TB/Pneumonia Flashcards
What are some differentials for cough, fever +/- chest pain?
- Pneumonia
green sputum, recent hospital admissions, acute URTI… - COPD exacerbation
smoking history, diagnosed COPD, wheezing - TB
occupational, social exposures (travelling, social workers), immunocompromised (HIV, steroids, IV drug, substance use)
constitutional symptoms –> chronic development - Lung cancer
smoking, FHx, hemoptysis, constitutional symptoms
Risk factors for TB
- Social and environmental factors
Travel or birth in a country with high TB prevalence (Asia, Latin America, sub-Sharan Africa, Eastern Europe)
Person/occupation contacts, homeless, prison, refugee camp, crowded living - Host factors
Immunocompromised (HIV, age, pregnancy, steroid use)
IV drug use
Systemic disease: end-stage renal disease, COPD, diabetes
Chemotherapy
Substance use (drug, alcohol, smoking can suppress cough reflex)
What is the organism cause TB?
mycobacterium tuberculosis
aerobe
duration of contact: 8 hours, lower for immunocompromised
Can latent TB pass to people?
NO
confined within Ranke complex
What factors can precipitate reactivation of latent TB?
Immunocompromised state, corticosteroids, malnutrition, elderly, HIV, diabetes, smoking, alcohol, drug, chemotherapy, transplant, pregnancy
How does TB escape macrophage killing?
- Cord factor: surface glycolipid prevents fusion b/w phagocytes containing TB and lysosomes
- Heat-shock protein
- Mycolic acid inhibits macrophage expression of IL12, TNF and other cytokines
- Resistance to ROS
Mech for active TB?
droplet inhalation –> alveolar macrophages are recruited to engulf TB –> intracellular destruction inside macrophages –> infected macrophages are activated and release inflammatory cytokines –> more immune cells are recruited (neutrophils) –> immune cells form a GRANULOMA to isolated TB within the region of the lung –> TB antigen are present to T cells by dendritic cells –> T cell response is delayed in immunocompromised hosts –> centre of granuloma necroses & liquifies –> TB escape from granuloma back to airway –> ACTIVE TB
- -> accumulation of cytokines + necrotic tissue in lung –> airway irritation –> chronic cough
- -> accumulation of cytokines –> systemic inflammation within the body –> inc basal metabolic rate –> fever, night sweats, weight loss
Mech for Ranke complex/ghon focus/granuloma formation
droplet inhalation –> alveolar macrophages are recruited to engulf TB –> intracellular destruction inside macrophages –> infected macrophages are activated and release inflammatory cytokines –> more immune cells are recruited (neutrophils) –> tissue inside granuloma undergo necrosis –> GHON FOCUS –> ghon focus (undergo calcification & fibrosis) + hilar lymphadenopathy –> RANKE COMPLEX
Mech for latent TB?
droplet inhalation –> alveolar macrophages are recruited to engulf TB –> intracellular destruction inside macrophages –> infected macrophages are activated and release inflammatory cytokines –> more immune cells are recruited (neutrophils) –> immune cells form a GRANULOMA to isolated TB within the region of the lung –> TB antigen are present to T cells by dendritic cells –> CD4 T cells release IFN gamma –> activate infected macrophages within granuloma to release enzymes –> resilient TB within granuloma survives and become dormant –> LATENT TB
when immunocompromised –> ranke complex reactivation –> memory T cells release cytokines –> more lung damage
Mech for extra-pulmonary TB?
droplet inhalation –> alveolar macrophages are recruited to engulf TB –> intracellular destruction inside macrophages –> infected macrophages are activated and release inflammatory cytokines –> more immune cells are recruited (neutrophils) –> infected macrophages travel to thoracic lymph nodes –> TB activate macrophage death –> release into lymph & circulatory system
What does RANKE COMPLEX do?
prevents spread of primary infection to other organs in infected individual –> scar tissue
What are some symptoms of TB?
SCREEN FOR RF
primary TB: asymptomatic, chronic cough, constitutional symptoms, haemoptysis
secondary TB: constitutional symptoms, haemoptysis + ORGAN DEPENDENT symptoms
physical exams of TB?
- Clubbing
- Lymphadenopathy: supraclavicular/Cervical lymph nodes enlargement
Occur in an organ - Hepatitis: hepatomegaly, abdo tenderness
- Meningitis: neck stiffness
- Long bones: osteomyelitis
- Spine: pott disease
- Adrenal (Addison’s disease)
- Kidney: sterile pyuria (inc WBC in urine)
investigations of latent TB/asymptomatic patients?
Purified protein derivative (PPD)
- Inject tuberculin –> if previously exposed, immune reaction on skin occur within 48-72 hrs –> large area of infection confirms the result
- Positive: patients have been exposed at some point, but DOES NOT differentiate active/latent/resolved
- False positive from TB vaccinations
IFN gamma release assay (IGRA)
- Measure the amount of interferon gamma released by T cells when exposed to TB antigens
- Fewer false positives as it does not detect antigens in vaccines or non-TB mycobacteria
If any of the two screening tests are positive + symptoms –> chest -ray for active TB
investigations of active pulmonary TB patients?
Chest X-ray
- Ghon focus with calcification (nodules around hilum of the lungs)
- hilar lymphadenopathy
- inactive TB: scarring in upper lobes (aerobes)
If positive –> sputum microscopy/culture
Whats the approach of diagnosing TB?
No symptoms –> latent screening tests (IGRA, PPD)
Symptoms –> chest x ray –> 3 sputum sample specimen for acid fast bacilli –> culture (gold standard) –> nucleic acid amplification test (NAAT)/PCR –> drug susceptibility test –> contact tracing
What happens in sputum acid fast bacilli?
3 specimens can be collected on the same day (at least one early morning), a minimum of 8 hour apart
Fast & inexpensive, but cannot differentiate TB bacilli and non-TB
Smear positive patients are FAR more contagious
appear red and pink
What is the gold standard investigation of diagnosing TB?
Cell culture
Identification takes 10-21 days
Paired with a fluorescence-based oxygen sensor –> when bacteria use up all oxygen, the sensor goes fluorescent, and it’s sensed by UV light –> positive vial
What happens in NAAT/PCR?
Gene Xpert assay: detect mycobacterium TB complex
Rapid diagnosis (24-48 hrs) by amplifying specific target region of DNA –> identify the organism
What happens in drug susceptibility test?
might take 15-30 days
Perform upon the culture/try DNA sequencing as it takes very long
where there is resistance to rifampicin, second line agents should be tested (MDR-TB)
What is the management of active TB?
RIPE for 2 months (intense phase)
RI for remaining 4 months (maintenance)
Rifampicin (6 months)
Isoniazid (6 months)
Pyrazinamide (2 months)
Ethambutol (2 months)
monitor with LFT
What is the prevention of TB?
BCG vaccine (live-attenuated), give to infants (10-15 years) but give adults immunity drops within 3 months (not economically viable to vaccinate the whole Australian population)
What is the discharging criteria of TB?
- Absence of cough with/without other symptoms
- 3 Cultures negative
- Assured treatment (RIPE is working)
MOA and side effects of RIPE
Rifampicin: inhibit bacterial RNA polyerase, red body fluids
Isoniazid: inhibit synthesis of cell wall, VIT B6 DEFICIENCY + PYRIDOXINE (peripheral neuropathy), rash, hepatotoxicity
Pyrazinamide: against TB within macrophages, most hepatotoxicity
Ethambutol: inhibit synthesis of cell wall, optic neuritis –> reversible
