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

[10] Tuberculosis Flashcards

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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
What groups are at high risk of TB?
* 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
26
By how much does HIV increase the risk of TB?
20-37x
27
What is the importance of TB in HIV patients?
TB is the leading cause of mortality and morbidity in HIV patients
28
Describe the symptoms in primary TB?
There are few symptoms, but lymph nodes may become enlarged in young people
29
What are the symptoms of secondary TB?
* Fever * Chills * Night sweats * Loss of appetite * Weight loss * Fatigue
30
When do you get the fever in secondary TB?
Generally towards the of the day, or at night
31
How is TB investigated?
* History and examination * Chest x-ray * Microbiology, e.g sputum sample * Nucleic acid amplification testing * Mantoux tuberculin skin test
32
What are the examination signs of TB?
* Pallor * Pyrexia * Clubbing * Palpable lymph nodes
33
What may the CXR show in secondary TB?
* Shadowing * Cavities * Consolidation * Calcification * Cardiomegaly * Miliary seeds
34
What is the purpose of microbiology testing in TB?
Confirm the diagnosis
35
What samples can be used in microbiology testing in TB?
* Sputum * Pus * Tissue biopsy
36
What is the problem with microbiological testing in TB?
The culture process is difficult because TB is a slow growing organism, and can take 2-6 weeks as a result
37
What is the result of microbiological testing to confirm a diagnosis of TB taking a long time?
Treatment is often begun before cultures are confirmed
38
What allows for rapid diagnosis of TB?
Nucleic acid amplification tests
39
Why are nucleic acid amplification tests not routinely used in the diagnosis of TB?
Because they rarely alter how a person is trated
40
What is the Mantoux tuberculin skin test often used for?
To screen people at high risk for latent TB
41
What happens in the mantoux TB skin test?
Tuberculin is injected intradermally
42
How long does a result from the Mantoux tuberculin test take to obtain?
48-72 hours
43
What happens in the Mantoux tuberculin test if a person has been exposed to the tuberculosis bacteria?
They will maintain an immune response in the skin, producing an induration (palpable raised, hardened area) on the forearm at the injection site
44
How is a Mantoux tuberculin test result read?
By measuring the diameter of the induration across in mm
45
What is a positive result in the Mantoux tuberculin skin test?
The persons risk factors determine whether 5mm, 10mm, or 15mm constitutes a positive result
46
What might give a false positive result to the Mantoux tuberculin skin test?
* If the person has had a BCG vaccination * Sarcoidosis * Hodgkin's lymphoma * Malnutrition * Active TB
47
What antibiotic regime is used in TB?
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
Why are multiple drugs used in the management of TB?
To combat resistance
49
Which of the tuberculosis drugs are associated with liver toxicity?
* Isoniazid * Rifampicin * Pyrazinamide
50
What should be done as a result of the association of liver toxicity with the TB drugs?
* 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
What is a common side effect of rifampicin in the first 2 months?
It causes a transient disturbance in liver function with elevated transaminases
52
Does the transient elevation of liver enzymes with rifampicin require a change in treatment?
No
53
What should be done regarding kidney function when on tuberculosis drugs?
Kidney function should be checked before treatment with antituberculous drugs, with appropriate dose adjustments made
54
What tuberculosis drug should be avoided in renal impairment?
Ethambutol
55
What should be done if ethambutol is used despite renal impairment?
The dose should be reduced and plasma-drug concentration measured
56
What is isoniazid?
A synthetic analoge of pyridoxine
57
How efficacious is isoniazid compared to other anti-TB drugs?
It is the most efficacious of the anti-TB drugs
58
Is isoniazid ever used as a single agent in TB?
No
59
Is isoniazid administered in its active form?
No, its a prodrug
60
What activates isoniazid in the body?
KatG
61
What is the target for the action of isoniazid?
InhA and KasA
62
What are InhA and KasA?
Enzymes that are found within the unique type II fatty acid synthase system involved in the production of mycolic acids
63
Where are mycolic acids found?
In the cell wall of *M. TB*
64
How does isoniazid stop the production of mycolic acid?
It covalently binds to the InhA and KasA enzymes, which are essential for the synthesis of mycolic acid
65
What are the therapeutic uses of isoniazid?
It is specific for the treatment of TB
66
Why is isoniazid not used as a single agent in the treatment of TB?
When used alone, resistance quickly emerges
67
What causes resistance of TB to isoniazid?
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
Is the incidence of adverse effects with isoniazid high or low?
Low
69
What are the adverse effects of isoniazid related to?
The dosage and duration of administration
70
What are the adverse effects of isoniazid?
* Peripheral neuritis * Hepatitis * Drug interactions * Optic neuritis
71
How does peripheral neuritis caused by isoniazid manifest?
As parasthesia of the hands and feet
72
When is parasthesia caused by isoniazid more likely to occur?
If there are pre-existing risk factors, such as diabetes, alcohol dependance, or pregnancy
73
How can peripheral neuritis caused by isoniazid be corrected?
By supplementation of 25-50mg/day of pyridoxine
74
Who is the adverse effect of hepatitis caused by isoniazid more common in?
* Older patients * Those who take rifampicin * Those who drink alcohol daily
75
Why can isoniazid cause drug interactions?
Because it inhibits the metabolism of phenytoin
76
What do hypersensitivity reactions to isoniazid include?
Rashes and fever
77
Is isoniazid readily absorbed after oral administration?
Yes
78
What impairs the absorption of isoniazid?
* If taken with food, particularly carbohydrates * Aluminium containing antacids
79
What can isoniazid diffuse into?
All body fluids, cells, and caseous material
80
What is caseous material?
Necrotic tissue that is produced in TB
81
How do isoniazid levels in the CSF differ to in the serum?
They are about the same
82

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

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