Resp18 - Tuberculosis

Question 1

5 features of tuberculosis

Organism Features
Transmission
Risk Factors x4
Risk of Active Disease
Signs and Symptoms x8

Answer 1

1. ) Organism - Mycobacterium tuberculosis (MTB)
   - TB bacilli are aerobic, acid and alcohol fast bacilli
   - non motile, obligate aerobe
2. ) Transmission - respiratory droplets (coughing etc.)
   - highly contagious but difficult to acquire an infection
   - require prolonged exposure (8 hrs/day up to 6 months)
3. ) Risk Factors
   - non-UK born: south asia, sub-saharan africa
   - immunocompromised: HIV, diabetes, etc
   - close contacts: homes, schools, prison
   - lifestyle: homeless, drug users
4. ) Risk of Active Disease - 10% lifetime risk of developing active disease in those affected with TB
   - 5% develop primary TB at time initial infection
   - 5% get post-primary TB due to latent TB reactivation (occurs up to 60 yrs after primary infection)
5. ) Clinical Features - gradual onset (weeks or months)
   - fever, sweats, malaise, tiredness, weight loss
   - dry or productive cough (mucoid sputum, blood)
   - crackles may be present on examination

Question 2

4 steps in the pathogenesis of tuberculosis

Inhaled Aerosols
Alveolar Macrophages
Cell Mediated Immunity
Granulomatous Reaction

Answer 2

1. ) Inhaled Aerosols - transmission via air droplets
   - MTB are depositied in the alveoli
2. ) Alveolar Macrophages - phagocytose MTB
   - cannot kill MTB because it’s cell wall blocks the fusion of phagosomes and lysosomes
3. ) Cell Mediated Immunity - initiated by macrophages
   - leads to emergence of activated macrophages with enhanced ability to kill MTB
   - takes about 6 weeks to develop
4. ) Granulomatous Reaction - occurs due to persistance of mycobacteria (long surviving infection)
   - granuloma with central caseous necrosis w/ Langhans giant cell (known as tubercles)

Question 3

Primary and Latent Infections

Primary Complex
Healing Primary Infections
Latent TB
Extrapulmonary TB

Answer 3

1. ) Primary Complex - primary (Ghon’s) focus + hilar nodes
   - development of a sub-pleural (primary) focus of tubercles w/ MTB draining to the hilar lymph nodes
   - occurs w/ primary infections on first exposure to MTB
2. ) Healing Primary Infections - w/ development of cell mediated immunity, the primary complex heals
   - the primary complex can heal w/ or w/out calcification
   - no healing –> active TB (primary TB)
3. ) Latent TB - where TB bacilli can persist within the human host without causing disease for years
   - even after healing, some TB remain viable
   - reactivation occurs when immunocompromised (age, HIV, chemo, steroids, DMARDs, malnutrition)
   - patient has no symptoms and is not infectious
4. ) Extrapulmonary TB - reactivation of latent TB in sites other than the lungs
   - before healing, some MTB can enter the bloodstream and spread to other parts of the lungs and other organs
   - lymph nodes, bones, joints, CNS, GI, urinary tract etc.

Question 4

6 features of post pulmonary tuberculosis

Location
Cavity Formation
Haemorrhage
Lung Spread
Pleural Effusion
Miliary TB

Answer 4

1. ) Location - common in the lung apex (especially right)
   - due to highest alveolar pO2
2. ) Cavity Formation - softening and liquefaction of the caseous material which is discharged into a bronchus
   - fibrous tissue forms around the periphery of such lesions but is unable to stop the tuberculous process
3. ) Haemorrhage - extension of the caseous process into blood vessels in the cavity walls
   - causes haemoptysis (coughing up blood)
4. ) Lung Spread - involves the rest of the lungs
   - through the bronchial tree to other lungs zones

5.) Pleural Effusion - seeding of TB bacilli in the pleura or hypersensitivity –> pleural effusion (exudative)

6. ) Miliary TB - dissemination throughout the body due to rupture of a pulmonary focus into a blood vessel
   - forms multiple miliary tuberculous foci in the lung and in other organs

Question 6

4 diagnostic tests for tuberculosis

Sputum Smears and Culture
QuantiFERON Test
Tuberculin Skin Test
Chest X-Ray

Answer 6

1. ) Sputum Smears and Culture - stained by the Ziehl-Nielsen method (identifies acid-fast organisms)
   - grows slowly on culture (2-6 weeks to form colonies)
   - culture is important to determine susceptibility to drugs
2. ) QuantiFERON Test - interferon gamma release assay
   - T lymphocytes from patient’s blood are cultured w/ MTB antigens that stimulate production of gamma infererons if the patient has latent TB
   - test can distinguish latent TB from previous BCG or atypical mycobacteria because the antigens used are only found in latent TB
3. ) Tuberculin Skin Test - tuberculin (protein) derived from mycobacteria is injected intradermally
   - presence of a skin reaction 48-72 hours later indicates previous exposure to TB because it suggests there has been a type 4 hypersensitivity reaction to tuberculin
4. ) Chest X-Ray - pulmonary shadowing which may be:
   - patchy or cavitated solid lesions
   - streaky fibrosis or flecks of calcification

Question 6

4 features of the treatment of tuberculosis

Time
Reason for Combination of Antibiotics
4 Antibiotics
Prevention

Answer 6

1. ) Time - 2 weeks of treatment removes infectivity
   - 6 months of treatment to fully eradicate pulmonary TB
2. ) Combination of Antibiotics - MTB contains naturally drug resistant organisms so 4 antibiotics given
   - likelihood of resistance to all 4 drugs is very low
3. ) 4 Antibiotics - RIPE
   - Rifampicin: 2 months then extra 4 months
   - Isoniazid (INAH): 2 months then extra 4 months (vit B6 given w/ INAH to prevent peripheral nerve damage)
   - Pyrazinamide: 2 months
   - Ethambutol: 2 months
4. ) Prevention - notify PH England
   - BCG vaccine given to high risk patients (not given to HIV patients because it is a live attenuated vaccine)