals luminescent yellow-green bacilli against a dark brown background.,Demonstration of on sputum smear: does not confirm tuberculosis, since saproph

38、ytic nontuberculous mycobacteria may colonize the airways or cause pulmonary disease.,A negative smear by no means excludes tuberculosis, for example the number of tb is not large, no cavity, no bacterial discharge A negative smear in the presence of extensive disease and cavitation makes the diagno

39、sis less likely. Particularly if the negatives are frequently repeated.,Sputum culture is often necessary to differentiate M. tuberculosis from other acid-fast organisms. Also identify drug-resistant bacilli and their sensitivity to antibiotic therapy. M. tuberculosis grows very slowly. It takes up

40、to 4-8 weeks for colonies to appear in culture. Therefore, sputum culture is not a routine method of diagnosis in clinical.,Summary,Tuberculosis is a chronic disease, it is common. The clinical manifestations were complex, divided into primary, secondary, miliary, pleurisy and extrapulmonary tubercu

41、losis. In different stage of tuberculosis, there are three basic pathologic changes: infiltration, hyperplasia, ulceration or calcification,Exercise,What is th Koch phenomenon? It refers that there is different reaction to TB infection between primary and secondary infection,To describe the clinical

42、 patterns of tuberculosis. Primary pulmonary tuberculosis, secondary pulmonary tuberculosis, miliary tuberculosis, tuberculous pleuritis, extrapulmonary tuberculosis,Exercise,To describe the clinical manifestations of pulmonary tuberculosis. Systemic symptoms: fatigue, weight loss, anorexia, low-gra

43、de fever, night sweats Pulmonary symptoms: dry cough, bloody sputum, productive of purulent sputum, chest pain, tachypenea or no symptoms. Physical signs: nonspecific. Rhonchi, amphoric breath sounds.,Exercise,Thank you for your attention.,Tuberculin testing,Identifies individuals who have been infe

44、cted at some time with M tuberculosis,but does not distinguish between current and past infection. PPD test: 0.1 mL of standard purified protein(5 TU) is injected intradermally on the volar surface of the forearm.The transverse width(in millimeters) of the induration at the skin test site should be

45、recorded after 48-72 hours.,Who should do PPD test?,The people with the following conditions should have PPD test: 1. People who have had close day-to-day contact with someone who has active TB disease. (a family member, friend, or co-worker) 2. People who has symptoms of TB, such as: a cough that h

46、angs on, fever, weight loss, night sweats, constant tiredness, loss of appetite. 3. Infants or young children who never contact with tuberculosis. 4. To estimate person if need give BCG vaccine.,1cm,Blister, The standard of judgement,48-72h skin node diameter：,A positive tuberculin test although it

47、is of great use in children, but limited diagnostic significance in older age groups. A positive tuberculin skin test indicates tuberculous infection, with or without disease.,The meaning of PPD,1. Negative reaction does not rule out the diagnosis of tuberculosis. 2. False-positive reactions are due

48、 to infection with nontuberculous mycobacteria. 3. False-negative reactions occur: Concurrent infection, malnutrition, old age, immunologic or lymphoreticular disorders, corticosteroid therapy, chronic renal failure, virus vaccinations or infections, fulminant tuberculosis, improper testing techniqu

49、e.,PCR test to detect TB,Key point Specific DNA primers DNA extraction of TB Detection of PCR products Advantage Early diagnosis The time is short, only 2-4h Evaluation of therapeutic effect False positive and false negative results when operation is Improperly,TB antibody testing,A positive TB anti

50、body testing indicates tuberculous infection, but cant identify the past or present. Not recommended as a clinical diagnosis basis.,Detection of T lymphocyte after TB infection,Whole blood test used for diagnosingM. tuberculosis infection, including latent TB infection. The principle is ELISPOT(T-SP

51、OT.TB). Single reaction cells can be detected even in patients with low immune function. There are false positive or false negative results. Positive result indicates tuberculous infection, with or without disease.,Additional methods,Bronchoscopy examination Brushing sputum specimens Bronchoalveolar

52、 lavage Transbronchial lung biopsies Percutaneous lung biopsy Pleura biopsy ESR M tuberculosis- blood cultured,Acid-fast bacteria (AFB) test Caseous Granuloma Caseous Lesion,Essentials of Diagnosis(summary),History and clinical symptoms: fatigue, weight loss, fever, night sweats, cough,or blood sput

53、um. Pulmonary infiltrates on chest radiograph, most often apical. Positive tuberculin skin test reaction (most cases). Acid-fast bacilli on smear of sputum or sputum culture positive for Mycobactenum tuberculosis.,Differential Diagnosis 1 2 3,Bronchiectasis may confused with chronic fibrocavenous pu

54、lmonary tuberculosis. They also have chronic cough, sputum production and hemoptysis. Usually we can use chest x-ray examination and CT scan to distinguish them.,Differential Diagnosis 1 2 3,Acute bacterial pneumonias may resemble florid tuberculosis in all particulars except for the sputum examinat

55、ion and response to antimicrobial drugs. Pneumonias image changes more rapidly.,Differential Diagnosis 1 2 3,Lung cacinoma may difficult to differential with tuberculosis. As in an isolated coin lesion. An obstructing and inconspicuous endobronchial tumor causing distal cbronic inflammation or a cav

56、iting neoplastic mass. (An irregular cavity wall suggests necrotic neoplasm.),Treatment,The two aims of tuberculosis treatment are to interrupt tuberculosis transmission by rendering patients noninfectious and to prevent morbidity and mortality by curing patients with tuberculosis disease. The princ

57、iples of antituberculous chemotherapy involve earlier, combination, appropriate, regularly and durations.,Support therapy Chemotherapy Surgical therapy,Support therapy,Oxygen Therapy - supplemental oxygen Bronchopulmonary Hygiene Therapy - enhance the mobilization of bronchial secretions Mechanical

58、Ventilation - acute ventilatory failure,Chemotherapy,Medicines used to treat tuberculosis are classified as first-line and second-line agents. First-line essential antituberculous agents are the most effective and are necessary components of any short-course therapeutic regimen. Use of combination t

59、herapy reduces the risk of developing resistance and relapse.,First-line drug,Isoniazid (INH) A principal agent used to treat tuberculosis Universally accepted for initial treatment Considered the best antituberculous drug Should be included in all TB treatment regmens unless the organism is resistant,Advantages included Inexpensive Readily synthesized Availabe worldwide Highly selective for mycobacteria Well tolerated (about only 5% of patients exhibiting adverse effects),Adverse effects