Pulm Week 2 Flashcards
Obstructive lung disease is caused by airway narrowing due to… (2)
1) Intrinsic airway narrowing (bronchospasm, plugging, inflammation/edema
2) Collapse (“floppy” airways) - decreased radial tethering or decreased airway integrity
Obstructive disease has increased lung volumes due to _______ and results in…(2)
due to incomplete emptying of alveoli - hard to exhale
1) Hyperinflation → increases RV, ERV, and thus FRC by decreasing IC
2) Flattening of the diaphragm → mechanical disadvantage
(Flat diaphragm generates less inspiratory pressure due to increased radius of curvature AND must generate more tension in order to generate same intrapleural pressure)
Increased airway resistance in obstructive disease result in…
increased work of breathing
Bronchoprovocation testing in asthma, vocal cord dysfunction, and emphysema
Asthma: REVERSIBLE
- Should go completely back to normal with bronchodilator
- Methacholine challenge: people with asthma react at level of 5 or less
Vocal Cord Dysfunction: minimally reversible with bronchodilator
Emphysema: no reversibility to bronchodilators
Asthma
- chronic inflammation of airways associated with airway hyperresponsiveness
- Recurrent episodes of wheezing, breathlessness, chest tightness, and coughing particularly at night or in the early morning
- Episode associated with airflow obstruction that is reversible spontaneously or with treatment
Types of asthma (Extrinsic vs. Intrinsic)
Extrinsic (Allergic): initiated by type I hypersensitivity reaction induced by exposure to an outside agent
-Mostly IgE mediated
Intrinsic (nonseasonal, nonallergic): initiated by diverse, non-immune mechanisms (ASA ingestion, viral infection, cold, inhaled irritants, stress, exercise)
- Chronic, persistent
- Altered arachidonic acid metabolites (increases leukotrienes, decreased prostaglandins - ASA)
Airway narrowing in asthma occurs due to…
Inflammation: inflammatory cells + inflammatory mediators
Structural airway changes
Structural airway changes in asthma (3)
1) Increase in airway smooth muscle cells due to hypertrophy and hyperplasia
2) Blood vessel proliferation
3) Mucus hyper-secretion (increased goblet cells and size of submucosal glands)
Clinical features of asthma (7)
1) Intermittent - PFTs can be normal between exacerbations
2) Reversibility of airflow obstruction
3) Cough, dyspnea, wheezing
4) Exacerbations with exposure to: exercise, cold air, allergens, air pollution, infection
5) Normal to increased DLCO
6) Bronchoprovocation demonstrates hyperreactivity
7) Severity of asthma determines by frequency of symptoms
Physical exam findings in asthma (3)
- May be normal in stable disease
- Respiratory distress: increased rate, use of accessory muscles
- Wheezing (expiratory)
- Distinguish inspiratory stridor (VCD) from expiratory wheezing (asthma)
Acute asthma
1) Hyperinflation
(shortened diaphragm)
2) Breathing occurs on flatter part of PV curve - more pressure required to get similar change in volume
3) Accessory muscle use
4) INCREASED WORK OF BREATHING
5) Can improve symptoms with bronchodilation → facilitates exhalation
Pathology of airways during acute asthma
Airway inflammation, edema, and mucus plugging lead to gas trapping and airflow obstruction in acute asthma
→ unable to fully exhale before taking next breath → breaths “stack” up on one another → increase lung volumes
Vocal cord dysfunction
inappropriate vocal cord motion results in airflow obstruction
Variable extrathoracic obstructive pattern due to adduction of vocal cords during inspiration
Physical exam findings in VCD
Symptoms mimic asthma (share similar triggers also) - Often coexists with asthma
- Stridor mistaken for wheezes - stridor = inspiratory
- Flow-volume loop suggestive (extrathoracic obstructive pattern)
- Diagnosed by fiberoptic laryngoscopy
Treatment of VCD
Acute: anxiolytics, helium-oxygen mixture
Long term: speech therapy, underlying triggers
COPD
fixed airflow limitation, FEV1/FVC less than 70%
3rd leading cause of death in the US
Smoking is a big risk factor
Chronic Bronchitis
Increased airway resistance due to changes in airway structure (edema, mucous, fibrosis)
-May have overlapping features with asthma
- Produces TONS of mucous
- -> Impaired ventilation
Diagnosis of chronic bronchitis
Productive cough at least 3 months over the past 2 years without other cause
Physical exam findings of chronic bronchitis (4)
1) *Cough, rhonchi, wheezing
2) Prolonged expiratory phase
3) Purse-lip breathing
4) Tripod positioning
Emphysema
- Loss of normal alveolar spaces with enlargement of distal airspaces
- Increased lung compliance
- Impaired gas exchange
- Dynamic airway collapse
What causes increased lung compliance in emphysema?
- Decreased elastic tissue
- Loss of balance between proteases and antiproteases in lung (alpha-1-antitrypsin deficiency)
- Increased apoptosis of alveolar cells
- Impaired repair mechanisms
What causes dynamic airways collapse in emphysema?
“floppy” airways and loss of elasticity of surrounding tissue allow for collapse
Physical exam findings in emphysema (5)
1) *Diminished breath sounds
2) *Hyper-resonant
3) Prolonged expiratory phase
4) Purse-lip breathing
5) Tripod positioning
Acute COPD exacerbation
- Increased cough, sputum volume and purulence, increased wheezing
- Worsening obstruction on PFTs
- Unchanged CXR
- Precipitated by infection, pollution PE, or unknown factors
Implications:
-Increased work of breathing due to hyperinflation, increased airway resistance
Treatment of acute COPD exacerbation
Bronchodilators, steroids, antibiotics
Common causes of death from COPD (5)
Respiratory failure Right ventricular failure Pneumonia Spontaneous pneumothorax Pulmonary embolism
Bronchiectasis
abnormal dilation of proximal bronchi
- Localized or diffuse
- Mucociliary escalator stops working
- Loss of airway wall integrity with dilation → collapsible airways result in obstruction (may be compounded by inflammation)
- Recurrent infections worsen bronchiectasis (CF, PCD, immunodeficiency)
Symptoms of bronchiectasis (4)
1) Cough, productive of purulent sputum
2) Sputum volume often copious (especially during exacerbation)
3) Wheezing, hemoptysis
4) Mild airflow limitation
Treatment of bronchiectasis
- Airway clearance to promote clearance of secretions
- Antibiotics (intermittent, chronic, rotating courses)
-Treat reactive airways disease
(Bronchodilators, corticosteroids)
Bronchiolitis
inflammation of the bronchioles
-usually occurs in young children
Cystic Fibrosis
- Heterogeneous recessive genetic disorder
- Mutation in cystic fibrosis transmembrane conductance regulator (CFTR) gene at locus 7q31.2
- Normal protein function: CFTR chloride channel in membranes of cells that line passageways of lungs, liver, pancreas, intestines, reproductive tract, and skin
Factors that influence development of asthma
1) Host factors (genetic predisposition to atopy or airway hyperresponsiveness, obesity, sex)
2) Environmental factors (exposure to allergens, viral infection, occupational exposures, tobacco smoke, air pollution, diet)
Differentiating chronic bronchitis, asthma and emphysema
Chronic Bronchitis: inflammation of the airways themselves
- Chronic productive cough
- Minimal reversibility (under stable conditions) with albuterol
- Normal to slightly increased DLCO
Asthma: increase in smooth muscle tone and airway inflammation
- Reversible, episodic
- Exacerbation with methacholine
- Normal to increased DLCO
Emphysema:
- Marked hyperinflation (due to tissue destruction)
- No reversibility to bronchodilators
- Decreased DLCO
- Shift in PV curve
Challenges delivering inhaled drugs
1) Airway bifurcations limit inhaled delivery
2) Entire blood volume contacts lungs → toxicity, also better drug efficacy
3) Particle size - Med must be contained within particles small enough to be aerosolized
-small enough to be inhaled and avoid the pharynx and reach small airways
-can’t be too small or they will be exhaled back out
[Respirable range = 1-5 um]
Benefits of inhaled (topical) drug
- Preferred over systemic route because delivery directly to site of action (bypasses need for absorption)
- Smaller doses required, rapid onset
- Minimize systemic onset
goals of asthma treatment
-reduce frequency and intensity of asthma symptoms, prevent exacerbations, and prevent long term consequences of poorly controlled asthma
Stepwise treatment of ashma
- Gradual increase in medications to control symptoms
- Need regular follow up (2-6 weeks) when initiating therapy
- Must ensure asthma control is achieved
Step down is IMPORTANT - minimum dose necessary to control symptoms and prevent adverse effects
-Step down if well controlled for 3 months
Steps of Asthma treatment: Step 1 - Step 5
Step 1: SABA as needed
Step 2: low dose ICS
Step 3: combination therapy: SABA + medium dose ICS + LABA
Step 4: High dose ICS + LABA +/- Omalzumab
Step 5: high dose ICS + LABA + oral corticosteroid +/- Omalzumab
What is well-controlled asthma?
- Symptoms no more than twice per week
- Nighttime symptoms no more than twice per month
- SABA should be used less than twice weekly (with exception of routine use prior to exercise)
- Peak flow near normal
- Oral steroid no more than once per year
- Urgent care visit no more than once per year
Long acting asthma medications include…(3)
1) Inhaled glucocorticoids
2) Long-acting inhaled B2-agonists (LABA)
3) Leukotriene modifiers
Inhaled glucocorticoids
preferred long-term control medication for tx of persistent asthma
Inhaled corticosteroids can impact growth in children
Long-acting inhaled B2-agonists (LABA)
- preferred supplementary long-term control agent for use with inhaled glucocorticoids (step 2, added to inhaled GCs)
- Should NOT be used as monotherapy, do not reduce inflammation
- Combine with inhaled corticosteroid to control inflammation
Leukotriene modifiers
-2 mechanism of actions
Mechanism of Action:
1) Leukotriene D4 antagonist (montelukast, zafirlukast)
2) 5-lipoxygenase inhibitor (zileuton)
→ bronchodilation, anti-inflammatory (block leukotrienes), and attenuates exercise induced asthma
Omalizumab
anti-IgE biologic
- Inhibit IgE binding to IgE receptor on mast cells/basophils
- Decreasing IgE bound → decrease release of allergic response mediators
Mepolizumab
anti-IL-5 biologic
Inhibit cytokine (IL-5) responsible for growth, differentiation, recruitment, activation, and survival of eosinophils
Allergen Immunotherapy
induce specific allergen tolerance
More effective for allergic rhinitis and conjunctivitis than asthma
Tiotropium
long acting anticholinergic for use in asthma age > 12 yrs
Theophylline
- limited use due to adverse effect profile
- Oral or IV
Mechanism of Action: inhibit PDE
→ bronchodilation and some anti-inflammatory activity
Cromolyn sodium and nedocromil
- limited use, better current meds
- Inhaled
Mechanism of action: inhibit mast cell mediator release
→ prevent exercise-induced asthma and allergen-induced pulmonary response
Quick relievers for asthma (3)
1) Short acting B2 agonists (SABA)
2) anticholinergics
3) Systemic glucocorticoids
Short acting B2-agonists (SABA)
preferred to relieve symptoms and to prevent exercise induced asthma
Mechanism of Action: Stimulate B-adrenergic receptor → bronchodilation via smooth muscle relaxation, inhibits production of respiratory secretions
Anticholinergics
- use in COPD NOT asthma
- Secondary reliever for significant asthma exacerbations
Mechanism of Action: inhibit cholinergic receptor → bronchodilation via smooth muscle relaxation
Inhibits production of respiratory secretions
Systemic glucocorticoids
- for severe acute asthma exacerbations
- Sometimes for continued use in managing severe asthma
Systemic glucocorticoids mechanism of action
phospholipase inhibition, inhibition of cytokine synthesis
→ anti-inflammatory (Reduce cellular infiltration, eosinophils, mast cells, lymphocytes)
→ Vasoconstrictor, reduces edema
Classifying COPD
Gold 1 - Gold 4
all have FEV1/FVC less than 0.70
Gold 1, Mild = FEV1>80% predicted
Gold 2, Moderate = FEV1 between 50-80% predicted
Gold 3, Severe = FEV1 between 30-50% predicted
Gold 4, Very severe = FEV1 less than 30% predicted
Steps of COPD pharmacologic treatment (4)
A → SAMA or SABA prn
B → LAMA or LAMA prn
C → ICS + LABA or LAMA
D → ICS + LABA and/or LAMA
Treatment of COPD
1) Smoking cessation - creates capacity to influence COPD
- Can add pharmacotherapy and nicotine replacement to reduce smoking
2) Regular physical activity
Refer to pulmonary rehab to make patients more comfortable with exercise - typically for more severe/symptomatic COPD
3) Pharmacology (SAMA, SABA, ICS)
- No biologics used in COPD
Bronchial circulation
supplies conducting airways (trachea, down to terminal bronchioles)
Supplied by aorta and intercostal arteries
→ Arterial pressure and oxygenated blood
Function of bronchial circulation (3)
1) Perfuses the large airways
2) Protects lung from infarction (PE, pneumonia)
3) Can “grow into” areas of diseased lung
Consequence of bronchial circulation
Typical source of hemoptysis
Much of the arterial flow drains into LA = shunt
Equation of PAP
PAP = (CO x PVR) + LAP
Properties of pulmonary circulation (4)
- Low resistance
- Low elastance/High compliance
- Low pressure
- CO = 5L/min (same as systemic)
Progression of pulmonary circulation
R ventricle → pulmonary trunk → R and L main pulmonary arteries (carry deoxygenated blood) → lobar branches
→ muscular intrapulmonary arteries
→ arterioles (precapillary vessels)
→ Capillary network (alveolar ducts and alveoli)
→ Veins -Single lobar vein emerges from each lobe
Normal pressures in heart and lungs
RA = 0-5 mmHg RV = 25/0-5 mmHg PA = 25/10 mmHg LA = 5-10 mmHg LV = 100/5-10
RV diastolic pressure = right atrial pressure (no tricuspid valve stenosis)
RV systolic pressure = pulmonary artery systolic pressure (no pulmonary valve stenosis)
Determinants of blood flow distribution in the lung (4)
1) High capacitance (high distensibility of perfused vessels)
2) Recruitment of previously unperfused vessels (zone 1 and 2)
3) Hypoxic pulmonary vasoconstriction
4) Endogenous vasodilators and vasoconstrictors (NO, prostacyclin, endothelin, thromboxane)
Hypoxic pulmonary vasoconstriction
Vasoconstriction in areas with alveolar hypoxia
Preserves V/Q matching
Physiologic zones on the lung:
Zone 1
no blood flow
- PA > Pa → capillaries always collapsed
- Not present in a healthy person
- Can get this with mechanical ventilation with positive pressure ventilation or with COPD
Physiologic zones on the lung:
Zone 2
- Intermittent blood flow (PA>Pa, and Pa>PA)
- *Blood only flows when Pa>PA
- Vascular reserve when CO increases
- Some zone 2 will be present in normal healthy lung
- Apex of lung
Physiologic zones on the lung:
Zone 3
Continuous blood flow
Bottom of the lung
Pa always > PA → capillaries always open
Pulmonary edema
Normal fluid leak vs. pathologic fluid leak
fluid in the lung
Originates in capillaries → interstitium → lymphatics
-Too much fluid → alveolus → acinus fills with fluid, interlobular septa enlarges, and pulmonary vein enlarges
Normally: there is some net fluid out of the vessels, but it is returned to circulation by lymphatics
-No fluid enters the alveoli
Determinants of water and solute balance in the lung (2)
1) Hydrostatic (cardiogenic)
2) Increased permeability (noncardiogenic)
Hydrostatic Pressure (cardiogenic)
- **Increased vascular pressure (increased pulmonary capillary wedge pressure)
- LV failure, CHF
- **Diuretics help
- Presents within minutes of an acute elevation of microvascular pressure and rapidly responds to therapy
- Typically has a history of heart failure, EKG changes, chest pain
Increased permeability (noncardiogenic)
- Proteins leave vasculature
- Due to ARDS, pneumonia
- Presents more slowly (6-24 hours after acute lung injury)
- Associated with an exposure (e.g. toxic gas, trauma, fever, cough/pneumonia, aspiration of gastric contents)
- **PCWP not elevated
- **diuretics don’t help
Pulmonary Hypertension
pulmonary arterial pressure > 25 mmHg (normal is 15-18)
Increased PA pressure DOES NOT MEAN increased PVR
Causes of pulmonary HTN
1) Increased pulmonary vascular resistance (pre or postcapillary)
2) Increase LA pressure
3) Increased CO (Rarely by itself)
Difference between precapillary and postcapilarry pulmonary HTN
Precapillary: PCWP less than 15 mmHg
Postcapillary: PMWP > 15 mmHg
-Pulmonary venous hypertension (PVH)
5 types of pulmonary HTN
1) PAH = precapillary
2) PH due to left heart disease = PVH, postcapillary
3) PH due to lung disease and/or hypoxia (COPD, ILD, OSA)
4) Thromboembolic pulmonary HTN
5) PH with unclear/multifactorial mechanisms
Acute Pulmonary Embolism
clinical presentation
Results in RV strain or failure
-Increased myocardial O2 demand, decreased myocardial O2 delivery → cycle leading to death
Acute Pulmonary Embolism
diagnosis (7 tests)
1) History and physical → Wells’ scores (PE risk score)
2) D-Dimer (breakdown product of thrombin, elevated with active clot)
3) ECG - S waves in I, Q waves in III and T waves in III (SI, QIII, TIII)
- Most commonly sinus tach
4) **CXR - usually NORMAL
5) V/Q scan - measure mismatch between ventilation and perfusion
6) CT pulmonary angiography
7) Echo
Acute Pulmonary Embolism (stable aka submassive)
treatment
- Parenteral Anticoagulation
- -> Heparin (UFH, LMWH)
- Catheter directed thrombolysis (tPA)
- Oral anticoagulation (Warfarin)
Acute pulmonary embolism
(massive, RV failure, hypotensive)
treatment
- Heparin
- Consider thrombolysis (tPA)
- Consider IVC filter
- Consider surgical thrombectomy
3 criteria for Pulmonary Arterial Hypertension
mean PAP > 25 mmHg + PCWP/LVEDP less than 15, and PVR greater than 3 woods units
Chronic precapillary disease
Physical exam findings in PAH (7)
1) Neck veins distended
2) Normal lung auscultation (no rales, no fluid in alveoli)
3) Loud P2
4) Tricuspid regurg murmur
5) LE edema
6) **Presents with abnormally low DLCO with normal pulmonary function (lung volumes and spirometry)
7) **Does not increase pressure in pulmonary capillary bed and thus pulmonary edema does not develop
Hemodynamic and clinical course of PAH
1) CO normal, but PVR and PAP slowly increasing
- Asymptomatic
2) CO begins to decrease, PVR, PVP continue to rise, BNP begins to rise
- Some symptoms present
- -> Smooth muscle hypertrophy, early intimal thickening
3) CO falls off, PVR increases, PAP increases until it drops due to heart failure, BNP elevated
- -> Smooth muscle hypertrophy, adventitial, intimal proliferation, thrombosis, plexiform lesions
