INF1 - E. TUBERCULOSIS-COVERED Flashcards

1
Q

what causes TB

A
  • mycobacterium tuberculosis
    (tuberculosis - refers to type of lesion, tubercle formed in response to infection with mycobacteria)
  • affects lymph nodes and lungs but can affect other parts of body
  • HIV/AIDS/immunocompromised at risk of being infected the most
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2
Q

where do you get mycobacterium bovis from

A
  • raw, unpasteurised milk and dairy products from infected cows
  • similar infection to TB
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3
Q

what does TB look like and made of

A
  • rod shaped
  • mycolic acid in cell wall
  • small amount of peptidoglycan
  • lipids, glycolipids and sugars - arabinogalactan, lipoarabinomannan, PIM (pathogenicity factors)
  • slow-growing due to mycolic acid
  • mycolic acid affects:
    acquisition of nutrients
    uptake of antibiotics/disinfectants
  • obligate aerobe: needs oxygen rich part of body ie - upper lung
  • survives inside macrophages so acts as an obligate parasite
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4
Q

how to identify mycobacterium tuberculosis

A
  • Ziehl-Neelsen stain (acid-fast stain)
  • growth on selective culture media/biochemical tests
  • PCR
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5
Q

pathogenicity and virulence of mycobacteria tuberculosis relating to the cell wall

A
  • mycolic acid: immune evasion
    impermeable/resistance to antimicrobials/biocides
  • cord factor (trehalose 6,6’ dimycolate)
    glycolipid which causes TB to grow in serpentine cords, linked with virulent strains
    toxic to mammalian cells, inhibitor of neutrophil migration
  • antigen 85 complex
    bind host tissues via molecules, ie - fibronectin
    involved in tubercle formation

DOESN’T PRODUCE MANY TOXINS

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6
Q

pathogenicity and virulence of mycobacteria tuberculosis relating to cell entry

A
  • binds to mannose receptors on macrophages and live inside macrophage - immune privileged site (can replicate in tissue)
    factors inhibit phagolysosome function and hence it survives
    damage of innate immune responses
  • cytokines can be released eg - tumour necrosis factor alpha
  • excessive production of TNF-alpha - symptoms of wasting (loss of muscle mass)
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7
Q

what social factors contribute to TB

A
  • immigration from high endemic prevalence areas
  • poverty
  • alcoholism
  • close contact with large groups
  • IV drug use
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8
Q

what age groups are at risk of TB

A
  • very young
  • elderly (reactivation of existing, dormant infection)
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9
Q

what immunocompromised subjects are at risk of TB

A
  • HIV
  • gamma interferon (chronic granulomatous disease)
  • severe combined immune deficiency
  • immunosuppression ie - transplant patients
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10
Q

what is primary TB

A
  • inhaled micro-droplets containing mycobacteria tuberculosis
  • taken up by alveolar macrophages , not activated initially, bacteria can replicate
  • t-cells induce a cell-mediated response to infection (inhibits phagolysosomes)
  • small foci of inflam (walls of bacteria) induced by bacteria with spontaneous healing - form a granuloma
  • ghon focus: mycobacteria can’t proliferate in this lesion but may persist and reactivate later in life
  • often clinically silent (not active), not regarded as infectious or a case of TB
  • active with symptoms is regarded as infectious/contagious and is a case of TB
  • most cases, cell-mediated, T-cell responses and uninfected macrophages wall off and destroy infected macrophages - form caseous granulomas which leave fibrotic, calcified scares (Ghon focus/complex)
  • lesions may contain few direct organisms which can lead to reactivation of the disease if not treated
  • some cases can lead to infectious disease (more so if immunocompromised
  • symptoms: persistent fever, night sweats, weight loss due to inflam response, persistent dry cough/wheezy cough, fluid of lungs, shortness of breath, chest pains, fatigue
  • can affect lymph nodes near lung/airways causing obstruction - cough (lung can’t repair)
  • pulmonary TB = lungs
  • extra-pulmonary TB = lymph nodes, skin, CNS, bones, joints
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11
Q

what is post-primary TB

A
  • reactivation due to a weakened cell-mediated immune system
  • rupture of granulomata (tubercles) release mycobacteria that establish more lesions
  • no spontaneous healing of granulomata, causing cavities and extensive damage to lung tissue, airways, blood vessel (irreversible)
  • fever, night sweats, weight loss (due to cytokine TNF-alpha)
  • cough may produce purulent sputum, maybe with blood
  • pulmonary TB - infectious TB
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12
Q

what is military/spreading TB (extra-pulmonary)

A
  • disseminated TB with spread of bacteria from ruptured tubercles/granuloma to blood (in the macrophages) and reaching many tissues
  • Tuberculous meningitis
    children with primary TB
    adults with extensive TB in other parts of body
    AID patients
    immunosuppressed
  • Renal TB
    may present as a UTI
    can form abscess in kidney - damage
  • TB of joints and bones
    affects cartilage with caseation lesions, spread to adjacent bones causing damage
    spine - deformity - Pott’s disease
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13
Q

what are the differences between TB infection and TB disease in lungs

A
  • chest x-ray shows lesion in disease
  • sputum smears and cultures positive in disease
  • symptoms like cough, fever, weight loss in disease
  • infectious before treatment in disease
  • defined as a case of TB in disease
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14
Q

what samples to take for identification

A
  • sputum if productive
  • bronchoscopy alveolar lavage (BAL)
  • pleural biopsy/fluid
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15
Q

what tests to take for diagnosis

A
  • Mantoux test
  • X-ray (granuloma/tubercle lesions)
  • microscopy of sputum, BAL, bronchial brushings
    (Ziehl-neelsen stain, PCR)
  • Culture
  • Take prophylaxis if positive after Mantoux test
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16
Q

what is the drug regime for sensitive TB

A

4 drugs for 2 months then
2 months for 4 months

17
Q

what is the drug regime for resistant TB

A

5-6 drugs for up to 2 years

18
Q

why is combination therapy used

A

to target different parts of the organism

19
Q

what are first line drugs for TB and what do they target

A
  • rifampicin: inhibits RNA synthesis in ribosome
  • isoniazid: inhibits cell wall synthesis (blocks mycolic acid)
  • pyrazinamide: disrupts plasma membrane and energy metabolism
  • ethambutol: inhibits cell wall synthesis (blocks arabinogalactan)
20
Q

what are second line drugs for TB

A
  • cycloserine
  • ciprofloxacin
  • clarithromycin
  • amikacin
  • streptomycin
21
Q

problems with TB treatment

A
  • liver toxicity due to high doses for long time
  • multiple therapy
  • prolonged treatment
  • drug interactions (anti-HIV drugs)
  • compliance (may need DOTS)
22
Q

why is TB re-emerging

A
  • HIV/AIDS
  • travel to and from countries where TB is endemic
23
Q

what vaccine is available for TB

A
  • Bacille Calmette-Guerin vaccine (BCG)
    live attenuated mycobacteria (M.bovis) - not lifelong protection