Tuberculosis Flashcards
explain the pulmonary and bronchial circulation
Pulmonary artery
- closely follows the airways and functions to pass deoxygenated blood through the capillary beds surrounding the alveoli and very quickly exchanges gases
- as the pressure with the pulmonary circulation is much lower than the systemic circulation the vessels have thinner walls
- pulmonary arteries have an important role in shunting to the most effectively ventilatde areas of the lungs to maximise gas exchange
Pulmonary vein
- do not closely match the airway bronching pattern within the lungs, thus do not run in matching patterns to the pulmonary arteries
- they collect oxygenated blood from the alveolar capillary beds and venules and drain via the intersegmental regions (follow the fibrous septa), where they receive connections from adjoin segments
Bronchial artery
- small branches off the aorta or nearby intercostal arteries that supply the primary bronchi and enter the lungs with the pulmonary arteries which follow the general course of the pulmonary arteries but have a different distribution
- blood supply is mostly for regions of the lung that are not near the highly oxygenated blood in the pulmonary system (eg airways, septa and visceral pleura)
- like any other systemic arteries in the body, they carry high pressure blood
Bronchial veins
- retrace the pathawys of the broncial arteries and drain with other thoracic structures into the azygous and hemiaxygous veins
what is haemoptysis
- expectorations (coughing up) of blood stained sputum from the bronchi, larynx, trachea or lung (Eg in TB or other respiratory infections or cardiovascular pathologies)
can be fatal because of asphyziation or haemorrhage
what are the aetiologies of haemoptysis
acute infection chronic bronchitis bronchiectasis lung abscess TB carcinoma mitral stensosi/congeintal heart disease autoimmune disease
degrade into the capillaries then blood leaks
how does TB cause haemoptysis
TB causes haemoptysis by causing necrotic lesions within lung parenchyma which may rupture blood vessels - blood enter airway also mechanism for haematogenous dissemination involving AFBs entering venous return –> systemic circulation
what are the risk population groups in Australia for TB
- low socioeconomic groups
- homeless
- alcoholics
- recent migrants from high risk areas
- immunocompromised
what is the epidemiology of TB
- TB is estimated to affect 1.7 billion individuals worldwide, with 8-10 million new cases per year and 1.3 million deaths per year
- infection with HIV makes people susceptible to rapidly professive tuberculosis, there is approx 50 million people infected with both
- major infectius disease proble worldwide - decreased incidence in australia
what is the microbiology behind TB
Mycobacterium tuberculosis, M bovis (human, bovine strains) - aerobic - no endo or exotoxins - virulence related to capsular glycolipids - nonspore forming - nonmotile - acid fast bacilli - gram positive routes of infection: inhalation
explain the immune response in TB
the immune response to TB is an example of cell mediated immunity
- Th1 cells drive the activation of macrophages and enhance intracellular killing through release of IFNy and CD40 ligand –> CD8 T cell play a role by destroying frustrated macrophages by cytotoxic means cause release of AFB in attempt to kill fresh macrophages
- MTb has proteins that are able to prevent the phagolysosome from forming or forcing it to burst. this allows the organism to escape from the degrading enzyme and continue to expand and grow in the cytoplasm of the macrophage. the macrophage become frustrated and recruit surrounding macrophages to excentually form a giant cell (huge cytoplasm with numerous nuclei) - proinflmmatory and grnulomtous autorecruited
- Th17 cells drive granuloma formation by induction of large numbers of phenotypically altered netrophils –> secret IL17 - Il17 neutrophil recrutiment if excessive –> exaggerated response if not sufficient - more likely that TB is not controlled or contained therefore balance between Th1 and Th17 cell function is critical
- Th17 cells play a role in host defenses against extracellular pathogens by mediating the recruitment of neutrophils and macrophages to infected tissue. moreover, it has become evident that aberrant regulation of Th17 cells may play a significant role in the pathogenesis of multiple inflammatory and autoimmune disorders, changing the homeostasis and phenotype of neutrophils and making them more likely to cause immunopathology
explain the pathology behind TB (macro and microscopic features)
Macroscopic: caseation necrosis and fibrosis
Microscopic
- necrotising granulomatous inflammation, gruloma in TB = tubercle, central necrosis without residual cell outlines (Compared with coagulative necrosis), usually containing acid fast bacilli in ZN stains, surround by activated epitheliod macrophages and giant cells including langhan’s cells outer layer of lymphocytes and fibrosis
explain the pathogenesis of TB
virulence factors (all to do with cell surface structure, assisting to evade immune system)
- waxy coat: protects against macrophage killing
- cord factor: surface glycolipid allowing organism to form cords (prevents fusion between macrophages containing MTb and lysosomes)
- Lipoarabinomanna (LAM): inhibits macrophage activation
- induces delayed (type IV) hypersensitivity the major culprit of damage
Bacillus resides in lysosomes but are not killed
initially there is a nonspecific inflammatory reaction, followed by a granulomatous response in 2-3 weeks. the centre of granulomas become caseous (necrotic)
explain the natural history and clinical presentation of primary infection with MTb
primary infection occurs in previously unexposed individuals
organisms enter the lung via inhalation of aerosolised droplets during person-to-erson contact. MTb only requires a small amount of inoculum to cause the disease, however, a relatively large number of organisms are required for smear postivity
healed lesion
- once in the lung, alveolar macrophages ingest bacilli and destroy them. most individuals are asymptomatic or experience only a mild inflamamtory illness and recover without disease. in these cases there has been successful induction of a cell mediated respinse
- the infection is localised to the peripheral lung parenchyma in a ‘tubercle’ formed from coalescing granulomata. this is known as a gohn focus. usually the gohn focus is necrotic in its center and organisms drain to the hilar lymph nodes, forming the Gohn complex
- dystrophic calcification leads to the characteristic xray appearance (ranke complex)
active infection
- MTb may resist intracellular killing and actively impede fusion with the lysosome. once the organism has evaded the initial destruction will multiply and cause disruption of macrophages and may manifest as an active TB disease
- if the infection cannot be controlled, it will result in systemic bacteraemia. macrophage activation results in secretion of IL-12 and MHC-II mediated presentation to CD4+ T cells, which enter a Th1 profile and secrete IFNy that induced further macrophage activation resulting in superoxide incuded killing and release TNFa –> chronic inflammation
- during a chronic inflammatory response, blood monocytes accumulate at the infection site. as MTb grows logarithmically with normal tissue damage, antigen specific T lymphocytes migrate to the infected side and multiply within the early tubercles, releasing pro-inflammatory cutokines such as IFN-y, activating macrophages to kill the intracellular MTb. this inflammatory response is a grnuloma = Typy IV hypersensitivity
Immunity to MTb
- T cell mediated immunity develops after two or three weeks of infection. during this time bacillary growth stops and the central dense necrosis in the granulomata primary lesion contians the extracellular growth of mycobacteria both dormant and non-viable
- minimally active MTb also infects lung parenchyma. this phase of infection is known as the latent phase where growth of mycobacterium is put in check
- reactivtion of latent TB can occur years afterwards when the immune system is weakened
- failure to kill MTb during primary infection can result in - latent disease and acute disease (proressive primary tuberculosis)
explain the natural history and clinical presentation of secondary TB
- arises in previosuly sensitised individuals that may be due to either reactivation or reinfection
clinical presentation - cavitating lesions in the apices of the upper lobes accompanied by: caseation, fibrosis, airway dissemination, possible lymphoaemoatogenous spread
existence of presensitised immunity may result in a rapid and massive response with less LN involvement. lymph
explain the natural history and clinical presentation of secondary TB
- arises in previosuly sensitised individuals that may be due to either reactivation or reinfection
clinical presentation - cavitating lesions in the apices of the upper lobes accompanied by: caseation, fibrosis, airway dissemination, possible lymphoaemoatogenous spread
existence of presensitised immunity may result in a rapid and massive response with less LN involvement. lymphatic drainage may lead to seeding of the right side of the circulation with military TB appearing in the lungs, as well as systemic miliary TB and extrapulmonary disease
what organs can be affected by extrapulmonary disease
cervical lymph node involvement bone esp the vertebrae kidney mmininges adrenals fallopian tubes/epididymis
cytokine - IL-1, TNFa can cause
IL1 - malaise, anorexia, fever
TNFa- wasting
