Pulmonary tb lec & practical
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A 44-year-old man presented with cough, breathlessness, night sweats and fever for four weeks. He recently developed blood-tinged sputum. Examination found a temperature of 37.8°C with no other abnormalities. Tests found elevated ESR and C-reactive protein, and a strongly positive Mantoux test. Chest X-ray showed bilateral upper and middle lobe haziness. Sputum smear was positive for acid-fast bacilli and culture grew Mycobacterium tuberculosis. The patient was diagnosed with pulmonary tuberculosis and started on anti-tuberculous treatment. His sputum became negative and chest X-ray improved, and he was discharged on continued treatment.
Pulmonary tb lec & practical
- 3. Theme: Hemoptysis conti…. Case Scenario: A 44-year-old man presented in the pulmonary clinic complaining of cough, breathlessness, night sweats and low grade fever from last four weeks. Now he had small amount of blood in the sputum from few days. He also had lost 2kg weight during this illness. Clinical examination: GPE: Temperature 37.8°C with no evidence of anaemia, clubbing and oedema. Systemic Examination: Chest auscultation crepitation's audible in the lung apices Lab investigations: Haemoglobin and white cell count were normal. ESR 70mm / hour C-Reactive protein 231 mg/l (normal below 3mg/L)
- 4. Cont….. Mantoux test: strongly positive Chest X-ray: bilateral upper and middle-lobe haziness Sputum Smear: positive for acid-fast bacilli Culture: reported Mycobacterium tuberculosis
- 5. Diagnosis: Pulmonary tuberculosis Treatment: Started anti tuberculous treatment (isoniazid and rifampicin for 6 months, together with pyrazinamide for the first 2 months) Progress: sputum became negative and chest X-ray much improved Discharged: on ATT with regular follow up till full recovery
- 6. Learning Objectives List the causative agents of pulmonary tuberculosis Identify routes of infection of pulmonary TB Explain the pathogenesis of Tuberculosis Classify pulmonary TB into; primary and secondary subtypes Identify components of primary complex of TB Know causes of secondary TB and list its complications Identify sites and morphology of secondary TB Correlate pathogenesis of TB with clinical presentation Identify pulmonary opporturnistic infections
- 7. Tuberculosis (TB) Communicable disease Chronic granulomatous inflammation with caseation necrosis leads to destruction of tissue or organs Epidemiology: WHO reported; 1.7 billion individual infected worldwide with 8-10 million new cases and 1.5 million deaths per year TB flourishes under conditions of poverty, crowding and chronic debilitating illness
- 8. Etiology and Routes of Transmission M. tuberculosis hominis; most cases of pulmonary TB; transmission usually direct, by inhalation of airborne organisms in aerosols or by exposure to contaminated secretions of infected individuals with active pulmonary disease Mycobacterium bovis; Oropharyngeal and intestinal TB contracted by drinking milk contaminated with Mycobacterium bovis Mycobacterium avium complex; much less virulent than M. tuberculosis, causes disease in immunocompromised individuals, in about 10% - 30% of AIDS patients and atypical mycobacteria in HIV infected cases
- 9. Spread of Tuberculosis Local spread Macrophages carrying M. bacilli into surrounding tissues Lymphatic spread Into the regional lymph nodes Hematogenous spread Tuberculous bacteremia producing miliary tuberculosis involving multiple organs By natural passages Transbronchial spread to adjacent lung segments and from lung lesions into pleura Swallowing of infected sputum into intestinal tract Tuberculous salpingitis into peritoneal cavity
- 10. Types of Tuberculosis (TB) Pulmonary TB Primary and Secondary Pulmonary TB Progressive primary and secondary TB Miliary TB Progressive primary and secondary TB may lead to miliary TB which may be; Pulmonary and Extra-pulmonary Miliary TB Isolated organ TB Involves ; intestine, lymph node, bone, skin, meninges, brain, kidney, adrenals, testis, epididymis, ovaries, fallopian tubes and endometrium
- 11. Pathogenesis Bacilli entry into alveolar macrophages After inhalation of coughed out infectious aerosol bacilli engulfed by alveolar macrophages - Internalization Replication in macrophages In earliest phase of primary TB (first 3 weeks) in non-sensitized patient, bacillary proliferation within alveolar macrophages and air spaces leads to bacteremia and seeding of bacilli to multiple sites Development of cell-mediated immunity Approximately 3 weeks after exposure, processed mycobacterial antigens by alveolar macrophages and dendritic cells reach the draining lymph nodes and is presented to T cells. Meanwhile IL-12 secreted by alveolar macrophage than generate CD4+T cells (TH1 subset) which secrete IFN-γ
- 12. Cont ……. T cell–mediated macrophage activation and killing of bacteria IFN-γ, secreted from TH1 cells activate macrophages to release; Tumor necrosis factor (TNF): which recruit monocytes at site of infection Inducible nitric oxide synthase (iNOS): raises nitric oxide(NO) levels to create reactive nitrogen species, important in killing of bacilli Anti-microbial peptides (defensins): toxic to bacilli Granulomatous inflammation and tissue damage Under the influence of IFN-γ, monocytes differentiate into “epithelioid histiocytes” and some multinucleated giant cells to form granulomas to halt infection, before significant tissue destruction, but in immune deficits individuals infection progresses to caseation necrosis and tissue damage
- 13. Natural History and Pathogenesis of Primary Pulmonary TB A- Inhalation of virulent M. tuberculosis results the development of cell-mediated immunity to the organism B- Initiation and consequences of cell mediated immunity to the organism, accompanied by a positive tuberculin test Langhans Giant Cell Epithelioid Cell
- 15. Primary Pulmonary TB Inhaled bacilli implant in distal air spaces of lower part of upper lobe or in the upper part of lower lobe of lung typically in the sub-plural region During the development of sensitization, 1 to 1.5cm gray-white inflammatory lesion appears in the sub-plural region called Ghon focus, in majority it shows central caseation necrosis Tubercle bacilli, either free or within phagocytes, travel via lymphatic vessels to hilar lymph nodes, which often caseate, this combination of sub-plural and lymph node lesion is called the Ghon complex Lymphatic and hematogenous spread to other parts of the body also occurs during the first few weeks but due to development of cell-mediated immunity this infection is controlled in approximately 95% of the cases
- 16. Primary Pulmonary TB Fibro calcified Ghon complex detectable as a Ranke complex on chest radiograph) Subpleural grey white tubercle (Ghon focus) Ghon focus+ Hilar lymphadenopathy = Ghon Complex
- 17. Outcome of Primary Pulmonary TB Depends on the balance of immunity to tissue destruction Healing with Fibrosis: In 95% cases cell mediated immunity healing in 3 weeks with fibrosis calcification Progressive Primary Pulmonary TB: Cavitary tuberculosis Tuberculous bronchopneumonia Miliary pulmonary TB via hematogenous spread to lungs and other organs
- 18. Secondary Pulmonary TB Initial lesion; lung apex a small focus of consolidation less than 2 cm in diameter, within 1 to 2 cm of the apical pleura (Simon focus) Grossly; sharply circumscribed, firm, gray-white to yellow areas with variable amount of central caseation and peripheral fibrosis. Favorable cases, the initial parenchymal focus get fibrocalcifed Progressive lesions cavitation is common
- 19. Secondary Pulmonary TB X-ray chest shows cavityUpper parts of both lungs shows cheesy-white areas of caseation and multiple areas of softening and cavitation
- 20. Microscopy Active lesions; caseating and non- caseating epithelioid granulomas Components of caseating granulomas Central caseation necrosis Surrounded by epithelioid cells Langhans multinucleated giant cells Circumferential collar of lymphocytes Enclosing rim of fibroblasts(old lesions) TB bacilli demonstrated by Z-N staining, but not in late fibrocalcified stages
- 21. Outcome of Secondary Pulmonary TB Secondary pulmonary TB may heal with fibrosis either spontaneously or after therapy, or may progress and extend into; Progressive Pulmonary TB Pulmonary or Systemic Miliary TB Amyloidosis delayed effect of chronic TB
- 22. Progressive Pulmonary TB Apical lesion enlarges and erode bronchus with evacuation of necrotic material in its lumen Cavity lined by caseous material is left behind, walled off by fibrous tissue Cavity remain intact or collapse and become fibrotic Erosion of blood vessels - hemoptysis Sputum positive for TB bacilli
- 23. Miliary Pulmonary TB Inadequate treatment or poor host defenses Infection spread by direct extension and through Airways and lympho-vascular channels Small 1-2 mm (millet seed) sized yellow-white areas of consolidation scattered throughout lung parenchyma Miliary pulmonary disease pleural effusion, empyema or obliterative fibrous pleuritis Mantoux test is frequently negative
- 24. Systemic Miliary TB Occurs when the tubercle bacilli disseminate hematogenously throughout the body Organs most commonly involved are liver, bone marrow, spleen, adrenal glands, meninges, kidneys, fallopian tubes, and epididymis Miliary TB of the spleen, cut surface shows numerous gray-white granulomas
- 25. Isolated-organ TB May appear in any one of the organs or tissues by hematogenous route; Meninges (tuberculous meningitis), Brain (tuberculoma) Kidneys (renal tuberculosis) Adrenal glands (Addison disease) Bones (osteomyelitis) Vertebrae (Pott disease), clinically paraspinal “cold” abscesses Genital TB (endometritis, salpingitis and epididymitis) Intestinal TB particularly ileoceacal, ingestion of contaminated milk or by swallowing coughed up infective material in advanced cases of secondary TB Tuberculous Lymphadenitis usually in the cervical region (“scrofula”)
- 26. Screening methods Mantoux test Based on intra dermal injection of Tuberculin - Purified Protein Derivative (PPD) used to detect active or latent infection (primary method) Gamma Interferon Release Assay (IGRA) In vitro blood tests of cell-mediated immune response; they measure T-cell release of IFN-γ following stimulation by antigens specific to the M. tuberculosis complex (with the exception of BCG sub strains) used for latent infection
- 27. Natural History and Spectrum of TB C/F May be asymptomatic Low grade afternoon fever Night sweats Chronic productive cough Hemoptysis Anemia Weight loss
- 28. Laboratory Diagnosis Raised ESR and CRP levels Sputum smears for acid-fast bacilli (AFB) AFB culture the most specific test for TB
- 29. Nontuberculous Mycobacteria Mycobacterium avium-intracellulare (or M. avium complex) , M. kansasii, and M. abscessus Most commonly cause; chronic localized pulmonary disease like; upper-lobe cavitary lesion, mimicking TB (especially in chronic smokers and alcoholics) COPD, cystic fibrosis and pneumoconiosis In immunosuppressed (primarily HIV positive) individuals M. avium complex infection manifest as a symptomatic disseminated disease (fever, night sweats, weight loss) In AIDS patients CD4+ T cell counts fall below 100 cells/μL disseminated M. avium complex infection occurs and tissue examination reveal foamy macrophages “stuffed” with atypical mycobacteria without any granulomas
- 30. Pulmonary: Fungal Infections Immunocompetent individuals Histoplasmosis Coccidiodomycosis Blastomycosis (all are diamorphic fungi) Clinically may manifests as: Acute primary pulmonary infection Chronic granulomatous pulmonary disease (with or without caseation necrosis) Disseminated miliary disease Macrophages loaded with yeast form of H. Capsulatum, appear black with silver stain
- 31. Pulmonary Fungal Opportunistic Infections Immunocompromised individuals • Candidiasis • Cryptococcosis • Mucormycosis • Aspergillosis • Pneumocystis (carinii) jiroveci Candidiasis : Common superficial mucosal infection Maybe invasive in patients having ; AIDS, renal transplant, neutropenia, heart valvular diseases Findings include abscesses in kidney, lungs, heart, Brain and GIT. Fungal lung abscess-Candia
- 32. Pulmonary Fungal Opportunistic Infections Mucormycosis: Immunocompromised host, specially in diabetics Mucor having non-septate hyphae Frequently infects sinuses, oral cavity, brain & lung Angioinvasive, hyphae growing in and around blood vessels causing ischemia Cryptococcosis : Minimal inflammation, usually in lung, may spread to meninges
- 33. Pulmonary Fungal Opportunistic Infections Aspergillosis: Infection by aspergillus, septate branching hyphae at acute angles, stain black with GMS Aspergilloma (fungus ball): fungus grows in existing cavities like tuberculous cavities, bronchiectasis, paranasal sinus and intracranial Invasive pulmonary aspergillosis: In immunocompromised, produces multifocal necrotizing pneumonia or may be angioinvasive vasculitis, occlusion and infarction or generalized dissemination Allergic bronchopulmonary aspergillosis: Patients with asthma or hypersensitivity pneumonitis, these patients have Ig E antibodies with peripheral eosinophilia
- 34. Pulmonary Fungal Opportunistic Infections Pneumocystis (carinii) jiroveci pneumonia In AIDS patients, often with CMV infection Clinical features: fever, dry cough, dyspnea & hypoxia Radiology: bilateral & basal infiltrates Pathology Septa thickened by edema and mononuclear infiltrate Intra-alveolar foamy pink exudate (Cotton candy) Encysted or trophozoite forms in exudate Diagnosis: Organism best demonstrated in bronchioalveolar lavage or in transbronchial biopsy cup shaped round cysts GMS positive GMS +
- 35. Pneumonia in Immunocompromised Bacterial Infections: by P. aeruginosa, typical or atypical mycobacterium spp. (M. avium and M. hominis) common in AIDS patient) atypical microgranulomas with minimal caseation Viral Infections: by cytomegalovirus (CMV) and herpesvirus by transplacental spread , in organ transplanted and AIDS patients. Produces necrotizing interstitial pneumonia with intracellular inclusions, may progress to acute respiratory distress syndrome (ARDS) Fungal infections: by Pneumocytis jiroveci, Aspergillosis, Candidiasis and Cryptococcus neoformans
- 38. Pulmonary Chronic Granulomatous Inflammation
- 39. Granulomatous Inflammation With Caseation Necrosis
- 40. Acid Fast Tuberculous Bacilli
- 43. Bronchopneumonia Cut surface of lung shows patchy distribution of a consolidated areas A bronchopneumonia is classically a "hospital acquired" pneumonia seen in persons already ill from another disease process. Typical bacterial organisms include: Staphylococcus aureus, Klebsiella, E. coli, Pseudomonas.
- 44. Lobar Pneumonia Lobar pneumonia consolidation of the entire lung lobes Most lobar pneumonias are due to Streptococcus pneumoniae (pneumococcus)
- 45. Pneumonia Microscopy Alveoli on left filled with a neutrophilic exudate that corresponds to the areas of consolidation seen grossly with the bronchopneumonia. At higher magnification a patchy area of alveoli filled with inflammatory cells, mainly neutrophils The surrounding alveolar walls shows congested capillaries filled with RBC's
- 48. KEY QUESTIONS Mention the differences between primary & secondary pulmonary TB? Identify classic clinical features of active pulmonary TB ? Define opportunistic infections and give examples.
- 49. References • Robbins Basic Pathology 10th edition 2017, Chapter 13 Lung, Pages 526-37 • https://webpath.med.utah.edu
Editor's Notes
- #14: The sequence of events in primary pulmonary tuberculosis, commencing with inhalation of virulent M. tuberculosis and culminating with the development of cell-mediated immunity to the organism. A, Events occurring in the first 3 weeks after exposure. B, events thereafter. The development of resistance to the organism is accompanied by the appearance of a positive tuberculin test. Cells and bacteria are not drawn to scale. iNOS, inducible nitric oxide synthase; MHC, major histocompatibility complex; MTB, M. tuberculosis; NRAMP1, natural resistance-associated macrophage protein
- #16: In countries in which bovine tuberculosis and infected milk have largely disappeared,
- #29: Absence of a positive smear result does not exclude active TB infection
- #30: Hepatosplenomegaly and lymphadenopathy, signifying involvement of the mononuclear phagocyte system by the opportunistic pathogen, is common, as are gastrointestinal symptoms such as diarrhea and malabsorption.