Pulmonology Flashcards
What protein mutation is associated with cystic fibrosis?
Abnormal posttranslational processing of CFTR, a transmembrane protein which prevents it from reaching the cell surface. This protein is thus absent in the apical membrane of affected epithelial cells.
What is the mechanism of action of echinocandid antifungals?
To block glucan synthesis.
Name two echinocandid antifungals.
Capsofungin and echinocandin.
What is 1,3-beta-D-glucan?
A polysaccharide component of the fungal cell wall.
What is the difference in mechanism of action between echinocandin antifungals and polyene and azole antifungals?
Polyene and azole antifungals target the fungal cell membrane; echinocandins suppress synthesis of the fungal cell wall.
What species is Capsofungin effective against? Ineffective?
Affective: Candida, Aspergillus; Ineffective: Cryptococcus neoformans, limited activity against Mucor and Rhizopus.
What is the mechanism of action of Amphotericin B?
Polyene antifungal that binds ergosterol in the fungal cell membrane to lead to pore formation and cell lysis.
What is the mechanism of itraconazole?
Azole antifungal that inhibits ergosterol synthesis
What is terbinafine used to treat?
Dermatophytosis
What is the mechanism of action of terbinafine?
It inhibits the fungal enzyme squalene-2,3-epoxidase resulting in decreased synthesis of ergosterol.
What is the mechanism of action of Griseofulvin?
Enters fungal cells, binds microtubules, inhibits mitosis. It is effective only against dermatophyte fungi.
What is the mechanism of action of flucytosine?
Inhibits synthesis of DNA and RNA in fungal cells. It is used synergistically with amphotericin B, especially to treat cryptococcal meningitis.
Assuming a normal rate of metabolic CO2 production, hypocapnia implies what state?
Alveolar hyperventillation.
What is the main indicator of total alveolar ventilation?
Arterial PaCO2.
What may cause alveolar hyperventilation?
V/Q mismatch that causes decreased O2 and CO2 exchange (ex pneumonia, PE)
What central changes occur due to hypoxemia?
Elevated respiratory drive causing excessive CO2 excretion by the lungs and resulting in hypocapnia.
Name four causes of alveolar hypoventillation.
Upper airway obstruction, reduced ventillatory drive, respiratory muscle fatigue, decreased chest wall compliance.
What is the histological presentation of asbestosis?
Localized pleural thickening with calcification, espeically of the posterolateral mid-lung zones and diaphragm.
How does asbestosis manifest radiographically?
Linear interstitial densities in the lower lobes.
How does silicosis present histologically?
Nodular densities and eggshell calcifications.
How does berylliosis present histologically?
Nodular infiltrates, enlarged lymph nodes, non-caseating granulomas (similar to sarcoidosis).
How does hypersensitivity pneumonitis due to inhalation of organic dusts present on chest xray?
Diffuse nodular interstitial infiltrates on xray
When does the trachea deviate towards the opacified lung on xray?
With volume loss- atelectasis
When does the trachea deviate away from the opacified lung on xray?
Large pleural effusion
An obstructive lesion in the mainstem bronchus may lead to what pathology?
Prevention of ventilation of an entire lung leading to lung collapse and opacification on CXR.
What type of drugs are the most effective agents for chronic prevention of inflammation associated with bronchial asthma?
Inhaled Glucocorticoids.
Where is resistance highest in the respiratory tract?
In the medium sized bronchi because of highly turbulent airflow. Resistance within the first 10 generations of bronchi contributes to most of the total airway resistance of the lower respiratory tract.
What is the mechanism of action of rifampin?
To inhibit DNA dependent RNA synthesis, preventing transcription
What alteration may cause bacterial resistance to rifampin?
Alteration of the structure of DNA dependent RNA polymerase. Rifampin is well known to induce resistance when used as monotherapy.
When is rifampin used as monotherapy?
In prophylactic treatment of those exposed to H. influenzae or N. meningitidis.
SVC syndrome is caused by what pathology?
Mediastinal mass.
What type of epithelium covers the true vocal cords?
Stratified squamous epithelium
What epithelium lines the paranasal sinuses?
Ciliated, pseudostratified, columnar, mucus secreting epithelium
What epithelium lines the laryngeal vestibule?
Ciliated, pseudostratfieid columnar, mucus secreting epithelium
What epithelium lines the trachea?
Ciliated, pseudostratified columnar, mucus secreting epithelium.
Thickened bronchial walls, neutrophil infiltration, mucous gland enlargement, patchy squamous metaplasia of the bronchial mucosa are characteristic of what condition?
Chronic bronchitis.
How does pulmonary hypertension manifest in patients with scleroderma?
Intimal thickening of pulmonary arterioles causes pulmonary hypertension, cor pulmonale, and right sided heart failure. It manifests with an accentuated pulmonary component of the second heart sound.
Which medication used to treat TB works best at relatively acidic pHs?
Pyrazinamide (PZA); it is therefore most bacteriacidal in organisms engulfed by macrophages in phagolysosomes.
What is the principle difference in efficacy of pyrazinamide vs. isoniazid, rifampin, and ethambutol?
Isoniazid, rifampin, ethambutol are more effective against extracellular mycobacteria.
What is the mechanism of action of N-acetylcysteine in the treatment of CF?
It cleaves disulfide bonds within mucus glycoproteins to loosen thick sputum.
What electrolyte secretion abnormalities are characteristic of CF?
Decreased chloride secretion and increased sodium reabsorption in mucous glands of the pulmonary airways.
Name four symptoms of small bowel obstruction in an infant.
Billious vomiting, abdominal distention, air fluid levels, small bowel dilation.
What is the most common cause of meconium ileus?
CF
What is meconium ileus?
A distal small bowel obstruction in a neonate due to abnormally dehydrated meconium. It is quite specific for CF.
Describe three acute findings in fat embolism syndrome.
Acute onset neurologic abnormalities, hypoxemia, petechial rash. It causes occlusion of the pulmonary microvessels by fat globules.
At rest is the equiibriation of oxygen in a normal individual perfusion or diffusion limited?
Perfusion.
When is O2 equilbriation diffusion limited?
Emphysema, pulmonary fibrosis, and in states of high pulmonary blood flow like exercise.
In a reactivated TB infection, where does infection and cavitation most commonly occur?
In the upper lungs (particularly the apex) due to better oxygenation and improved lymphatic flow.
Where does primary TB infection occur?
Formation of Ghon foci occurs in the lower lungs
Describe three physiologic findings associated with ARDS.
Decreased lung compliance, increase in work of breathing, worsened V/Q mismatching.
What is responsible for the green colour of pus and sputum in bacterial infections?
Neutrophil myeloperoxidase released from neutrophil azurophilic granules.
What does the Reid index calculate?
Ratio of the thickness of the mucous gland layer in the bronchial wall submucosa to the thickness of the bronchial wall between the respiratory epithelium and bronchial cartilage.
Reid indices of greater than 40% correlate well with the duration and severity of what pathology?
Chronic bronchitis.
How does emphysema affect lung elastic recoil?
It decreases elastic recoil resulting in air trapping.
Dilated airspaces are indicative of what condition?
Emphysema
What is the pathogenesis of emphysema?
Release of proteinases (esp elastase) from infiltrating neutrophils and alveolar macrophages. Protease-antiprotease imbalance leads to acinar wall destruction and airspace dilation.
What is the function of club cells?
To secrete club cell secretory protein and surfactant components and to detoxify inhaled substances.
What are mycolic acids and what bacteria incorporate them into their cell walls?
Mycobacteria; they are long branched saturated fatty acids that contain about 90 carbon molecules. They make mycobacterium acid fast.
What is the mechanism of action of isoniazid and what compound is it structurally similar to?
Structurally similar to pyridoxine; inhibits mycolic acid synthesis in mycobacterial cells.
What drug causes M. tuberculosis to rapidly stop proliferating and to lose their acid-fastness?
Isoniazid.
What histologic findings are characteristic of malignant mesothelioma?
Hemorrhagic pleural effusions and pleural thickening.
What is the gold standard for diagnosis of malignant mesothelioma?
Electron microscopy.
Deficiency of what vitamin in a patient with CF causes squamous metaplasia of mucus secreting columnar epithelium of the pancreas and other exocrine ducts?
Vitamin A.
Honeycomb lung is characteristic of what disease?
Idiopathic pulmonary fibrosis.
Name three adverse effects of amphotericin B.
Nephrotoxicity, hypokalemia, hypomagnesemia.
Stimulation of what receptor is believed to cause nicotine dependence?
a4b2 nicotinic acetylcholine receptor of the CNS.
What is the mechanism of action of Varenicline and what is it used to treat?
Partial agonist that competes with nicotine, preventing it from binding the a4b2 nicotinic acetylcholine receptor. It can be used in smoking cessation by reducing cravings and by attenuating the rewarding effects of nicotine.
What symptoms are associated with acute theophylline intoxication?
Abdominal pain, vomiting, diarrhea, cardiac arrythmias, seizures.
How does the CFTR function in sweating?
Eccrine sweat is isotonic with extracellular fluid when it is first produced. As it travels to the skin surface, Cl is resorbed by the CFTR and sodium follows. Thus the CFTR facilitates the production of hypotonic sweat in healthy patients.
Deficient CFTR proteins cause what change in sweat?
Inability to resorb chloride and sodium in eccrine ducts, causing sweat to be high in sodium and chloride. This can cause hypovolemia due to execssive sodium loss and intravascular volume contraction.
What xray finding is indicative of sarcoidosis?
Bilateral hilar adenopathy.
What is the difference between biopsy results in a patient with TB vs sarcoidosis?
TB- caseating granulomas and acid fast bacilli; sarcoidosis: non caseating granulomas.
In lung transplant patients, how does chronic rejection manifest?
Bronchiolitis obliterans- lymphocytic inflammation, necrosis, and fibrosis of the bronchiolar wall. This causes obstructive lung disease of the small bronchioli.
Name the four morphologic stages of lobar pneumonia.
Congestion (first 24 hrs), red hepatization (2-3 days), grey hepatization (4-6 days), resolution.
How is arterial PO2 measured? Alveolar PO2?
Arterial- ABG; alveolar- alveolar gas equation
Immediately following TB exposure, what is the physiologic response?
Engulfement by alveolar macrophages which allows for intracellular bacterial proliferation.
What antifungal drugs inhibit ergosterol synthesis by the fungal cytochrome P450 enzymes (in addition to suppressing the human P450 system)?
Azoles (ketoconazole, fluconazole, itraconazole, voriconazole)
What is the mechanism of action of griseofulvin?
Enters fungal cells and binds microtubules, inhibiting mitosis.
What is the mechanism of action of ethambutol?
Antimycobacterial agent that inhibits carbohydrate polymerization, preventing peptidoglycan cell wall synthesis.
What is seen in sputum samples of a patient with extrinsic allergic asthma?
Eosinophils and charcot leyden crystals.
What causes relative erythrocytosis?
Decrease in plasma volume.
Normal red cell mass indicates what cause of polycythemia?
Plasma volume contraction.
Under what conditions do individuals with stiff lungs minimize work of breathing?
When respiratory rate is high and tidal volume is low; i.e. rapid, shallow breaths.
Under what conditions do individuals with obstructive lung diseases minimize work of breathing?
slow deep breaths (i.e. low rate, higher tidal volume
Wedge shaped, pleural based infarctions of the lungs are caused by what condition.
Pulmonary emboli.
What lung findings are characteristic of ARDS?
Non cardiogenic pulmonary interstitial and intra-alveolar edema, inflammation, and alveolar hyaline membranes.
What is the most common type of lung cancer in the US?
adenocarcinoma in situ.
Describe the features of adenocarcinoma in situ as seen on microscopic examination.
Growth along intact alveolar septa without vascular or stromal invasion–> well differentiated, dysplastic columnar cells with or without intracellular mucin
What lung findings are reflective of chronic rejection following transplant?
Bronchiolitis obliterans syndrome –> immune reaction affecting the small airways causing inflammation, narrowing, and fibrosis of the bronchiolar walls.
From where is elastase derived?
It is a neutral protease contained in macrophage lysosomes and in azurophilic granules of neutrophils.
What is a major contributor to the development of centriacinar and panacinar emphysema?
Excess protease activity (i.e. increased elastase)
What is a superior sulcus tumor?
Pancost tumor (i.e. tumor in lung apex).
What is the superior sulcus?
The groove formed by the subclavian vessels.
Name five symptoms of pancoast syndrome.
Ipsilateral horner’s syndrome, rib destruction, atrophy of hand muscles, pain in the distribution of C8, T1, and T2 nerve roots.
How does RA affect the lungs?
It can cause a form of interstitial lung disease similar to idiopathic interstitial pneumonia. Methotrexate which is frequently used for rheumatoid arthritis can also cause interstitial pneumonitis and fibrosis.
How does pulmonary fibrosis present on chest xray?
Bilateral reticulonodular opacities
What causes lung tissue damage and abcess formation?
Lysosomal enzyme release from neutrophils and macrophages.
What most commonly causes acute obstruction of the small airways in infants and how is this best treated?
RSV; treated with Ribavirin.
What three factors are released by neutrophils and macrophages in response to injury?
TNF-a, IL-1, IL-6. They mediate the systemic inflammatory response.
What causes erythrocytes to form stacks in an ESR?
Fibrinogen as mediated by release of IL-1, IL-6, and TNF-a in response to injury and inflammation.
In the respiratory tract, where are cilia present?
Through the respiratory bronchioles but not in the alveolar ducts or alveoli themselves.
What prevents bronchiolar mucus accumulation and airflow obstruction?
The presence of cilia beyond the most distal mucous producing cells (goblet cells end in the smallest bronchi just before the bronchioles begin).
What drug is used as antibiotic prophylaxis for mycobacterium avium complex in an HIV positive patient with a CD4+ count of less than 50 cells/uL?
Azithromycin.
What is used as prophylaxis for histoplasma capsulatum in HIV positive patients with a CD4+ count of less than 150?
Itraconazole.
What is a distinguishing test between M. tuberculosis and MAC?
MAC grows well at high temperatures and will exhibit optimum growth at 41 degrees C.
What type of membrane receptor is the CFTR transmembrane protein?
An ATP-gated chloride channel.
What is the mechanism of action of Cromolyn and nedocromil?
Mast stabilizing agents that inhibit mast cell degranulation to prevent the release of chemical mediators.
What component of inflammatory exudate stimulates migration of neutrophils to the site of inflammation?
Leukotriene B4 (it is chemotactic)
What is the function of IFN-y in the inflammatory cell response?
Recruitment of leukocytes and activation of phagocytosis; it is produced by activated T cells.
What symptoms are indicative of a vitamin B6 deficiency?
Peripheral neuropathy.
Which pneumoconioses produces eggshell calcifications of hilar lymph nodes?
Silicosis. Birefringent particles surrounded by fibrous tissue on histologic exam are also seen.
What is seen in berylliosis and hypersensitivity pneumonitis?
Noncaseating granulomas
What is characteristic of asbestosis?
Calcified pleural plaques and ferrunginous bodies.
What are the most common benign lung tumors and how do they present?
Hamartomas- they present as asymptomatic, peripherally located coin lesions in patients ages 50-60.
What comprises hamaratomas?
Disorganized cartilage, fibrous, and adipose tissue.
What causes caseous necrosis in M. tuberculosis?
Host immune activation and inflammation through a type IV delayed hypersensitivity reaction. The reaction stems form the TH1 lymphocyte stimulation of both macrophages and CD8+ cytotoxic T lymphocytes. Ultimately macrophages undergo epitheliod and Langhans giant cell transformation and fibroblasts are activated.
What is a Ghon complex?
A lower lobe lesion accompanied by ipsilateral hilar adenopathy.
When do Ghon complexes occur?
During primary TB infection only.
How are hyaline membranes formed in ARDS?
Result from alveolocapillary membrane leakage and they consist of fibrin exudate and plasma protein rich edema fluid mixed with cytoplasmic and lipid remnants of necrotic epithelial cells.
