Tuberculosis Flashcards

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1
Q

What is the organism responsible for TB?

A

Mycobacterium tuberculosis

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2
Q

What is the name of the stains that can stain the mycobacterium tuberculosis bacteria?

A

Ziehl Neelsen Stain - most common

Auramine staining - not as specific as the Ziehl Neelsen stain

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3
Q

What are the other subtypes of Mycobacteria?

A
M.Tuberculosis 
M.Bovis 
M.Kansasii
M.Chelonae
M.Abscessus 
M.Fortuitum
M.Leprae 
Some are environmental and some are fast growing
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4
Q

How does TB become an established infection?

A
M.Tuberculosis is inhaled into the lungs. Cavities open into the bronchi allowing the spread of the bacteria through coughing 
Haematogenous spread (occur in most people). This can progress to the next stage if reactivated (which some people get immediately)
- cavitary TB
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5
Q

What is a Ghon Focus?

A

A primary lesion (usually sub-pleural) caused by mycobacterium tuberculosis.

  • found in the mid to lower zones of the lungs
  • developed in a nonimmune host
  • occurs in primary tuberculosis
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6
Q

Once someone has inhaled the bacteria and become infected, what two things can happen to them?

A

Immediately develops a primary infection

No initial infection occurs and the disease remains latent within the body

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7
Q

Describe the pathogenesis of a primary TB infection.

A

The bacteria end up in the alveoli where they are recognised as foreign and are attacked by macrophages
The macrophages engulf the bacteria and try to dissemble them, but given the microbiology of TB, this doesn’t work
The surviving bacteria hijack the macrophages and infect them, while also increasing the bacteria population.
The bacteria within the macrophages then multiply until they burst, causing extracellular infection
The infected area becomes a granuloma (a wall of macrophages designed to contain the infection)
- the cells within the centre of this start to be killed by the bacteria, causing a necrotising centre = blood and sputum in the lungs

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8
Q

Once a granuloma has formed in the lungs, what happens to the infected person?

A

Most cases
- necrotising lesions heal with some scarring and calcification
- disease hasn’t gone, just become latent (for years/decades)
- less than 10% of these progress to secondary TB (80% of active TB cases)
Or the host can’t contain the infection -> secondary TB

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9
Q

Describe the pathogenesis of secondary TB.

A

The host tries to contain the growing infected areas by killing off the tissue around them and deploying T-cells - leads to inflammation
The bacteria still attack the immune system cells leading to steadily growing areas infested with bacteria known as tubercles
- these can break off and travel through the blood and cause extrapulmonary TB infections
- in some cases the tubercles liquefy, causing bacteria-rich environments and thick sputum. The lungs then fill with free floating bacteria and clusters in the linings of the lungs

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10
Q

What is miliary TB?

A

Widespread dissemination of the bacteria via haematogenous spread
Looks like seeding of TB bacilli in the lung on an X-Ray
Makes up 1-3% of all TB cases

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11
Q

What are the three clinical categories of CNS TB?

A

TB meningitis
Intracranial tuberculoma - appears as abscesses in the brain on MRI
Spinal tuberculous arachnoiditis

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12
Q

Briefly describe renal TB.

A

Multiple granuloma form at the site of metastatic foci (typically bilateral and adjacent to the glomeruli and may remain inactive for decades)
Although both kidneys are seeded, clinically significant disease (capillary rupture and delivery of proliferating bacilli to the proximal tubules) usually only develops in one kidney

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13
Q

Describe what you would expect to see in a mycobacterium tuberculosis granuloma biopsy.

A

Giant cells as the body tries to remove the infection - multinuclear
Lymphocytes
Epitheliod cells
Caseous necrosis

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14
Q

How can a person be immune to mycobacterium tuberculosis?

A

Cell mediated immunity is the most important aspect of this

  • macrophages are the key controlling cell
  • T cells produce interferon gamma
  • cytokines also help destroy the bacteria
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15
Q

Why doesn’t our immune response normally clear the mycobacterium tuberculosis bacteria?

A

Once the macrophage tries to engulf the bacteria, a protein called Ptpa is secreted
- this disables the mechanisms of the macrophage to create an acidic environment in which to destroy the bacteria

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16
Q

How does the Mantoux test determine if someone has TB or not?

A

Tuberculin (a glycerol extract of the tubercle bacillus) is injected intradermally in an individual.
If the patient has been exposed to the bacteria, then they mount an immune response against the protein in the skin
If the immune response was activated, the person gets a hard, raised area on the skin.
- if there is no raised area, then the person doesn’t have/has never had the bacteria

17
Q

How does the Spot test diagnose TB?

A

This test counts the number of anti-mycobacterium effector T cells that produce interferon gamma in a sample of blood
- using mycobacterium tuberculosis-specific antigens
This gives an indication of the host immune response against mycobacteria, revealing the presence of mycobacterium tuberculosis
This test is fast, not influenced by any previous BCGs and can detect latent TB

18
Q

Why is the drug treatment of tuberculosis so long and contain so many different drug classes?

A

Long duration (6 months) as the antibiotics have to penetrate the granuloma
Combination of drugs used to reduce risk of resistance
- at least two drugs to which the bacilli are sensitive must be present
- some drugs are only effective when bacilli are dividing rapidly (lack effect against slower growing forms)

19
Q

What antibiotics are given for treatment of TB?

A

Rifampicin - used for the full 6 months (most effective treatment)
Isoniazid - used for the full 6 months (most effective treatment)
- also give prophylactic pyridoxine to prevent neuropathy
Pyrazinamide - only works on fast growing types, so is dropped after two months
Ethambutol - stop this if it is sensitive to Rifampicin and isoniazid

20
Q

Describe the toxic side effects of the treatments for TB.

A

Rifampicin induces cytochrome P450 and thus alters metabolism of many drugs (e.g. Steroids). It also turns the urine reddish
Rifampicin, isoniazid and pyrazinamide are all metabolised in the liver - so there is a potential for toxicity
Ethambutol can affect vision