PBL LOs Flashcards
What are pulmonary nodules?
Isolated radiographic opacity that is spherical and well circumscribed measuring
What is the prevalence of pulmonary nodules?
- Solitary pulmonary nodule found on up to 0.2% of all chest films.
- Solitary pulmonary nodules found on up to half of all lung CT scans.
What is the differential for a solitary pulmonary nodules?
- Malignant neoplasm
- Benign neoplasms
- Infections
- Measles
- Septic emboli
- Abscess
- Congenital causes: bronchogenic cyst, bronchial atresia with mucoid impaction, sequestration
- Other stuff: amyloid, sarcoidosis, RA, granulomatosis with polyangiitis
What is a pulmonary cavity?
Gas-filled area on the lung in the center of a nodule or area of consolidation (lung tissue filled with water) that is produced by the expulsion of a necrotic part of a lesion. The can be seen as a lucent area within consolidation, mass, or nodule on X-ray or CT.
What are noninfectious disease associations with pulmonary cavities?
- Malignancy
- Granulomatosis with polyangiitis (Wegener’s)
- Pulmonary infarct due to embolism
What are infectious associations with pulmonary cavities?
- Necrotizing pneumonias
- Lung abscesses
- Mycobacterium tuberculosis
- Fungal infections
- Septic emboli
What does a pulmonary calcification indicate?
Usually indicates a benign disease. Benign patterns of calcification: central nidus, laminated, diffuse, popcorn. If it has 1 of these 4 patterns and is
What organism can cause a pulmonary infection in HIV patients with normal CD4+ counts?
Strep. pneumoniae!
What are the traits of Strep. pneumoniae?
- Gram +
- Catalase -
- alpha-hemolytic
- Bile-Esmulin Negative
- Optochin susceptible
- Quellung positive
- IgA protease
What organisms cause pulmonary infections in HIV patients with CD4+ counts less than 200?
- Pneumocystis jirovecii pneumonia
- Histoplasmosis
- Toxoplasmosis
- Invasive aspergillosis
What is pneumocystis jirovecii pneumonia?
A fungal organisms that colonizes and infects human hosts
What are three interesting things about Pneumocystic jirovecii pneumonia?
- Ubiquitous distribution
- Cannot be cultured outside of the lung
- Source in nature unidentified
What is the mechanism of Isoniazid? What can it be used for and what can it cause?
Decreases synthesis of mycolic acids. Can be used for prophylaxis. Can cause functional B6 deficiency.
What are the Rifamycins?
Rifampin, Rifabutin
Inhibits DNA-dependent RNA polymerase.
What are the four Rs of Rifampin?
- Ramps up P-450
- Red body fluids
- Rapid resistance
- RNA polymerase inhibitor
What is pyridoxine?
A vitamin B6 supplement. Give it with Isoniazid to prevent neurotoxicity.
What is the mechanism of Pyrazinamide?
Unknown. Maybe thought to acidify intracellular environment via conversion to pyrazinoic acid.
What is the mechanism of Ethambutol?
Decrease carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase.
What is the standard cocktail for AIDs treatment?
2 NRTIs + 1 NNRTI or 1 Protease inhibitor or 1 integrase inhibitor
What is the mechanism of protease inhibitors?
End in -navir
Blocks HIV protease –> unable to cleave HIV polypeptide into functional groups (gag, pol, env)
Why is Ritonavir special
It blocks CP450 and can cause pancreatitis.
What is the mechanism of NRTI drugs?
Inhibit reverse transcriptase which prevents conversion of HIV RNA to cDNA
Why would you add a low dose of rittonavir to an HIV regimen?
Ritonavir is a P-450 (CYP) 3A4 inhibitor so it is used to “boost” other drug concentrations
What does TLR2 detect?
Mycolic acid wall glycoproteins
What does TLR2 release after it detects mycolic acid?
NF-kB/AP1 gets activated –> releases pro inflammatory cytokines –> IL-2, TNF-alpha, IL-12, IL-6
What causes night sweats and fever in TB?
Proinflammatory cytokines –> Release of PGE2 –> Hypothalamus –> Inc. set point –> Night sweats + fever
What do M1 macrophages release in TB that recruits more macrophages to the site of a granuloma in the lungs?
TNF-alpha!
What part of the lung is better ventilated?
Base (lower portion)
What part of the lung has higher oxygen content?
APEX - helps mycobacterium grow in 2ndary TB infection
How does immunosuppression contribute to granuloma formation?
Low CD4+ counts cause lower production of INF-gamma and lower production of TNF-alpha
What agents cause TB?
- M. tuberculosis - causes great majority of human disease
- M. africanum - causes human tuberculosis (TB) in tropical Africa
- M. bovis - primarily isolated from cattle but causes 1-2% of TB disease
What other three mycobacteria might cause pulmonary infections?
- M. avium complex
- M. kansasii
- M. abscessus
What does M. avium complex cause?
Pulmonary infection in immunocompromised patients (productive cough, weight loss, fever, lethargy, night sweats).
What does M. avium complex cause in advanced AIDs patients?
Disseminated infection
- Sweating
- Weight loss
- Fatigue
- Diarrhea
- SOB
- RUQ abdominal pain
What does M. kansasii present with?
It presents like TB and is clinically indistinguishable. Symptoms may be less sever and more chronic.
What does M. abscesses cause?
Usually causes Skin/soft tissue infections but can cause pulmonary infection in immunocompromised individuals or people with chronic lung diseases, such as cystic fibrosis.
What is latent TB infection?
TB bacteria is alive in the body but the immune system is preventing it from spreading. Individual is asymptomatic and NOT contagious. Only indication of infection would be a positive TB skin test. Skin test only tells you that body has TB infection, not if it is active.
What is Active TB infection?
If immune system becomes weak. bacteria become active and multiply destroying lung tissue. Individual will likely feel sick and have symptoms (cough, fatigue, loss of appetite) and these are contagious.
What is PPD?
Purified Protein Derivative
- Heterogenous mixture of proteins from M. tuberculosis.
- Antigens used in mixture also used in tuberculosis vaccine available in some countries
What will cause a false positive tuberculin test? What should you use instead in these patients?
False positives can occur if the person was vaccinated for TB.
-If vaccinated against TB, it is preferable to use the IFN-gamma release assay.
What is the IFN-gamm release assay?
- Uses ESAT and CFP-10 antigens which are not found in pure protein derivative
- No false positives with this test (basically - even in vaccinated individuals)
What if someone vaccinated for TB has a positive IFN-gamma release assay?
That person is infected with Mycobacterium tuberculosis, not immune to it!
What can PPD and IFN-gamma release assay not tell the difference between?
Active and latent infections.
How is the TST (tuberculin skin test) administered?
0.1 ml of tuberculin purified protein derivative (PPD) is injected into the inner surface of the forearm. It is an intradermal injection and when placed correctly, it should produce a wheal 6-10 mm in diameter.
How and when is the TST read?
It should be read within 48-72 hours after administration. A patient who does not return in this time frame needs to be scheduled for another skin test.
How do you measure the TST test?
The reaction should be measured in millimeters of induration (palpable, raised, hardened area or swelling). The reader should not measure redness (erythema). The diameter of the indurated area should be measured across the forearm, perpendicular to the long axis.
What two factors does skin test interpretation depend on?
- Measurement in millimeters of the induration
- Person’s risk of being infected with TB and of progression to disease if infected
In what populations is an induration of 5 mm or more considered a positive TST?
- HIV-infected persons
- A recent contact of a person with TB
- Persons with fibrotic changes on chest radiograph consistent with prior TB
- Patients with organ transplants
- Persons who are immunosuppressed for other reasons (taking prednisone, TNF-alpha antagonists)
In what populations is an induration of 10 mm or more considered a positive TST?
-Recent immigrants (
In what populations is an induration of 15 mm or more considered positive?
ANY PERSON, including persons with no known risk factors for TB. However, targeting skin testing programs should only be conducted among high-risk groups.
How do you calculate PPV?
TP/ (TP+FP)
How do you calculate NPV?
TN (TN+FN)
What does a high PPV indicate?
It is more likely that your patient actually has the condition he or she tested positive for!
What does a low PPV indicate?
It is more likely that your patient has tested FALSELY positive and does not actually have the condition.
What is an example of how PPV can be impacted based on the population being tested?
For example, if you were testing babies in Northern MN for HIV (where there is low likelihood of the baby having the condition), then your PPV would be MUCH LOWER than in a population of IV heroin users, where your PPV would be higher.
What is sensitivity?
TP/ (TP + FN = all positives)
What is specificity?
TN/ (TN+FP = all negatives)
What requirements must immigrants under 2 years old moving to the US under go (in terms of TB)?
No tests unless the child has signs or symptoms of TB or has been in contact with a person with TB.
What requirements must immigrants 2-14 years old moving to the US under go (in terms of TB)?
TST (tuberculin skin test) or IGRA (interferon-gamma release assay) test. If either is positive, they must undergo chest X-ray. If chest x-ray is positive, they must undergo sputum smear and cultures. If the sputum is positive they have to undergo DST (drug sensitivity testing) and DOT (daily observed therapy)
What requirements must immigrants 15 years old and up moving to the US under go (in terms of TB)?
Chest X-ray. If it’s positive, must undergo sputum smear and cultures. If sputum positive, must undergo DST and DOT.
