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Flashcards in Respiratory - TB Deck (24):
1

What bacterium causes TB?

TB is caused by mycobacterium tuberculosis. This is an acid-alcohol-fast bacillus (AAFB) that is positive on Siehl-Nielson staining.

Infection predominantly affects the lungs, lymph nodes and GIT.

2

What is the mode of infection of TB?

TB is commonly acquired as a result of infection from "open" cases due to inhalation or ingestion of infected material in the form of droplets in dust, food or milk. Routes of entry are:
1) Respiratory tract - by inhalation
2) Intestinal tract - by ingestion
3) Skin - by inoculation
4) Placenta - by transplacental spread

3

What factors predispose to TB infection?

1) Access of organism: close contact with open cases of disease - e.g. crowded unhygienic working and living conditions

2) Susceptibility: the old, very young, Black and Asian populations have an increased susceptibility

3) Nutrition: often a disease of the undernourished

4) Occupation: there is increased incidence of tuberculosis in some types of pneumoconiosis, particularly silicosis and in health workers

5) Other disease: pre existing chronic lung disease corticosteroid and other immunosuppressive and cytotoxic drugs, DM, alcoholism and most immunodeficiencies

This last group is also an important group of factors predisposing to reactivation of latent TB

4

What is primary TB? Describe where the infection localises to? What is the difference between a Ghon focus and a Ghon complex?

This pattern of disease is due to first infection of an individual with M.tuberculosis.

The lung is by far the most common primary site of infection. Other sites include the pharynx, larynx, skin and intestine. The primary parenchymal focus - Ghon focus - is usually situated subpleurally at the apex of the lower lobe or base of the upper lobe. This appears as a small circumscribed grey or white nodule with a soft necrotic caseous centre. It is associated with enlarged caseous hilar lymph nodes. The lung and lymph node lesions constitute the primary or Ghon complex.

5

What is the mechanism of primary TB?

In primary disease the organism causes a minimal polymorphonuclear inflammatory response in the tissue during the first 10 days. During the first 24 hours the polymorphs phagocytose organisms but do not kill them, and they drain these viable organisms into the regional lymph nodes.

At approximately 10 days a type 4 hypersensitivity cell mediated immune reaction develops to cell wall constituents - e.g. glycolipids. They cause decreased fusion of lysosomes and phagosomes and increased intracellular survival of organisms in macrophages.

Release of cytokines (e.g. IL-1, TNFa) from stimulated T cells, cells which form the constituents of the tubercle accumulate. There is activation of macrophages with enhanced killing of intracellular bacteria and surrounding tissue necrosis, both within the lesions at the primary site and in the involved lymph nodes.

6

What are the outcomes following primary TB?

Healing:
Vast majority of cases heal with fibrosis and eventual calcification and only 10% are symptomatic. Organisms may remain viable long term within the cells in the centre of the resulting scar. Reactivation - post primary TB - may develop from this.

Spread: (rare, common in infants and immunocompromised)
- Direct
- Bronchial
- Haematogenous

Blood dissemination of the organism occurs rarely from a primary complex.

7

Describe the direct spread of primary TB?

Direct spread of primary TB leads to progressive primary tuberculosis. It is the result of continued enlargement of the primary complex with local destruction of parenchyma. Pleural involvement can occur to produce an effusion or empyema. The lymph nodes can enlarge, obstruct bronchi and cause collapse and bronchiectasis of the distal lung.

8

What happens following bronchial spread of primary TB?

Erosion into the bronchial tree with spread of infectious material can produce:
1) Foci of infection in other parts of the lung
2) Tuberculous bronchopneumonia
3) Laryngeal TB, from coughed infected sputum
4) Intestinal TB, from swallowing infected sputum

9

How does haematogenous spread of TB occur?

Erosion into blood vessels can produce:
1) Foci of infection in other parts of the lung
2) Miliary TB - generalised
3) Single organ TB - e.g. bone, kidney, joint, brain

10

What is a tubercle?

The basic lesion of tuberculosis is the tubercle, this appears as a pinhead sized white or greyish minute focus in the tissues.

It has several layers:
1) A central zone of acellular caseous necrosis
2) A surrounding zone of large pale pink staining cells which are modified histiocytes - epithelioid cells
3) Langhans' giant cells derived from the the fusion of epitheliod cells with a characteristic peripheral distribution of the nuclei in a "horseshoe" arrangement
4) Lymphocytic rim of variable thickness
5) Peripheral zone of fibroblastic tissue merging with surrounding structures and increasing in amount with the age of the lesion

11

What is post primary TB?

Tuberculous infection occurring in a previously sensitised individual and due to: (1) reactivation of quiescent but viable organisms, or (2) inhalation of further organisms - reinfection.

12

What is the appearance of post primary TB?

Post primary TB usually begins in the apical segments of the lungs and consists of confluent caseous granulomas which spread directly and locally, but without lymph node lesions. This can either heal spontaneously with fibrosis and calcification - though viable organisms remain without producing a clinical symptoms - or spread to produce various types of progressive TB.

13

How can post primary TB spread?

1) Apical cavitating fibrocaseous tuberculosis - direct extension and continuing caseation and a progressive area of lung destruction ensures

2) Progressive cavitating pulmonary tuberculosis - initial apical infection may continue to spread by direct extension involving progressively more pulmonary parenchyma

3) Tuberculous bronchopneumonia - spread into the bronchial tree may establish new foci of infection throughout the lung or in highly sensitised individuals produce tuberculous bronchopneumonia

4) Miliary tuberculosis - erosion of a blood vessel or lymphatic involvement may disseminate the organisms into the blood to produce numerous systemic miliary tubercles in multiple organs - e.g. liver, spleen, kidney and meninges

5) Progressive isolated organ tuberculosis - when spread via blood or lymph occurs it may result in miliary disease but many or most organisms are rapidly destroyed by the immune system. The organisms may persist in specific isolated organs to produce continued progressive disease at those sites.

14

What are the presenting features of TB?

Symptoms occur relatively late and therefore in established disease. The earliest are non specific, such as malaise, fatigue, anorexia, and weight loss. Of more specific symptoms the most common is cough, often with mucoid sputum. Other symptoms include repeated small haemoptysis, pleural pain, fever, and exertional dyspnoea.

Signs also occur late in disease and are not very specific - e.g. crepitations (usually apical) and later signs of consolidation, pleural effusion and cavitation.

15

What groups are at risk of developing TB?

Clinical suspicion should be particularly high in in high risk groups:
- the hostel dwelling "down and out" and the alcoholic
- Pakistani and Indian immigrants (lymph node tuberculosis is common in Pakistani and Indian patients)
- diabetics
- patients with AIDS
- patients on immunosuppressive therapy (steroids or cytotoxic drugs)

16

How is TB diagnosed?

Ideally, the diagnosis is made by repeated examination for AAFB in sputum and bronchial washing on direct smear or culture. At least 3 sputum samples, including one early morning sample should be sent for culture and microscopy.

Tuberculin skin tests and interferon gamma assay are also used in the diagnosis of TB.

Tuberculosis is a notifiable disease in the UK

17

What are the immune based tests used to diagnose TB?

1) Tuberculin skin test: involve the detection of delayed type hypersensitivity reaction to a purified protein derivative (PPD) containing a mixture of antigens shared by several mycobacteria. In the Mantoux test PPD is inoculated by intracutaneous injection and the size of any skin reaction is measured after 48-72h.

2) IFN gamma assay: blood from the person being tested is incubated with mycobacterial antigens (including early secretory antigen target 6 (ESAT-6)) which are specific for mycobacterium tuberculosis and absent from the BCG vaccine strain. In people with latent or active TB, T lymphocytes within the blood sample produce interferon gamma as a marker for infection or active TB.

18

How is TB managed?

Admit patients who are sputum culture positive to a single room with negative pressure if multi-drug resistant TB is suspected.

Close contacts should be screened with CXR, Mantoux test and/or interferon gamma assay dependent on their age and BCG status.

People identified as having latent TB are usually treated with 3 months of rifampicin or isoniazid or 6 months of isoniazid.

TB is generally treated with a 6 month regime - 4 for 2, and 2 for 4.

19

What drugs are used to treat TB? What are their common side effects?

- Rifampicin: abnormal LFTs, colours bodily fluids pink/ red
- Isoniazid: given with pyridoxine, peripheral neuropathy and encephalopathy - these are extremely rare, occur in slow acetylators and respond to pyridoxine, often given prophylactically
- Pyrazinamide: hepatotoxic (rare but fatal)
- Ethambutol: optic neuritis with colour vision and acuity reduced
- Streptomycin: vertigo and nerve deafness. In the elderly and in the presence of raised blood urea, the dosage is reduced to maintain blood levels of 1-2mg/ml

20

What causes leprosy?

The other major mycobacterial pathogen is mycobacterium leprae causing leprosy. Both M.tuberculosis and M.leprae only affect humans

21

What are the clinical manifestations of leprosy?

Lepromatous leprosy (LL) is the most severe form of leprosy because patients CANNOT mount a cell mediated immune response to mycobacterium leprae. There is low cell mediated immunity and organisms are found everywhere (organs and blood).

Particularly affected are skin, nerves, eyes and testes. These are involved bilaterally with multiple skin lumps and bumps, leonine facies, saddle nose and peripheral neuropathy (with palpable nerves). There can also be digit absorption, blindness and infertility in men (from testicular damage).

Tuberculous leprosy (TL) occurs in patients with intact cell mediated immunity. It is difficult to isolate M.leprae from skin or blood and there is only limited skin and nerve involvement (1 or 2 superficial unilateral lesions).

Intermediate forms of leprosy BL, BB, BT represent a continuum between LL and TL.

22

How is leprosy treated?

1) Rifampicin
2) Dapsone
3) Clofazimine

NB - Leprosy reactions can occur with treatment

23

How is leprosy diagnosed?

M.leprae cannot be grown on artifical lab media. It can only be cultured in certain animals, such as mice foot pads, armadilos and Monkeys.

Skin or nerve biopsy will show acid fast bacilli (lepromatous) or granulomas (tuberculoid).

The Lepromin skin test is NOT useful for diagnosis but allows positioning of patients on the immunologic spectrum

24

In what patients does Mycobacterium avium-intracellulare affect?

1) In AIDS patients: disseminated infection with fever, weight loss, hepatitis, bone marrow suppression and chronic watery diarrhoea

2) In normal hosts (rare): pulmonary TB and cervical lymphadenitis

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