RESP 1 (TB) Flashcards
What is TB
TB IS A BACTERIAL DISEASE OF THE LUNGS
Caused by Mycobacterium tuverculosis is responsible for most cases of TB
Inhalation of TB into the lungs
IMPORTANT THINGS TO KNOW ABOUT TB
Involves “activated macrophages”
NEURTOPHILS ARE NOT INVOLVED AT ALL
Granulomatos (Chronic) Inflammation IS INVOLVED
How is it acquired?
Infection is caused by the prescence of organisms which may or may not cause significant disease
To be sick - you need ACTIVE disease in spectum (If you have the dormiant disease incapable of transmission)
Factors which predict the outcome of TB
- number of organisms inhaled
- Immune response (malnutrituin, old age, other diseases such as diabetes and steroids), immunosupressove therapy
AND the availability of antibiotics
Most COMMON - malnourished countries with underprivileged, drug dependence and overcrowding.
NOTE HIV and TB = LETHAL COMBO
Poor immunity often leads to MILARY TB or throughout the lung - TB BRONCHOPNEUMONIA)
Stages of TB
PRIMARY - first time of contact with the bacteria
SECONDARY - cannot develop without primary exposure
How is TB characterised?
TB is characterised by GRANULOMATOUS INFLAMMATION comprising of granulomas with a central area of CASEOUS NECROSIS surrounded by ACTIVATED MACROPHAGES, GIANT CELLS and LYMPHOCYTES.
It is a SPECIAL type of inflammation. The SECOND time you are infected the inflammatory response is HUGE.
PRIMARY TB
What is it?
Detailed process? (VERY DETAILED STEP BY STEP)
No previous exposure to the organism
GHON FOCUS in PERIPHERY of lung containing organisms and lymph node involvement = GOHN COMPLEX
PROCESS (VIP)
- inhaled mycobacteria enter macrophages by endocytosis
- naive macrophages cannot kill as the bacteria block the fusion of the phagosome and therefore bacteria PROLIOFERATE IN THE MACROPHAGE (Some macrophages carry organisms to lymph nodes (v bad as can go to blood)
- As the bacteria multiply, macrophages degrade some of the bacteria and present the antigen to T LYMPHOCYTES. Once response by TH1 cell mounted (3 weeks) = HYPERSENSITIVITY RESPONSE
- The TH1 produces INFEREON GAMMA which is a critical mediator and activates macrophages to become “bactericidal” (epitheliod macrophages” = CELL MEDIATED RESPONSE
- Inferon gamma increases concentration of lytic snzymes in macrophages and stimulates the formation fo the phagolysosome withing the infected macrophages and therefore anables the “activated Macrophages” to destroy the bacteria
ALSO.. T Helper cells play a crucial role in the formation of granulomas with much necrosis occuring.
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Summary of TB
= HYPERSENSITIVITY RESPONSE (Development of Activated T Lymphocytes responsive to the M TB antigen
= CELL MEIDATED RESPONSE (Development of activated macrophages capable of ingesting and destroying bacteria)
TAKES 3 WEEKS
This process in many people stops the infection before significant damage and tissue destruction. However, in some poor countries there is signficant tissue damage
HISTOLOGY OF A GRANULOMA
CENTRAL AREA OF NECROSIS (pale area)
MERGED MACROPHAGES (giant cell)
LYMPHOCYTES (purple dots)
See image PAGE 7 OF LECTURE SLIDES
Primary TB
OUTCOMES
Most people the LESION HEALS (90%) and they are asymptomatic
10% (malnourished) may spread throughout the body (pulmonary arteries) = MILIARY TB or erosion into the bronchi (Tuberculosis bronchopneumonia)
SECONDARY TB
FOLLOWS PRIMARY TB
May either be straight after TB or years later after host resistance is weakened and there is an activation or progression from primary disease.
Reactivation - dormant disease from OLD granulomas (which is usually the case e.g. cancer, HIV, chemotherapy)
Secondary TB - What presents?
APICAL LESION rather than GHON focus in one or both lungs
Appears in the APEX of the lungs - why? high 02 levels
Little lymph node involvement because of the pre-existing hypersensitivity and the prompt inflammatory response
The T-CELL CELL MEDIATED IMMUNE RESPONSE is now the TB antigen leading to tissue necrosis and the production of TUBERCULOUS CAVITIES and DESTRUCTION of lungs
Symptoms of SECONDARY TB?
Still may be asymptomatic
Some possible symptoms are related to CYTOKINES released by activated macrophafes (TNF and IL-1)include MALAISE, ANOREXIA, WEIGHTLOSS and FEVER
Progressive pulmonary involvement leads to increasing amounts of PURALENT SPUTUM and HAEMOPTYSIS
PLEURITIC PAIN (moving into plueral space)
What does SECONDARY TB look like?
Top of the lungs
WHITE HOLES AND NECROSIS
See Page 10
What are the OUTCOMES of SECONDARY TB?
Healthy? Healing of apical lesion by FIBROSIS and no further spread. COLLAGENOUS WALL (built by fibroblasts) WITH CALCIUM SALTS DEPOSITED ON EDGE
Poor Immune Response? Enlargement of Aypical lesion - DESTRUCTION OF LUNG
Lesion erodes blood vessels –> miliary spread, other organn involvement, haemoptysis
Lesion erodes airwayrs –. TB Bronchopneumonia
Lesion erods into pleura –> TB Empyema
UNTREATED - Must be treated is a wasting disease tht is EVENTUALLY FATAL.
IT CAN BE CURED WITH ANTIBIOTICS. STRAINS OF BACTERIA HAVE EMERGED!!!
