Restrictive & Obstructive Lung Diseases Flashcards
What is the qualitative definition of Interstitial Lung Disease?
inflammatory-fibrotic infiltration of the alveolar septa
What are the biophysical consequences of Chronic diffuse ILD?
decrease in diffusion capacity, FVC, lung volume, lung compliance
What are radiographic hallmarks of chronic diffuse ILD?
hazy gray shadows; glass opacities; End-stage: honey-comb” lung
Compare & contrast differences b/t COPD & pulmonary fiborsis?
Emphysema (COPD): pt. can’t exhale b/c lungs have decreased ability to recoil (lungs prefer to stay inflated); Pulmonary fibrosis: pt. can’t inhale b/c recoil pressure is too high (lungs prefer to stay deflated)
Describe the epidemiology of Idiopathic pulmonary fibrosis?
most common in elderly men > 60 yrs. especially those w/ familial risk for pulmonary fibrosis
what are the clinical presentations of IPF?
insidious progressive onset of unexplained dyspnea on exertion; bibasilar inspiratory crackles; cyanosis, myositis & clubbing may also be present; PE findings: augmented P2, S3 gallop
What are the histological hallmarks of IPF?
follows a UIP pattern: honeycombing cysts w/ reticular septal thickening; minimal glass opacities & basal predominance
What would a pulmonary function test show for a pt. w/ suspected IPF?
reduced VC, increased FEV1/FVC ration; decreased DLCO
What are pre-existing risk factors for pulmonary fibrosis?
neoplasm; mutations of TGF-beta; collagen vascular diseases including RA, SLE, & progressive systemic sclerosis
What are environmental factors of pulmonary fibrosis?
smoking; metal fumes; wood dust; occupational exposure
How do fibroblasts contribute to IPF?
fibroblasts are activated in response to epithelial injury and deposit collagen in interstitial spaces leading to interstitial fibrosis and respiratory failure; abnormal increased signaling through PI3K/AKT
Describe the pathogenesis of Familial IPF?
mutant telomerase: mutations in TERT & TERC leading to pathologically short telomeres; MUC5B mutation: increases secretion of mucin and alter mucociliary clearance
What histological findings can be used to distinguish UIP & IPF from other restrictive lung diseases?
honeycomb interstitial fibrosis w/ fibroblast hyperplasia; no necrosis or substantial inflammation; mostly lymphocytes and very few neutrophils
What are major histological distinctions b/t IPF & NSIP?
NSIP: no fibroblastic foci; notable inflammation & diffuse fibrotic lesions rather than honeycomb
What are clinical hallmarks of desquamative interstitial pneumonia?
large collections of pigmented macrophages containing remnants of necrotic type 2 pneumocytes; Smoking is the biggest risk factor; presents in 4th & 5th decade of life
What other interstitial lung disease is assoc. w/ smoking
respiratory bronchiolitis: similar histological patterns as DIP
What is the proposed etiology of sarcoidosis?
cell-mediated response to an unidentified Ag
what lab findings are indicative of sarcoidosis?
increased CD4/CD8 ratio; increased levels of TH1 cytokines (IL-2 & IFN-gamma) promotes T-cell expansion and macrophage activation; increased levels of IL-8 & TNF promotes formation of granulomas; polyclonal hypergammaglobulinemia (manifestation of helper T-cell dysregulation; impaired dendritic cell function
What histologic characteristics would you expect to find if sarcoidosis is suspected?
GRANULOMATOUS INFLAMMATION; giant cell nodular aggregates; NO NECROSIS
What are other more non-specific histological findings that can also be found for sarcoidosis?
schaumann bodies: basophilic laminated concretions of calcium & proteins; asteroid bodies: stellate inclusions enclosed in giant cells
What other lung abnormality is commonly seen in pts. w/ sacoidosis?
bilateral hilar lymphadenopathy
What are other conditions besides sarcoidosis that are assoc. w/ pulmonary granulomas?
Histoplasmosis; TB; neoplasm; lymphoma; foreign bodies
What skin test is performed for diagnosis of sarcoidosis?
cell mediated immunity to tuberculin
What are clinical presentations of sarcoidosis?
progressive dry cough & dyspnea; polyarthralgia; T-cell alveolitis w/ activated Mo-Ma
What is the proposed mechanism for increased ACE activity in sarcoidosis?
thought to be produced by epithelioid cells and macrophages of the granulomas
Sarcoidosis-induced lung disease can progress to what?
pulmonary fibrosis & cor pulmonale
What is the major pathological hallmark of Pulmonary Langerhans Cell Histiocytosis?
involves langerhans cells (immature dendritic cells); +S100 stain for langerhans
How does progressive PLCH present on a CXR?
reticulonodular infiltrate predominantly distributed to upper & middle lobes only
What is the proposed pathogenesis of PLCH?
cigarette-smoke induced activation of langerhans cells to lungs
What is the qualitative definition of hypersensitivity Pneumonitis?
immune mediated interstitial lung disorder caused by long-term exposure to inhaled organic dusts
What are distinctive histological features of hypersensitivity pneumonitis?
interstitial pneumonitis w/ lymph, plasma cells, & macrophages
What type of hypersensitivity is assoc. w/ hypersensitivity pneumonitis?
t cell-mediated delayed type hypersensitivity reaction against the Ag
Pulmonary eosinophilic syndromes are characteristic of what?
elevated alveolar levels of IL-5
What is the criteria for diagnosis of AEP vs. CEP?
> 25% is acute; > 40% for chronic; parameter is increased eosinophils in BALF
What are common secondary causes of pulmonary eosinophilic syndrome?
parasitic, fungal & bacterial infections; durg allergies; churg-strauss syndrome (vasculitis)
What is the pathogenesis of pulmonary alveolar proteinosis?
deficient GM-CSF resulting in macrophage dysfunction; Macrophage dysfunction causes accumulation of alveolar precipitates containing surfactant proteins in intra-alveolar spaces
PAP precipitates stains are positive for what?
PAS+
What is the qualitative definition of pneumoconiosis?
macrophage activation
Describe the pathogenesis of asbestosis.
pneumoconiosis induced by inhalation of asbestos fibers
Asbestos are naturally occuring fibers composed of what substance?
hydrated magnesium silicates
Why are serpentine asbestos less toxic than amphibole asbestos?
Aerodynamics: serpentine fibers are more susceptible to removal by mucociliary defense mechanisms; amphibole fibers are more pathogenic due to shape & greater solubility
Pts. w/ amphibole asbestosis are at increased risk for what neoplasm?
mesothelioma
What occupations increase risk of development of asbestosis?
Mining; Construction; any other occupation where pt. comes into contact on a daily basis including but not limited to cement,, insulation, shipbuilding, & textiles
Describe the molecular mechanisms of asbestosis?
asbestos are toxic to pulmonary parenchymal cells; these toxic fibers stimulate release of mediators by inflammatory cells; chronic deposition of asbestos leads to interstitial pulmonary fibrosis
why are pts. w/ asbestosis at increased risk for developing cancer?
build up of ROS: byproduct of inflammatory response; free radicals can reaact w/ and damage the structure of DNA
What is the neoplastic derivative of mesothelioma?
bronchogenic adenocarcinoma
What are common clinical presentations of asbestosis?
cor pulmonale, clubbing, peripheral edema, JVD, hepatojugular reflux; gallops; respiratory failure
what are radiographic hallmarks of asbestosis?
visceral fibrosis & exudative pleural infiltrates
what are histologic hallmarks of asbestosis?
ferruginous bodies w/ hemosiderosis in bronchoalveolar lavage
Asbestosis starts at which level of the lung?
lower lobes
what are gross characteristics of malignant mesothelioma?
thick sheath that surrounds the entire lung; looks like sirloin steak encased in a ring of fat
Berylliosis is caused by exposure to what toxic chemical?
beryllium
What occupations increase risk for development of chronic berylliosis?
nuclear plants; smelting (working around metal); alloys; ceramics
Describe the criteria of acute beryllium disease in humans?
dose-related acute lung injury characterized by acute inflammatory reactions in upper airways causing bronchiolitis, pulmonary edema, & chemical pneumonitis
Describe the criteria for chronic beryllium disease.
multisystem disease: noncaseating granulomas throughout the body and upper lung lobes
Berylliosis has similar clinical presentations of what other restrictive lung disease?
sarcoidosis
What is the gold standard for diagnosis of berylliosis?
beryllium lymphocyte proliferation test
What states have the most cases of coal workers pneumoconiosis?
west regions: NM, CO, UT, WY; east regions: KC, TN, AL, MI, WV, VA, PA, OH, IN
In which region of the lungs would you expect to find most of the gross pathology of CWP?
upper lobes
describe the histologic findings of CWP?
CWP = focal centriacinar emphysema + coal macules; thick layers of haphazard aligned collagens
describe the pathogenesis of CWP?
as lung burden of dust increases, alveolar macrophages are activated and ROS is released and triggers inflammation cascade leading to fibrogenesis
What are common clinical presentations of CWP?
chronic bronchitis; palpable coal macule nodules; CXR: opacities within the lung parenchyma itself
CWP has ben shown to cause both obstructive & restrictive lung diseases; what would you expect to find on a pulmonary function test in both scenarios?
What occupations increase risk of developing silicosis?
foundries; quarrying; glass making; ceramics
Describe the histologic characteristics of silicosis.
whorled hyalinized collagen fibers w/ dust-laden macrophages; weak birefringent on polarization
Describe the pathogenesis of silicosis.
silica particles are phagocytosed by macrophages; they stimulate release of IL-1 & IL-18 which activates interstitial fibroblasts to lay down collagen
Freshly fractured silica generated during sandblasting is more toxic than aged silica. Why?
freshly made silica has a greater redox potential
What are radiographic hallmarks of silicosis?
eggshell calcification around hilar lymph nodes
What is the proposed explanation for why there is such a high correlation b/t silicosis & TB?
silica is thought to inhibit ability of pulmonary macrophages to kill phagocytosed mycobacteria
If a person is exposed daily to 30% crystalline silica how long it take before they start showing symptoms of silicosis?
10-30 yrs.; referred to as chronic silicosis
If a person is exposed daily to dust > 30% crystalline silica, how long will it take to start showing symptoms?
heavier exposure to the silica crystals is referred to as accelerated silicosis; typically present within decade of initial exposure
A pt. presents to your clinic w/ symptoms of dyspnea on exertion & bronchitis; when you ask about their occupation, they tell you they work at a sandblasting factory. Based on this information alone, what would be at the top of your DDx?
silicoproteinosis (AKA acute silicosis); follows intense exposure to dust with very high silica content; although rare, it usually occurs within weeks or months after the exposure rather than years later
both acute & chronic silicosis can progress to what disease?
Progressive massive fibrosis; AKA complicated silicosis
Why is the FEV1;FVC ratio decreased for obstructive lung diseases?
airflow is limited due to epithelial destruction
TLC is increased for OLDs b/c air bubbles get trapped in the alveolar spaces; Knowing this, what gross findings would you expect to see on CXR of a pt. w/ OLD?
Increased AP diameter (barrel chest); widened intercostal spaces, hyperlucency of lung tissue; narrow heart alignment
Compare & contrast gross findings of panacinar vs. centriacinar emphysema?
Panacinar: pathology of the lower lobe; centriacinar: pathology of the upper lobes
Gold Stage I COPD is diagnosed If FEV is….
> 80%; Mild
Gold Stage II Moderate COPD is diagnosed as FEV greater than……but less than…..
> 50 but <80%
Gold Stage III severe COPD is diagnosed as FEV greater than ………. but less than …….?
> 30% but <50%
Gold Categories A & B have what criteria in common?
not leading to hospital admission
Gold categories A & C have what criteria in common?
mMRC 0-1 or CAT > 10; lower symptom burden
Gold Stage IV of very severe COPD is clinically defined as…….
FEV < 30%
Gold Categories B & D have what criteria in common?
mMRC > 2 or CAT < 10; higher symptom burden
What do Gold categories A & B criteria have in common?
H/O 0-1 exacerbations
What do Gold categories C & D criteria have in common?
H/O > 2 exacerbations
What nonpharmacological treatments can reduce risk of COPD?
smoking cessation; oxygen supplementation decreases mortality and increases survival outcomes
compare & contrast the clinical presentations of Blue bloaters & pink puffers.
Blue bloaters: cyanosis, purulent sputum, chronic productive cough, crackles & wheezes
Pink puffers: pink skin, minimal cough, decreased breath sounds
compare & contrast complications that arise from chronic bronchitis & emphysema.
Chronic bronchitis: polycythemia vera, PHTN, Cor pulmonale (Right-sided HF)
Emphysema: pneumothorax (due to bullae), weight loss due to consistent labored breathing
What are the histologic hallmarks of asthma?
curschmann spirals & charcot-leyden crystals
What are complications that can arise from asthma?
pulsus paradoxus & status asthmaticus
List the differences of Flow-Volume parameters assoc. w/ OLD & RLD.
For OLD: FEV1, FVC, & FEV1/FVC are decreased; RV, FRC, & TLC are increased
For RLD: all parameters are decreased except FEV1/FVC which is normal or increased in advanced stages
What pt. population is commonly assoc. w/ IPF?
50-70 yr. old males
IPF can also be assoc. w/ what OLD?
bronchiectasis
What complications are assoc. w/ IPF?
lung cancer; PHTN; RHF; arrhythmias; CAD, RF
Extrinsic allergic alveolitis (AKA hypersensitivity pneumonitis) encompasses which types of hypersenstivites?
III & IV
Sarcoidosis is more common in what pt. populations?
african american & scandinavian females 30-55 yr. of age
What kind of WBCs would you expect to find in the lymph nodes of a pt. w/ suspected sarcoidosis?
activated dendritic cells
How do pulmonary alveolar macrophages contribute to sarcoidosis?
pulmonary alveolar macrophages increases expression & activity of 1-alpha hydroxylase involved in synthesis of calcitriol
What immunoglobin is naturally elevated in pts. w/ sarcoidosis?
IgG
What are complications assoc. w/ sarcoidosis?
lung cancer, malignant lymphomas, bronchiectasis, PHTN, aspergilloma, Chronic kidney failure
Caplan syndrome is assoc. w/ what pulmonary disease and pt. population?
pneumoconiosis; pts. w/ h/o rhermatc diseases
What would you expect to see on a CXR of a suspected sarcoidosis pt.?
“Ivory white” calcified subdiaphragmatic and pleural plaques
Define inspiratory reserve volume
The amount of inspiratory volume with exertion Minus the tidal volume
Define tidal volume
Volume of passive respiration
Define exploratory reserve volume
The amount of exploratory volume with exertion minus the tidal volume
Define inspiratory capacity
Title volume plus inspiratory reserve volume
Define residual volume
Volume of air that remains in lungs after maximum expiration
Define functional residual capacity
Residual volume plus exploratory reserve volume
Define vital capacity
Total volume of maximal respiration
What does a spirometry measure
Measures the rate of change in lung volume during forced breathing maneuvers
Define forced vital capacity
Total volume of air that can be exhaled forcefully from the total lung capacity
For a normal lung what is the average fvc
Less than three seconds
What are the normal parameters for forced vital capacity
80 - 120%
What is the definition of forced exploratory volume
It’s the volume of air forcefully expired from full inflation in the first second
what are the normal parameters for Fev
75 to 80%
What are the parameters for an obstructive pattern
decreased FEV, decreased FVC and decreased FEV to FVC ratio defined as less than 70%
What parameter is used to measure the severity of COPD
FEV
what are the parameters for a restrictive pattern
decreased fev, decreased fvc, and normal or increased fev to fvc ratio
What are common extra thoracic conditions of restrictive lung disease
Obesity, pregnancy, ascites, and peritonitis
What is an example of fixed obstruction
asphyxiation; Tracheostenosis, Tracheo Gorditer, Hypertrophy tonsils, Large foreign body
Give an example of variable extra thoracic obstruction
Vocal cord dysfunction
Give an example of variable intra thoracic obstruction
Endo bronchial carcinoma
What are variable extra thoracic causes of airway obstruction
Edema of Epiglottis, vocal cord paralysis, vocal court adhesions, and foreign body
what are variable intra thoracic causes of upper airway obstruction
polypoid tumor, tracheomalacia, and polychondritis
Spirometry cannot measure total lung capacity. Additionally FVC is decreased for both obstructive and restrictive lung disease Therefore the way to tell the difference is by assessing the TLC And how is this done
Obtaining a lung volume reading
What are the lung volume parameters for an obstructive pattern
TLC greater than 120%; in other words residual volume greater than 120%
What are the volume parameters for a restrictive pattern
less than 80%; In other words residual volume less than 80%
What variables influence diffusing capacity?
Surface area of Alveoli, thickness of alveolar membrane, Volume of blood in capillary bed
How is diffusing capacity measured?
DLCO; this is defined as the reaction rate of the test gas with hemoglobin
Decrease DLCO is clinically defined by what parameter?
Less than 80%
What diseases are associated with decreased DLCO?
emphysema, Interstitial fibrosis, pulmonary hypertension, and anemia
Increased DLCO is defined by what parameter?
Greater than 120 to 140 percent of the predicted value
what are diseases associated with increased DLCO?
Asthma, pulmonary hemorrhage, polycythemia, left to right shunt
Why is DLCO usually normal for chronic bronchitis?
because chronic Bronchitis affects the more proximal Airways which is not where the gas exchange takes place
If a patient comes to you with complaints of asthma but has a normal pulmonary function test what is the next best thing to do?
Bronco provocation: methacholine challenge
What is a classic example of idiosyncratic asthma?
Exercise induced
Exercise induced asthma can be managed by what?
longer warm up periods and beta agonist
What is another example of idiosyncratic asthma?
aspirin intolerance: Symptoms typically appear after three hours of taking aspirin
Asthma is categorized under which type of hypersensitivity reaction?
Type I
What are typical clinical presentations of asthma?
Wheezing, breathlessness, chest tightness, nighttime and early morning coughs
describe the pathophysiology of asthma.
Airway obstruction due to smooth muscle dysfunction and increased edema and mucus in the airway
What are the three characteristics of acute response to asthma?
Bronchial hyperactivity, mucosal edema, and airway secretions
What are the three characteristics of chronic response to asthma?
Increased inflammatory cell numbers, epithelial damage, airway remodeling
What would you expect to find histologically for a patient with suspected chronic asthma?
Basement membrane thickening, vascular dilation, edema, inflammatory cell infiltration, Epithelial damage, smooth muscle hypertrophy, mucus gland hypertrophy, perankyema intact
What are the histologic hallmarks of asthma?
Charcot Leyden crystals: needle-like structures formed from breakdown of eosinophils; curschmann spirals: coiled basophilic plugs of mucus formed in lower airways
What chromosomes are directly involved in risk factors for asthma?
chromosome 5 and 12
What cytokines are encoded on the 5th chromosome?
IL 4, 5, 9, 13
what are potential receptors encoded on chromosome 5 that are involved in asthma?
Beta adrenergic receptors and glucocorticoid receptors
Genetic induced asthma associated with genes on chromosome 12 Encode what?
atopy and hyper responsiveness
Besides aero allergies, what are other factors that can cause IgE induced asthma?
Neoplasia, chronic adrenal insufficiency, and parasites
What are risk factors for asthma?
occupational exposure to toxic chemicals, smoking, RSV
What history findings indicate asthma?
Coughing at night or after physical activity, colds that last over 10 days, history of a topic dermatitis, family history, relief with medication
How is diffusion capacity affected For asthma?
Normal or elevated: elevated indicates recruitment of capillaries
Although rare how does hypoxemia affect the aa gradient for asthma?
AA is elevated
what would you expect to find on arterial blood gas of a suspected asthma patient?
Hypercapnia and respiratory alkalosis
List the asthma classifications.
See slide 49 on clinical asthma powerpoint
What are common biological agents associated with increased risk for asthma?
Cat, Cockroaches, house dust mite, mold, dog, RSV, domestic birds, chlamydia, mycoplasma pneumonia
what are common chemical agents associated with increased risk for asthma?
tobacco products, nitrous oxide exposure, formaldehyde, and fragrances
Common factors that exacerbate asthma?
Menstrual cycle, pregnancy, aspirin and nsaids, Beatty adrenergic blockers, sulfate
Circadian induced asthma episodes is associated with what neurotransmitters?
decreased levels of Catecholamines; increased levels of histamine
The gastroesophageal reflux & nasal secretions are mediated by which cranial nerve?
Vegas
What are asthma and COVID 19 regulations?
Slides 50 to 60 on the clinical asthma powerpoint
What recommendations can you give to reduce house exposure to dust mites?
Use bed encasements, wash bedlines weekly, limits stuffed animals, reduce humidity
What are the medication guidelines for asthma?
Slide 68 of the clinical asthma powerpoint
What is the MOA of omalizumab?
anti-IgE
what is the MOA of mepolizumab & reslizumab?
anti-IL-5
What does PCWP assess?
Assesses left ventricular function and pressure
What is the normal parameter for PCWP?
Four to 12 milligrams of Mercury
A PCWP greater than 18 milligrams of Mercury indicates what?
Heart failure
A PCWP greater than 12 but less than eighteen millimeters of mercury is indicative of what?
ARDS
What risk factors account for over 85% of ARDS cases?
Pneumonia, aspiration of gastric contents, and sepsis
What chest x-ray findings would indicate ARDS rather than CHF and vice versa?
For ARDS: bilateral infiltration with a wideout appearance; for CHF: bilateral plural effusions
Would you expect PCWP to be normal decreased or elevated for ARDS?
Left ventricular function is normal hence PCWP is also normal
For congestive heart failure would you expect pcwp to be normal decreased Or increased?
elevated
Make sure to know the phases of ARDS
Slides 15 and 16 of the ARDS powerpoint
What genes are thought to be involved in ARDS?
Ace, il-10, TNF, VEGF
Why do you want to lower tidal volume for ARDS patients?
to avoid barotrauma
Describe the mechanism of COVID nineteens involvement in Ards?
Ace 2 protein is the receptor for Covid 19 Stimulation of this protein can can activate RAAS
How is acute respiratory failure type 1 clinically defined?
Hypoxemia without hypercapnia
what are risk factors for acute respiratory failure?
Pulmonary embolism, alveolar hypoventilation, parenchymal disease, right to left shunt
how is acute respiratory failure type 2 clinically defined?
hypoxemia with hypercapnia
What physiological consequences contribute to type 2 ARF?
Increased airway resistance; reduced breathing effort; decreased surface area of the lungs; neuromuscular disease; musculoskeletal rigidity
what is an example of ARF caused by increased airway resistance?
Chronic obstructive pulmonary disease
What are examples of acute respiratory failure induced by reduced breathing effort?
Opioid induced respiratory depression, brainstem lesion
what is a classic example of acute respiratory failure induced by decreased surface area of the lawn?
ARDS
what neuromuscular disease is commonly associated with ARF?
Gillian bear disease
What are common musculoskeletal deformities associated with ARF?
Kyphoscoliosis, ankylosing spondylitis
How is ARF type one Quantitatively defined?
Decrease partial pressure of oxygen and carbon dioxide; increased AA gradient; normal PH
How is ARF type 2 quantitatively defined?
Decreased partial pressure of oxygen; increased partial pressure of carbon dioxide; normal AA gradient; decreased PH
Decreased partial pressure of oxygen as quantitatively defined as
less than sixty millimeters of Mercury
Increased partial pressure of oxygen or CO2 is quantitatively defined as
greater than fifty millimeters of Mercury
Under what circumstances would you suspect air conditioner lung?
Patient works around heated water reservoirs
A farmer presents to your clinic with symptoms indicative of an interstitial lung disorder. the farmer tells you that the symptoms started after harvesting hay for the season. what interstitial lung disorder does this patient most likely have?
Farmers lung: A type of hyper sensitivity pneumonitis
A patient with a parent respiratory distress presents to your clinic with symptoms indicating an interstitial lung disorder. the patient states that they are a pigeon breeder. what is the most likely interstitial disorder?
pigeon breeders lung: provoked by proteins from serum, excreta, or bird feathers; This is a type of Hypersensitivity pneumonitis
What kind of microbes would you suspect are involved in hypersensitivity pneumonitis of organic dust exposures?
thermophiles
