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Respiratory Unit > 10.1. TB > Flashcards

10.1. TB Flashcards

1
Q

What caused TB infection?

A

Mycobacterium tuberculosis

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2
Q

How is TB infection identified?

A

Demonstrated on smears (e.g. sputum smears) stained by the Ziehl-Nielsen method and grow slowly on culture (on media such as the Lowenstein-Jensen Medium) taking 2-6 weeks to form colonies.

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3
Q

How is TB spread?

A

Person to person by infected droplets

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4
Q

Is a person of anti-TB chemotherapy infective?

A

Yes. Though the infectivity of sputum becomes minimal after 2 weeks of commencing treatment with effective anti-TB chemotherapy.

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5
Q

How long does it take to eradicate pulmonary TB with anti-TB chemotherapy?

A

Six months of treatment

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6
Q

What is cell mediated immunity?

A

When T lymphocytes respond to altered cells such as APC, cancer, viruses. T cells will have a CD4 receptor that binds to Ag-MHC complex on APC to recognise the attack. T-helper cells release interleukins, and proliferates and differentiates to become t-memory and t-killer cells. Stimulate formation of plasma cells from B cells. More phagocytosis by macrophages.

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7
Q

How does the immune system defend against TB?

A

Alveolar macrophages phagocytose MTB deposited in alveoli but are unable to kill them. These macrophages initiate the development of cell mediated immunity which eventually leads to the emergence of activated macrophages with enhanced ability to kill MTB. This takes about 6 weeks to develop.

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8
Q

Why can macrophages initially not kill MTB?

A

Possibly due to the cell wall lipids of MTB blocking the fusion of the phagosomes & lysosomes.

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9
Q

Why do tubercles form in TB?

A

Due to ingestion of MTB by macrophages causes a granulomatous reaction.

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10
Q

What are tubercles?

A

A characteristic lesion of TB. Is a spherical granuloma with central caseation.

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11
Q

How does a TB granuloma (tubercle appear microscopically?

A

Core of caseous necrosis surrounded by epithelioid macrophages, langerhans giant cells and lymphocytes

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12
Q

When does primary infection occur?

A

On first exposure

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13
Q

What is a Ghons focus?

A

A sub pleural focus of tubercles caused by TB

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14
Q

What is the primary complex?

A

The primary Ghons focus and the infected draining hilar lymph nodes together

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15
Q

How does TB enter other organs (extra pulmonary sites)?

A

Haematogenous spread = TB bacilli enter the blood stream, probably via lymph drainage into the venous system

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16
Q

What is latent tuberculosis?

A

When TB bacilli lies dormant in the human host without causing any disease for years or until death. Small number of organisms remain viable in the body and have the potential for reactivation

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17
Q

When does reactivation of TB usually occur?

A

When patients immune mechanisms wane or fail/immunocompromised patients

  • HIV
  • old age
  • malnutrition
  • immunosuppression
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18
Q

How do we test for a latent TB infection?

A

Latent infection is characterised by a positive ‘QuantiFERON’ test/ interferon gamma release assay IGRA or a positive tuberculin skin test

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19
Q

What is interferon gamma?

A

A cytokine critical to both innate and adaptive immunity, and functions as the primary activator of macrophages in addition to stimulating natural killer cells and neutrophils

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20
Q

How does the interferon gamma release assay test ( QuantiFERON) work?

A

Lymphocytes from the patients blood are cultured with mycobacterium tuberculosis antigens. If the patient has been exposed to TB before, T lymphocytes produce interferon gamma in response.

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21
Q

Why is a positive interferon gamma release assay test and a tuberculin skin test not a useful indicator in a symptomatic patient?

A

Both will test positive for a patient that is currently infected/previously infected/latent infection. Can not differentiate the stage of the infection

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22
Q

How can the interferon gamma release assay test distinguish latent TB from atypical mycobacterium exposure or previous BCG vaccine?

A

Antigens used in the test are not present in non-TB mycobacterium (atypical mycobacteria) or in the bacilli used in the BCG vaccine.

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23
Q

How does the tuberculin skin test / tuberculin sensitivity test work?

A

Tuberculin, a protein derived from mycobacteria, is injected intra-dermally.
The presence of a skin reaction (induration) 48 – 72 hours later at the site indicates previous exposure to TB and is due to a type IV hypersensitivity reaction to proteins derived from Mycobacteria.

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24
Q

Describe the pathogenesis of progressive secondary infection of TB?

A

Aerosols of mycobacterium tuberculosis inhales
Engulfed by alveolar macrophages in the sub pleural space
Enter local lymph node at the lung hilum
Primary complex formed
Progression to active disease (5%) or initial containment of the infection (95%)
Latent infection
Reactivation (compromised immune system)
Progressive secondary infection of TB

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25
Q

How common is it to develop the active disease after exposure to TB?

A

10% life time risk of developing active disease

  • 5% develop primary TB at the time of initial infection
  • 5% develop secondary active TB due to reactivation of latent TB after a variable period of time following primary infection
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26
Q

What is primary TB?

A

Occurs when the primary complex does not heal but progresses to cause active TB

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27
Q

What is post primary TB?

A

The vast majority of clinical cases of TB are due to reactivation of latent TB and occurs most often in the lungs.

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28
Q

Where is post primary pulmonary TB commonly seen and why?

A

In the upper lung zones, especially the right apex.
Higher alveolar pO2 in upper zones of the lungs relative to the rest of the lung is believed to predispose to reactivation of TB bacilli at these sites.

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29
Q

What are some of the common sequelae of post primary TB infection?

A 
Cavity formation
Haemorrhage
Spread to involve rest of the lung
Pleural effusion
Military TB
30
Q

What occurs in cavity formation?

A

Softening and liquefaction of the caseous material which is discharged into a bronchus results in cavity formation. Fibrous tissue forms around the periphery of such lesions but is usually unable to limit
extension of the tuberculous process.

31
Q

Why does haemorrhage occur during post primary TB?

A

Due to extension of the caseous process into vessels in the lug walls. Causes haemoptysis

32
Q

How does mycobacterium tuberculosis spread across lung in post primary infection?

A

Caseous and liquefied material in the cavity can spread through the bronchial tree to other lung zones

33
Q

How can post primary TB cause a pleural effusion

A
  • TB bacilli in the pleura

- Hypersensitivity reaction

34
Q

What are miliary?

A

Widespread numerous small (0.5 - 2mm) tuberculosis foci in the lungs and in other organs.

35
Q

What causes miliary TB?

A

Rupture of a caseous pulmonary focus into a blood

vessel may result in widespread dissemination of bacilli throughout the body, resulting in miliary tuberculosis

36
Q

What is extra pulmonary TB?

A

Reactivation of latent TB in sites other than the lung, resulting in active TB at these sites.

37
Q

Where can extra pulmonary TB occur?

A 
Lymph nodes
Bones
Joints
CNS
GI tract
Urinary tract
Can occur anywhere
38
Q

What are the initial symptoms of active TB infection?

A 
Tiredness
Malaise 
Weight loss 
Fever
Sweats
Cough (dry or productive of mucous sputum, may have haemoptysis)
Onset is gradual over weeks or months
39
Q

Describe the typical CXR of a patient with active TB infection

A

CXR shows:
pulmonary shadowing often in apex of lungs
patchy solid lesions
cavitated solid lesions, usually within consolidation
streaky fibrosis flecks of calcification
Pleural effusion if pleura involved

40
Q

How is active Tb diagnosed?

A

Identification of the tubercle bacillus in the appropriate body fluid (usually sputum) by direct smear, culture and other tests when indicated.
Ziegler-Neeson stain or fluorescent auramine stain

41
Q

How is active TB treated?

A

Combination of 4 antibiotics over 6 month period. Antibiotics:
Rifampicin
Isoniazid (INAH)
Pyrazinamide
Ethambutol
All 4 drugs for 2 months followed by Rifampicin and INAH for a further 4 months (total 6 moths)

42
Q

What other medication should be given alongside antibiotics in the treatment of active Tb infection?

A

Pyridoxine (vitamin B6)

Given alongside isoniazid to prevent peripheral nerve damage.

43
Q

Why are 4 drugs used to treat active TB infection?

A

Mycobacterium tuberculosis strain contains small number of naturally drug resistant organisms. Using a single drug allows selection of these resistant strains to emerge. Likelihood of such organisms being resistant to all 4 drugs is highly unlikely.
Allows successful treatment of patient and reduces ,ikelihodd of resistant strains emerging.

44
Q

Where are common sites that mycobacterium tuberculosis go in primary infection?

A

Fissures

Sub-pleural space

44
Q

How is a granuloma formed in primary exposure to TB?

A

Primarily T cell mediated disease
Reaction between lymphocytes and MTB which damages the lung parenchyma.
Inflammatory cells surround the caseous necrosis. May see from action of giant cells.

45
Q

After a primary infection with TB, a CXR may appear normal. Why is this?

A
  1. MTB is dead and body has successfully killed the infection
  2. MTB is lying dormant, still alive within the macrophages. Latent infection
46
Q

Where is the incidence of TB infection highest globally?

A 
Africa
India
Indonesia 
Pakistan
China
Philippines 
Cambodia
47
Q

In recent years there has been a decline in the incidence number of Tb infections within the Uk. Why is this?

A

Screening of all migrant entering the country from a country of high incidence of TB.

48
Q

What are risk factors for developing TB?

A 
• Non-UK born/recent migrants
– South Asia 54.8%
– Sub-Saharan Africa 29.5% 
• HIV 
• Other immunocompromised conditions 
• Homeless 
• Drug users, prison 
• Close contacts 
• Young adults (also higher incidence in elderly)
49
Q

What is the causative agent of tuberculosis?

A

Most commonly caused by mycobacterium tuberculosis.
Can be cause by 6 other bacteria belonging to the mycobacterium tuberculosis complex such as:
Mycobacterium Bovis
Mycobacterium Africanum

50
Q

MTB is an obligate aerobe. What does this mean?

A

An organism that requires oxygen to grow. Through cellular respiration, TB uses oxygen to metabolise substances.

51
Q

Describe the structure of MTB

A

Non-motile rod-shaped bacterium.
Long-chain fatty (mycolic) acids, complex waxes & glycolipids in cell wall, which gives organism structural rigidity and difficult staining characteristics

52
Q

How is MTB stained?

A

Cannot stain with H&E stain due to high fat content of cell wall.
Must be stained with a acid-fast stain such as Ziehl-Neelson stain.

53
Q

Why does it take a long time to produce a culture of MTB?

A

As generation time is relative slow (15 to 20 hours).

TB cultures are cultivated for 6 to 12 weeks

54
Q

Describe the transmission of MTB

A

Spread by respirator droplets (coughing/sneezing)
Inhalation of droplet nuclei
Small infectious dose but require long exposure
Classically transmitted in households/prisons/schools where there is prolonged exposure

55
Q

What are droplet nuclei?

A

Respiratory droplets carrying the MTB bacilli

Are very small particles that can stay suspended in the air for a long time

56
Q

How does a latent TB infection vary from an active TB infection?

A

Latent: inactive contained tubercle bacilli in the body, normal CXR, negative sputum smears and cultures, no symptoms, not infectious

Active: active multiplying tubercle bacilli in the body, abnormal CXR, positive sputum smear and cultures, symptomatic, infectious

57
Q

Why are post-primary TB patients more symptomatic than primary TB patients?

A

Due to previous exposure, the inflammatory response is more rapid and cause more damage to the lungs.

58
Q

What are the risk factors for reactivation of latent TB?

A 
Infection with HIV 
Substance abuse 
Prolonged therapy with corticosteroids 
Other immunosuppressive therapy
Tumor necrosis factor- alpha [TNF-α] antagonists 
Organ transplant 
Haematological malignancy
Severe kidney disease/haemodialysis
Diabetes mellitus 
Silicosis
Low body weight
59
Q

How do we investigate a patient with suspected pulmonary TB?

A

CXR
Microscopy, culture and sensitivity
NAAT
Sputum - 3 early morning samples, minimum volume of 5ml
Induced sputum if patient isn’t producing (physio)
Bronchoscopy in patients with dry cough

60
Q

How does MTB appear under a Ziehl-Neelson stain?

A

Thin Pink stained bacilli in sputum.

61
Q

what are the problems with using microscopy to diagnose tuberculosis?

A
  1. Need large number of bacilli in sputum to test as positive. May test as smear negative case but have an active infection
  2. Cannot differentiate from MTB and non-tuberculous mycobacteria (NTM can cause lung infection but not tuberculosis)
  3. Cannot differentiate between live and dead organisms
62
Q

Why is it beneficial to do a NAAT for suspected TB samples?

A

Rapid diagnosis of smear +ve, can prevent transmission of disease
Can detect Drug resistance mutations
Can do whole genome sequencing to accurately identify causative organism

63
Q

What are the advantages and disadvantages of tuberculin skin testing?

A

Advantages: relatively quick (2-3 days), easy, laboratory infrastructure not required, cheap

Disadvantages: subjective interpretation, false positives as tuberculin found in other mycobacteria, false negatives if T lymphocytes arent present (HIV/drugs)

64
Q

Why might a patient on treatment for Tb complain of orange urine?

A

Rifampicin can turn secretions/urine orange

65
Q

How is drug resistance of TB promoted?

A 
Improper drug regiments
Poor drug compliance
Diagnostic delays
Overcrowding
Inadequate infection control
66
Q

TB is a notifiable disease. What does this mean?

A

Doctors are legally obligated to notify public health England if a clinical diagnosis of Tb is made

67
Q

How is spread of TB prevented?

A

Contact tracing
Active case finding of symptomatic patients
Use of PPE in hospital
Use correct medication, in line with guidelines
Negative pressure isolation
Vaccination
Chemoprophylaxis of patients with latent TB

68
Q

What is the BCG vaccine?

A

A live attenuated Mycobacterium bovis strain vaccine used to treat tuberculosis. Very infective, protection wanes

69
Q

Who should not be given BCG vaccine?

A

HIV patients. As vaccine is live (attenuated) so canc abuse disease.

70
Q

why are multidisciplinary team decisions important when treating lung cancer?

A

As patients can present to a wide variation of departments, need to consider presentation of lung cancer as can be so variable

Respiratory Unit (12 decks)

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