Pulmonology UWorld Flashcards
What are the two classes of CD4+ T-cells and what cytokines do they secrete?
Th1: IFN-gamma (activates macrophages), IL-2 and other cytokines to activate and CD8+ T-cells. Th2: IL-4 (promotes B-cell class switching to IgE when associated with IL-13), IL-5 (activates eos and promotes IgA synthesis) and other cytokines to activate B-cells.
Change in venous oxygen content in a patient with cyanide poisoning?
Decreased. Cyanide inhibits Fe3+ in cytochrome C of the electron transport chain, decreasing O2 consumption
A patient has a chronic cough, biopsy reveals well-differentiated mucin-producing dysplastic columnar cells lining the alveolar membrane without invasion. What is the most likely diagnosis?
Adenocarcinoma in situ. These tumors have a tendency to undergo aerogenous spread.
How to differentiate sarcoid from hypersensitivity pneumonitis, cryptogenic organizing pneumonia and lymphocytic interstitial pneumonitis?
CD4:CD8 ratio will be increased > 2 in sarcoidosis.
How is the heart oriented in the thoracic cavity?
Anterior = RV. Inferior = LV and RV. Posterior = LA.
Injured organs if there is a penetrating injury to the left chest at the 5th intercostal space in the midclavicular line.
1st the lung because it is most anterior. 2nd the heart because the apex hides behind the lung at this point.
3 ways aspergillus affects the lungs
1) Colonizes pre-existing cavities 2) Invasive infection in immunocompromised 3) ABPA hypersensitivity reaction in asthmatics that causes high levels of IgE and transient pulmonary infiltrates and later proximal bronchiectasis.
Aspiration when supine
Posterior segment of upper lobes and superior segments of lower lobes.
Ipratropium mechanism of action
Anti-muscarinic that reverses vagally mediated bronchospasm
Theophylline mechanism of action
Inhibits PDE and increases cAMP causing bronchodilation. It also inhibits adenosine-induced bronchoconstriction.
What is the major factor that limits exercise tolerance in patients with COPD?
Dynamic hyperinflation: increased respiratory rate leads to decreased exhalatory time, causing increased air trapping and exercise intolerance.
What makes elastin so stretchy and good for pulmonary compliance? Why does it like alpha-1 AT so much?
The lysine is covalently cross-linked with desmosine by extracellular lysyl hydroxylase, allowing it to return to its original form after being stretched. Alpha-1 antitrypsin prevents elastase from breaking it down.
How does elastin differ from collagen
Few lysine and proline residues are hydroxylated
Elastin does not form a triple helix
A patient on theophylline presents with tremors, arrhythmia and GI symptoms. What drugs could be the cause of his symptoms?
Cimetidine, ciprofloxacin, macrolides and verapamil all inhibit CYP450 and increase serum theophylline levels.
How does the influenza vaccine work?
The killed vaccine induced neutralizing antibodies against viral hemagglutinin. This prevents hemagglutinin binding to sialylated receptors on the host cell. The live vaccine stimulates MHC I receptors and generates CD8+ T-lymphocytes that kill infected cells.
Oseltamivir mechanism of action
It competitively inhibits viral neuraminidase and prevents the virus from cleaving sialic acid residues on glycoconjugate receptors. This inhibits release of new virions from infected cells.
Immunodeficiency with sinopulmonary infections, ataxia and telangectasias.
Ataxia-telangectasia
Immunodeficiency with oculocutaneous albinism, pyogenic infections and progressive neurologic dysfunction.
Chediak-Higashi syndrome
Immunodeficiency with severe bacterial and fungal infections with granuloma formation.
Chronic granulomatous disease
Immunodeficiency with congenital heart disease, dysmorphic facies and hypocalcemia
DiGeorge
Immunodeficiency with severe bacterial and viral infections in infancy, thymic aplasia, chronic diarrhea and mucocutaneous candidiasis.
SCID. Labs show absent CD3+ T-cells and hypogammaglobulinemia.
Immunodeficiency with recurrent Neisseria infections
C5-C9 complement deficiency
Immunodeficiency with recurrent infections that worsen with age, easy bleeding and eczema
Wiskott-Aldrich syndrome
Pathophysiology of hyper-IgM syndrome
The normal enzymes that excise the exons that code for other Ig classes makes it so a particular B-cell cannot specialize and produce a specific type of Ig. Also, mutations in the CD40 ligand can cause this because stimulation of this ligand promotes class switching.
Factor that induces class switching to IgA
TGF-beta
Weird findings associated with Legionella infection
Hyponatremia, transaminitis, bradycardia despite fever, diarrhea and fever > 102.2.
How to diagnose Legionella
Urinary antigen and growth on buffered charcoal yeast extract with supplement L-cysteine and iron.
Mesothelioma histopathology
Tumor cells with long, slender microvilli and abundant tonofilaments that stain well for pancytokeratin.
Cause of Potter syndrome
Oligohydramnios, commonly secondary to bilateral renal agenesis.
Which portion of the respiratory tract is lined by pseudo stratified ciliated columnar epithelium?
The nasopharynx, larynx and tracheobronchial tree (up to the start of the terminal bronchioles).
Which portion of the respiratory tract is line by stratified squamous epithelium?
Oropharynx, laryngopharynx, epiglottis and true vocal cords.
Most common mutation resulting in CF
Deletion of Phe at position 508 in the CFTR gene on chromosome 7, resulting in a frameshift mutation.
How does the CFTR work?
ATP binding allows the transporter to pump Cl- across its concentration gradient. Na and H2O follow, loosening up the mucus and promoting excretion from the exocrine pancreas. In the eccrine glands, it is responsible for removing excess salt from sweat in the ductal lumen.
3 phases of pertussis
Catarrhal (flu-like), paroxysmal (coughing spells) and convalescent (cough improves)
Virulence factors associated with the gram negative coccobacillus that causes post-jussive emesis.
Bordetella pertussis has pertactin (allows it to stick to respiratory epithelium), tracheal cytotoxin (local tissue destruction), adenylate cyclase toxin and pertussis toxin (both prevent macrophage phagocytosis).
Why give MgSO4 during an asthma attack?
It induces Ca influx, causing bronchodilation. It also stabilizes T-cells and inhibits mast cell degranulation.
Dimorphic fungus that is inhaled as hyphae but is diagnosed and spherules with endospores inside.
Coccidioides immitis. Diagnose on Sabouraud’s, 10% KOH and silver stain.
What type of virus is CMV
Double-stranded, enveloped DNA herpesvirus
What type of virus is influenza?
Enveloped single-stranded RNA virus.
What type of virus is rhinovirus?
Non-enveloped single-stranded RNA virus.
What type of virus is adenovirus?
Double-stranded non-enveloped DNA virus
How to diagnose a patient with PJP pneumonia
Eosinophilic foamy alveolar infiltrate and a cup-in-saucer appearance when stained with Giemsa or silver.
Dimorphic fungus that is inhaled as spores and seen as small intracellular oval bodies on light microscopy (most commonly inside macrophages).
Histoplasmosis
Budding yeast with a thick capsule found in immunocompromised patients
Cryptococcus neoformans
Dimorphic fungus inhaled as a mold that transforms to a yeast at body temperature with broad-based budding.
Blastomyces
Gram-positive, catalase-positive rod that is partially acid-fast and shows branching/beading on light microscopy, respiratory symptoms and single ring-enhancing brain lesion in immunocompromised patients.
Norcardia.
Proteinase/anti-proteinase balance in alveoli
PMNs and Macrophages: elastase, cathespin G, MMPs.
Serum: alpha-1 anti-trypsin, alpha-2 macroglobulin and TIMPs
Timeline of lung transplant rejection
Hyperacute: occurs within minutes due to ABO or HLA incompatibility. Graft turns white due to graft vasospasm and ischemia.
Acute: occurs 1-2 weeks after transplant, CD8 T-cell mediated rejection due to HLA mismatch, perivascular and peribronchial lymphocytic infiltrate is seen
Chronic: occurs months to years after transplant, small bronchiole obliteration (bronchiolitis obliterans)
Thick rope-like cords that grow in a serpentine pattern on culture media.
Mycobacterium. This is due to the virulence factor cord factor, which inhibits neutrophils, destroys mitochondria and induces release of TNF.
How do patients with increased elastic resistance minimize the work of breathing?
Increase the respiratory rate and decrease the tidal volume.
How do patients with increased airflow resistance minimize the work of breathing?
Increase the tidal volume and decrease the respiratory rate.
What types of viruses lose their infectivity after exposure to ether and other organic solvents?
Encapsulated viruses.
Ligamentum teres is a remnant of what
Umbilical vein
Portion of the respiratory tract with the highest resistance?
Medium sized bronchi due to turbulent flow. Then the trachea, then resistance decreases with decreasing size of the airway because the total cross sectional area increases.
23 airway generations
CONDUCTING ZONE: 0 = trachea 1 = primary bronchi 2 = lobar bronchi 3 = segmental bronchi 4 = subsegmental bronchi 5-10 = small bronchi 11-15 = bronchioles 16 = terminal bronchioles
RESPIRATORY ZONE:
17-19 = respiratory bronchioles
20-22 = alveolar ducts
23+ = alveolar sacs
How does the methacholine challenge work?
It is a muscarinic agonist that induces bronchoconstriction. A reduction > 20 in the FEV1 is diagnostic of asthma.
Nerve that innervates the sternohyoid, omohyoid and sternothyroid muscles of the anterior neck?
Ansa cervicali (C1, C2 and C3)
Where should thoracentesis be performed in the midclavicular, midaxillary and paravertebral lines?
2 intercostal spaces above the parietal border:
Midclavicular = 5-7
Midaxillary = 7-9
Paravertebral = 9-11
How to diagnose chronic granulomatous disease?
DHR flow cytometry: DHR should convert to rhodamine with ROS and demonstrate increased fluorescence.
Nitroblue tetrazolium: PMN ROS should turn compound from yellow to blue
Antibiotic of choice for alcoholic with aspiration pneumonia? How does it work?
Clindamycin covers common anaerobes associated with aspiration pneumonia (bacteroides, prevotella, fusobacterium and peptostreptococcus). It works similar to macrolides and inhibits the ribosomal 50S subunit.
Cheyne-Stokes breathing
Cyclic breathing pattern with apnea followed by gradually increasing, then decreasing tidal volumes followed by another period of apnea. It is seen in CHF because patients hyperventilate and the PaCO2 falls below the apneic threshold. During apnea, CO2 builds up and stimulates respiratory centers again that overshoot and drop the PaCO2 below the apneic threshold again. This is also seen in neurologic diseases.
Kussmaul breathing
Slow deep breathing associated with severe metabolic acidosis.
Why does smoking predispose patients to emphysema?
It can functionally inactivate alpha-1 antitrypsin and activate macrophage elastase, which is not inhibited by alpha-1 AT (unlike PMN elastase).
A patient presents with recurrent sinus infections, giardia enteritis, failure to thrive, pan-hypogammaglobulinemia and absent peripheral B-cells. What is the cause of his condition?
(Bruton’s) X-linked agammaglobulinemia is due to mutation in Bruton tyrosine kinase gene. This results in failure of marrow pre-B cells (CD 19 &20) to develop into mature B-cells (CD 19, 20 and 21)
Most common primary immunodeficiency? How does it present?
Selective IgA deficiency due to failure of class switching from IgM to IgA. It presents with recurrent acute or chronic sinopulmonary and GI infections. Of note patients may present with anaphylaxis after blood transfusion due to presence of anti-IgA IgG antibodies in their serum.
What are patients with C1 complement deficiency at increased risk of developing?
SLE
Vaccine conjugated with diphtheria toxoid as the protein
H. influenzae
Mechanism of lung parenchyma damage in patients with Tb
Delayed type hypersensitivity reaction leading to granulomatous inflammation and caseous necrosis.
Mechanism of lung parenchymal damage in patients with S. pneumoniae pneumonia.
Fluid extravasation -> Red hepatization (PMNs and RBCs) -> Grey hepatization (fibrinous material deposited)
Causes of polycythemia
Relative: dehydration and excessive diuresis with normal RBC mass
Polycythemia vera if all 3 cell lines increase and EPO is low
Secondary erythrocytosis from EPO-secreting tumor or hypoxemia (SaO2
What determines how a naive CD4+ T-cell will differentiate?
1) Binding to APC
Th-1 = IL-12 and IFN-gamma released from APC (which is usually a macrophage)
Th-2 = IL-4 released from APC
Th1 vs Th2 helper T-cells
Th1: secrete IL-2, IFN-gamma and lymphotoxin beta to activate macrophages and cytotoxic T-cells to mediate cytotoxicity and delayed hypersensitivity.
Th2: secrete IL-4, IL-5, IL-10 and IL-13 to activate B-cells and promote class switching for humoral immunity.
Treatment for patients with IL-12 receptor deficiency
IL-12 stimulates macrophages, you must give IFN-gamma to stimulate them in the absence of IL-12
At what point of the respiratory cycle is pulmonary vascular resistance the highest?
At FRC (end-tidal expiration). Resistance is high at inspiration because of lengthening of interstitial alveolar capillaries. It is also high at full expiration due to decreased radial traction on extra-alvolar large arteries.
Gram negative pleomorphic coccobacilli that are, oxidase positive rods and grow on media supplemented with factors X (hematin) and V (NAD+) or lysed RBCs (chocolate agar)
H. influenzae type B
Why is non-typeable H. flue resistant to vaccination?
It does not have a capsule.
Beta-hemolytic gram-positive cocci in chains that are bacitracin resistant
Group B strep
Varenicline mechanism of action
Partial alpha4beta2 nAChR agonist. This alleviates withdrawal symptoms and attenuated the DA reward effects of nicotine.
Perfusion-limited gas exchange
Normal pulmonary state. Complete equilibration occurs before venous blood exits the pulmonary capillary, increased blood flow = increased gas exchange. Decreased blood flow = decreased gas exchange as in a PE.
Normal FiO2, PAO2 and PACO2.
FiO2 = 160, PAO2 = 104, PACO2 = 40
Diffusion-limited gas exchange.
Pathologic pulmonary state. Complete equilibration does not occur by the time venous blood exits the pulmonary capillary. Seen in COPD, heavy exercise and pulmonary fibrosis.
Arachidonic acid pathway metabolites
5-lipoxygenase pathway -> 5-HPETE
- LTB4 (chemotaxis)
- LTC4, LTD4, LTE4 (vasoconstriction, increased permeability and bronchospasm)
- Lipoxin A4 and B4 (anti-inflammatory and decrease leukocyte recruitment)
Cyclo-oxygenase pathway -> PGH2
- TxA2 (vasoconstriction and platelet aggregation)
- Prostacyclin (vasodilation and decreased platelet aggregation)
- PGD2 and PGE2 (vasodilation and increased permeability)
Important PMN chemotactic factors
LTB4 is most potent. 5-HETE, C5a and IL-8
Gram-positive alpha-hemolytic diplococci that are bile-soluble and optichin-sensitive
Strep pneumoniae
S. pneumoniae virulence factors
Polysaccharide capsule (prevents phagocytosis), IgA protease, adhesins (adhere to epithelial cells) and pneumolysin (creates pores in cell membranes and causes lysis)
Most common causes of SVC syndrome
Lung cancer > Hodgkin’s lymphoma
3 types of point mutations
Silent (no effect), missense (codon codes for the incorrect amino acid) and non-sense (codon codes for stop codon and transcription is cut short).
Pleomorphic gram-negative coccobacilli that only grow with NAD+ and hematin supplementation.
H. influenzae
Virulence factors of H. influenzae type B
PRP (pentose monosaccharide capsule) prevents phagocytosis and factor H (degrades C3b)
Most common type of Hodgkin lymphoma
Nodular sclerosis type: Reed-Sternberg cells and nodular growth pattern surrounded by fibrosis
How is surfactant released from type II pneumocytes?
Stored and released by lamellar bodies that unravel when they get to the cell membrane (exocytosis).
What are the satellite colonies of bacteria that form around staph aureus colonies on culture media?
H. influenzae. Staph hemolyzes sheep agar, releasing hematin (factor X) and staph secretes NAD+ (factor V), both which are necessary for H. influenzae growth.
Alcoholic with pneumonia and encapsulated gram-negative bacilli that grow as pink mucoid colonies on MacConkey agar
Klebsiella pneumoniae
Gram-negative fast lactose fermenters (pink)
Klebsiella, E. coli and enterobacter
Gram-negative slow lactose fermenters (pink)
Citrobacter and serratia
Gram-negative non-fermenter (white) that is oxidase positive
Pseudomonas
Gram-negative non-fermenter (white), oxidase negative without H2S production on TSI agar
Shigella
Gram-negative non-fermenter (white), oxidase negative with H2S production on TSI agar (black colored)
Salmonella and proteus
What RNA polymerase is restricted to the nucleolus?
RNA polymerase I: it transcribes the 45S pre-RNA gene into a templet that is processed into 18S, 5.8S and 28S rRNA segments.
Why do malignant cells have prominent nucleoli?
There is increased synthesis of rRNA a genes
RNA polymerase II function
Synthesize mRNA, snRNA and miRNA. It is the most highly regulated polymerase.
RNA polymerase III function
Synthesize tRNA and 5S rRNA
How does bee venom initiate an IgE response
Hyaluronidase and phospholipase
Why are patients with RA at risk for pulmonary fibrosis?
Inherent extra-pulmonary manifestation of the disease and treatment with methotrexate.
Conditions with cold hemagglutinins
Mycoplasma, EBV and hematologic malignancy
Pneumoconiosis with eggshell hilar calcifications and birefringent particles surrounded by collagen fibers in the upper lobes.
Silicosis
Pneumoconiosis with lower lobe pleural plaques and ferruginous bodies seen best with Prussian blue stain
Asbestosis. Ferruginous bodies are fusiform rods with a translucent asbestosis center covered in iron-proteinaceous material.
Pneumoconiosis with noncaseating epithelioid granulomas identical to sarcoid
Berylliosis
Pulmonary edema’s effect on pulmonary mechanics
Decreased compliance
Blood gas effects on cerebral blood flow
Most prominent when MAP is 60-140
PaCO2: 25-100mmHg = linear dilation/constriction of cerebral blood flow
PaO2: 50-100mmHg = constant cerebral blood flow
PaO2
