Respiratory Pathology Flashcards

Question

emphysema pathophysiology

Answer 1

- irritants activate neutrophil elastases, lead to progressive breakdown of elastin in bronchiolar walls - becomes more compliant and loses recoil (becomes less like a balloon and more like a plastic bag) - air becomes trapped in alveoli, leading alveoli to "burst" - burst alveoli can't hold air, and "mega alveoli" created from multiple alveoli bursting and fusing together have less surface area to exchange gas - can lead to increased inflammation and fibrosis over time - often accompanies chronic bronchitis as both are caused by similar irritants

Answer 2

``` clinical: SOB esp w/ exertion tachypnea *hypOcapnic *pursed lip breathing + red cheeks + lack of cyanosis = "pink puffers" *barrel chest minimal cough w/ small amounts of mucus, unless +chronic bronchitis reduced breath sounds hypER-resonant ``` spirometry req'd for dx: - FEV1, FVC, and FEV1/FVC ratio all decreased (FEV1 decreases more than FVC) - because harder to expel air - progressive worsening over time imaging: CT preferred, XR also can see many changes *hyperinflation, flattened hemidiaphragms increased, irregular radiolucency (more white) --- most common type, centrolobular (termed based on the part of the alveolus it affects) is primarily seen in the upper part of all lobes, patchy distribution --- panlobular (again, named based on effect on alveolus) is associated with alpha-1-antitrypsin deficiency and affects lower lobes diaphragmatic tenting fewer blood vessels, distorted note that emphysema dx is based mostly on structural changes while chronic bronchitis dx is based mostly on clinical presentation

Answer 3

- lungs have natural response to vasoconstrict to damaged or blocked alveoli, to shunt to functioning alveoli - too many damaged or blocked alveoli --> too much vasoconstriction (pulmonary hypertension) - increased afterload to right ventricle --> RVHF

Answer 4

an inherited form of emphysema d/t lack of enzyme that breaks down proteases that break down elastin (overall result is elastin breakdown) clinical suggestions: - usually onset b/f age 30 - little to no exposure history - familial - distribution in lower lobes

Answer 5

``` *cigarette smoke (1st or 2nd hand) indoor open-flame/coal stoves (developing countries) environmental/smog occupational (asbestos, coal, ...) genetic (alpha-1-antitrypsin deficiency) ```

Answer 6

lot of air not a lot of gas exchange happens in emphysema due to air trapping that results in breakdown of alveoli

Answer 7

- inflammation of bronchial walls (neutrophils and lymphocytes) - smooth muscle cell proliferation and reactivity --> bronchospasms, cough, wheezing - goblet cell proliferation and hypertrophy --> too much mucus (blocks airways) - squamous metaplasia (structural changes) --> cilia not as effective at clearing mucus --> too much mucus (blocks airways)

Answer 8

``` clinical *persistent productive cough (3+ mo/yr x 2+ yr) SOB esp w/ exertion in later stages tachypnea *wheezing + crackles/rales *hypERcapnic hypoxia *cyanosis = "blue bloaters" reduced breath sounds hypER-resonant ``` r/o other causes of chronic cough spirometry req'd for dx: - FEV1, FVC, and FEV1/FVC ratio all low (FEV1 decreases more than FVC) - same as emphysema - because harder to expel air - worsens over time - same as emphysema imaging: not always done - larger, more defined bronchi(oles) ("circled" due to thickening of bronchi) - bronchi(oles) may be blocked by mucus - concomitant emphysema and/or fibrosis may be observed note that emphysema dx is based on structural changes while chronic bronchitis is a clinical dx

Answer 9

- increased susceptibility to lung infections (mucus plugs trap bacteria in and make it harder to expel them via mucus) - RVHF (d/t pulmonary htn d/t reactive vasoconstriction)

Answer 10

- reduce modifiable risk factors (smoking, occupational exposures) - beta-adrenergic agonists (albuterol, LABAs) - LAMAs - sometimes ICS - oxygen, at-home may be needed - treat complications

Answer 11

airway dilation --- associated mucosa thinning can lead to exposed capillaries and hemoptysis causes: - chronic/repetitive injury, such as infections - TB most common cause - autoimmune disease or impaired host response - CF - primary ciliary dyskinesia tx: - airway clearance regiments - sometimes bronchodilators and ICS

Answer 12

coughing up blood | usually related to bronchiectasis, which exposes capillaries d/t mucosa thinning

Answer 13

COPD: - FEV1 decreases - FVC may also be decreased in severe disease, but less (actual lung damage causing reduction in ability for air to flow out) - low FEV1/FVC ratio * * FEV1/FVC ratio does not improve (<12%) with administration of bronchodilators Asthma - also an obstructive disease, so similar to COPD - FEV1 decreases - FVC normal to near-normal (can still blow out the same amount of air because there's nothing wrong with their lungs, just takes longer b/c of airway obstruction) - low FEV1/FVC - only low during exacerbation or uncontrolled disease * * FEV1/FVC improves >12% with administration of bronchodilators Restrictive disease - preserved FEV1/FVC ratio (ability to expel air is fine) - -- BUT both FEV1 and FVC are lower because absolute volumes are smaller (d/t reduced TLC) - -- this is why ratio is more important than FEV1 or FVC alone - -- no change with bronchodilators - reduced TLC d/t inhalation difficulty, reduced space in lungs (d/t all the fibrosis) FEV1: forced expiratory volume in one second FVC: forced vital capacity (expiratory volume during an entire breath) TLC: total lung capacity

Answer 14

*in all groups reduction of risk factors e.g. smoking is most important Group A: 0-1 exacerbations not requiring hospitalization w/in year AND CAT <10 - SABA only Group B: 0-1 exacerbations not requiring hospitalization w/in year and CAT ≥10 - LABA or LAMA Group C: ≥2 exacerbations or ≥1 requiring hospitalization w/in year AND CAT <10 - LAMA Group D1: ≥2 exacerbations or ≥1 requiring hospitalization w/in year and CAT 10-20 - LAMA ± LABA Group D2: ≥2 exacerbations or ≥1 requiring hospitalization w/in year and CAT ≥20 - LAMA + LABA Group D3: ≥2 exacerbations or ≥1 requiring hospitalizations w/in year and CAT ≥20 and eosinophils ≥300 - ICS-LABA ± LAMA - SABA: short-acting beta AGonist, e.g. albuterol - LAMA: long-acting muscarinic ANTagonist, e.g. tiotropium bromide; may be used in place of LABA if other LABAs cannot be used - ICS-LABA: combined formulations e.g. budenoside-formoterol (Symbicort), fluticasone-salmeterol (Advair) - note that formoterol onset is fast enough to be used as a rescue inhaler; LABAs otherwise must me combined with a SABA rescue inhaler - ICS: inhaled corticosteroid, e.g. fluticasone, budesonide - LABA (should not be used w/o ICS): long-acting beta AGonist, e.g. albuterol SULFATE, formoterol, salmetrol

Answer 15

initial: - SABA (albuterol) via nebulizer ± short-acting inhaled anticholinergic (ipatropium) - O2 via nasal canula or if severe HF-NRB - if very severe give CPAP or BiPAP; intubation is last resort f/u: - most commonly d/t respiratory infections: give antibiotics if bacterial suspected (common) - 5-7 days of systemic corticosteroids - switch to LABA or LAMA if not done already, consider increasing dose

Answer 16

asbestos plaques - benign collagen deposits (least severe) asbestosis - pulm parenchymal fibrosis bronchogenic carcinoma - esp in smokers malignant mesothelioma - rare, pleura or peritoneum, presents with large pleural effusion (most severe)

Answer 17

benign collagen deposits in parietal pleura | least severe of asbestos-related pathologies

Answer 18

pulmonary parenchymal fibrosis secondary to asbestos exposure

Answer 19

carcinoma of bronchi | 40-60x increased in dual asbestos–tobacco exposure

Answer 20

malignancy of pleura or peritoneum presents with large pleural effusion rare, asbestos related not affected by smoking

Answer 21

- mining - milling - fabrication - building fireproofing, maintenance, demolition, installation, thermal insulation - shipbuilding, repair, refitting (esp seen in WWII vets) - brake work - plumbers, electricians, welders - geologists, archeologists, bricklayers, sculptors, others working with many types of rock

Answer 22

fibrogenic silicate mineral | cheap, easy to mine "magic mineral"

Answer 23

allergic sensitization over time to any workplace chemical, for example: - - health care workers and latex - - isocyanate in auto spray paints, plastic or rubber manufacturing - - carpenters and wood dust after sensitization, even very low dose can cause asthma attack

Answer 24

- single exposure to highly toxic material - -- e.g., paper mill explosions (SO2), chlorine, mustard gas (bleach + HCl) - sx w/in 24 h - can be acutely fatal w/o tx - tx w/ oral + inhaled corticosteroids - may not improve with time PREVENTION: respirators, occupational controls

Answer 25

``` iron tin barium titanium glass wool ```

Answer 26

talc - after significant cancer risk was observed in miners, strong market push toward non-talcum powders - talcum powders in standard usage are less likely to cause any problems but are definitely not recommended in babies, everyone else maybe steer clear jic - unclear evidence on frequent use of talcum for feminine hygiene and cervical cancer kaolin - found as a filler in many medications, is safe in normally ingested amounts - dangerous in frequent inhalation of large doses, e.g. mining, milling, lab synthesis

Answer 27

``` silica/silicon dioxide silicates - asbestos - talc - kaolin coal dust aluminium ```

Answer 28

pneumoconiosis - coughing - inflammation, fibrosis - dust inhalation - occupational hypersensitivity pneumonitis - type iii hypersensitivity - microorganisms, plants and animal proteins, chemicals - inflammation, fibrosis drug-induced lung disease - typically rare adverse event of many drugs - nitrofurantoin, Amiodarone, methotrexate are among top offenders - often identified late in development or post-marketing vasculitis connective tissue disease including RA, SLE, systemic sclerosis, polymyositis idiopathic interstitial pneumonia (IIP), e.g. - idiopathic pulmonary fibrosis (IPF) - cryptogenic organizing pneumonia (COP) - acute interstitial pneumonitis (AIP) - others Others: sarcoidosis, eosinophilic pneumonia, pulmonary langerhans cell histiocytosis, etc.

Answer 29

- diffuse parenchymal lung disease - coughing - inflammation, fibrosis - dust inhalation - occupational

Answer 30

- diffuse parenchymal lung disease - type iii hypersensitivity - microorganisms, plants and animal proteins, chemicals - inflammation, fibrosis

Answer 31

- diffuse parenchymal lung disease - typically rare adverse event of many drugs - nitrofurantoin, Amiodarone, methotrexate among top offenders - often identified late in development or post-marketing

Answer 32

- bronchiole obstruction due to inflammation (an airway disease) - "popcorn lung" based diacytel in popcorn butter - dry cough, SOB, wheezing, fatigue - worsen weeks to months - can be occupational d/t chemical exposure, e.g. - -- nylon flocking - -- polyamide-amine dyes used in textile prints - -- thionyl chloride in battery manufacture - -- diacetyl flavorings manufacture - can also be non-occupational, e.g. - -- connective tissue disorders including RA, SLE, systemic sclerosis, polymyositis - -- bone marrow or heart-lung transplant - -- certain respiratory infections

Answer 33

sx: - generally chronic, often dry cough; subacute, acute also possible; acute on chronic common - SOB - tachypnea - nail deformities - weight loss - exercise intolerance dx: restriction on PFTs low DLCO ground-glass opacities, micronodules, consolidation, UIP pattern (UIP pattern = lower lobe honeycombing, reticular opacities, ground glass opacities, traction bronchiectasis)

Answer 34

- diffuse parenchymal lung disease - idiopathic interstitial pneumonia (IIP) sx: - cough, usually insidious onset - SOB - other DPLD sx - r/o toxic exposure pe: - inspiratory crackles - r/o rheum: rash, synovitis (joint swelling) dx: * radiographic UIP pattern - labs normal - --r/o rheum (CRP, ANCA, ANA) - surgical biopsy is gold standard but not common risk: - age >60 - smoking - familial tx: - limited, both drugs slow but don't halt progression, don't improve lung function, difficult to tolerate - pirfenidone - unknown mechanism - Nintedanib - multi-TYRK inhibitor (anti-fibrotic) - among most common indications for lung transplant (UIP pattern = lower lobe honeycombing, reticular opacities, ground glass opacities, traction bronchiectasis)

Answer 35

lower lobe honeycombing reticular opacities ground glass opacities traction bronchiectasis seen in diffuse parenchymal lung diseases, especially idiopathic pulmonary fibrosis (IPF)

Answer 36

VO2 ~250 ml/min VCO2 ~200 ml/min R = VCO2 / VO2 = 200/250 = 0.8

Answer 37

VO2 & VCO2 = resting rate of O2 or CO2 consumption in ml/min R = VCO2 / VO2 V•E = minute ventilation (minute volume) in L/min = total volume expired in one minute = VT * fR • over V indicates that it is the volume per minute VT = tidal volume = expired breath volume per breath fR = respiratory rate (frequency) = breaths per minute VD(anat) = anatomical dead space = amount of air in L that remains in conducting airways and does not reach alveoli VA = volume reaching alveoli per breath = VT - VD V•A = V•E - V•D (anat) VD(alv) = alveolar dead space = volume of air distributed to non-functional alveoli VD(physiol) = physiological or effective dead space = VD(anat) + VD(alv)

Answer 38

V•E (minute ventilation) ~ 8 L/min VD(anat) (anatomical dead space) ~ 150 ml at fR of 10 breaths/min: V•A = V•E - (VD * fR) = 8 L/min - (0.150 L/breath * 10 breaths/min) = 6.5 L

Answer 39

V•A = V•E - (VD * fR) tachypnea increases fR --> decreased V•A emphysema increases VD d/t air trapping --> decreased V•A restrictive lung disease decreases minute ventilation (volume exhaled per minute) = V•E --> decreased V•A with many diseases a combination of factors will be affected and all should be taken into account to estimate or directly measure V•A

Answer 40

A = alveolar I = inspired/atmospheric P = partial pressure F = fraction O2 lower than normal air as it is moved into the capillaries CO2 higher than atmospheric air as it is moved into the alveolus V•CO2 = amount exhaled - amount inhaled = (volume exhaled * FACO2) - (volume inhaled * FICO2) FICO2 ~ 1, so FACO2 ~ V•CO2 / VA VA = VT - VD(physio)

Answer 41

hyperpnea = any increase in ventilation (more air into lungs), including hyperventilation and metabolic hyperpnea (such as when exercising) hyperventilation = increased ventilation (volume into lungs) without increased V•CO2, i.e., is not related to metabolic demand --> low arterial PCO2 tachypnea = fast breathing; also typically shallow so may not result in hyperpnea

Answer 42

often surgical sgx yes: localized sgx maybe: - ipsilateral LN involvement sgx no, radiation + chemo yes: - contralateral or supraclavicular LN involvement - invasion through chest wall or mediastinum - metastasis - other c/i such as age, frailty, etc sgx approach: - usually lobectomy - more conservative resections considered if low lung reserve but success rate lower - total pneumonectomy may be needed e.g. in hilum involvement - usually open thoracotomy - video assisted and robotic b//c more common b/f surgery: - lymph node eval mediastinoscopy or endobronchoscopic US + fine needle aspiration - possible neoadjuvant immunotx, chemotx, and/or radiation post-sgx: - adjuvant tx not always needed or done - immunotherapy fairly common - platinum chemo b//c less common

Answer 43

common sites: - brain (esp in SCLC but also common in NSCLC) - bone standard tx: 1) chemo + radiation or chemo then radiation 2) immunotx radiation: - common - whole brain sometimes done (in brain metastasis) but has many side fx such as memory loss - localized ideal, relatively low morbidity chemo: - usually platinum-based (cytotoxic) - pemetrexed (anti-metabolite) common in non-squamous, not effected in squamous targeted: - VEGFi in NSCLC, caution in squamous d/t hemorrhage risk - Ab-drug conj more common - EGFRi recently approved immunotx: - anti–PD-1/PD-L1

Answer 44

- ~15% of cases - ~99% d/t smoking - most responsive to initial chemo - sgx removal only possible in ~2% of cases - relapse almost always occurs - in local metastasis, usually chemo + radiation - - invasion thru mediastinum or pleura, or - - contralateral LN involvement - in advanced metastasis, usually immunotx + chemo - in recurrent disease, few to no effective tx

Answer 45

- SCLC (~15%) - NCSLC (~85%) - - squamous cell carcinoma: - --- adenocarcinoma (most common) - --- large cell carcinoma - - non-squamous cell carcinoma

Answer 46

big picture: - correcting endothelial dysfunction - vasodilation - endothelin-1 blockade - - ambrisentan - - bosentan - - macitentan - PGI2 (prostacyclin) AGonist - - epoprostnol - - treprostinil - - iloprost - - selexipag - nitric oxide AGonist - - sildenafil - - tadalafil - - riosiguat

Answer 47

- pulmonary vascular remodeling - plexiform lesions - exertional SOB - syncope - elevated JVP - LE edema - right HF, dilation, remodeling possible (depending on cause): - connective tissue disease/AI - HIV - liver disease - substance use (esp meth) - toxic exposures - family hx precapillary PH w/ mPAP >20, PAWP <15, PVR >3

Answer 48

PAH: - idiopathic - heritable - drug and toxin - connective tissue disease/autoimmune - HIV - portal (liver) hypertension - congenital heart disease - schistomiasis - calcium-channel blockers (long term) - persistent PH of newborn other PH: - left HF - restrictive and/or obstructive lung disease - hypoxia ± lung disease - thrombus/embolus - more rarely: - - heme - - metabolic - - chronic renal failure

Answer 49

type I = hypoxemic PaO2 < 60 mmHg despite supplemental O2 type II = hypercapnic/ventilatory PaCO2 > 50 mmHg

Answer 50

widened A-a gradient: - ventilation/perfusion (V/Q) mismatch - - dead space = V w/o Q; V/Q --> ∞ - - shunt = Q w/o V; V/Q = 0, e.g. - --- ASDs, VSDs (septal defects) - diffusion impairment - - barrier e.g. edema, fibrosis - - surface area = emphysema, pneumonectomy - - decreased O2–Hgb association e.g. CO poisoning, anemia ------------------------------- normal A-a gradient: - low fractional inspiration of O2 (FiO2) - - e.g. high altitude, enclosed spaces - mixed type I/type II failure: hypoventilation - - can't breathe in enough O2 - - can't breathe out enough CO2 - multifactoral

Answer 51

alveolar–arterial gradient difference between alveolar and atmospheric O2 (PAO2 - PaO2) due to physiologic shunts and dead space, not all atmospheric O2 reaches alveoli normal A-a gradient = (age + 10)/4

Answer 52

clinical algorithm/flowchart: 1. PaO2 (arterial O2) is low 2. Calculate A-a gradient (PAO2 - PaO2) and normal A-a gradient (age + 10) / 4 3a. if normal, is hypoventilation or low FiO2. - -- is there enough oxygen in the air? if yes, hypoventilation. if no, low FiO2. 3b. if A-a is increased, give 100% O2. 3b. 1. If PaO2 increases, it is V/Q mismatch or diffusion impairment. 3b. 2. If PaO2 does not increase, it is shunting.