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3: MED1 Y3 - Respiratory [18] > [10] Tuberculosis > Flashcards

[10] Tuberculosis Flashcards

1
Q

What is tuberculosis?

A

An infectious disease

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2
Q

What organism causes TB?

A

Mycobacterium tuberculosis

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3
Q

What kind of bacterial species is M. TB?

A

An obligate pathogenic bacterial species

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4
Q

What covers the surface of M. TB?

A

A waxy coating

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5
Q

What is the waxy coating of M. TB due to?

A

The presence of mycolic acid

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6
Q

What is the clinical relevance of the waxy coating of M. TB?

A

It makes it impervious to gram-staining, so acid-fast stains such as Ziehl-Neelson must be used to visualise it under the microscope

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7
Q

Is M. TB anerobic or anaerobic?

A

Highly aerobic, requires high levels of oxygen

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8
Q

Where does TB affect?

A

Generally affects the lungs, but can also affect other parts of the body, including abdomen, bones, and nervous system

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9
Q

What is latent TB?

A

TB infection without symptoms

Most infections of TB are latent

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10
Q

What % of latent TB infections progress to active disease?

A

About 10%

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11
Q

What is the mortality of untreated active TB?

A

50%

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12
Q

How is TB spread from person to person?

A

Aerosol route

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13
Q

What is the result of TB being spread by the aerosol route?

A

The lungs are the first site of infection

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14
Q

What happens to most new infections of TB?

A

They resolve with local scarring

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15
Q

What is it called when TB resolves with local scarring?

A

Primary TB

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16
Q

What is post-primary T?

A

The development of infection beyond the first few weeks

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17
Q

What is it called when TB infection spreads throughout the body?

A

Miliary spread

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18
Q

Give an example of a localised infection that TB can develop into?

A

Meningitis

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19
Q

What happens to M. TB in the body?

A

It is ingested by macrophages

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20
Q

What happens once M. TB has been ingested by macrophages?

A

It escapes from the phagolysosome to multiply in the cytoplasm. At the same time, it provokes an immune response

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21
Q

What is the result of the immune response is provoked by M. TB?

A

It stimulates the release of IL-12, which in turn drives the release of IFN-gamma and TNF-alpha from NK and CD4 cells

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22
Q

What do the cytokines activated by the immune response stimulated by M. TB do?

A

They activate and recruit more macrophages to the site of the infection

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23
Q

What is the result of the recruitment of macrophages to the site of TB infection?

A

Formation of granulomas

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24
Q

What does the intense immune reaction stimulated by TB cause?

A
  • Cavitation in the lungs
  • Cytokine-mediated systemic effects, including fever and weight loss
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25
Q

What groups are at high risk of TB?

A
  • HIV
  • Silicosis
  • Malnutrition
  • People who live in overcrowded areas, e.g. prisons, homeless shelters
  • IV drug abusers
  • People with chronic lung disease
  • Those of Asian ethnicity
  • People with diabetes
  • People on corticosteroids or infliximab
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26
Q

By how much does HIV increase the risk of TB?

A

20-37x

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27
Q

What is the importance of TB in HIV patients?

A

TB is the leading cause of mortality and morbidity in HIV patients

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28
Q

Describe the symptoms in primary TB?

A

There are few symptoms, but lymph nodes may become enlarged in young people

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29
Q

What are the symptoms of secondary TB?

A
  • Fever
  • Chills
  • Night sweats
  • Loss of appetite
  • Weight loss
  • Fatigue
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30
Q

When do you get the fever in secondary TB?

A

Generally towards the of the day, or at night

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31
Q

How is TB investigated?

A
  • History and examination
  • Chest x-ray
  • Microbiology, e.g sputum sample
  • Nucleic acid amplification testing
  • Mantoux tuberculin skin test
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32
Q

What are the examination signs of TB?

A
  • Pallor
  • Pyrexia
  • Clubbing
  • Palpable lymph nodes
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33
Q

What may the CXR show in secondary TB?

A
  • Shadowing
  • Cavities
  • Consolidation
  • Calcification
  • Cardiomegaly
  • Miliary seeds
34
Q

What is the purpose of microbiology testing in TB?

A

Confirm the diagnosis

35
Q

What samples can be used in microbiology testing in TB?

A
  • Sputum
  • Pus
  • Tissue biopsy
36
Q

What is the problem with microbiological testing in TB?

A

The culture process is difficult because TB is a slow growing organism, and can take 2-6 weeks as a result

37
Q

What is the result of microbiological testing to confirm a diagnosis of TB taking a long time?

A

Treatment is often begun before cultures are confirmed

38
Q

What allows for rapid diagnosis of TB?

A

Nucleic acid amplification tests

39
Q

Why are nucleic acid amplification tests not routinely used in the diagnosis of TB?

A

Because they rarely alter how a person is trated

40
Q

What is the Mantoux tuberculin skin test often used for?

A

To screen people at high risk for latent TB

41
Q

What happens in the mantoux TB skin test?

A

Tuberculin is injected intradermally

42
Q

How long does a result from the Mantoux tuberculin test take to obtain?

A

48-72 hours

43
Q

What happens in the Mantoux tuberculin test if a person has been exposed to the tuberculosis bacteria?

A

They will maintain an immune response in the skin, producing an induration (palpable raised, hardened area) on the forearm at the injection site

44
Q

How is a Mantoux tuberculin test result read?

A

By measuring the diameter of the induration across in mm

45
Q

What is a positive result in the Mantoux tuberculin skin test?

A

The persons risk factors determine whether 5mm, 10mm, or 15mm constitutes a positive result

46
Q

What might give a false positive result to the Mantoux tuberculin skin test?

A
  • If the person has had a BCG vaccination
  • Sarcoidosis
  • Hodgkin’s lymphoma
  • Malnutrition
  • Active TB
47
Q

What antibiotic regime is used in TB?

A

Patients are given rifampicin, isoniazid, pyrazinamide, and ethambutol for 2 months, and then continue rifampicin and isoniazid are continued for a further 4 months

48
Q

Why are multiple drugs used in the management of TB?

A

To combat resistance

49
Q

Which of the tuberculosis drugs are associated with liver toxicity?

A
  • Isoniazid
  • Rifampicin
  • Pyrazinamide
50
Q

What should be done as a result of the association of liver toxicity with the TB drugs?

A
  • Liver function should be checked before traetment with these drugs
  • Those with pre-existing liver disease or alchol dependance should have frequent checks, particularly in the first 2 months
51
Q

What is a common side effect of rifampicin in the first 2 months?

A

It causes a transient disturbance in liver function with elevated transaminases

52
Q

Does the transient elevation of liver enzymes with rifampicin require a change in treatment?

A

No

53
Q

What should be done regarding kidney function when on tuberculosis drugs?

A

Kidney function should be checked before treatment with antituberculous drugs, with appropriate dose adjustments made

54
Q

What tuberculosis drug should be avoided in renal impairment?

A

Ethambutol

55
Q

What should be done if ethambutol is used despite renal impairment?

A

The dose should be reduced and plasma-drug concentration measured

56
Q

What is isoniazid?

A

A synthetic analoge of pyridoxine

57
Q

How efficacious is isoniazid compared to other anti-TB drugs?

A

It is the most efficacious of the anti-TB drugs

58
Q

Is isoniazid ever used as a single agent in TB?

A

No

59
Q

Is isoniazid administered in its active form?

A

No, its a prodrug

60
Q

What activates isoniazid in the body?

A

KatG

61
Q

What is the target for the action of isoniazid?

A

InhA and KasA

62
Q

What are InhA and KasA?

A

Enzymes that are found within the unique type II fatty acid synthase system involved in the production of mycolic acids

63
Q

Where are mycolic acids found?

A

In the cell wall of M. TB

64
Q

How does isoniazid stop the production of mycolic acid?

A

It covalently binds to the InhA and KasA enzymes, which are essential for the synthesis of mycolic acid

65
Q

What are the therapeutic uses of isoniazid?

A

It is specific for the treatment of TB

66
Q

Why is isoniazid not used as a single agent in the treatment of TB?

A

When used alone, resistance quickly emerges

67
Q

What causes resistance of TB to isoniazid?

A

Resistance is associated with several different chromosomal mutations, each of which results in one of;

  • Mutation or deletion of KatG, producing mutants incapable of prodrug activation
  • Varying mutations of acyl carrier proteins
  • Over expression of InhA
68
Q

Is the incidence of adverse effects with isoniazid high or low?

A

Low

69
Q

What are the adverse effects of isoniazid related to?

A

The dosage and duration of administration

70
Q

What are the adverse effects of isoniazid?

A
  • Peripheral neuritis
  • Hepatitis
  • Drug interactions
  • Optic neuritis
71
Q

How does peripheral neuritis caused by isoniazid manifest?

A

As parasthesia of the hands and feet

72
Q

When is parasthesia caused by isoniazid more likely to occur?

A

If there are pre-existing risk factors, such as diabetes, alcohol dependance, or pregnancy

73
Q

How can peripheral neuritis caused by isoniazid be corrected?

A

By supplementation of 25-50mg/day of pyridoxine

74
Q

Who is the adverse effect of hepatitis caused by isoniazid more common in?

A
  • Older patients
  • Those who take rifampicin
  • Those who drink alcohol daily
75
Q

Why can isoniazid cause drug interactions?

A

Because it inhibits the metabolism of phenytoin

76
Q

What do hypersensitivity reactions to isoniazid include?

A

Rashes and fever

77
Q

Is isoniazid readily absorbed after oral administration?

A

Yes

78
Q

What impairs the absorption of isoniazid?

A
  • If taken with food, particularly carbohydrates
  • Aluminium containing antacids
79
Q

What can isoniazid diffuse into?

A

All body fluids, cells, and caseous material

80
Q

What is caseous material?

A

Necrotic tissue that is produced in TB

81
Q

How do isoniazid levels in the CSF differ to in the serum?

A

They are about the same

82
Q
A

3: MED1 Y3 - Respiratory [18] (15 decks)

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