pulmonology Flashcards
def negative predictive value? how do you calculate it? relation to dz prevalence
- probability that pt truly does not have disease given a negative result
- d/ [(c+d)] (true negatives/total negative tests)
- varies inversely based on disease prevalvence
calculate specificity and sensitivity
spec-d/(b+d) (true negatives/total disease negatives)
sens- a/(a+c) (true positives/total disease positives)
codon vs frameshift mutation
codon has to be multiples of 3
frameshift can insertion or deletion of bases that are not multiples of three
frameshift vs point mutations
frameshift is insertion or deletion that results in new reading frame
point mutations aka base substitutions do not affect the reading frame
pt with killed viral vaccine will cause? not destruction by T-lymphoncytes because
hummoral response (i.e. impaired entry of influenza entry into cells by targeting HA). not cell-mediated b/c it’s a killed vaccine instead of attentuated
cell type found in respiratory tract, nose, paranasal sinuses, nasopharynx, most of larynx and trachobronchial tree? cell type found in oropharynx, laryngopharynx, anterior epiglottis, upper half of posterior epiglottis and vocal folds (true vocal cords)
- pseudostratified columnar, mucus secreting epithelium
- stratified squamous epithelium
mediators of granuloma formation/cellular response
vs
mediators of humoral responses
- IL-2, ad IFN-gamma which stimulate Th1 type CD4+ helper cells, and macrophage activation respectively
- mediated by Th2 type CD4+ helpers cells- produce IL-4 to activate IgE antibody production by B-cells, and Il-5 which promotes eosinophil activation and iGA synthesis from b-cells
pts neutrophils fail to turn blue upon nitroblue tetrazolium test indicates what type of infection?inheritance? role of the enzyme missing? which bacteria are resistant?
chronic granulomatous disease (CGD)- results from a deficiency in NADPH oxidase (produces reactive oxygen species “oxidative burst” that reduce nitroble tetrazolium to make blue pigment). X-linked. bacteria that have catalase are resistant neutrophils
alpha 1-antitrypsin deficiency definition. pulmonary and liver complications
alpha1-AT is a serum elastase inhibitor, without it elastin is disproportionately degraded.
associated with emphysema and liver cirrhosis.
tell pts to avoid smoking
mech of N-acetylcysteine in CF patients
cleaves disulfide bonds within mucus glycoproteins- loosening thick sputum
which antifungal drug acts on cell wall vs cell membrane?
echinocandins (caspofungin and micafungin), inhibits synthesis of polysaccharide glucan (essential component of fungal CELL WALL) vs membrane with other anti-fungals
-amp B and nystain bind ergosterol and form pores in cell membrane
is there a HIV vaccine? what is used as maternal prophylaxis during pregnancy? mech of action?
NO! nucleoside analog zidovudine (ZDV,AZT), a retroviral reverse transcriptase inhibitor.
in pts with COPD at what RR is work of breathing minimized? in increased elastic resistance?
work of breathing is minimized in pts with increased elastic resistance when RR is high and tidal volume is low (fast, shallow breaths)
vs pts with diseases that increase air flow resistance (COPD, asthma) work of breathing is minimized when rate is low and tidal volume is higher (slow deep breaths)
minute ventilation=
what happens if one of the two variables change?
tidal volume*RR.
if tidal volume changes body with change RR to maintain constant minute vent and save energy
i.e COPD increases TV or RR decreases
Restrictive pulomonary disease decreases TV and increases RR
hypoventilation has what A-a gradient?
normal
binding of O2 in lungs does what to H+ levels and CO2 levels? what is this called?
increases RBC release of H+ and CO2
-Haldane Effect
HHb-H+ + Hb (Hb is free to attach to O2)
H+ + HCO3-=H2CO3=H2O +CO2 (via carbonic anhydrase)
high concentrations of CO2 and H+ does what to O2 on Hb? what is this called?
causes release of O2- Bohr effect
H+ Hb (hemoglobin is released from O2)-HHb
CO2 +H2O=H2CO3=H+ + HCO3
when taking inhaled glucocorticoids pt should be warned to
rinse mouth, b/c of association with oropharyngeal candidiasis
which gas is major stimulator of respiration?
PaCO2
what happens to respiratory drive in prolonged hypercapnea? why should physicians be careful to replenish O2 in these pts
drive to breath is stimulated by hypoxia b/c hypercapnia no longer stimulates the respiratory drive
-rapid increased in the fraction of inspired O2 can lead to respiratory failure in these patients.
minute time vs alvelolar ventilation equations
minute vent= tidal vol* RR
alv=(TV-dead space vol) *RR
infection that causes cold agglutins resulting in agglutination at low temps
mycoplasma pneumoniae,
EBV
and hematology malignancy
phosphatidylcholine and phosphatidylglycerol are components of? which rises more sharply after 30 wks? 36 wks? which is known as lecithin and used in an pulmonary function ratio? value of ratio?
surfactant-dipalmitoyl phophatidylcholine aka lecithin (L)-phosphatidylglycerol-lecithin/sphingomyelin ratio should be above 2 for adequate surfactant production
which bacteria have polysaccaride capsules and can have their capsule components be bound to protein carriers to be used as a vaccine.
streptococcus pneumoniae, neisseria meningitidis, and Haemophilus influenzae type b (Hib)
commonly bound to diphtheria toxoid
lamellar bodies of type II pneumocytes-action, complication if deficient, example
store and release surfactant, deficiency can cause patchy alveolar atelectasis as is seen in neonatal respiratory distress syndrome
which measurement is resistance to outliers in a dataset
mode
structures in bronchi vs terminal bronchioles (globlet cells, cartilage, smooth muscle, pseudostratified ciliated columnar cells)
- cartilage and goblet cells extend to end of bronchi
- pseudostratified columnar ciliated epithelium extend to beginning of terminal bronchi then transition to cuboidal cells
- smooth muscle extend to end of terminal bronchi
treatment for severe asthma if oral and inhaled steroids and long acting beta agonist don’t work? not H1 histamine receptor antagonist because?
- give anti IgE antibodies-Omalizumab (IgG1 antibody that binds IgE to inhibit it’s action on mast cells)
- treats chronic urticaria and allergic symptoms but not asthma
proteases in intra-alveolar fluid are derived from what pulmonary cell
alveolar macrophages or infiltrating neutrophils. can cause emphysema if secretion is unchecked by anti-trypsin
Clara cells secrete? purpose of this secretory product?
clara cell secretory protein (CCSP)-inhibits neutrophil recruitment and activation
prolonged ACTH stimulation causes hyperplasia to what level of adrenal gland? why not hypertrophy?
- zona fasciculata and reticularis
- hyperplasia not hypertophy is primary feature of increased ACTH
condition associated with hyperplasia of
- glomerular layer
- fasciculate/reticularis layer
- adrenal medulla
- atrophy of cortex
- Conn’s syndrome (increased aldo)
- Cushing’s syndrome (increased cortisol)
- rare-pheochromocytoma or neuroblastoma can sometimes occur here
- Addison’s disease. medulla is spared
why is fructose rapidly metabolized in glycolytic pathway?
b/c it bypasses PFK-1 which is rate limiting step in glycolysis.
fructose-fructose 1-phosphate (via fructokinase)
F-1-P to dihydroxy acetone phosphate (DHAP) and glyceraldehyde (aldolase B)
glyceradehyde to G3P (via trioskinase)
galactose enters glycolysis where? mannose?
-glucose 6 phosphate-fructose 6 phosphate
4 major causes of hypoxemia (low PaO2)? what is A-a gradient used for? normal value
alveolar hypoventilation, ventilation-perfusion mismatch, diffusion impairment, and right to left shunting
-if normal than alveolar hypoventilation is only reason for hypoxemia (normal 10-15; PAO2-paO2)
how are macrophages activated? describe their role in granuloma creation?
T- helper cells produce IFN-gamma to mature macrophages. macrophages produce TNF to recruite monocytes. monocytes differentiate into epithelioid histiocytes to cluster around invading pathogen.
Potter syndrome
pulmonary hypoplasia Oligohydraminios (trigger) Twisted facies (low set-ears, retrognathia) Twisted skin Extremity defects Renal agenesis
hyper IgM syndrome-def, causes (2)
inability of B-lymphocytes to class switch from IgM to other isotypes (IgD, IgG, IgE, IgA genes are arranged in this order on DNA) -genetic absence of CD-40 ligand on T-lymphocytes or deficiency in enzymes responsible for DNA modification in isotype switching
most common mutation in cystic fibrosis
3-base pair deletion that removes phenylalanine at a.a position 508. leads to mistakes in postranslational protein modifications causing early degredation of protein before is can be transported to the cell surface.
pt with bacterial pneumonia secondary to viral infection has what bacteria? not listeria monocytogens because
- listeria monocytogens is a occasional cause of septicemia and purulent meningitis in neonates
- pathogens most often responsible are Strep pneumo, staph aureus, and haemophilis influ
s.pneumoniae is sensitive to optochin and? appearance on gram stain?
bile.
- “lancet-shaperd gram positive diplococci”
name 5 materials needed to perform PCR
DNA template, 2 primers (must know flanking sequence not entire sequence to make these), DNA polymerase (thermostable ones like Taq), deoxynucleotide triphosphates
measurement used to determine alveolar ventilation-normal, if decreased, if increased, equation
- PaCO2 (normal 33-45mmHg)
- hyocapnia implies hyperventilation
- hypercapnia implies hypoventilation
- PaCO2=basal metabolic rate/alveolar ventilation
when is pulmonary vascular resistance the lowest? not at end of maximal expiration or maximal inspiration because?
- functional residual capacity (at end of normal expiration) (balance between intra and extra alveolar blood vessels)
- end of maximally expiration compress extra-alveolar blood vessels by reducing radial traction (force opening vessels from extra cellular space) from adjacent tissues
- end of maximal inspiration compresses interstitial alveolar blood vessels
overview of legionella pneumonia clinical features (4) lab findings (3) diagnosis (1) treatment (2)
-high fever with relative bradycardia
-HA and confusion
-watery diarrhea*
lab -hyponatremia, sputum stain with many neutrophils by no organisms
diagnosis
-legionella urine antigen test
-respiratory fluoroquinolones (levofloxacin) or macrolides (azithromycin)
ratio of CD4+/CD8+ in sarcoidosis vs interstitial lung disease vs lymphocytic interstitial pneumonitis (AIDS pts)
these three diseases have similar presentations
can use bronchoalveolar lavage to rule out sarcoidosis
-CD4+/CD8+ ratio is increased in sarcoidosis (granulomas) but decreased in the other two diseases
organ most likely removed during laparotomy in pt with abdominal trauma from motor vehicle accident? pt is susceptible to which type of infection?
spleen from splenic rupture. pt is susceptible to encapsulated species (SHiN bacteria)
what factor affects cerebral blood flow?
PCO2 , decrease cerebral vascular resistance leading to increased cerebral perfusion and ICP.
which nerve mediates cough reflex? location? damaged how?
internal laryngeal nerve
above vocal cords, deep to piriform recess
-foreign bones (fish, chicken) can cause damage or efforts to retrieve them
abestos exposure leads to increased risk of? which is more likely? HY!!
- bronchogenic carcinoma and mesothelioma
- bronchogenic carcinoma!!!
which antibiotics cause bacteria to lose the ability to survive osmotic stress?
the ones that attack the cell wall. penicillins, cephalosporins, vancomyocin
name P-450 inhbitiors- what is mnemonic?
A cute gentleman “Cipped” Iced Grapefruit Juice Quickly And Kept Munching on Soft Cinammon Rolls
Acute alcohol abuse, gemfibrozil, ciprofloxacin, isoniazid, grapefruit juice, quinidine, amiodarone, ketoconazole, macrolides, sulfonamides, cimetidine, ritonavir
which antibiotics work by degrading cell wall. which bugs is resistant to them? treat instead with what?
- penicillins, cephalosporins, carbapenems, and vanc
- all organisms of mycoplasma genus
- treat instead with anti-ribosomal agents (tetracycline and erythromycin)
when should advanced car planning for end of life issues be discussed?
- best during outpatient visits with primary care docs
- must also be readdressed during admission process for acute admissions
- pt with multiple co-morbidities after completing history, physical and stablization
how to treat individuals with IL-12 receptor deficiency?
- IL-12 is required for T-helper cell transformation to TH1.
- TH! then secretes IL-12, IFN-gamma and lympotoxin beta to activate mac, CD8+ Tcells and mediate delayed type hypersensitivity
- so give IFN gamma
histological appearance of bronchioloalveolar carcinoma. benign or malignant? location? pt pop
- tall columnar cells that line alveolar septa without evidience of vascular or stromal invasion
- malignant
- lung periphery
- nonsmoker
most common benign lung tumor? presentation? histo?
- hamartomas
- asymptomatic
- mature hylaine cartilage mixed with connective tissue, smooth muscle, and fat
what happens 1 wk after TB infection. not epithelioid transformation of monocytes b/c? what else happens during this time?
- intracellular bacterial proliferation that due to phagocytosis by macs
- granuloma formation doesn’t occur without signaling (interferon release) form T-helper (type 1) cells which come 2-4 wks after initial infection this created ghon focus
- b cell are activated by TH2 helpers cells to make antibodies but they are not as effective as TH! signaling
types of pneumonia
- bronchopneumonia-patchy inflammation of a number of lobules
- interstitial-inflammatory infiltrate confined to alveolar walls
- lobar-entire lung
stages of lobar pneumonia
-congestion (1st 24 hrs)
red hepatization (2-3 days)
gray hepatization (4-6 days)
resolution
describe macro and micoscopic appearance of congestion red hepatization gray hepatization resolution
- macro:affected lobe is red, heavy and boggy. micro: vascular dilation, alveolar exudations contain bac
- macro: red-firm lobe,like liver. micro: alvelolar exudate has RBCs, neutrophils, and fibrin
- macro: gray-brown firm lobe micro: RBCs disintegrate, alvelolar contains neutrophils and fibrin
- macro: restoration of normal architecture micro: enzymatic digestion of exudate
presentation of anaphylaxis. marker for mast cell activation? not 5-hydroxyindoleacetatic acid b/c
- urticaria, with or w/o cutaneous angioedema, laryngeal edema (causing dyspnea)
- tryptase
- this is breakdown product of serotonin used to screen for carcinoid tumors
treatment for pt with PHTN not due to diabetes or CHF. mech?
anything that will vasodilate vessels
-bosentan is a competitive antagonist of endothelin receptors used for treatment of primary (idiopathic pulm arterial HTN)
etanercept-mech, uses (3)
humanized monoclonal antibody that binds TNF thereby decreasing its concentration in serum
-anti-inflammatory agent used for RA, psoriasis, and psoriatic arthritis
PE leads to what metabolic disturbance?
- hypoxemia leads to hyperventilation causing decreased CO2 and O2 and metabolic alkalosis
- bicarb compensates late and determines pH
normal ranges for PaO2, PaCO2, HCO3-
- 80-95
- 35-45
- 22-26
an unaffected individual with sibling with an autosomal disease has what chance of passing on allele to offspring? not 2/4 because?
2/3 chance of being a carrier. not 2/4 b/c we already know that person is does not have disease so that only leaves 3 options not 4.
which ion is used to determine cause of metabolic alkalosis? what are expected levels in 3 types?
- urinary Cl
- vomiting (decreased urinary Cl; can be corrected with saline)
- loop diuretics and furosemide (increase urinary Cl (follows Na+); can be corrected with saline and chloride)
- primary hyperaldosteronism (Conn syndrome) (increased urinary Cl concentration; does not correct with chloride or saline)
- role of antibiotic in protein syntheis
- streptomycin
- chloramphenicol
- clindamycin/erythromycin
- tetracycline
- aminoglycosides
- linezolid
- binds 30S and prevents formation of initation complex (can also cause misreading of RNA)
- binds 50S aminoacyl-tRNA binding
- bind 50S and prevent translocation
- binds 30S and prevent amionacyl-RNA to A site binding
- binds 50S and blocks binding of initiator tRNA (step before aminoglycoside)
HR and BP in tension pneumothorax, location of lung apices
- above level of clavicle and first rib through superior thoracic aperture (lateral to manubrium sterni)
- HR increases, BP decreases
how to injury ansa cervicalis? carotid body? not near clavicle b/c
- trauma to neck superior to cricoid cartilage
- this lies at birfircation of CCA just inferior to hyoid bone
- trauma near clavicle can lead to pneumothorax
multiple linear regression
used to compare linear relationship between a dependent variable and 2 or more independent variables
what give elastin it’s plasticity and ability to recoil upon release of tension?
- demosine crosslinking between 4 different lysine residues on four different elastin chains
- accomplished by action of extracellular lysl hydroxylase
compare and contrast elastin and collagen
- both have non polar residues
- collagen proline and lysine are hydroxlyated while elastin is not
- triple helix is formed in collagen but not in elastin
- triple helix is initiated by hydroxylation, glycosylation, and interchain disufide bridges at C-terminus of procollagen. these modifications are not seen in elastin molecules
- collagen crosslinking is mediated by lysyl oxidase and elastin crosslinking is mediated by lysyl hydroxylase
which anti TB drug works best in acidic environment
pyranzinamide
- works intracellularly (inside macs where it’s acidic)
- other anti-TB drugs work better extracellularly
which viruses utilize eukaryotic ribosomes for protein synthesis by production of a polyprotein product from a single mRNA transcript?
-positive sense mRNA, which non segmented genomes (picorno, calci, hepes, flavi, toga, retro, corona)
which anti TB drug needs catalase-peroxidase to be active? coded by which gene? mech of drug?
- isoniazid
- KatG
- decrease synthesis of mycolic acids
equation for ARR
event rate (control)-event rate (treatment)
levels of HCO that indicate acute vs chronic respiratory acidosis
30 chronic
-usually take 3-5 days to have maximal effect
location of left ventricle vs other heart chambers vs lung
- reaches as far at 5th intercostal space at left midclavicular line
- all other chambers lie medical to left clavicular line.
- lungs overlap much of anterior surface of heart
spec and sens of methacholine challenge test
- test for asthma
- high sensitive but low spec
- good for ruling out?
explain lower border of lung pleura on right and left at midclavicular line, midaxillary, and paravertebral lines. where is lower border of lung located relative to this?
- 7th rib, upper border of 10th rib, 12th rib
- 7th rib, lower border of 10th rib and 12th rib
- two intercostal spaces above pleural border
where should thoracentesis be performed? (ribs, midclavicular line, midaxillary, and paravertebral)
- upper border of rib (avoid risk of intercostal vein, artery, or nerve puncture)
- 5-7th ribs along midclavicular line
- 7th-9th ribs at midaxillary
- 9-11th ribs at paraverterbral
- higher risk injury to lung
- lower risk injury to liver
what causes toxicity of AMP B
- although it binds to ergosterol in fungi it can also bind to human cholesterol
- nephrotoxicity, hypokalemia, hypomagnesemia, acute infusion related rxn, anemia, thrombophlebitis
which antifungals inhibit P450 enzymes
-triazole antifungals (fluconazole, itraconazole, ketoconazole)
mech of scilicosis increasing risk of TB infection. not pulmonary fibrosis b/c?
- impaired killing by macs b/c of internalized silica particles
- fibrosis would not inhibit mac functioning, and instead would make it more difficult for bac to infect or help contain infection
which drug can reduced withdrawl symptoms and attenuate rewarding effects of nicotine? mech? not nictotine patch b/c?
- varenicline is a partial agonist
- competed with nicotine and prevents it from binding
- patch doesn’t reduce reduce stiumulation of receptor thereby not helping to attenuate rewarding effects
topirimate-uses (2)
- anticonvuslant used to treat epilepsy in children and adult
- prophylaxis against migraine headaches
location of cilia vs mucus secreting cells
- level of terminal bronchioles
- smallest bronchi
When to think of lead time bias?
-when you see a “new screening test” for a poor prognosis disease like lung or pancreatic cancer
what are symptoms of superior vena cava syndrome?
intrathoracic spread of bronchogenic carcinoma (mediastinal mass) can lead to compression of SVC causing impaire venous return
-dsypnea, facial swelling, dilated collateral veins in upper trunk, HA, dizziness
another name for pancost tumor?
superior sulcus tumor
-shoulder pain, Horner’s syndrome (ptosis, miosis, and anhydrosis), hoarseness, SVC syndrome, senorimotor deficits
how can infection with mycoplasma bacteria cause anemia?
- phospholipid bilayer of bac shares antigens with human erythrocytes
- body’s response to bac cause lyse of RBCs
- these antibodies are called cold agglutinins and go away once infection has been cleared
acid fasteness is a property inherent to all bac with? name 2 examples
- mycolic acid
- mycobacterium and norcadia
what pattern does mycobacteria grow in? wht causes this and what other effect does this have on bac?
- sepentine cord
- b/c of cord factor (a mycoside)
- allows for virulence, mycoplasma without it can’t cause disease
how does cord factor help mycoplasma establish virulence?
- neutrophil inhibition
- mitochondrial destruction
- induces release of TNF
name the fungi
- multinucleated spherules
- ovoid cells within macs
- budding yeast with thick capsule
- pseudohyphae and blastocondia
- septate hyphae with dichotomous branching
- coccidiodes immitis
- histoplasma capsulatum
- crytococcus neoformans
- candida, blastocondida are spores that grow as bid on candida hyphae
- aspergillus fumigatus
fungi from bats and bird droppings? found where in US
- histoplasma capsulatum
- Central america (misssissippi and ohio river basins)
CD 16
surface marker for NK cells and other cell types
CD 19, 20, 21
B cell surface marker
CD 15
marker for neutrophils
Reed-Sternburg cells (Hodgkin Lymphoma)- also has CD 30
young child with low levels of b cells, circulating immunoglobuiins, and recurrent respiratory infections and persistent giardiasis
-Bruton’s agammaglobulinemia
complications of obstructive sleep apnea
-pulm HTN and RH failure
how do eosinophils look on blood smear? what do they release that can kill helminths and mediate atopic (extrinsic allergic) asthma
- bilobed nuclei with eosinophilic granules
- major basic protein
how do neutrophils appear on blood smear?
-multilobed nuclei (>3) with pale cytoplasm and heterogeneously staining ganules
how do basophils appear on blood smear?
granules stain dark blue are irregularly sized and usually obscure stained nucleus
how do organisms become resistant to rifampin?
-structural alteration of enzymes involved in RNA synthesis (DNA-dependent RNA polyerase)
describe Cheyne-Stokes breathing. seen when? different from restrictive pulmonary disease how?
- cyclic breathing in which apnea is followed by gradually increasing tidal volumes and then gradually decreasing tidal volumes until nxt apneic period
- CHF or neurological disease
- restrictive has fast breathing, but it’s shallow so tidal volume curve should have smaller length
stimulation of vagus nerve has what effect on lung? which receptors mediate this? what effect on work of breathing? drugs (2) that antagonize this effect?
- bronchoconstriction and increased mucus secretion
- via M3 receptors
- increased work of breathing
- tiotropium and ipratropium
CFTR protein is what type of channel? what role does it have on sweat production?
- ATP-gated chloride channel
- cause hypotonic sweat by pumping in Cl- (and Na+) before ductal lumen before it reaches surface
allergic triad
-allergic rhinitis
atopic dermatitis
asthma
having one predisposed to having the other
methacholine test-disease, mech, results
induces bronchoconstriction and increased mucus production in pts with asthma
- cholinergic agonist
- FEV1 decreases by more than 20% (prolonged expirations)
best target for asthma: histamines or leukotrienes
- although both substances are thought to play a role in symps of asthma only leukotrienes (LTC4, LTD4 and LTDE) blockade provides relief.
- zafirlukast and montelikast
what happens to perfusion as you go from apex to base? ventilation? V/Q?
- perfusion greatly increases
- but ventilation only slightly increases
- so V/Q decreases from apex to base
which zone is all of lung when a pt is supine?
zone 3. heart does not have to pump against gravity anymore
At FRC what is airway pressure? what is intrapleural pressure?
- 0
- about -5cm H20 (chest wants to expand lungs want to collapse)
what effect does PCO2 have on cerebral blood flow?
- decreased blood flow if hypocapneic
- increased blood flow if hypercapneic
if a patient has hypoxiema (define this) what is first value to calculate? give equation. how does this help determine causes (3)?
- hypoxiemia is low PaO2
- first value to calculate is A-a gradient. normal is 10-15
- PaCO2 is measured from blood gases
- PAO2 is measured from 150-PaCO2/0.8
- amt in alveolar space=FIO2-PaCO2/R
- if increased then hypoxiema is due to decreased diffusion, shunting, or V/Q mismatch
which variables affect total oxygen content of blood
- hemoglobin concentration
- oxygen saturation (SaO2)
- partial pressure of dissolved oxy in blood (PaO2)
what is problem if SaO2 is normal, PaO2 is normal but total oxygen content is decreased?
-Hb concentration (i.e bleeding or another form of anemia)
what happens to venous SaO2 in cyanide poisioning? two mechs
- it increases b/c of less O2 delivery to tissue
- cyanide inhibits O2 release by binding to Hb and by inhibiting cytochrome C oxidase (failure of electron transport chain means O2 is not used)
describe resistance of airways in lower respiratory tract (curve shape, most contribution from?)
- curve increases and then decreases
- in first 10 generations of bronchi contribute to most of total airway resistance
- maximal 2nd-5th generation airways including segmental bronchi (b/c of turbulent flow)
- airways less than 2mm in diameter (bronchioles) contribute <20% of total airway resistance
which law explains the need for surfactant? what does surfactant help prevent?
- Laplace’s law P=2T/r
- as the radius of a sphere with constant surface tension decreases the distending pressure increase.
- smaller sphere collapse before larger ones
- surfactant helps to decrease surface tension as radius decreases so as to keep distention pressure the same and alveoli open
chloride shift
occurs in RBC when HCO3- is forms and diffuses out of cytoplasm
- used to maintain electric neutrality
- reason for high Cl- content in RBCs in venous blood
why is pO2 in left atrium lower than pO2 in pulmonary capillaries?
-b/c majority of deoxygenated blood supplied by bronchial arteries is returned to the left heart in deoxygentated form via pulmonary veins
what clears particles 2.5-10um in size? 10-15um in size? less than 2um?
- less than 2= these reach alveoli and are taken up by macs and also stimulate connective tissue growth
- trapped in upper respiratory tract
- cleared by mucociliary transport
how does isoniazid decrease B6 levels?
- it’s structurally similar to pyridoxine and increases it’s urinary excretion
- competes for vit B6 binding sites leading to decreased synthesis of neurotransmitters like GABA
mc cause of meconium ileus? presents how?
- CF
- distal small bowel obstruction in neonate due to abnormally dehydrated meconium
- bilious vomiting, abdominal distention, air fluid levels, and small bowel dilatation with “inspissated (dry, dehydrated) green mass”
describe structure of MHC I vs MHCII
- heavy chain and beta2 microglobulin
- alpha and beta polypeptide chains
presentation of fat embolism syndrome
hypoxemia (fat emboli in pulmonary microvessels)
- acute-onset neruologic abnormalities (fat emboli that pass through lungs becomes trapped in CNS)
- petechial rash and thrombocytopenia (fat embolism that arise secondary to plt adherence and coating of fat microglubules)
brassy barking cough and recent history of repsiratory infection in child is? mc cause? not RSV b/c?
- viral laryngotracheitis (croup)
- parainfluenza virus of paramyxovirus
- RSV causes bronchiolitis, pneumonia in babies.
H. influ vaccine is only effective against which strain? why? what do other strains cause?
- type B
- other stains without capsules (non typeable) are a part of normal flora of upper respiratory tract can cause otitis media, sinusitis, and bronchitis.
theophylline-class, mech intoxication cause of morbidity (2), metabolized by
methylxanthine,
- bronchodilation by inhibiting phosphdiesterase (increase cAMP levels due to decreased cAMP hydrolysis), blocks action of adenosine
- seizures and tachycardia
- P-450 system
major virulence factor of S.pneumoniae. what happens when antibodies are made against it in vitro?
- polysaccharide capsule
- capsule swells-quellung rxn
silicosis vs asbestosis vs berylliosis vs coal miner’s lung-location, histo
- silicosis- eggeshell calcifications of hilar lymph nodes and birefringent particles surrounded by fibrous tissue
- calcified pleural plaque and ferruginous bodies (prussian blue staining)
- non caseating granulomas
- perilymphatic accumulations of coal dust laden macrophages
what is reid index used for? define it? what’s it’s normal value?
used to measure severity and duration of chronic bronchitis
- ratio of thickness of mucous gland layer in bronchial wall submucosa to thickness of the bronchial wall between respiratory epithelium and cartilage wall
- normal is 40%
presentation of MAC vs TB
- both present with fever, weight loss and diarrhea
- mycobacterium avium complex affects HIV pts with CD4+ count<50cells/uL. presents as anemia, hepatosplenomegaly, and elevated alkaline phosphatase and LDH b/c of involvement in reticuloendothelial system, also grows in higher temps 41C
- treat prophylactically with MAC with azithromycin to avoid MAC
- treat prophylactically with isoniazid to avoid TB
opportunistic infections in HIV: CD4+ counts and prophylaxis
- Pneumocystis jirovecii
- Toxoplasma gondii
- Mycobacterium avium complex (M. avium and M. intreacellulare)
- Histoplasma capsulatum
-CD4+
infiltrate in asthma vs bronchitis
-eosinophils and mast cells vs neutrophils
describe histology of bronchitis. leading cause?
- thickened bronchial walls, neutrophil infiltration, mucous gland enlargement, patchy squamous metaplasia
- smoking
recurrent sinopulmonary infections and exocrine gland fibrotic atrophy in young Caucasian
-CF
loss of vit A in CF leads to
- vit D
- vit E
- vit K
- usually maintains orderly differentitaion of specialized epithelia, deficiency leads to squamous metaplasia of epithelia to keratinizing epithelium
- ricket’s in children and osteomalacia in adults
- infertility and decrease serum phospholipids
- coagulopathy (bleeding diathesis)
why is Hib vaccine PRP capsular polysaccahride conjugated? what is it usually conjugated to?
- purpose is to increase immunogenicity (activated T cell to promote B cells class switching and memory cell formation). this would not occur with pure polysaccharide immunization
- tetanus or diphtheria toxoid
what stain colors fat black?
-osmiun teroxide
treat treponema with
penicillin
DiGeorge vs SCID vs Wiskott-Aldrich syndrome
all have thymic shadow loss
- only T cell impairment and there are other organs affected (parathyroid and cardiac)
- both T and B, no outside organ involvement, just young child with lots of infections and hypogammaglobulinemia
- both T and B cells are impaired also see thrombocytopenic purpura and eczema only IgM is low
single encapsulated yeast with broad based bud? diagnosed how? no cryptococcus neoformans or coccidioides immits b/c?
- blastomyces dermatidis
- KOH prep
- forms narrow based buds and stains with india ink
- spherules (round encapsulated structures with many endospores)
mc liver pathology in sarcodisis
scattered noncaseating granulomas near portal triads
presentation of sarcoidosis
Strawberry cheeks and nose (lupus pernio)
ACE level elevated
Restrictive lung disease
-hyperCalcemia
-NOdes (erythema NOdosum, and lymph nodes)
-bIlateral hIlar lymphadenopathy
-Droopy face (bell’s palsy) and increased vit D
-Schaumann and aSteroid bodies
-Inflammaiton of eye “I” (uveitis)
-Sistas (African american women)
tissue damage in resultant abscess formation is primarily caused by? not IL-12 secretion by neutrophils b/c?
- caused by release of lysosomal enzymes from macs and neutrophils
- iL-12 stimulates natural killers cells to destroy target cells not parenchyma
presentation of histoplasma capsulatum
-systemic symptoms (fever and weight loss), painful oral ulcers, lymphadenopathy and hepatosplenomegaly
which drug has effect on mycolic acid synthesis? not ethambutol b/c?
- isoniazid
- ethambutol inhibits cell wall synthesis by another mechanism
treatment of plague and tularemia
streptomycin
Langhan giant cells-define, formed from? found where?
- multiple nuclei peripherally organized in shape of horseshoe
- formed from acs activated by CD4+ th1 lymphocyctes
- seen in granulomas
when can isoniazid monotherapy be used?
in pts with positive PPD but negative chest X-ray. not evidence of clinical disease
bronchiolitis obliterans
chronic rejection in lung transplant pts
-affect small airways leading to occlusion of bronchiolar lumen
leading cause of death in lung transplant pts
infection due to CMV
why is pus green?
neutrophils release myeloperoxidase which is a heme containing pigmented molecule
blastomyces dermatitidis is characterized how in immunocompromised vs immunocompetent adults?
- competent: pulmonary disease with granuloma formation
- compromised: can also lead to dissemenated disease (mycosis) in immunocrompromized host (pulmonary symptoms + skin and bone involvement)
X-rays findings in
- pulmonary edema
- interstitial lung disease
- pnuemothorax
- pleural effusion
- atelectasis
- PE
- fluffy appearing infilrates, bilateral
- reticular markings in both lungs on chest x-ray
- increased lucency on affected side
- trachea deviated away from opacified side
- unilateral pulmonary opacification and deviation of mediastinum towards the opacified lung
- normal X-ray
EM of mesothelioma vs adenocarinoma
- both like to arise at periphery of lung
- mesotheliome has numerous long slender mucrovillli and abundant tonofilaments
- adeno has short plump microvilli
anti asthmatic drug mechanism
- reverse vagally-mediated bronchospasm
- bronchodilation by decreasing enzyme activity and increasing cAMP
- inhibit A. acid pathway leukotriene synthesis
- prophylactic treatment
- block calcium influx into bronchial smooth muscle cells
- antimuscarinics (ipratropium of tiotropium)
- methylxanthines (theophylline and aminophylline)
- zileuton
- flunisolide
- nifedipine
characteristics of lung transplant rejection
- hyperacute
- acute
- chronic
- rejection to ABO. graft blood vessel spasm and diffuse intravascular coagulation with ischemia “white graft” rxn. irreversible
- rejection to HLA. CD8+ cell mediated. perivascular and peribronchial lymphocyctic infiltrates. reversible with immunosuppressants
- bronchiolitis obliterans. inflammation of small bronchioles leads to fibrosis and narrowing of bronchi
chronic transplant rejection of lung vs kidney
- in lungs bronchi are affected
- in kidney vasculature is affected
what is used to prophylactically treat group B strep? when? what can this bac cause?
- screen for group B strep colonization of rectal and vag cultures at 35-37 wks
- INTRAPARTUM antibiotics (penicillin or ampicillin*)
- sepsis, pneumonia, and meningititis
describe process of acid fast stain? which bac are acid fast stainers? (2)
applying aniline dye (carbolfuchsin*) to a smear and then decolorizing with acid alcohol (HCl and ethanol) to reveal whether organisms have mycolic acid in their membrane
- mycoplasma and norcardia
- acid fast
- it’s an aniline dye
type of granulomas seen in sarcoidosis vs TB
- TB caseating
- sarcoid- non caseating
which cytokines can increase ESR? how?
- IL-1, IL-6, TNF-alpha (released by local neutrophils and macs)
- these stimulate hepatic secretion of acute phase reactants
- one of them fibrinogen can increase sed rate
name 3 eicosanoids. what is their precursor and enzyme that makes them?
- all arachidonic acid precursors
- prostaglandins and thromboxanes (COX 1,2)
- leukotrienes (5-lipoxygenase)
- lipoxins (12-lipoxygenase)
PGD2, PGE2, and PGF2 name 2 functions
-vasodilation and edema
PGI2. aka? name 2 functions
- prostacyclin
- vasodilation and inhibition of plt aggregation
TxA2 aka. name 2 function
- thromboxane
- vasoconstriction and promotion of plt aggregation
5-HETE and leukotriene B4. name func
-chemotaxis
leukotriene C4, D4, and E4. name 3 func
-vasoconstriction, bronchospasm, increased vascular permeability
-lipoxin A4 and lipoxin B4. name 3 functions
-vasodilation, inhibition of neutrophil chemo and stimulation of monocyte adhesion
name three chemotatic agents
-leukotriene B4, C5a, and 5-HETE (leukotriene precursor)
shape of coccidiodes vs histoplasma capsulatum
- sphere (look for no lymphs on blood smear)
- ovid (look for inside macs and perhaps other lymphs on blood smear)
role of pyrimidines in antifungal therapy
role of polyene, triazoles, and echiocandins too
- flucytosine* is converted to 5-FU and interferes with fungal RNA and protein synthesis
- bind ergosterol in membranes causing pores and lysis in cell membrane
- inhibits ergosterol synthesis in cell membrane
- inhibits glucagon synthesis in cell wall (capsofugin* and micafugin*)
b1 blocker effects on heart
- decreased HR, contractility, CO, heart O2 consumption, SA and AV node activity
- this leads to lower BP, reduced chest pain and removes atrial arrhythmias
b2 blocker effects on muscle vasculature, bronchi, and glucagon secretion. why contraindicated in pts with asthma and DM?
- vasospasm, bronchoconstriction, diminished
- exacerbate peripheral art disease, worsen asthma and COPD, and hypoglycemia in pts with DM
which lung cancer can’t be treated with surgery?
small cell carcinoma
aspiration pneumonia and lung abscesses are associated with
-altered consciousness, immunosupression, impaired swallowing (NGt ube or mechanical vent) and poor oral hygiene
mc cause of lung abscesses
-s. aureus or anaerobic bacteria in gingivodental sulcus (fusobacterium, peptostreptococcus and bacteroides)
lung cancer with pneumonia-like consolidation
bronchioloalveolar carcinoma subtype of adenocarcinoma
mc benign tumor of lung
hamartoma
fever, pneumonia, hyponatreumia and GI and CNS symptoms. pt pop? gram stain results
legionella!!! don’t confuse with step. pneumo
- look for in pts with access to contaminated water (cruise ship, hotel stay)
- neutrophils but no organisms
interstitial pneumonia with intranuclear and cytoplasmic inclusion bodies
-CMV
naturally compentent bac-def and give 3 examples
when bac can undego transformation. take up exogenous DNA fragments from lysed bac around them
-SHiN
lung finding in acute vs chronic heart failure
- acute like MI can lead to transudate in lung interstitium and alveoli
- chronic left heart failure can lead to hemosiderin containing macs (siderophages or heart failure cells)
compensatory hyperinflation-def, can cause pneumothorax yes or no?
- occur in normal lung parenchyma when adjacent lung segments or lobes are surgically removed
- no
obstructive hyperinflation-define, examples, can cause pneumothorax yes or no?
- lung semgent or lobe expands due to a subtotal (ball valve) ostruction of bronchiole or bronchus supplying it (i.e mucus plug or bronchogenic carcinoma)
- no
capsule of H.influnzae
type B is most invasive and has a capsule with a linear polymer of polyribitol phosphate
levels of calcium in Cf pt why?
low due to pancreatic insufficiency causing fat malabsorption and vit D defiency
dermatomyositis-def, presentation, labs
- autoimmune
- proximal muscle weakness, skin involvement (violaceous discoloration of upper eyelids), raised violaceous, scaling eruption of knuckles (Gottron’s sign)
- CPK levels are elevated
rash on malar prominences
butterfly rash SLE
healing of Ghon complex or Ghon focus
- TB lies dormant here
- healing can lead to activation of bac and abscess formation
beryllious vs sarcoidoisis lung symptoms
- basically present the same way. non caseating granulomas and hilar lymph
- use pt pop!
- beryllious-past coal miner or aerospace worker
- sarcoidosis-young african american
bac that requires cholesterol to grow
-mycoplasma pneumoniae
ground glass filtrates on x-ray. pt pop. diagnose
- PCP,
- HIV+ pts with CD4+ less than 200
- silver staining fluid collected during bronchoscopy
clinical associations of
- squamous cell carcinoma
- adenocarcinoma
- large cell carcinoma
- small cell carcinoma
- hypercalcemia
- clubbing and hypertrophic osteoarthropathy
- gynecomastia and galactorhea
- cushing syndrome, syndrome of inappropriate ADH and lambert-eaton syndrome
loud S2. not Pulmonary stenosis because?
- pulmonary HTN
- would not cause increase sound, perhaps a systolic murmur instead like AS?
granulomas diseases lead to what ion disturbances? give some examples?
hypercalcemia and hypercalciuria
-sarcoidosis, TB, Hodgkin’s, non-Hodgkin’s lymphoma
paroxysmal breathlessness and wheezing in young pt unrelated to asprin, infection, irritants, stress or excercise is? classic suptum finding? interlukins involved?
- extrinsic allergic asthma
- eosinophils with charcot-leyden crystals
- eosinophils are recruited and activated by IL-5 from TH2 cells
