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Dr G.O OGUN Dept of pathology College of Medicine University of Ibadan
to affect 1.7 billion people world wide- about a third of the world’s population 8-10 million cases each year 1.7 million deaths each year 2nd leading infectious cause of death after HIV Infection with HIV makes people susceptible to rapidly progressive tuberculosis
The disaster called T.B
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Tuberculosis thrives where there is poverty and ignorance completes the cycle. Diseases that increase the risk for TB are Diabetes mellitus Hodgkin's lymphoma Chronic lung disease like – Silicosis Chronic renal failure Malnutrition Alcoholism Immunosuppresion
Microbiology of TB
is caused by M. tuberculosis which belong to the genus Mycobacterium They are slender aerobic rods that grow in straight or branching chains. Mycobacterium have a waxy cell wall composed of mycolic acid which makes them acid fast This implies they retain the red colour of carbol fushin even after treatment with acid alcohol during ZN staining
Is Based on the immune status and immune response of an individual who inhales the organism Non – Immune – Previously unexposed individual- PRIMARY T.B (Source of
organism is always exogenous)
Immune- previously exposed SECONDARY T.B
effector cells that mediate immunity also mediate hypersensitivity and tissue destruction Therefore the state of hypersensitivity also signals acquisition of immunity to the organism
Macrophages are the primary cells infected by M.tuberculosis Enters macrophages by endocytosis Mannose receptor bind lipoarabinomannan(LAM) on the organism Complement receptor (CR) bind opsonised mycobacteria
Inside the pulmonary alveolar Macrophage/ air spaces It replicates within the phagosome formed by blocking fusion with the lysosome. It blocks calcium signal and block protein assemblage involved in phagolysosome formation. Prevent acidic pH in the phagosome Maturation arrest of the phagosome
Other factors come into play in the proliferation of the mycobacterium in the macrophage NRAMP 1 gene polymorphism Complement activated on the surface of M.tuberculosis opsonise the organism and facilitate its uptake by CR3 without triggering respiratory burst necessary to kill the organism
EQUENCE SEQUENCE OF EVENTS IN PRIMARY PULMONAR TUBERCULOSIS APC To Th1 Ac Mac Monocyte TBag TCR HS recruitment Presentation Class II MHC NO
Free radicals Bactericidal (Immunity) IL12 IFN
Granuloma HS formation
HS- Hypersensitivity TCR- T-cell receptor TBag- M.Tuberculosis antigen
a non immunized individual – typically children Lesion typically in subpleural zones of lung –(distal airspace in the lower part of upper lobe or upper part of lower lobe )- can be at other sites Brief acute inflammation – neutrophils. Within 3 weeks of infection, granuloma formation occurs Ghon focus- a 1-1.5cm area of consolidation and hilar lymph node Ghon complex Develop immunity – Mantoux positive
tuberculosis is the pattern seen with initial infection with tuberculosis in children.
In Non Immunized individuals (Children) Primary Tuberculosis:
Limited disease Ghons focus, Ghon complex or Primary complex.
TB and TB Meningitis. Common in malnourished children 10% of adults, Immuno-suppressed individuals
PRIMARY TB AND OUTCOME
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Primary complex can become Healed (organism dead) Latent lesion( organism dormantpulmonary and extrapulmonary) Progressive Primary T.B
Primary in immunized individuals. Cavitary Granulomatous response. Reactivation or Reinfection Apical lobes or upper part of lower lobes – O2 Caseation, cavity formation Pulmonary or extra-pulmonary Local or systemic spread / Miliary
– via left ventricle to whole body Artery – miliary spread within the lung
Results from Reactivation of latent lesions of primary TB especially when host resistance is weak. Commoner in low-prevalence areas. Reinfection – due to waning of protection offer by the primary disease or from a large innoculum. Especially in areas of high prevalence
Is the most frequent form of extra-pulmonary TB In HIV- negative patients, lymphadenopathy tends to be unifocal and patients do not usually have features of ongoing extranodal disease In HIV- positive patients, there is multifocal disease, systemic symptoms and either pulmonary and other organ involvement by active tuberculosis Cervical lymph node with a discharging sinus- Scrofula
Primary TB- occur in the elderly and immunosupressed. Apical lesion expands Erosion into a bronchus evacuates caseous material creating an irregular ragged cavity poorly walled off by fibrous tissue. Erosion into blood vessel leads to haemoptysis. Treatment call halt this leading to healing by fibrosis.
Progressive Primary TB
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If treatment is inadequate or host defence is impaired, then infection can spread by direct expansion by Airways Lymphatics Vascular system
Lung TB - Cavitation
Typical cavitating granuloma
Microscopic or Small (2mm) foci of yellowish- white consolidation through out the whole lug parenchyma. Thru lymphatics into lymphatic ducts to right side of the heart blood or bronchial spread Low immunity Pulmonary or Systemic types.
Pulmonary Miliary TB
SYSTEMIC MILIARY TB
when infective foci in the lungs seed or rupture into one of the branches of the pulmonary venous return to the heart. Organism subsequently disseminate via systemic arterial circulation Typically affects- liver, bone marrow, spleen, adrenals, meninges, kidneys, fallopian tubes and epidydymis
necrotic tissue is coughed up cavity. Cavitation is typical for large granulomas. Cavitation is more common in the secondary reactivation tuberculosis upper lobes.
Cavitary Secondary TB
Complication of Post primary TB/cavitations in the lungs
of Aspergillus infection of a pulmonary cavity in healed tuberculosis forming aspergilloma. Pneumothorax Bronchietasis Progressive pulmonary fibrosis Lung destruction Systemic amyloidosis possible
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Progressive pulmonary Tuberculosis typically can cause involvement of the pleura as Serous pleura effusions Tuberculous empyema Obliterative fibrous pleuritis
UPPER AIRWAY TB
laryngeal TB Typically develops when infective material is spread through the lymphatic channels or from expectorated infectious material
Epitheloid cells in Granuloma
Systemic Miliary TB
Adrenal TB - Addison Disease
TB Epididymitis / Orchitis.
TB Peritonitis + liver Miliary TB
TB Brain – Caudate n.
Spinal TB - Potts Disease
meningitis and TuberculomasIn TB meningitis the pus gravitate mainly basally. (basal meningitis) .Other causes of basal meningitis are fungal aetiology and H.infuenza. The tuberculomas are mainly found in the temporal lobe. pericarditis – Either by direct spread from the lung or by haematogenous route. Calcification and fibrosis typically leads to profound features of right heart failure can present with deranged liver enzymes
MORPHOLOGY - Contd
Morphology - contd
– osteomyelitis, TB arthritis- Knee and hip joint are the most commonly affected joints. Ovary, Fallopian tubes and endometriumTB of Female genital tract typically start from the fallopian tubes. The organism arriving there by the blood stream. TB epididymitis is most frequent site in the male genital tract. Tb orchitis is rare Intestine – typically occur in children. The children are usually malnourished. Ulcers formed are typically transverse ulcers in the terminal ileum but most are irregular in shape. Tuberculous peritonitis can occur either
Potts disease- typically involve children and T9T11 thoracic vertebrae are most frequently involved. Cervical spine involvement is more common than Lumbar involvement. In Potts disease there is destruction of the vertebra body resulting in collapse causing formation of Gibbus or Kyphosis, causing pain and local tenderness. Paraspinal cold abscesses in patients with potts disease may track along tissue planes to present as an abdominal mass or pelvic mass. Paraplegia complicate potts disease which is spastic . The pathogenesis of the paraplegia is a combination of spinal angulation, paravetebra abscess compression and more importantly, tuberculous vasculitis of the spinal blood vessels resulting in infarcts and necrosis of the spinal cord
Diagnosis of TB
Clinical and radiographic features are not confirmatory. Fine needle aspiration of lymph nodes ZN Stain - 1x104/ml, 60% sensitivity Auramine - Rhodamine by florescence 3 negative smears to assure low infectivity* Culture most sensitive, specific and the Gold standard Conventional Lowenstein Jensen media up to 10 wks Liquid media culture 2weeks
innoculation- 9 band armadillo PCR is available
AFB - Ziehl-Nielson stain
Colony Morphology – LJ Slant
Granuloma or LH giant cell is not pathognomonic of TB…! Foreign body granuloma. Fat necrosis. Fungal infections. Sarcoidosis. Crohns disease.
What is New…?
14-30% of TB patients also HIV infected. New drugs - Rifapentine, Interferons, Thalidomide. Immune therapy : Killed M. vaccine stimulates CD8 cells (increased INF and IL-12). The genome of TB has been identified (~4000 genes) potential to develop new vaccines and tests.
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