Pulmonary Diseases Flashcards
pink puffer phenotype
a condition of the lung characterized by abnormal permanent enlargement of airspaces distal to the terminal bronchiole, accompanied by the destruction of their walls, and without obvious fibrosis
Airway walls are destroyed –> enlargement and overdistension of the airspaces without interstitial fibrosis and minimal/absent interstitial inflammation
Interstitial framework of the lung is destroyed –> simplification of the lung parenchyma and reduced surface area of gas exchange
Little scarring or fibrosis
early dyspnea and late cough, minimal sputum production, few infectious exacerbations, loss of elastic recoil, and hyperinflation of the CXR (increased AP diameter, barrel chest)
Complications: respiratory insufficiency, CO2 retention/respiratory acidosis, secondary pulmonary hypertension, right ventricular hypertrophy, cor pulmonale, pneumothorax
smoking: increase in proteases; centriacinar pattern, severe in upper lobe
alpha 1 antitrypsin deficiency: decreased anti-proteases, panacinar pattern, severe in lower lobe, cirrhosis of the liver may occur
Decreased FEV1, Decreased FEV1/FVC ratio, Increased RV, Decreased diffusion capacity, hypoxemia
Emphysema
blue bloater phenotype characterized by a cough productive of sputum on most days during at least three consecutive months for more than two successive years
More profound hypoxemia at rest, elevated PaCO2 with chronic respiratory acidosis, cor pulmonale with right heart failure
Associated with smoking and environmental pollutants, characterized by persistent cough with airway hypersecretion and inflammation and sputum production
Chronic asthmatic bronchitis is associated with bronchospasm
Chronic airflow obstruction and acute infectious exacerbations may develop in later stages
Predominantly involves the proximal airways without the parenchymal injury and loss associated with emphysema
Particulate/noxious inhalants –> inflamed airways with increased mucus secretions and mucopurulent exudates
Airway epithelium may show mucous metaplasia and squamous metaplasia, mucosa will have increased mucus glands with productive secretions with mucus plugs
Peribronchiolar fibrosis is present in later stages
Reid index measure the ratio of mucus gland layer to the entire mucosa (normally less than 0.4). increased mucosal inflammation and mucous plugging leads to airway obstruction, mucosal fibrosis may occur in later stages
Initial symptoms are related to bronchial and bronchiolar inflammatory irritation and cough
With increased mucus secretions, airway obstruction –> atelectasis, dyspnea on exertion, air trapping
Retained CO2 (hypercapnia) --> respiratory acidosis Inadequate oxygenation --> hypoxemia and cyanosis
Late complications include repeated airway infections, pneumonia, right-sided heart failure, respiratory insufficiency
Treatment
Increase airflow and decrease resistance with bronchodilators (anticholinergics and beta agonists)
Corticosteroids and antibiotics are used in severe cases
Chronic bronchitis
Abnormally dilated airway resulting from prolonged destructive inflammation/infection of the airway and supporting structures
Clinical presentation:
Airway infection, cough, purulent foul-smelling sputum production, squeaks, crackles, wheezes, airflow obstruction, CXR shows tram tracks indicating dilated airways
Damage airways are permanent and result from CF, Kartagener’s syndrome, bronchial obstruction (tumor or foreign body), immunodeficiency diseases and necrotizing bronchopneumonias
Airways show remodeling and dilation with an inflamed mucosa, luminal purulent mucoid secretions, and fibro-inflammatory airway walls
complications: hypoxemia, cor pulmonale, secondary amyloidosis
Bronchiectasis
chronic relapsing inflammatory airway disorder
more common children, females, and African Americans
Allergic inflammation (eosinophils), goblet cell metaplasia, mucous gland hyperplasia, luminal allergic mucus, airway muscular hypertrophy Inflammation limits airflow via acute airway smooth muscle constriction, swelling of the airway wall, chronic mucus plug formation, and airway wall remodeling
Anti-inflammatory therapy is the cornerstone of treatment
Therapy to suppress inflammation must be long term
Early intervention with therapy may modify the disease process and prevent remodeling
Episodic attacks of dyspnea, wheeze, bronchospasm, cough, and chest tightness – vary over time and in intensity
Bronchial hyperresponsiveness is an exaggerated bronchoconstrictor response to many different stimuli
Status asthmaticus involves marked mucus plugging, air trapping, and dyspnea – may cause death
Pathophysiology: increased airway resistance (airflow limitation worse on expiration), increased work of breathing, non-uniform distribution of ventilation (V/Q mismatch, low V/Q units develop, localized alveolar hypoxia)
Diagnosis: compatible history and physical exam with documentation of variable airflow obstruction
Spirometry before and after inhalation of short-acting bronchodilator (12% improvement that is at least 200mL after use of bronchodilator indicates asthma over COPD)
Low FEV1 but no symptoms, consider poor perception of control or restricted activity
bronchoprovocation testing with methacholine or exercise may be used
Frequent symptoms in the absence of abnormal FEV1 consider cardiac disease, deconditioning
Treatment requires a step-wise approach; persistent disease is most effectively controlled with daily anti-inflammatory therapy with inhaled glucocorticoids
Long term control medications: corticosteroids, long-acting beta agonists, leukotriene modifiers, anti-IgE
Rescue medications: short-acting beta agonists (relief of acute symptoms, preventative prior to exercise)
asthma
Onset is usually in childhood and is often preceded by allergic rhinitis, urticaria, or eczema
Family history of atopy is common
Disease is triggered by environmental antigen
Skin prick tests for antigen are positive (IgE mediated reaction)
atopic asthma
The mechanism of inflammation and airway hyperresponsiveness is less clear; may involve viral infections of respiratory tract, inhaled air pollutants (sulfur dioxide, ozone, nitrogen dioxide)
Airway hyperresponsiveness is more severe and sustained
Family history, associated allergies, and abnormal IgE levels are uncommon
intrinsic asthma
immunologically mediated lung disease that arises from inhalation of organic dusts, animal proteins, and/or molds
Inciting antigen may be occupational or recreational and in a sensitized individual it induces a type III and type IV hypersensitivity reaction
Bronchiolitis with interstitial lympho-plasmacytic infiltration with poorly formed interstitial granuloma
Infiltration of lymphocytes and macrophages (not mast cells, eosinophils)
Clinical presentation: dyspnea, cough, fever
Acute and sub-acute presentations with rapidly progressive flu like signs and symptoms
Chronic exposure may lead to chronic disease that may progress to interstitial fibrosis and restrictive lung disease
CXR shows nodular diffuse infiltrates
Treatment: remove antigen (usually improves symptoms and reverses the pathological process); glucocorticoids to reverse the inflammatory condition
By removing exposure, condition may be reversed if no scarring or fibrosis has occurred
hypersensitivity pneumonitis
single pitch, inspiratory or expiratory sound that is produced by large airways with severe narrowing
May be caused by severe obstruction of any proximal airway (larger airways)
Acute –> immediate consultation with ENT or anesthesia
Inspiratory = Supraglottic: epiglottis, larynx, aryepiglottic fold, false vocal cords
Epiglottitis, retropharyngeal abscess, diphtheria
Expiratory = Intrathoracic: portion of the trachea within the thorax and mainstem bronchi
Congenital disorders, foreign bodies, compression by lymph nodes or tumors
Biphasic = Glottis and subglottic: vocal cords to the extrathoracic segment of the trachea
Laryngotracheitis (croup), vocal cord paralysis, critical obstruction
Stridor
musical sound pronounced primarily during expiration by airways of any size (usually in smaller airways)
chronic: asthma, COPD, bronchiectasis, HF
acute: asthma, HF, aspiration, URI
wheeze
inflammation of the bronchioles
Predominantly affects the smallest air passages of the lungs
Symptoms include increased effort for work of breathing
Scattered areas of expiratory wheezes
Usually occurs in children less than two years of age with the majority of cases due to viral pathology
Most common virus is RSV which is easily spread via mucosal droplets and is most common in late fall to early spring; premature infants are at the highest risk, Palivizumab monthly injections
Most cases are mild and self-limiting, symptoms last for 2-3 weeks
Early symptoms: runny noses, cough, similar to a cold
Severe cases may require hospitalization or frequent bronchodilator therapy for wheezing responsive to therapy
bronchiolitis
Idiopathic pulmonary fibrosis
Process of rapidly progressive respiratory failure with diffuse homogeneous interstitial infiltrates on CXR
Fibrosing alveolitis, interstitial fibroblastic proliferation, interstitial fibrosis, proliferative interstitial scarring
Lung proceeds to fibrosis, cystic changes and diffuse scarring
Acute Interstitial Pneumonia = Hamman-Rich Syndrome
Idiopathic pulmonary fibrosis
Chronic fibrosing interstitial lung changes that present in adults with slowly progressive onset
Dyspnea and sometimes cough
Patchy distribution, CXR show subpleural and bibasilar reticulo-nodular opacities
Respiratory failure occurs over 2-5 years
Patchy interstitial fibrosis alternating with areas of spared lung, accentuation of interstitial fibrosis in a subpleural location, presence of interstitial inflammation and active fibroblastic proliferative regions with dense collagen interstitial deposition
Earliest interstitial lesions = fibroblastic foci = proliferative fibroblasts with myxoid collagenous matrix
Progresses to end stage lung with pulmonary fibrosis and cystic change (honeycomb lung)
Usual interstitial pneumonitis
idiopathic pulmonary fibrosis
Clinical features similar to UIP but there is a more homogenous chronic interstitial pneumonia throughout the lung
Pulmonary intersitium is expanded with lympho-plasmacytic infiltrate that appears temporally uniform (unlike in UIP)
Better clinical outcome than UIP, may also be responsive to steroid therapy
Nonspecific interstitial pneumonitis
idiopathic pulmonary fibrosis despite known cause
Inflammation in the terminal bronchioles and alveolar ducts with production and desquamation of hemosiderin-laden macrophages
RBILD may continue to involve pulmonary interstitium –> restrictive disease
Appears to be associated with smoking, improvement with smoking cessation and glucocorticoids
DIP involves diffuse involvement of alveolar units with desquamated pneumocytes and macrophages
Active alveolar disease gives ground glass appearance on high resolution CT
Respiratory bronchiolitis interstitial pneumonia/desquamative interstitial pneumonia
idiopathic pulmonary fibrosis
commonly seen in African American females
dyspnea, cough, elevated ACE, hypercalcemia
inflammatory systemic disease of unknown etiology with inflammatory foci composed of non-caseating granuloma
Pulmonary involvement begins with mediastinal and hilar granulomatous LAD and progresses to lung involvement with granulomatous inflammation in a lymphatic distribution
Proliferating CD4 cells activate macrophages –> epithelioid histiocytes in type IV hypersensitivity pattern
Increased CD4:CD8 ratio with activation of Th1 cytokines
May lead to interstitial fibrosis and end-stage lung but most cases resolve or are indolent
asteroid body = configuration of giant cells
Exclude mycobacterial and fungal infection before making the diagnosis
sarcoidosis
interstitial fibrosis due to chronic occupational exposure
Particles lodge at bifurcations of the distal airways, terminal bronchioles, and respiratory ducts
Inflammatory response depends on size, solubility, chemical nature and other properties of the dust/fumes
Decreasing lung clearance mechanisms (smoking) increases the retained inhalant particles
Macrophages attempt to engulf and digest particles; inflammatory mediators, lysosomal enzymes, and fibrogenic factors are released causing lung damage and fibrosis
pneumoconioses
Sclerotic nodules
Results from exposure to silica - mining, tunneling, stone cutting, excavation, road building, sandblasting, glassmaking
Macropahges interact with silica at the bifurcations of the distal bronchioles and ducts –> release of inflammatory mediators, lysosomal enzymes, ROS, fibrogenic factors
Nodules of dense collagen are formed retaining silica particles
In simple cases the nodules are scattered throughout the lung fields but do not compromise function; may progress to coalescent massive fibrosis with pulmonary dysfunction. Nodules most often seen in upper lobe.
Simple: asymptomatic, gradually progressive dyspnea on exertion
Complicated: marked dyspnea on exertion, cough, sputum, progression to cor pulmonale and respiratory failure
Clubbing is not seen
Increased incidence of mycobacteria infection due to impaired phagolysosome function
silicosis
Interstitial fibrosis
Results from inhalation of asbestos silicates during the processing of asbestos fibers - mining, milling, transporting, manufacturing fibers; domestic exposures
Increased fiber burden in the lung over years –> pleural effusion, pleural plaques
Injury progresses to interstitial fibrosis with interstitial ferruginous bodies
Associated with malignant pleural mesothelioma and bronchogenic carcinoma (in smokers)
Inhalation and deposition of fibers at respiratory bronchioles and alveolar ducts
Pulmonary alveolar macrophage alveolitis is dependent on fiber load
Increased release of oxidants and inflammatory mediators
Damage to parenchymal cells with remodeling of connective tissue
Chronic interstitial lung disease
asbestosis
results from the inhalation of coal dust –> anthracotic coal macules with pigmented macrophages embedded in collagen adjacent to respiratory bronchioles
Progresses overtime to massive fibrosis with coalescent dense collagen bundles –> pulmonary dysfunction
coal workers pneumoconiosis
diverse group of pulmonary disorders that are classified together because of similar manifestations
In general, the major problem is a disruption of the distal lung parenchyma but airways, blood vessels, or pleura may be affected as well
Characterized by infiltration of cellular and noncellular material into the lung parenchyma
CXR: diffuse interstitial infiltrates, smaller lung size
Thickening of the interstitium between the blood and airspace decreases gas exchange
injury to the alveolar epithelial cells that initiates the disease
An inflammatory response ensues that results in scarring and structural remodeling
Inflammatory cells, proliferating epithelial cells, fibroblasts, and ECM components drive the repair process that results in remodeling and may become dysregulated
results in reduced lung compliance
Restrictive ventilator defect, higher pressures are needed to inflate the lung to a given volume (increased work of breathing)
Smaller tidal volumes are moved more often; this is inefficient
DLCO is decreased; there is a thickening and loss of surface area of the membrane
V = AD(P1-P2)/T where D is proportional to solubility/sqrt MW
Both FRC and TLC are lower than normal
Abnormal resting gas exchange
Exercise desaturation
PO2 is normal at rest but falls with movement
Increased PCO2 is only seen with severe disease because it is more soluble than O2
Diagnosis
Nonspecific respiratory complaints
Dyspnea that is usually progressive, dry cough
CXR : Diffuse parenchymal infiltrates, May be normal
Chronic: ground glass opacities, alveolar filling, cystic appearance, LAD, pleural disease, pneumothorax
Interstitial infiltrates and LAD: sarcoidosis, silicosis, infections, malignancy
Interstitial infiltrates and pleural disease: infections, malignancy, collagen vascular disease, drug hypersensitivity, CVD, asbestos-related disease
Investigation of pulmonary hypertension due to the change in pulmonary vascular resistance
Patient history: family history, exposure history, smoking history, medications, previous radiation exposure, age and sex of the patient
Physical exam findings
Velcro crackles = mid to late inspiratory crackles in the lower lung field due to the lesser negative trans pulmonary pressure that is no longer able to hold open alveoli, crackling is heard with alveolar opening
Digit clubbing is seen in IPF but is not specific for IPF
Skin lesions, eye findings, peripheral LAD, CV findings, hepatosplenomegaly, musculoskeletal
Diffuse parenchymal lung disease
chronic interstitial lung disease
Unlikely if all of the following are absent
Fever >/= 38 degrees C
Tachypnea >/= 24 breaths/min
Tachycardia >/= 100 beats/min
Evidence of consolidation: rales, egophony, fremitus
Management of community acquired pneumonia
Applies to non-immunocompromised adults (not to hospitalized patients or non-ambulatory residents of long term care facilities)
CXR to confirm diagnosis
Tests to establish microbiologic diagnosis are optional in outpatients
Additional tests to consider in hospitalized patients
Blood culture before antibiotic regimen
Sputum gram stain and culture
Urine antigen tests for pneumococcus and Legionella
Common bacterial etiologies Streptococcus pneumoniae Haemophila influenzae Mycoplasma pneumoniae Chlamydophila pneumoniae Legionella Staphylococcus aureus (especially during an influenza outbreak)
Less common bacterial etiologies
Moraxella (especially in COPD patients)
Gram negative rods (especially with chronic inhaled steroids, alcoholics, COPD)
Viral etiologies
Influenza, adenovirus, RSV, parainfluenza, MERS/SARS
Empiric therapy should target bacteria unless influenza is expected
Outpatient management in a previously healthy patient that has not used antibiotics in the preceding 3 months (low risk of resistance): oral macrolide (azithromycin, clarithromycin) is preferred, oral doxycycline is an alternative
For children, amoxicillin is used due to lower incidence of atypical pneumonia (Chlamydophila and Legionella)
Outpatient management in a patient with comorbidities (CHF, diabetes, COPD, alcoholism, immunocompromised) or antibiotic use in the last 3 months (increased concern of resistance): respiratory quinolone (levofloxacin, moxifloxacin, gemifloxacin) or beta lactam with macrolide (high dose of amoxicillin or amoxicillin-clavulonate (PO)/ceftriaxone (IM)/cefpodoxime (PO)/cefuroxime (PO) with azithromycin)
Inpatient management in a non-ICU patient: respiratory quinolone (levofloxacin, moxifloxacin, gemifloxacin) or beta lactam with macrolide (high dose of amoxicillin or amoxicillin-clavulonate (PO)/ceftriaxone (IM)/cefpodoxime (PO)/cefuroxime (PO) with azithromycin)
Start with IV and switch to PO with improvement (hemodynamically stable, clinical improvement, able to take PO medications)
Treatment should last for at least 5 days
Patient should be afebrile for 48-72 hours and without signs of clinical instability before stopping treatment
Most cases are treated for 7-10 days
pneumonia
Viral etiologies (more than 90%) Influenza Parainfluenza Respiratory syncytial virus Coronavirus Rhinovirus Adenovirus
Bacterial etiologies (less than 10%):
Mycoplasma pneumoniae, Chlamydophila pneumoniae, Bordatella pertussis
Usually no treatment is required
No proven benefit to antimicrobial use
Macrolide is used in pertussis to decrease transmission
Bronchodilators and antitussives may provide symptomatic relief
acute bronchitis
Spread by airborne droplets from patients in the early stages of infection (not aerosolized)
Highly contagious
Infects 80-100% of exposed susceptible individuals
Spreads rapidly in school, hospitals, offices, and homes
Infected adults often spread infection to schools/daycares
Caused by Bordetella pertussis a gram negative coccobacillus for which humans are the reservoir
Incubation period 7-10 days
Symptoms can be similar to those of a common cold (rhinitis)
Mortality is highest in infants
Pertussis
Spores deposited into the terminal bronchioles and alveoli is aerosolized in 1-10 um particles (bioterrorism)
ingested by macrophages which migrate to peribronchial and mediastinal lymph nodes (widened mediastinum and possible pulmonary infiltrate on CXR)
incubation period of 10 days but may last up to 6 weeks
fever, fatigue, chest pain, nonproductive cough
hemorrhagic mediastinitis after 1-3 days with an abrupt onset of severe respiratory distress and stridor
septic shock and death within 24-36 hours
meningitis may occur
mortality 80-90%
management
empiric ciprofloxacin
alternatives include doxycycline and penicillin/amoxicillin/rifampin depending on sensitivities
isolation: standard precautions, no person to person transmission
post-exposure prophylaxis for 60 days with ciprofloxacin or doxycycline (penicillin/amoxicillin based on sensitivities)
prevention: vaccine is available but requires 6 doses followed by annual booster, not widely used
inhalational anthrax
Pressure in the pulmonary vessels increases, RV systolic pressure increases to preserve CO, continuous high pressure in pulmonary vessels leads to progressive remodeling of the vasculature
atherosclerosis of the pulmonary trunk, smooth muscle hypertrophy of pulmonary arteries, intimal fibrosis
The ability of the RV to adapt to high pulmonary vascular pressure is inversely related to how fast the increase in pressure occurs
With a progressive increase in RV systolic pressure there will be ischemic changes in the right ventricle myocardium and eventually RV failure
PH: MPAP >/= 25 mmHg
PAH: MPAP >/= 25 mmHg, PCWP = 15 mmHg, PVR > 3 wood units
Dyspnea at rest, cough, dizziness, syncope, edema, chest pain, fatigue, dyspnea on exertion
Presymptomatic/compensated --> symptomatic/decompensating --> declining/decompensated (right heart dysfunction) At the time of diagnosis more than 60% of patients fall into class III or IV (on a scale of I-IV)
Diagnosis: physical exam, ECG, PFTs, CXR, CT scan, V/Q mismatch, right heart catheterization
Treatment:
General: avoid pregnancy, avoid physical exertion, sodium restricted diet, avoid ihgh altitude, diuretics, anticoagulation, oxygen
Medical: vasodilator, NO, prostacyclin analogs, phosphodiesterase inhibitors, endothelin receptor antagonists
Surgical: atrial sptostomy, transplant, embolectomy (for CTEPH)
pulmonary hypertension
occurs in smokers and nonsmokers, more common in females
Glandular differentiation and mucin production
Tumors tend to be peripheral, may be associated with a scar or produce desmoplastic stromal response
in situ form (bronchioalveolar carcinoma) is a variant that spread along alveolar surfaces and shows no stromal invasion or pleural involvement; better prognosis that classical form
Minimal invasive form with a lepidic peripheral growth pattern is associated with a better prognosis than the classical form
adenocarcinoma
occurs in smokers, more common in males
Production of cytoplasmic keratinpearls and intercellular bridges corresponding to desmosomes and tonofilaments
Tumors tend to be central and bulky with central cavitary necrosis
Atypical form invades the superior sulcus and may present with superior vena cava syndrome
Production of parathyroid-like peptide leading to hypercalcemia
squamous cell carcinoma
occurs in smokers
Arises from endogenous neuroendocrine cells and is associated with aggressive clinical behavior, disseminated spread, and poor survival
Tumors have dense core neurosecretory granules that may secrete hormonally active factors leading to paraneoplastic syndromes
Production of ACTH resulting in Cushing’s syndrome
Production of ADH leading to hyponatremia
Commonly presents with advanced disease and distant spread
Tumor staging divided into localized and disseminated or may follow staging for non-small cell types
Responsive to chemo and radiation, but mean survival is one year after diagnosis
small cell undifferentiated carcinoma
occurs in smokers
Undifferentiated carcinomas
Tumors may present centrally and have cytologically large bizarre tumor cells, malignant giant cells, or clear cells
large cell carcinoma
Extravasation of fluid as a result of increased pressure gradient
Contains low protein and low LDH
Contains normal cell count and chemistry
Almost always benign
Heart failure, liver failure, nephrotic syndrome, peritoneal dialysis, trapped lung, lung entrapment
transudative pleural effusion
