Pulmonary Diseases Flashcards
Describe the pathogenesis of CF?
Mutation on Ch. 7 of CFTR (epithelial Na/Cl transmembrane protein); most common type is absence of a phenylalanine group
What are the physiological consequences of CF?
impaired ability to clear mucous secretions increases risk of opportunistic infections; inability to remove salt & chlorine from the body causes endogenous dehydration
What congenital defect do male CF pts. have?
absence of vas deferens
What are GI indications of CF?
meconium ileus (first stool blocking small intestine due to thick mucus); steatorrhea (fatty stool)
What is the proposed pathophysiology for asthma?
increased ECM proteins & vascular hyperplasia leading to airway remodeling and decreased pulmonary function
Intermittent Asthma is clinically defined as what?
FEV1 > 80%; FEV1/FCV > 85%;; does not interfere w/ daily routine with daytime episodes <2d/wk & nightly episodes <2/month
What would be the treatment plan for intermittent asthma?
short-acting beta agonist once before bed time
Mild asthma is clinically defined how?
FEV1: > 80%; FEV1/FVC > 80%; minor limitation of activity; daytime episodes > 2d/wk and nightly episodes 3-4/mo
What would be the treatment plan for mild asthma?
Intermittent + low-dose inhaled corticosteroid
How is moderate asthma clinically defined?
FEV1: 60-80%; FEV1/FVC: 75-80%; daytime symptoms daily (1/day) & nightly episodes > 1/wk.; moderate limitation of activities
What would be the treatment plan for moderate asthma?
medium does ICS
How is severe asthma clinically defined?
FEV1 < 60%; FEV1/FVC < 75%; daytime symptoms daily and last all day long w/ nightly episodes every night; extremely limited activity
What would be the treatment plan for severe asthma?
refer to pulmonologist; medium does ICS + long-acting beta agonist
What are the clinical hallmarks of meconium aspiration syndrome?
foul-smelling amniotic fluid upon delivery; CXR: increased AP diameter & flattened diaphragms bilaterally; PHTN assoc. w/ increased PVR
What is the most common cause of bronchiolitis in neonates?
RSV
What is the preferred drug for treatment of neonatal bronchiolitis?
nirsevimab
What are PE findings indicative of pneumonia?
bronchophony in right lower lobe; dullness to percussion; prolonged expiratory phase assoc. w/ expiratory wheezing & crackles
dullness to percussion indicates what?
segmental infiltrates
what do the auscultatory findings indicate on PE of pneumonia?
consolidation
Neonates 1-3 months old are most susceptible to what RI?
RSV
Neonates within their first month of life are most susceptible to what RIs?
S. pneumoniae, strep B., E. coli; gram - bacilli
from 3 months - 5 yr of age, what RIs are these pts. most susceptible to?
RSV, S. pneumoniae, H. influenzae
ped pts. in age range 5-18 yrs are most susceptible to what RIs?
mycoplasma & S. pneumoniae
What are RIs that pts. >18 yrs. contract?
S. pneumoniae, M. pneumoniae, H. Influenzae, influenza, adenovirus
What are common Afebrile pathogens that cause RIs in neonates?
C. trachomatis, CMV, B. pertussis, M. hominis, U. urealyticum
What PE findings are indicative of epiglottitis?
high-pitched noise over trachea on inspiration w/o presence of wheezes or rales
What are the most common pathogens assoc. w/ epiglottitis?
Strep A. S. aureus. H. influenzae
What is the most common mutation of CF?
F508 deletion results in a misfolded CFTR protein being retained in the endoplasmic reticulum
What CF screening test is given for newborns?
elevated immunoreactive trypsinogen
What are common sinopulmonary symptoms of CF?
nasal polyposis, chronic cough, recurrent RIs, atelectasis, bronchiectasis
What are common GI manifestations of CF?
recurrent pancreatitis due to pancreatic insufficiency; hepatic dysfunctions including fibrosis, cholethiasis, & cirrhosis
What physiologic insult arises due to perfuse excretion of NaCl for CF pts.?
salt-loss syndrome: chronic metabolic alkalosis
If both parents are carriers for CF, what is the probability of passing the gene onto offspring?
25%
If one parent is affected and the other a carrier for CF, what is the probability of offspring that will become affected?
50% chance
If both parents are affected w/ CF, what is the probability of it being passed down to offspring?
100%
What is the pathogenesis of genetic acquired AAT deficiency?
mutations of the SERPINA1 genes
What is the function of alpha-1-antitrypsin in the lungs?
anti-inflammatory protease inhibitor that inhibits neutrophil elastase from damaging the lungs
What long-term complications can arise due to AAT deficiency?
emphysematous COPD
AAT deficiency can cause what other extra pulmonary symptoms?
panniculitis, vasculitis, glomerulonephritis, & hepatitis/cirrhosis
Why should AAT serum levels not be tested if pt. has HPI of acute illness?
b/c AAT is an acute phase reactant will be naturally elevated during the acute phase of infection
What is the qualitative definition of atelectasis?
incomplete/reduced expansion of the lungs or collapse
What are clinical hallmarks of atelectasis?
pain on affected side assoc. w/ dyspnea; dullness to percussion on involved side; absent breath sounds, absent chest excursion; tracheal deviation towards affected side
What is the definition of obstructive atelectasis?
mucus plugs, exudates in bronchi, aspiration of foreign bodies; intrabronchial tumors
What are the physiological consequences of resorption atelectasis?
gas absorption from the alveoli promotes retraction of the lung & an airless state within affected regions of the alveoli leading to arterial hypoxemia ; the unaffected lung distends and displaces the surrounding structures resulting in a mediastinal shift towards the atelectatic area
How is compression atelectasis defined clincally?
accumulation of fluid within the pleural cavity
What are PE findings of compression atelectasis?
mediastinum and trachea deviation away from affected side & hyperresonance
how is contraction atelectasis clinically defined?
reduction of lung volume subsequent to severe parenchymal scarring
What are examples of contraction atelectasis?
fibrosis of narrowed bronchial lumen; granulomatous lung disease (TB) or necrotizing pneumonia
RSD is a special form of atelectasis that is caused by what?
loss of surfactant
For babies that have to be delivered prematurely, what can the mother be given to reduce development of RDS?
glucocorticoids
What is the clinical definition of pulmonary edema?
accumulation of excess fluid in the alveoli
describe the pathogenesis of hemodynamic edema.
caused by increased left ventricular & atrial filling pressures; this subsequently raises pulmonary venous pressure leading to decreased cardiac output which will activate RAAS which will lead to pulmonary edema
What diseases can potentially cause hemodynamic induced pulmonary edema?
liver failure, nephrotic syndrome
what are causes of pulmonary edema assoc. w/ microvascular injury?
RDS, pneumonia, radiation, lung trauma, high altitudes, opioid overdoes
Why does edema accumulate in the basal pulmonary regions first?
b/c hydrostatic pressure is greatest in these regions
what are the histological findings of hemodynamic pulmonary edema?
diffuse alveolar spaces flooded w/ fluid; dilated alveolar capillaries, microhemorrhages; hemosiderin-laden macrophages (commonly asscoc. w/ HF)
What is the pathogenesis of microvascular injury assoc. pulmonary edema?
primary injury to the vascular endothelium and alveolar epithelial cells; this produces an inflammatory exudate into the interstitial space and alveoli
What metabolic insult results from ARDS?
respiratory acidosis
describe the exudative phase of ARDS?
immune-mediated destruction of epithelial-interstitial-endothelial barrier which allows fluid to flow into the interstitium and airspaces
describe the proliferative phase of ARDS?
recovery of destroyed alveolar barrier
describe the fibrotic phase of ARDS?
impaired removal of alveolar collagen limits functional recovery
What casues surfactant to be reduced in ARDS?
protein rich edema interacts w/ alveolar surfactants during exudative phase which decreases pulmonary compliance and promotes formation of hyaline membranes
how long does the exudative phase last?
first 1-7 days after insult
How do the lungs compensate for The loss of type 1 pneumocytes during exudative phase in the proliferative phase?
Type II pneumocytes differential into type 1 pneumocytes; Type II pneumocytes also drain alveolar edema during this phase as well and promote proliferation of myofibroblasts and endothelial vascular proliferation
the proliferative phase takes place how long after the initial insult?
1-3 weeks
When does the fibrotic phase start to manifest and what can be expected to find histologically?
3 weeks after initial insult; telangiectasia w/ collagenous fibrosis and refractory rigidity of alveoli due to architectural remodeling
What would a pulmonary function test reveal for a case of obstructive lung disease?
increased RV & TLC; decreased FEV1, FVC, & FEV1/FVC (<0.7)
centriacinar emphysema is most commonly assoc. w/ what risk factor?
cigarette smoking
Panacinar emphysema is commonly assoc. w/ what deficiency?
AAT
describe the pathogenesis of AAT-deficiency induced panacinar emphysema?
genetic deficiency on Ch. 14
what bronchioles are affected in centriacinar emphysema?
central and or proximal parts w/ distant alveoli spared; affected area mostly localized to upper lobes
what bronchioles are affected in panacinar emphysema?
ALL are uniformly enlarged from apex to base w/ most severe damage done to the lower lobes
Describe the pathogenesis of emphysema?
damage to respiratory epithelium resulting in parenchymal destruction: this can be caused by inflammatory mediators, oxidative stress, and infections
How does chronic use of tobacco products casue emphysema?
substances from tobacco smoke cause oxidative stress on lung tissue which can promote inflammation and endothelial dysfunction leading to permanent tissue damage; Also, it is important to note that ROS inactivate antiproteases like AAT
What physiological consequences result form emphysema?
increased lung compliance w/ decreased elasticity and obstructive air trapping; during exhalation, terminal bronchioles collapses due to radial traction which traps air distally where elastic tissue has been lost
What are the histological features of emphysema?
abnormally large alveoli separated by thin septa w/ focal centriacinar fibrosis
What are clinical hallmarks of emphysema?
barrel-chest, pt. must sit in forward-hunched pos. to breath with expiration being prolonged; weight loss is also common
What is the qualitative definition for DLCO and is it reduced or increased in the case of emphysema?
ability of lung ot transfer gas from inhaled air into the blood stream; decreased in emphysema: serves as an indicator for extent of lung damage
What would an ABG indicate for suspected emphysema?
low PaO2 (ooo shocker there); decreased PaCO2 assoc. w/ respiratory alkalosis
What CXR findings are indicative of emphysema?
hyperlucency ( bigger area of dark space due to more air being trapped in the lungs); increased AP diameter; heart displaced more vertically and flattened diaphragm
What would you expect to find for paraseptal emphysema?
proximal bronchioles intact; distal ones affected
what is the main cause of paraseptal emphysema?
spontaneous pneumothorax
If there are irregularities in the uniformity of affected bronchioles, what is the emphysema classified as?
irregular emphysema
What is the clinical criteria for chronic bronchitis?
persistent cough w/ sputum production for at least 3 months in at least 2 consecutive years
describe the pathogenesis of chronic bronchitis?
Must have an initiating factor such as exposure to noxious stimuli activating secretion of inflammatory mediators; these mediators then cause mucus hypersecretion and hypertrophy of submucosal glands; excessive mucus production eventually leads to airway obstruction and increased number of goblet cells
how does tobacco smoke lead to chronic bronchitis?
damage of airway lining leads to chronic inflammation which can interfere with ciliary action to clear mucus and debris from the airway
In addition to the histological characteristics of inflammation, the bronchial epithelium may also show what else?
squamous metaplasia: Lungs’ response to adaptation of consistent airway irritation
What physiological insults arise from chronic bronchitis?
hypercapnia & hypoxemia leading to cyanosis and PHTN
Would you expect the lung elasticity to be lower or normal for chronic bronchitis?
normal
Describe the pathogenesis of atopic asthma?
allergen sensitization; Th2 and IgE mediated Type 1 Hypersensitivity rxn.
what are common causes of non-atopic asthma?
viral RIs, inhaled air pollutants
What drug is assoc. w/ drug-induced asthma?
aspirin via inhibition of COX pathway and decreased PGE2 production
IL-5 plays what role in the pathogenesis of asthma?
activates eosinophils
IL-13 plays what role in the pathogenesis of asthma?
stimulates mucus secretion from submucosal glands
What role does IgE play in the pathogenesis of asthma?
binds to Fc receptors on submucosal mast cells; mast cells release granule contents and produce and recruit more inflammatory mediators
Describe what happens during the early phase reaction assoc. w/ asthma?
bronchoconstriction triggered by direct stimulation of subepithelial vagal receptors
What happens during the late-phase rxn. assoc. w/ asthma?
recruitment of leukocytes (eosinophils and neutrophils)
leukotrienes C4, C5, & E4 promote what?
prolonged bronchoconstriction, increased vascular permeability, and increased mucous secretion
What role does acetylcholine play in the pathogenesis of asthma?
causes airway smooth muscle constriction via direct stimulation of M3 receptors
Eosinophiles release what substance and what is the clinical significance of this?
galectin-10 forms charcot-leyden crystals: strong induces of inflammation and mucus production
histamine also plays a role in the pathogenesis of asthma; what does it do in this context?
promotes bronchoconstriction
susceptibility locus for asthma is located on which chromosome?
Ch. 5q
what HLA class is linked to production of IgE antibodies against antigens like ragweed pollen?
Class II HLA alleles
Variations of the gene that encodes for IL-33 lead to what consequences?
IL-33 and its receptor ST2 induces production of Th2 cytokines
Variants of the gene encoding for TSLP, is released by what cells and thought to have a role in initiating allergic rxns.
cytokines produced by epithelium
What are some of the histological characteristics of asthma?
hypertrophy & hyperplasia of bronchial smooth muscle; epithelial injury; increased airway vascularity; hyperplasia of goblet cells; hypertrophy of subepithelial mucous gland; subepithelial fibrosis w/ type I type III collagens; thickening of airway wall
curschmann spirals result from what?
extrusion of mucus plugs from subepithelial mucous gland ducts
what would labs of suspected asthma reveal for acute and chronic cases?
respiratory alkalosis for acute; respiratory acidosis for chronic
what is the qualitative definition for brochiectasis?
destruction of smooth muscle and elastic tissue by inflammation from persistent or severe infections
what are some long-term consequences of bronchiectasis?
permanent dilation of bronchi and bronchioles; chronic necrotizing infections
What are the most common congenital and hereditary conditions assoc. w/ bronchiectasis?
CF; primary ciliary dyskinesia; kartagener
How does CF cause bronchiectasis?
chronic bacterial infections due to thick mucus build up causes widespread damage to airway epithelium
How does primary ciliary dyskinesia result in bronchiectasis?
mutations of ciliary proteins ( such as dynein) can lead to ciliary dysfunction and impair mucociliary clearance opening a floodgate for recurrent infection
Kartagener is a type of primary ciliary dyskinesia; describe its pathogenesis.
assoc. w/ ciliary dysfunction during embryogenesis leading to congenital malrotation of organs; assoc. w/ situs inversus and male infertility due to sperm dysmotility
What immune disorders are assoc. w/ bronchiectasis?
RA, SLE, IBD, post-transplant
What are the gross features of bronchiectasis?
bilateral lower lobe pathology w/ dilated airways that appear cystic and filled with mucopurulent secretions; permanent dilation w/ secondary infection
What are some of the histological features of bronchiectasis?
inflammatory exudate; desquamation of epithelial lining; squamous metaplasia; necrotizing ulceration; bronchial fibrosis
What are some of the clinical hallmarks assoc. w/ bronchiectasis
severe, persistent cough w/ foul smelling hemoptysis in sputums; orthopnea
