Tuberculosis: Mycobacterium tuberculosis Flashcards
1) Understand the unique cell wall of MBT 2) Know the stages of the disease 3) Know the importance of adherence to therapy
Classify MTB
Large, non-motile rod-shaped bacterium
Obligate aerobe
Facultative intracellular parasite (macrophage)
Acid fast (no gram staining characteristics)
Serpentine cord colonies (from cord factor)
Name 4 strains of mycobacteria
1) M. bovis (cows)
2) M. avium (birds; seen in AIDS)
3) M. leprae
4) M. tuberculosis
What is significant about TB being a facultative intracellular parasite?
(this goes for all other bugs that are similar, i.e. chylamydia)
1) Hard to treat
2) Body uses cell-mediated immunity (Type IV)
3) People exhibit delayed-type hypersensitivity (Type IV)
**when doing an antigen test (PPD skin TB test), people who’ve been exposed will develop a nodule about a day later
What’re 3 components of the lipid cell wall of MTB?
1) Mycolic acid
2) Cord factor
3) Wax-D
Significance of mycolic acid?
Hydrophobic “shield” to prevent destruction by phagocytosis and complement.
**Also prevents staining and killing from antibiotics
Significance of cord factor?
1) Morphology (serpentine cording)
2) Toxic + inhibit neutrophil migration
- *more cord factor = more virulent
- *allows parallel growth of other bacteria
Significance of Wax-D?
Major component of Freund’s complete adjuvant
How does MTB gain access into macrophage?
Uses mannose receptors (LAM) or Fc receptors
What is the secreted protein that can wall off the immune system from MTB?
Antigen 85
How does MTB’s slow generation time contribute to it’s virulence?
It can grow “under the radar” of the immune system.
What does “TB infection” mean?
It means that MTB is in the body but the immune system is keeping it under control.
Are people with TB infection contagious?
NO.
People with TB infection are not infectious. You have to have TB disease to be contagious.
**TB infection = positive PPD skin test
What is the #1 predisposing factor for MTB infection?
HIV infection
How many stages of TB disease are there?
What is the frequency of people who progress through these stages?
5 stages.
**only 3-4% infected people progress to disease, and very few of those progress to stage 5
Which stage is defined by inhaling aerosolized droplet nuclei, followed by ingestion by alveolar macrophage?
How big are the most infective droplet nuclei?
Stage 1.
5 micrometers in diameter
Order these by which transmits the most droplet nuclei:
Coughing, talking, singing, sneezing
Sneezing > coughing > singing > talking
**sneezing is the worst since it projects the droplets about 10 feet
When does TB infection truly begin?
When droplets reach the alveoli.
**must be sufficiently small to reach it; larger droplets get trapped by airway cilia and do not cause infection
Which phase is characterized by MTB replicating in macrophages, bursting them, and then being swallowed by more recruited (but inactivated) macrophages?
Stage 2
**unactivated macrophages cannot destroy MTB
Which stage involves T-cell lymphocyte infiltration?
Stage 3
What do T-cells release to activate macrophages?
Interferon gamma
**this form cell-mediated immunity to kill MTB
Which stage does the infected person become tuberculin positive?
Stage 3
What is responsible for the pathological signs/symptoms of TB?
Cell-mediated immunity, which damages the body
What are the important cytokines that mediate the immune response to TB?
Interleukin-1 (stimulate fever and immune cells)
TNF (aka cachexin; responsible for the massive weight loss in patients)
Interferon-gamma (activate macrophages + stimulate presentation of infected cells)
At which stage does tubercle formation occur?
What is a tubercle?
Stage 3
Localized area of caseation necrosis (they’re big granulomas); has low pH and is anoxic, thereby preventing further MTB replication. However, MTB can hide there for a long time.
Which stage involves the growth of tubercles?
How does this happen?
Stage 4
MTB targets unactivated macrophages in the tubercle
If a tubercle grows big enough to invade a bronchus, what is the significance of this?
It can spread/disseminate to other parts of the lung or body.
What is the hematogenous extrapulmonary spread of TB called?
Miliary tuberculosis
*called this it will look like millet seeds
What are the most common sites of TB spread?
1) Genitourinary system
2) Bones (especially lower back)
3) Joints
4) Lymph nodes
5) Peritoneal cavity (i.e. the liver, intestines, etc)
What are the two types of lesions formed from miliary tuberculosis? Describe them.
What stage is this?
1) Exudative lesions: accumulated PMN around the tubercle, forming a “soft tubercle.” MTB replicates with no resistance.
2) Granulomatous lesions: body has a hypersensitivity reaction to tuberculoproteins, forming a “hard tubercle”
**This is all stage 4
Which stage involves the formation of a Ghon complex?
Describe this.
Stage 5
Tubercles/granulomas will liquefy/cavitate, allowing rapid extracellular replication of MTB, necrosis of the bronchi, and spilling of contents into the airways. These will eventually fibrous, heal, and calcify.
On a CXR, what is a Ghon complex? Ghon focus?
Ghon complex = calcified nodules or consolidations in the lung + hilar lymph nodes
Ghon focus = small calcified nodule/consolidation in the lung only (these are also called Simon focus)
Where in the lung does primary TB cause damage?
Where does reactivated/secondary TB cause damage?
Primary = upper part of the LOWER LOBES
Reactivated/secondary = lower part of the UPPER LOBES
What is multi drug-resistant TB (MDR TB)?
TB that is resistant to isoniazid and rifampicin, the first-line drugs of TB
What is extensively drug resistant TB (XDR TB)?
Rare type of TB that is resistant to isoniazid, rifampicin, any fluoroquinolone, and at least one other second line drug (amikacin, kanamycin, capreomycin)
Who gets MDR TB or XDR TB?
What method is in place to prevent this?
Patients who do not comply to their treatment regimens and HIV patients
This is the importance of Directly Observe Therapy
How do you diagnose TB?
1) Symptoms (esp. night sweats, weight loss, hemoptysis)
2) Signs (cachexia, consolidation, sterile pyruria, etc.)
3) PPD skin test (if positive, then it’s a latent infection, not active disease)
4) CXR
5) Patient history
6) Sputum samples
How do you treat TB?
6-9 months of **RIPE: rifampicin, isoniazid, pyrazinamide, ethambutol
- at least two drugs must be used.
- never add a single new drug
- Directly observe therapy
- Monitor toxicity
When is a patient no longer infectious?
1) Adequate multi-therapy
2) Respond well the therapy
3) 3 negative cultures
What is preventative treatment for TB? Why do this?
1) Take isoniazid 2x/week for 9 months
**keeps those infected from progressing to disease
