patoloji-ders-notlari
Title
Serdar Balcı
Tuberculosis
Serdar BALCI, MD
Tuberculosis
- WHO estimates that tuberculosis causes 6% of all deaths worldwide
- Most common cause of death resulting from a single infectious agent
- Communicable chronic granulomatous disease
- Mycobacterium tuberculosis
- Involves the lungs, may affect any organ or tissue
- Caseous necrosis
Diseases increasing risk of Tbc
Diabetes mellitus
Hodgkin lymphoma
Chronic lung disease
Silicosis
Chronic renal failure
Malnutrition
Alcoholism
Immunosuppression
HIV
Tuberculosis
Tbc infection
Seeding of a focus with organisms
May not cause clinically significant tissue damage
If there is clinically significant tissue damage → Tbc disease
Mycobacteria
- Slender rods
- Acid-fast
- High content of complex lipids that readily bind the Ziehl-Neelsen (carbol fuchsin) stain and subsequently resist decolorization
M. tuberculosis hominis
- Responsible for most cases of Tbc
- Reservoir in persons with active pulmonary disease
- Transmission usually is direct
- Inhalation of airborne organisms in aerosols generated by expectoration
- **Exposure to contaminated secretions of infected persons **
Mycobacterium bovis
Oropharyngeal and intestinal tuberculosis
Contracted by drinking milk contaminated with infection
Mycobacterium avium complex
Much less virulent than M. tuberculosis
Rarely cause disease in immunocompetent
Cause disease in 10-30% of AIDS
- Inhibit normal microbicidal responses
- Prevent the fusion of the lysosomes with the phagocytic vacuole
- Unchecked mycobacterial proliferation
Robbins Basic Pathology
- Mycobacteria enters into macrophage endosomes
- Macrophage receptors
- Macrophage mannose receptor
- Complement receptors
Robbins Basic Pathology
- Earliest phase of primary tuberculosis
- First 3 weeks in nonsensitized patient
- Bacillary proliferation within the pulmonary alveolar macrophages and air spaces
- Bacteremia and seeding of multiple sites
- Asymptomatic or have a mild flu-like illness
Robbins Basic Pathology
- Polymorphisms of the NRAMP1 gene
- Natural resistance–associated macrophage protein 1
- Transmembrane ion transport protein found in endosomes and lysosomes that is believed to contribute to microbial killing
- Disease may progress from this point without development of an effective immune response
Robbins Basic Pathology
- 3 weeks after exposure
- Development of cell-mediated immunity
- Processed mycobacterial antigens reach the draining lymph nodes
- Presented to CD4 T cells by dendritic cells and macrophages
Robbins Basic Pathology
Macrophages secrete IL-12
CD4+ T cells of the TH1 subset are generated
T cells secrete IFN-γ
Activate macrophages
Robbins Basic Pathology
- Activated macrophages
- TNF
- Responsible for recruitment of monocytes
- Undergo activation and differentiation into epithelioid histiocytes
Robbins Basic Pathology
- Activated macrophages
- Expression of the inducible nitric oxide synthase (iNOS) gene
- Elevated nitric oxide levels at the site of infection
- Excellent antibacterial activity
Robbins Basic Pathology
- Activated macrophages
- Generation of reactive oxygen species
- Antibacterial activity
Robbins Basic Pathology
- Defects in any of the steps of a TH1 response
- IL-12, IFN-γ, TNF, nitric oxide production
- Poorly formed granulomas
- Absence of resistance
- Disease progression
Robbins Basic Pathology
Primary Tuberculosis
-
Develops in a previously unexposed, unsensitized patient
- Elderly persons, immunosuppressed patients may lose their sensitivity to the tubercle bacillus
- Primary tuberculosis more than once
-
5% of newly infected acquire significant disease
-
Bovine tuberculosis is rare
-
Mostly pulmonary Tbc
-
Bacilli implant in the distal air spaces
- Lower part of the upper lobe
- Upper part of the lower lobe
- Close to the pleura
-
Sensitization develops
-
1-1.5 cm area of gray-white inflammatory consolidation
- Ghon focus
-
Center of this focus undergoes caseous necrosis
-
Travel in lymph drainage to the regional nodes
- Caseafication develops
-
Parenchymal lesion + Nodal involvement → Ghon complex
Primary pulmonary tuberculosis
Ghon complex
Gray-white parenchymal focus under the pleura in the lower part of the upper lobe
Hilar lymph nodes with caseation
Robbins Basic Pathology
Autopsy Pathology: A Manual and Atlas
Autopsy Pathology: A Manual and Atlas
95% of cases, development of cell-mediated immunity controls the infection
Ghon complex undergoes progressive fibrosis
Radiologically detectable calcification (Ranke complex)
Despite seeding of other organs, no lesions develop
Robbins Basic Pathology
Robbins Basic Pathology
immunosuppressed patient, sheets of foamy macrophages packed with mycobacteria
Robbins Basic Pathology
Consequences of primary Tbc
- Induces hypersensitivity and increased resistance
- Foci of scarring may harbor viable bacilli for years, perhaps for
life
- Nidus for reactivation at a later time when host defenses are compromised
- Uncommonly, lead to progressive primary tuberculosis
- Immunocompromised
- Malnourished children
- Elderly persons
- Lack of a tissue hypersensitivity reaction results in the absence of
the characteristic caseating granulomas
- Nonreactive tuberculosis
Irrespective of the presence or absence of caseous necrosis, use of special stains for acid-fast organisms is indicated when granulomas are present
Robbins Basic Pathology
Secondary Tuberculosis Reactivation Tuberculosis
- Arises in a previously sensitized host
- Shortly after primary tuberculosis
- More commonly many decades after initial infection
- when host resistance is weakened
- Exogenous reinfection
Secondary Tuberculosis
-
Classically localized to the apex of one or both upper lobes
-
High oxygen tension in the apices
-
Preexistence of hypersensitivity
- Prompt and marked tissue response
-
Regional lymph nodes are less prominently involved early in the disease than they are in primary tuberculosis
-
Cavitation occurs readily in the secondary form
- Erosion into and dissemination along airways
- Patient produces sputum containing bacilli
-
Initial lesion
- Small focus of consolidation
- Less than 2 cm in diameter
- Within 1 to 2 cm of the apical pleura
- Sharply circumscribed, firm
- Gray-white to yellow areas
- Variable amount of central caseation
- Peripheral fibrosis
-
Characteristic coalescent tubercles with central caseation
-
Undergoes progressive fibrous encapsulation
- Leaving only fibrocalcific scars
-
Progress and extend along several different pathways
- Erosion into a bronchus
- Erosion of blood vessels
- Spread by direct expansion
- Airways
- Lymphatic channels
- Vascular system
Secondary pulmonary tuberculosis. The upper parts of both lungs are riddled with gray-white areas of caseation and multiple areas of softening and cavitation.
Robbins Basic Pathology
Autopsy Pathology: A Manual and Atlas
Miliary pulmonary disease
Organisms drain through lymphatics into the lymphatic ducts
Empty into the venous return to the right side of the heart
Pulmonary arteries
2 mm foci of yellow-white consolidation scattered through the lung parenchyma
Progressive pulmonary tuberculosis
Pleural cavity is involved
Serous pleural effusions
Tuberculous empyema
Obliterative fibrous pleuritis
progressive primary tuberculosis
Autopsy Pathology: A Manual and Atlas
Endobronchial, endotracheal, and laryngeal tuberculosis
Lymphatic channels
Expectorated infectious material
Systemic miliary tuberculosis
Organisms disseminate through the systemic arterial system to almost every organ in the body
Granulomas are the same as in the lung
**Liver, bone marrow, spleen, adrenals, meninges, kidneys, fallopian tubes, epididymis **
Miliary tuberculosis of the spleen. The cut surface shows numerous gray-white granulomas.
Robbins Basic Pathology
Isolated-organ tuberculosis
- Tuberculous meningitis
- Renal tuberculosis
- Adrenals
- Osteomyelitis
- Salpingitis
- Pott disease
- Scrofula
- Cervical Lymphadenitis
- GIS
- Contaminated milk
- Swallowing of coughed-up infective material
Robbins Basic Pathology
Diagnosis of Tbc
- Demonstration of acid-fast organisms
- Acid-fast stains
- Fluorescent auramine rhodamine
- Conventional cultures
- Liquid media–based radiometric assays
- PCR
- Liquid media
- Tissue sections
Tuberculin (Mantoux) test
2-4 weeks after the infection has begun
Intracutaneous injection of 0.1 mL of PPD
Visible and palpable induration (at least 5 mm in diameter)
Peaks in 48 to 72 hours
- A positive tuberculin skin test
- Cell-mediated hypersensitivity to tubercular antigens
- Does not differentiate between infection and disease
- False-negative reactions (or skin test anergy)
- viral infections, sarcoidosis, malnutrition, Hodgkin lymphoma, immunosuppression, overwhelming active tuberculous disease
- False-positive reactions
- Infection by atypical mycobacteria
- Tuberculin negativity in a tuberculin-positive patient
- sign that resistance to the organism has faded
Nontuberculous Mycobacterial Disease
Chronic, localized pulmonary disease in immunocompetent persons
Mycobacterium avium-intracellulare (M. avium complex)
Mycobacterium kansasii
Mycobacterium abscessus
- In immunosuppressed persons, HIV
- M.avium complex infection as disseminated disease
- Occur late in the clinical course
- CD4+ counts have fallen below 100 cells/μL
- Tissue examination does not reveal granulomas
- Foamy histiocytes filled with atypical mycobacteria
**Mycobacterium avium complex **
Autopsy Pathology: A Manual and Atlas