Tuberculosis Flashcards
What is the epidemiology of tuberculosis?
Tuberculosis is most common in lower and middle income countries, especially in areas with a high incidence of HIV. Within the UK, socially deprived areas and ethnically diverse areas tend to have higher cases and has resulted in recent increases in cases due to migration.
Which groups of people have a higher incidence of TB?
People with limited access to healthcare such as:
Alcoholics
Homeless people
Prison inmates
Intravenous drug users
Chronic conditions which reduce the immune system function
What is the epidemiology of TB in the UK?
There are greater cases of tuberculosis in the south of England, especially London which has the highest number of cases due to ethnic diversity and migration greatest here, from countries with a high TB incidence and social deprivation.
What is the Tuberculosis pathogen?
It is a gram positive bacilli mycobacterium, with a cell wall containing a waxy coat formed of mycolic acid which makes it acid fast and resistant to Kiehls-Nelson stain and remain bright red.
It is an obligate aerobic bacterium which requires oxygen to survive and therefore colonises the lungs.
How does the body deal with tuberculosis?
Alveolar macrophages take up tuberculosis pathogen and form a phagosome and fuse with a lysosome to degrade it and cleared from the body.
However, TB may inhibit the lysosome fusion and
1) Lay dormant and result in TB latency
2) Become a primary progressive disease
3) Successive clearing of TB, with scar formation of Ghon focus
How is the immune defence to tuberculosis generated?
Main agent involved in immunity to tuberculosis is macrophage phagocytosis and the inflammatory cytokines:
IFN-gamma
TNF-alpha
What is the role of IFN-gamma?
Increases macrophage activation for phagocytosis of tuberculosis.
What is the role of TNF-alpha?
Produced by macrophages which affects cells by causing apoptosis or death.
What is latent TB infection?
Lack of clinical disease but evidence of an immunological response to tuberculosis. They are not able to pass on tuberculosis to others.
What is secondary tuberculosis?
Latent infection of tuberculosis results in reactivation in later life when immunosuppression occurs or older age.
Which conditions increase the risk from tuberculosis reactivation?
There is the greatest risk of TB reactivation with conditions associated with immune suppression:
HIV is the most major factor
Organ transplant
Silicosis
Chronic renal failure
TNF-alpha blocker therapy
Diabetes
Under nutrition
What is Gohn focus?
Localised area of caseous necrosis in the mid to lower zones of the lungs within the sub pleural space.
It is caused by a resolved primary infection of TB where lysosome inhibition of the macrophage so the macrophages will try to contain the mycobacterium tuberculosis by clustering together at the site to form a granuloma. The tissue in the granuloma dies and causes caseous necrosis.
What is the pathogenesis of TB?
Inhalation of droplet nuclei of tuberculosis after prolonged exposure with an infected person who is coughing, sneezing or talking. The nuclei proliferate in the alveolar space or within macrophages after inhibiting lysosome fusion and the host has no defense for the first few weeks.
It typically affects the upper lobes or the upper part of the lower lobes.
What is silicosis?
Pulmonary fibrosis caused by the inhalation of silica dust, typically occurring in occupations with construction work. Which can result in shortness of breath and persistent cough. The timecourse of development depends on the level of exposure but this is typically after 5-10 years.
Why does chronic renal failure increase TB risk?
Kidneys are responsible for immune homeostasis and Renal failure results in systemic inflammation and immune cell deficiency.
What is caseous necrosis?
Death of cells results in a hard, cheese-like appearance which tends to occur in the lung cells. Caseous necrosis is unstable in the lungs and tends to liquify, making it a type of exudative tissue reaction.
In Secondary TB, a cavity forms called cavitating necrosis when it involves the wall of the airway.
What is the composition of a granuloma?
Collection of macrophages and foamy cells (macrophages with lipids) which fuse together during infection to form a multi nucleated Langhan giant cell. The individual macrophages resemble epithelia and are called epithelioid macrophages. Granuloma formation occurs after phagocytosis of the pathogen and release of TNF by the macrophage, and expression of adhesion molecules on macrophage surface.
What is the hilum of the lung?
Located between 5th-7th vertebrae in centre of medial lung surface where pulmonary artery, pulmonary vein and bronchial arteries enter the lungs.
What are the hilar lymph nodes?
Located close to the lymph nodes near the bronchi and the pulmonary vasculature. Enlargement of these due to TB infection can result in erosion towards the bronchi and result in bronchial collapse or distal atelactasis.
What is the Ghon complex?
Formation of Ghon focus and enlargement of hilar lymph nodes due to Primary TB infection, results in hypersensitivity and necrosis. When this calcifies, it becomes a Ranke complex.
