Tuberculosis Flashcards
TB
Bacterial disease caused by rod shaped mycobacterium
Mycobacteria
Mycobacterium tuberculosis Slow Growing Rod shaped 02 rich environment (e.g. lungs) Lipid rich walls Waxy coat- prevents penetration of toxic compounds
TB Spread
Air- cough, sneeze
Epidemiology
1 in 3 infected
Healthy people- contain it in inactive form
Bacteria active when person’s immunity reduced- HIV, age
Classification
Difficult + slow to grow in culture
Require Lowenstein-Jensen media
M. leprae
Can’t be grown in vitro
V slow- doubling time is 2 weeks
Primary TB
Inhaled mycobacteria settle in middle regions of lung, just under pleura –> O2 rich
Excite acute inflammatory response from neutrophils
–> neutrophils phagocytose bacteria, sequester them in intracellular phagosome
Healthy vs immunocompromised response to TB
Healthy- release toxic compounds into phagosome + kill bacteria
Immunocompromised- neutrophils can’t destroy bacteria as have waxy coat that prevents penetration of toxic compounds
Immunocompromised Primary TB
Neutrophils release cytokines when fail to kill bacteria
Neutrophils die –> caseous necrosis
Bacteria survive in caseous tissue
Cytokines attract macrophages + T cells to area
Macrophages accumulate in rings around caseous tissue –> start to phagocytose bacteria
Soma bacteria killed but some survive even in macrophages
Macrophages can fuse to form giant cells –> more effective at attacking bacteria
Macrophages release more cytokines –> attract lymphocytes
Lymphocytes form layer around macrophages
Outer wall of fibroblasts form
Granuloma
Accumulation of macrophages + other cells
Wall off/contain TB and stop it spreading
Ghon Focus
Granuloma around a tuberculous necrotic centre
Calcium deposited in outer layer of focus (collagen layer) –> can be seen on X ray
Langhans cells
Giant cells formed by macrophages being fused together in granuloma
Ghon Complex
Calcified Ghon focus and any associated affected lymph node
Chest X Ray
Opacities, mainly in upper zone, with a patchy or nodular appearance
Cavitation
Calcification
Hilar shadowing
Miliary TB
Diffuse nodular shadowing
Post-primary TB
Bacteria remain alive in Ghon Complex
Later if patient immunocompromised, bacteria escape + TB symptoms recur
Open or active TB
Bacilli in sputum
Active TB signs
Fever Malaise Weight loss Night sweats Cough Haemoptysis Chest pain
Bronchus TB
Tuberculosis Bronchopneumonia
Vessel TB
Miliary or isolated organ TB
TB Diagnosis - Constitutional signs
Fever
Malaise
Weight loss
Night sweats
TB Diagnosis- Focal signs
Cough
Haemoptysis
Chest pain
TB Diagnosis
Signs Chest X Ray Sputum swab Sputum sample culture Skin test
Extrapulmonary spread
15-20% cases of active cases of progressive primary TB
Infection spread outside lungs –> other kinds of TB
More common in immunosuppressed + young children
Occurs in more than 50% in those with HIV
Extrapulmonary spread sites
Pleura- TB pleurisy CNS- TB Meningitis Lymphatic system- Scrofula of the neck Genitourinary system- Urogenital TB Bones + Joints- Potts disease of the spine
Staining/Culture samples
3 early morning sputum specimens from different days
3 early morning urine specimens
Staining methods
Ziehl-Neeson Stain with heated strong carbol-fuchsin Decolorise with acid/alcohol Counterstain with malachite green Show up as pink rods against blue tissue
Fluorescent stain with Auramine
Mycobacteria fluoresce against dark background
PCR
Culture takes too long
Mantoux test
Tuberculin (glycerol extract of TB) inject intradermally
Skin reaction viewed 48-72 hours later
Reaction read by measuring diameter of induration in mm
Small 5-9mm - Active infection in “high risk” individuals
Medium 10-15mm - Active infection in “medium risk” individuals (injecting drug users, homeless, prisoners)
Large >15mm - Sign of active infection in individuals with no risk factors
BCG vaccine
Strain of attenuated live bovine tuberculosis bacillus, Mycobacterium bovis, that has lost its virulence in humans
0-80% effective for 15 years
Treatment
Isoniazid
Rifampicin
Pyrazinamide
Ethambutol/Streptomycin
Treatment once TB isolate known to be fully susceptible
Ethambutol/Streptomycin stopped
Treatment after 2 months
Pyrazinamide stopped
Isoniazid + Rifampicin
Daily or intermittent therapy for 4 more months after stop pyrazinamide
Isoniazid resistance
Rifampicin, pyrazinamide + ethambutol for entire 6 months
Directly Observed Therapy
Recommended for all patients
Can switch to 2-3 times/week dosing after initial 2 weeks daily dosing
Isoniazid
Prevent synthesis of mycolic acid (part of TB wall)
Bactericidal to rapidly dividing bacteria
Bacteriostatic to slow growing bacteria
Isoniazid side effects
Can cause neuropathy
–> B supplements
Rifampicin
Antibiotic
Inhibits bacterial DNA-dependent RNA synthesis by inhibiting DNA-dependent RNA polymerase
Pyrazinamide
Thought to inhibit the enzyme fatty acid synthase (FAS) I
–> fatty acid production
Ethambutamol
Bacteriostatic against actively growing TB
Prevents cell wall formation
Streptomycin
Antibiotic Aminoglycoside
Streptomycin side effects
Ototoxicity
Nephrotoxicity
Multi drug resistant TB
Resistant to Rifampicin + Isoniazid
40-50% mortality rate
80% mortality in HIV patients
Second line TB drugs
Aminoglycosides- amikacin
Fluoroquinolones- levofloxacin
Thioamides- ethionamide
MDR- TB drug length
18-24 months
