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Pulmonology Quiz 2a

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eem8u's version from 2016-11-21 20:31

Asthma ***LOOK at slides****

Pathophysiology of asthma
Question Answer
asthma, definedINFLAMMATORY PROCESS w/ airway obstruction (at least partially reversible) and **airway HYPERRESPONSIVENESS
extrinsictype 1 hypersensitivity / atopic (allergenic) or occupational
intrinsicnon immune - due to aspirine, exercise, cold, stress, pneumonia
**Key histologic features of asthma (2)EOSINOPHILS and thickened BASEMENT MEMBRANE (as well as increased mucosal goblet cells and submucosal glands(
U.S. prevalence7-8% and rising (around half of children “grow out of it”)
describe change in elastic recoil forces in asthmaairway remodeling due to fibrosis > lungs become stiff/will not expand == uncoupling!
***define radial tractiontissue framework around small airways -> prevents collapse a/g negative pressure during INSPIRATION
low Fev1/FVC defined as< 0.7 normally should be 80% of vital capacity in 1s
******reversibility with bronchodilator in PFT measured by (2)1) FEV1/FVC normalized 2)FEV1 increases by 12%/200mL
VC/RV values in air trappingRV increase/VC decrease
pco2 in mild vs severe attacksFALLS (b/c of hyperventilation and compensation by “good” v/q units) vs RISE due to respiratory muscle fatigue
V/Q in asthma attack (why?)low units b/c of TRAPPING >> hypoxemia compensation by vasoconstriction (but not always sufficient to correct)
**key histologic features of airway mucus in asthma (3)1- increased inflammatory cells / 2- increased inflammatory mediators / 3- increased mucin concentration
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Allergic asthma
Question Answer
pathophys of allergic asthma allergen —> TH2 response —> il-4 STIMULATES Ig-E production —> crosslink at mast cell —> release of inflammatory mediators // TH2 also releases Il5 —> eosinophil response
****explain biphasic reaction(FEV/time axis following antigen exposure...) first drop due to immediate bronchoconstriction/mucous…. second drop to inflammatory cells that have arrived
hygiene hypothesisearly exposures to allergens > up regulation of TH1 (CD4 protective immunity) and down regulation of TH2 (mediates allergic disease)
***Th2 cytokine - IL-4directs B-­‐cells to synthesize IgE (plasma cell class switch)
Th2 cytokine - IL‐5 for eosinophil recruitment & maturation:
Th2 cytokine - IL-9mast cell recruitment
Th2 cytokine - IL-13mucous hypersecretion/ airway hyper responsiveness
how is mast cell activatedallergen binds and causes cross linking of IgE
histamine induces (2)vasodilation (arteriole) / increased vascular permeability (esp post-capillary venule)
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Question Answer
****pathophys of aspirin-induced diseaseINHIBITION of cyclooxgenase pathway (arachadonic acids) >> shift to production of LEUKOTRIENES >> bronchconstriction/congestion/mucous plugging
Samter’s triadasthma + aspirin/NSAID sensitivity + nasal polyposis
clinical symptoms of asthma (4)cough, dyspnea, wheezing, chest tightness (*episodic)
***2 pulmonary exam featureswheezing, *** prolonged expiratory phase
***cutoff for bronchoprovocation testfall in FEV1 by 20% with methacoline (8mg/mL or less)
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****Treatment
Question Answer
****beta-agonist- biochem mechanism of action (2)GPCR > adenylate cyclase >> cAMP increase >> 1) airway smooth muscle relation + 2) inhibition of chemical mediator release from mast cells (***use local inhalation form to reduce ionotropic/chronotropic SE’s)
***albuterol-type & durationb2 AGONIST (short acting, 3 hours)
salmeterol- typeb2 agonist (long acting, ~12 hours)
Anticholinergic-mechanism of actionblock cholinergic tone to airway smooth muscle (M1- pregang. post sympathetic, M3 - Airway smooth muscle)
ipratropropium-mechanismanticholinergic (6 hour duration) blocks M1/m2/m3 (not ideal b/c blocks m2 autorgulatory receptor that inhibits further Ach release from the post-ganglionic nerve > muscle)
tiotropium--mechanismanticholinergic (~24 hours) blocks M1/M3 (dissociates quickly from M2 — good b/c m2 is inhibitory) “2 and go”
***umeclidium-mechanism & useanticholinergic (elongating) blocks *M3* alone —only for COPD “unico”
why can’t atropine be used as anticholinergic (be specific)TERTIARY structure - neutral = crosses all membranes (including BBB), quaternary preferred to stay local (in airway)
Methylxanthines-mechanism(works like caffeine) >> Inhibit phosphodiesterase (which degrades cAMP) > increase cAMP > bronchodilation // inhibits adenosine receptor
theophylline-typemethyxanthine - oral
(phosphodiesterase inhibitor)
aminophylline-typemethyxanthine - IV or PO (phosphodiesterase inhibitor) -- AMBHIBOphylline
corticosteroids- 2 targeted effectsdecrease airway inflammation (many mechanisms) & clear inflammatory infiltrate
beclomethasone vs fluticasoneboth are INHALED corticosteroids — beclo has MUCH higher bioavailability = systemic SE’s
***zileuton-mechanism(arachidonic acid pathway) - direct Lipooxygenase inhibitor --> blocks 5-lipoxoygenase pathway >> inhibits leukotriene formation (esp in aspirin related asthma)
***montelukast (cingular)-mechanism(arachidonic acid pathway) cysteinyl LT1 Receptor antagonist (inhibits LTE4 formation) >> bronchodilation
***Omalizumab-mechanism & clearancerecombinant IgG binds Fc portion of IgE (hepatically cleared) = down regulates IgE receptor on Mast cells and basophils
***Mepolizumab/Reslizumab-mechanismanti- IL-5 monoclonal antibodies (prevent eosinophil maturation in EOSINOPHILLIC asthma)
h1-mediated actions (4)UP vascular permeability / UP bronchial/intestinal smooth muscle contraction / UP mucus production / UP vasodilation
diphenhydramine &hydroxyzine -type and SE’s1st gen H1 blocker (lipophilic — BBB cross, sedation)
loratadine-type2nd gen H1 blocker (lipophobic, avoids unwanted CNS effects)
fexofenadine-type2nd gen H1 blocker (lipophobic, avoids unwanted CNS effects)
cetirizine-type2nd gen H1 blocker (lipophobic, avoids unwanted CNS effects)
****drug cleared by hepatic reticuloendothelial systemOmalizumab
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bronchiectasis & other lung disease lecture

Bronchiectasis
Question Answer
bronchiectasis, definePERMANENT, abnormal dilation of PROXIMAL bronchi (focal or diffuse) due to destruction of support structures of bronchial wall (**there is usually other underlying etiology)
bronchial obstruction causes of bronchiectasis (3)(usually local) tumor, foreign body, inspissated mucus
congenital causes of bronchiectasis (3)(usually diffuse) CF, immunodeficiency, ciliary dyskinesia/kartageners
***5 infectious causes of bronchiectasismeasles, pertussis, necrotizing pneumonia (staph or TB) , MAC, ABPA
vicious cycle hypothesispredisposed impaired clearance mechanism >> external insult >> > infection >> inflammation >> respiratory tract. damage (PMNs disrupt elastic and support structures of bronchial wall) > further damage > >> further infection, etc.
***3 infection vulnerabilities in bronchiectasis (perpetuate cycle)1) decreased propulsion of cilia, 2) enlarge airway > bacteria colonization 3) collapsible airways > unable to cough
***pathogenesis of bronchiectasis begins in _________(part of lung)___, causingsmaller airways w/ inflammation — causing dilation (and protease overflow to larger airways) -- see 11.7
***3 causes of recurrent airway infection (in general)1) obstruction (mucus, tumor, foreign body) 2) impaired mucous clearance (CF, primary ciliary dyskinesia) 3) immune defect
2 classical sxcough w/ copious sputum (due to secretory c hyperplasia) +/- purulence AND hemoptysis
cause & blood source of hemoptysisinflammation > angiogenesis (bronchia arteries) >> anastomoses
3 CXR patternscylindrical (smooth bronchial DILATION instead of NARROWING), cystic (progressive dilatation terminating in cysts), varicose (focal narrowing along dilated bronchus) - see 11.11
****3 clinical fea. (on exam)CLUBBING , normal auscultation or wheezing, rhonci, crackles, normal or HYPOEXEMIA/HYPERCAPNIA (can’t breathe)
PFT resultslow FEV1/FVC and air trapping (with increased RV and RV:TLC ratio)
3 types of txantibiotics (sometimes chronic tx), bronchopulmonary drainage (vibrators, oscillators, PT), bronchodilators (in setting of obstruction)
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Cystic Fibrosis Overview
Question Answer
type of genetic disorderautosomal recessive
2 locations of CFTR in lungepithelial airways, serous cells of submucosal glands
CFTR fx in airwaysvolume absorbing (salt and water)
CFTR fx in sweat ductsalt (but not volume) absorbing
CFTR fx in pancreas & intestinevolume secreting (salt and water)
***depletion of periciliary liquid layer/ defined asASL (airway surface liquid) volume lower than 7μm (microns) - easier to propel
***maintenance of normal ASL in high volumeincrease absorption> CFTR opens > Na+ rushes (b/c inside of cell is - due to Na/K pump) > Cl and h20 follow paracellularly
***maintenance of normal ASL in LOW volumeCFTR channel closed > Cl- leaves cell through CFTR (b/c inside of cell is - due to Na/K pump) > Na and h20 follow paracellularly
CFTR/CF in pancreasCFTR secretes bicarb, in CF- viscous/acid secretions >> retained enzymes >> destruction of pancreas
CFTR in intestineCFTR secretes for Cl- / h20, in CF- failure to flus mucins/molecules >> dehydrated intralumen >> obstruction
CFTR in sweat glandsreabsorbs cl- from ISOTonic sweat, in CF- retains cl-
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CFTR Pathology
Question Answer
earlier vs later findingsthick mucous plugs in bronchi/broncioes vs. pneumonitis/bronchiectasis/abscess
neonatal presentation and prevalence10%, meconium ileum (w/ dilated bowel loops)
childhood presentation*pancreatic insufficiency and/or *bronchial infection
common sx (2)severe cough w/ mucopurulent (FOUL) sputum (+/- hemoptysis)
common colonizing organismspseudomonas, staph a. (also ABPA)
4 GI findingsexocrine pancreas insufficiency (90% of patients… leads to DIABETES), rectal prolapse, intestinal obstruction, malabsorption
renal/endo findingshypovolemia, hypochloremic metabolic alkalosis —> excessive loss of salt
how to diagnose CFclinical sx plus one of: 1) abnormal sweat ( high Na, Cl, K) 2) nasal mucosa electric potential abnormality 3) **HOMOZYGOUS for one of genes
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**** CFTR treatment
Question Answer
Pulm sx treatment (general)(same as bronchiectasis) antibiotics / bronchopulm drainage / bronchodilation
2 tx for sputum viscocityrecombinant deoxyribonuclease (DNA release from inflammatory cells), hypertonic saline inhalation (draws out h20)
Ivacaftor - mechanismincreases time activated CFTR remain open (specific for Class III and class II w/ Lumacaftor) iva wide open
Lumacaftor - mechanismcorrects CFTR misfolding (specific for class II, much use with Ivacaftor) looming to help with folding
Kartagener’s syndrome - cause, 3 key characteristicsPRIMARY CILIARY DYSKINESIA (*caused by dyne arm DEFECT), bronchiectasis (due to obstruction/inflammation?) + sinusitis + situs inversus (reversed organs, 50% chance)
3 types of ciliary defectsabsent dynein arms, microtubule (usually in central and radial formation) disorganization, lack of radial spokes
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CFTR mutations
Question Answer
class Iunstable/truncated RNA >>absent CFTR
class IImisfiled protein >> protease destruction
class IIIdefective regulation of channel >> d/n open
class IVdefective CFTR
class Vreduced CFTR synthesis (scarcity)
class VICFTR not stable in membrane > taken away quickly
most common CFTR mutation and CLASSΔF508 mutation responsible for ~70% of cases, CLASS 2 (misfiled protein)
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Bronchiolitis
Question Answer
bronchiolitis, definedNONSpecific inflammation (+/-fibrosis) affecting small airways
define small airway ≤ 2 mm in diameter WITHOUT cartilage (terminal and respiratory bronchioles
describe wall of small airway (3 layers) nonciliated/ciliated COLUMNAR epithelium, CT, smooth muscle
acute bronchiolitis - 2 common causesRSV / rhinovirus
local and systemic sx of acute bronchiolitisfever/cough/respiratory distress +/- URI 1-3 days before
obliterative bronchiolitis (constrictive), defined SYNDROME of dyspnea + airflow not reversible with bronchodilator and assc w/ SMALL AIRWAY injury
***obliterative/constrictie seen often withchronic transplant rejection (or graft versus host disease)
pathologic change seen in epithelium w/ constrictiveFIBROUS tissue (COLLAGEN) between epithelium and smooth muscle
primary vs secondary bronchiolitisobliterative vs secondary to many causes (bronchiectasis, asthma, COPD, hypersensitivity … )
***2 path patterns of bronchiolitiscellular (inflammatory) vs fibrotic (can be combined)
2 types of fibrotic small airway diseaseconstrictive (obliterative) , intralumenal bronchiolitis obliterates)
***bronchiolitis obliteratans assc w/PNEUMONIA
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