Tuberculosis and Leprosy

Question 1

describe the route of entry and outcomes for tuberculosis

Answer 1

• route of entry:
  
  • inhalation (most common)
  • ingestion (abdominal TB)
• outcome:
  
  • in most persons the body gets rid of the bacteria → no clinical disease
  • only in some persons the bacteria multiply in the lungs and causes infxn
  • only 5% newly infected persons develop disease

Question 2

describe the body’s response to TB

Answer 2

• histological response takes 3 weeks to develop because it needs cell-mediated immunity
• the body forms what is called tubercles (granulomas)
  
  • small nodular lesion with central caseation
  • composed of epithelioid cells +/- Giant cells
    
    • Langhans giant cells (nuclei arranged in the cell periphery-horseshoe-shaped pattern)
    • foreign body type (nuclei arranged in disorganized manner)
  • surrounded by macrophages, lymphocytes, plasma cells and area of fibrosis

Question 3

describe epithelioid cells

Answer 3

• macrophages activated by IFN-gamma differentiate into the “epithelioid histiocytes” that aggregate to form granulomas
• they are large eosinophilic cells resembling epithelial cells
• they have secretory fxn but lost their normal phagocytic abilities
• may be responsible for inducing necrosis

Question 4

describe the morphology of a TB infection

Answer 4

• gross: chalk-like or cheesy
• micro: pink to red with eosin stain
• tissue structure destroyed, no outlines can be made out (unlike coagulative necrosis where the individual cells are dead but the tissue architecture is preserved)
• it is caused by type IV hypersensitivity reaction

Question 5

describe primary tuberculosis

Answer 5

• the first infection with the tuberculosis bacilli is called primary tuberculosis
• can occur in the lung, tonsils, intestine, skin
• usually include initial lesion and draining lymph nodes
• lungs are the most common site of infxn

Question 6

describe the pathogenesis of primary tuberculosis

Answer 6

• pathogenesis:
  
  • inhalation of mycobacteria → located in the lower part of upper lobe or upper part of lower lobe of the lung → primary lesion called Ghon’s lesion
  • infxn then spreads by lymphatics to hilar lymph nodes → hematogenous spread to other organs
  • the triad of Ghon’s lesion + lymphatics + enlarged hilar lymph nodes = Ghon’s complex

Question 7

describe the clinical features and investigations for primary tuberculosis

Answer 7

• clinical features:
  
  • usually asymptomatic with mild flu-like illness, fever and dry cough
• investigations:
  
  • CXR: lesion +/- hilar lymph nodes
  • sputum: rarely produce and usually -ve
  • PCR

Question 8

describe the outcome of primary tuberculosis

Answer 8

• heals in most people → fibrosis, calcification
• some bacteria may remain dormant in the lungs or distant organs and can get reactivated later (causing secondary TB)
• in immunosuppressed patients the primary tuberculosis may progress into:
  
  • primary progressive complex
  • miliary tuberculosis

Question 9

describe the sequence of events during a TB infection

Answer 9

Question 10

describe the pathogenesis of progressive primary complex

Answer 10

occurs in immunosuppressed patients

• pathogenesis:
  
  • failure of the primary lesion to heal (rare) → progressive involvement of surrounding lung → invades blood vessels and spreads all over the body
  • miliary TB, may end fatally
    
    • “millet” sized granulomas all over
    • lungs, liver, spleen kidney, brain, gut can be affected

Question 11

to develop secondary TB the patient should have had:

Answer 11

• to develop secondary TB the patient should have had:
  
  • an earlier exposure to tubercle bacilli without developing disease
  • or recovered from primary TB
• and subsequently:
  
  • gets a new 2nd time infection (reinfection)
  • or the bacteria from an earlier primary lesions that had become dormant get activated (reactivation) due to lowered immunity

Question 12

describe the pathogenesis of secondary TB

Answer 12

• pathogenesis:
  
  • the tissue response will be different because the person already had developed the CMI → rapid development of caseation within few days → cavity formation
  • the lesions of secondary tuberculosis are usually located at the apex
  • associated with fibrosis, quick healing and calcification

Question 13

describe how the cavities in secondary TB develop

Answer 13

• caseous mass located near bronchial passages erodes through the wall of bronchi → necrotic contents spill out into the bronchial tree → coughed out in sputum → the lesions is now empty and becomes a cavity
• this is NOT a feature of primary TB

Question 14

Answer 14

Question 15

describe the clinical features of secondary tuberculosis

Answer 15

• clinical features:
  
  • fever, night sweating, loss of weight
  • productive cough +/- hemoptysis
  • chest pain, SOB (pleural effusion)

Question 16

describe progressive secondary tuberculosis

Answer 16

• occurs in less than 5% of secondary TB → no healing
• direct spread to rest of lung, pleura and lymph nodes
• pneumonia, caseation, cavity, fibrosis, calcification
• bronchiectasis (destruction, dilatation of bronchi)
• pleural effusion, thickening
• blood spread → miliary TB = all over the body

Question 17

describe what is seen in the image

Answer 17

Question 18

describe how TB can affect the GIT

Answer 18

• GIT: ileocecal ulcers, intestinal obstruction, peritonitis

Question 19

describe how TB can affect the vertebra

Answer 19

• vertebra (Pott’s disease): cold abscess of the spine → cord compression, rupture into paravertebral soft tissue

Question 20

describe how TB can affect the kidneys

Answer 20

• kidney: hematuria, pyuria

Question 21

describe how TB can affect the heart

Answer 21

heart: constrictive pericarditis

Question 22

describe how TB can affect the brain

Answer 22

• CNS: chronic meningitis, tuberculoma (behaves like a brain tumor)

Question 23

describe how TB can affect the liver, spleen

Answer 23

• liver, spleen: organomegaly

Question 24

describe how TB can affect the endometrium

Answer 24

• endometrium: infertility

Question 25

describe how TB can affect the adrenals

Answer 25

* adrenals: Addison's disease (insufficiency)

Question 26

describe the tuberculin (PPD) test

Answer 26

* inject tubercle protein into the skin * check the response after 48-72 hours * measure the extent of induration * if beyond a particular diameter, assume active TB and treat * the exact cut off point varies with the geographic area, previous vaccination with BCG and presence of HIV infxn

Question 27

describe the PPD criteria to treat

Answer 27

Question 28

describe lab investigations for TB

Answer 28

Question 29

\_\_\_\_ is the gold standard test for TB

Answer 29

**interferon-gamma release assay** is the gold standard test for TB

Question 30

describe tuberculoid leprosy

Answer 30

* tuberculoid type: * granuloma, intact cellular immunity, few bacteria present * **positive lepromin test** * localized skin lesions with nerve involvement

Question 31

describe lepromatous leprosy

Answer 31

* lepromatous: * absence of granuloma, depressed CMI * **negative lepromin skin test** * numerous bacteria present in foamy macrophages * nodular lesions; classic leonin facies

Question 32

describe the diagnosis of leprosy

Answer 32

* diagnosis: * punch biopsy or nasal scrapings; acid-fast stain * lepromin test is only positive in tuberculoid

Question 33

lepromin test is only positive in \_\_\_\_\_

Answer 33

lepromin test is only positive in **tuberculoid**