Pulmonary Flashcards
Silicosis
sx, cxr and biopsy
disease associations
a pneumoconiosis from mineral dust inhalation
often no sx; dyspnea on exertion + productive cough 10-20 years after 1st exposure
cxr shows MANY BILATERAL NODULES, mostly APICAL + calcified hilar nodes
biopsy of CALCIFIED HILAR NODE shows birefringent particles surrounded by WHORLED collagen fibers + dusty macrophages
assoc. with TBC risk via impaired macrophage function
Asbestosis
sx, cxr, biopsy
dyspnea on exertion
cxr shows interstitial involvement in LOWER zones +/- PLEURAL PLAQUES
histo shows FERRUGINOUS bodies (fusiform rod with translucent asbestos center + iron coating)
Berylliosis
sx, cxr, biopsy
dyspnea
cxr shows ill-defined nodular + irregular opacities
histo shows NON-CASEATING GRANULOMA with associated particles (diff from HS pneumonitis)
Coal Pneumoconiosis
sx, cxr, biopsy
exertional dyspnea
cxr shows nodular interstitial opacities
histo of node/perinodal lung shows COAL-LADEN MACROPHAGES (“coal macules”)
Hypersensitivity Pneumonitis
sx, cxr, histo, associations
exertional dyspnea
cxr shows diffuse nodular interstitial infiltrate
histo shows NON-CASEATING GRANULOMA (no particles as on berylliosis)
assoc. with bird/birdcage contact, Aspergillus fumigatus and other organic dusts (T2/T3 HS rxns)
ARDS
causes + pathogenesis
Sepsis, pneumonia
Trauma
Pancreatitis
direct or indirect pulmonary insult (irritants, trauma, aspiration, pancreatitis, sepsis) causes CYTOKINE release > endothelial activation > increased permeability > NEUTROPHIL activation + degranulation plus alveolar edema with hyaline formation and atelectasis
ARDS
clinical features, effects on various breathing parameters
distinguishing feature from cardiogenic pulmonary edema?
hypoxia
CXR shows bilateral infiltrates
decreased compliance, increased work of breathing
V/Q mismatch via inadequate perfusion
ARDS has NORMAL pulmonary capillary wedge pressure (6-12 mmHg) which would be increased in cardiogenic causes of pulmonary edema
FRC
what is it? how does it change in COPD
FRC = ERV + RV
ERV = expiratory reserve volume = the amount that can still be exhaled after expiration of tidal volume
RV = residual volume
FRC will INCREASE in COPD (ERV decreases but RV increases greatly)
Categorization / mechanisms of OCCUPATIONAL ASTHMA (2 categories)
Immunologic - usual Th2 asthma mechs; often has LATENT period before sx during sensitization; causes include cereals, latex and chemicals (formaldehyde, amines, dyes)
Non-immunologic - aero-irritants cause airway denudation > persistent inflammation; usually after accidents involving CHLORINE/AMMONIA; sx onset is sudden + severe
Mechanisms in Oxygen-Induced Hypercapnia in COPD patients (3)
- V/Q MISMATCH - pulmonary vessels normally constrict in poorly ventilated areas; upon giving high concentration O2, vasodilation in poorly ventilated areas shunts blood away from well ventilated areas (incr. physiological dead space)
- HALDANE EFFECT - oxygenation of blood displaces CO2 from Hb; in hypoxic state Hb carries CO2 well > administer high conc. CO2 and Hb does not rid body of excess CO2 well
- DECREASED MINUTE VENTILATION - in chronic hypercapnia, hypoxia becomes major driving force for respiration with PERIPHERAL CHEMORECEPTORS; administer O2 and this driving force diminishes
Oxygen Toxicity
why + when does it happen? s/s?
increased ROS production can damage airways + lung parenchyma
within 24 hrs of breathing pure O2 > SUBSTERNAL HEAVINESS, PLEURITIC chest pain, cough + dyspnea
Fusion protein in some cases of NSCLC
what is it? who has it?
EML4-ALK fusion protein (inversion of 2p)
causes constitutive activation of a kinase (like in CML)
usually young non-smokers with adenocarcinoma lacking EGFR or K-Ras mutations
(echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase)
Mesothelioma
early presentation? histo? IHC? EM?
early - multiple nodules on parietal pleura grow + encase parenchyma; EFFUSIONS +/- HEMORRHAGE; sx include slow progressive dyspnea, cough, chest pain and weight loss
histo - cuboid/flattened cells (epithelium-like) or SPINDLE cells (stromal-like)
IHC - almost all CYTOKERATIN-positive; many CALRETININ positive
EM - polygonal cells with long, slender MICROVILLI and TONOFILAMENTS
4 asbestos related lung conditions
- pleural plaques
- asbestosis - parenchymal scarring
- bronchogenic carcinoma
- malignant mesothelioma
Lung tumors:
type, incidence, location + associations
ADENOCARCINOMA - up to 50%; PERIPHERAL; clubbing + hypertrophic osteoarthropathy; non-smoker women
SQUAMOUS CELL - up to 25%; CENTRAL with necrosis + cavitation; hypercalcemia; smokers
SMALL CELL - up to 15%; CENTRAL; Cushing, SIADH, or Lambert-Eaton; smokers
LARGE CELL - up to 10%; PERIPHERAL; gynecomastia + galactorrhea (large polygonal cells; mix of squamous + adeno characteristics)
Pulmonary Fibrosis
imaging? s/s? pulmonary function testing?
CXR - bilateral, diffuse, RETICULONODULAR opacities mostly in lung BASE
sx - gradual-onset progressive dyspnea; dry cough; fatigue; eventual weight loss/failure to thrive
signs - END-INSPIRATORY CRACKLES at base
RESTRICTIVE function - decr. volumes, decreased FEV1 and FVC with normal/high Tiffeneau and decreased CO diffusion
Drugs causing pulmonary fibrosis
3 categories, 3/1/2 examples
immunosuppressants - MTX, cyclophosphamide, sulfasalazine
Antiarrhythmics - amiodarone
Chemo - MTX, bleomycin
Centriacinar vs. Panacinar Emphysema
causes? location?
CENTRIACINAR - via smoking, mostly UPPER lobes (higher V/Q ratio)
PANACINAR - via a1-antitrypsin defic.; mostly LOWER lobes (more Q > more neutrophil elastase); family history of liver/lung disease
Protease - Antiprotease balance in lung
which cells release proteases?
what inhibits the proteases?
other proteases + inhibitors present?
Neutrophils - neutrophil elastase; inhib. by a1-antitrypsin
Macrophages - macrophage elastase; inhib. by TIMP (tissue inhibitors of metalloproteinases)
Other proteases - Cathepsin G and MMPs
Other inhibitor - alpha-2 macroglobulin
What and where are club cells?
nonciliated cells in the terminal parts of bronchioles
secrete CLUB CELL SECRETORY PROTEIN which protects against airway inflammation and oxidation, as well as surfactants that prevent bronchiolar collapse
Chronic Lung Transplant Rejection
histo?
causes what?
presentation?
first - lymphos destroy small airway epithelium
then - fibrinopurulent EXUDATE and GRANULATION tissue in BRONCHIOLI > fibrosis, obliteration
called BRONCHIOLITIS OBLITERANS
within 5 YEARS of transplant, dyspnea, dry cough and DECREASED FEV1 and tiffeneau
ABG changes in pulmonary embolism
Compensation? when does it occur?
Decreased Q to certain lung region > “dead space ventilation” > redistribution of flow
Central respiratory drive increases (via dyspnea + inflammatory mediators > HYPERVENTILATION
LOW PAO2 - Hb is nearly fully saturated already, so faster breathing can’t help
LOW PACO2 - carbon dioxide removal more dependent on breathing rate > hypocapnia via hyperventilation
RESPIRATORY ALKALOSIS
with renal compensation
at first: NORMAL BICARB
after 48 hours: LOW BICARB
CXR differences in…
pleural effusion vs. mainstem bronchus obstruction
both can cause hemithorax opacification (1 via fluid, other via atelectasis)
diff by TRACHEAL DEVIATION
effusion - deviates AWAY from effusion due to compression
bronchus obstruction - deviates TOWARD obstruction due to collapse of lung
Hyperacute Lung Transplant Rejection
onset? etiology? pathophys?
minutes to hours
PREFORMED HOST Abs to donor ABO or HLA
NEUTROPHILIC infiltration with FIBRINOID NECROSIS and THROMBOSIS
Acute Lung Transplant Rejection
onset? etiology? pathophys?
up to 6 months after
CELL-MEDIATED response to MISMATCHED DONOR HLA
perivascular (SMALL VESSELS) and submucosal (BRONCHIOLES) infiltrates of LYMPHOCYTES
Chronic Lung Transplant Rejection
onset? etiology? pathophys?
6 months to years after
chronic, slowly progressive CELL-MEDIATED response to HLA antigens
SUBMUCOSAL inflammation causes GRANULATION, scarring and BRONCHIOLOTIS OBLITERANS
Main triggers of COPD exacerbation?
4 things: 2 categories and 2 separate items
- Viral infections
- Bacterial Infections
- Air pollution
- PE
main viral (3) and bacterial (3) exacerbators of COPD
Viral - rhino-, influenza (orthomyxo), parainfluenza (paramyxo)
Bacterial - M. catarrhalis, S. pneumo, H. flu
(M S H genuses of bacteria increase mucus production in copd pt…. lungs become “MuSHy” … gross)
What are the cellular changes seen in the lung in idiopathic pulmonary fibrosis?
type 1 pneumocytes are lost
type 2 pneumocytes undergo hyperplasia but do not differentiate into type 1 as usual
fibroblasts + myofibroblasts migrate + proliferate
What is respiratory quotient?
What does it estimate?
What is its normal value?
ratio of CO2 to O2 across alveolar membrane
used to estimate metabolic rate
normal value is 0.8
How can total blood O2 content be calculated (formula)?
What 3 parameters are used?
Blood O2 content = (O2-binding capacity x % saturation) + dissolved O2
How does carbon monoxide poisoning affect the Hb-O2 dissociation curve?
leftward shift
decreased tendency for O2 to dissociate in tissues
Normal “ALVEOLAR-ARTERIAL OXYGEN GRADIENT” values
10-15 mmHg in healthy adult (can be as low as 5)
rises some with age
If hypoxemia presents with NORMAL alveolar-arterial O2 gradient, what can the 2 causes be?
(2 categories, 3 examples in first cat)
indicates that BOTH the alveolar and arterial pO2 are low (either less fresh O2-rich air gets in, or air has lower Po2)
can be due to:
- HYPOVENTILATION - acute as in opioids/barbiturates; chronic as in obesity hypoventilation syndrome or neuromuscular disorder
- HIGH ALTITUDE - inspired pO2 is low
If hypoxemia is present with ELEVATED alveolar-arterial O2 gradient, what can the 3 causes be?
(3 categories + examples)
elevated A-a gradient means O2 in alveoli is higher than in arteries; can be due to:
- V/Q MISMATCH - pulm. embolism, COPD
- R-TO-L SHUNT - septal defect, pulmonary edema
- IMPAIRED DIFFUSION - interstitial lung disease
What results from OBESITY HYPOVENTILATION SYNDROME?
3 main changes
- SLEEP-DISORDERED BREATHING - incl. obstructive sleep apnea
- INCREASE CO2 PRODUCTION - via increased mass + surface area
- REDUCED VOLUMES + COMPLIANCE - compression of lungs by excess abdominal fat
results in fatigue, chronic hypoventilation, dyspnea, difficulty concentrating, increased PaCO2
General pathophysiological cause of Kussmaul breathing
Mnemonic for specific causes?
Metabolic acidosis
KUSSMAuL
Ketones (DKA) Uremia Sepsis Salicylates Methanol Aldehydes Lactic acidosis
Lung Adenocarcinoma
location, clinical associations, who gets it?
PERIPHERAL
clubbing + hypertrophic osteoarthropathy
non-smoker women (most common lung cancer)
Lung SCC
location, clinical associations, who gets it?
CENTRAL (with necrosis + cavitation; in larger bronchi from squamous metaplasia)
hypercalcemia (PTHrP)
smokers
SCLC
location, clinical associations, who gets it?
CENTRAL (basal cells of bronchial epithelium; neuroendocrine)
Lambert-Eaton
SIADH
Cushing
smokers (almost exclusively)
Large Cell Lung Carcinoma
location, clinical associations
PERIPHERAL
Gynecomastia + galactorrhea
(undifferentiated; features of both ADC and SCC)
How does oxidized “ferric” iron (Fe3+) in hemoglobin affect the Hb-O2 dissociation curve?
first, ferric iron can not bind O2
also, any residual ferrous (Fe2+) iron left in the Hb molecule has INCREASED AFFINITY (left shift of curve) for O2
what does one of the common mutations to alpha1-antitrypsin cause?
the “Z mutation” causes improper folding
specific auscultatory sign of pulmonary arterial hypertension
P2 louder than A2
indicates high pulmonary P closing pulmonary valve strongly
What is FiO2? What is the FiO2 of normal inspired air?
Fraction of inspired oxygen - the fraction of oxygen in the volume being measured
normally 0.21 (21%)
Equation for physiologic dead space
mnemonic
Taco Paco Peco Paco
VD = VT x (PaCO2 - PeCO2)/PaCO2
normally equal to anatomical dead space; increases in V/Q mismatch
Vt normally 500 mL and VD normally 150 mL
How are MINUTE VENTILATION and ALVEOLAR VENTILATION different?
equations
minute ventilation includes entire tidal volume; alveolar ventilation removes the dead space
VE = VT x RR
VA = (VT - VD) x RR
Equation for total oxygen content of blood
O2 content = (1.34 x Hb x SaO2) + (0.003 x PaO2)
Aspiration usually occurs in what lobe / segment?
What if supine?
apical/posterior segments of LOWER LOBE OF RIGHT LUNG
if supine, may also enter posterior segment of UPPER LOBE R LUNG
Airway resistance
how much of total R do upper airways account for? (nasal passages, mouth, larynx + pharynx)
about 50%
Airway resistance
how does airway resistance compare between TRACHEA, BRONCHI, BRONCHIOLES and TERMINAL BRONCHIOLES?
how does the graph look?
in order of most resistant to least (numbers not important but relative relationships are; unit is cm-h20/L/sec) :
- MEDIUM BRONCHI - 0.085; most resistant due to turbulent flow
- TRACHEA + mainstem bronchi - 0.07; small total cross sectional area, but less turbulence
- BRONCHIOLES - 0.02; total cross-sectional area is increasing
- TERMINAL BRONCHIOLES - near zero; large total CSA causes slow, laminar flow in airways < 2 mm diameter
3 forms of CO2 in blood
- HCO3- makes up 70%
- Carbaminohemoglobin (21-25%)
- Dissolved CO2 (5-9%)
Where does CO2 bind hemoglobin?
N-terminus of globin protein
NOT on the heme… so O2 and CO2 do NOT compete for binding sites, but CO2 favors the deoxygenated form of Hb
Why does CO2 bind Hb better in deoxygenated blood?
HIGH H+ IONS in deoxygenated blood BIND HEMOGLOBIN and cause a “rightward shift” > O2 unloading …
and an Hb conformation that favors CO2 binding (Bohr effect)
(nbme question phrased this as “because Deoxy-Hb is a better buffer of hydrogen ions than Oxy-Hb”)
What is most likely to slow the rate of pulmonary function decline in a COPD patient?
smoking cessation
PROPHYLAXIS vs. TREATMENT of deep vein thrombosis / pulmonary embolism
prophylaxis - LMWH (eg, enoxaparin)
treatment - tPA
(streptokinase and all the “-plase” drugs: alteplase, reteplase and tenecteplase)
1 lung cancer in US
location?
growth and spread pattern?
adenocarcinoma in situ (aka bronchioloalveolar carcinoma)
in PERIPHERY
grows along INTACT ALVEOLAR SEPTA (no vascular/stromal invasion) and undergoes AEROGENOUS SPREAD
lung adenocarcinoma in situ
histo?
WELL-DIFF but DYSPLASTIC COLUMNAR cells in the alveoli
+/- intracellular MUCIN
lung adenocarcinoma in situ
presentation (3 basic, 1 special sign)
imaging (2 possibilities)
- cough
- SOB
- hemoptysis
- BRONCHORRHEA - copious watery tan-colored sputum from variants with high mucin production
- discrete mass, or…
- pneumonia-like consolidation
Measurement that can differentiate between cardiogenic and noncardiogenic pulmonary edema
Values
Cardiogenic would have increased PULMONARY CAPILLARY WEDGE PRESSURE (more than 6-12 mmHg)
Noncardiogenic (ARDS, high altitude) has normal PCWP (but lowered lung compliance, capillary permeability, V/Q ratio and increased work of breathing)
