Chapter 15: The Lung - Congenital through Obstructive Flashcards
Except for the vocal cords, the entire respiratory tree is lined by what type of epithelium?
Pseudostratified, tall, columnar, ciliated epithelium
Bronchia mucosa contains population of neuroendocrine cells with neurosecretory granules containing which factors?
- Serotonin
- Calcitonin
- Gastrin-releasing peptide (bombesin)
Numerous mucus-secreting goblet cells and submucosal glands are dispersed throughout the walls of which parts of the respiratory tree?
- Trachea
- Bronchi
- NOT the bronchioles
What are 2 functions of the Type 2 pneumocytes of the alveolar epithelium?
- Produce surfactant
- Repair of alveolar epithelium by giving rise to type 1 pneumocytes
Pulmonary hypoplasia occurs in utero and what are 2 major causes?
- Congenital diaphragmatic hernia
- Oligohydramnios
Foregut cysts are most often located where in the lungs and which classification/type is most common?
Treatment?
- Hilum or middle mediastinum
- Bronchogenic = most common
- Excision = curative!
Pulmonary sequestration refers to a discrete area of lung with what 2 features?
- Lacks any connection to the airway system
- Has abnormal blood supply arising from aorta or its branches
Congenital pulmonary adenomatoid malformations (CPAM/CCAM) are caused by what?
“Arrested development” of pulmonary tissue –> formation of intrapulmonary cystic masses WITH connection to tracheobronchial airways and pulmonary vasculature
Via which imaging modality can congenital pulmonary adenomatoid malformations be detected?
Fetal ultrasound
Congenital pulmonary adenomatoid malformations can be deadly due to what complications?
- Hydrops or pulmonary hypoplasia
- Can get infected later in life
Extralobar pulmonary sequestrations most commonly come to attention in infants how?
- As mass lesions
- Associated w/ other congenital anomalies
When do intralobal pulmonary sequestrations typically present and are often due to what?
- Older children/adults
- Due to recurrent localized infection or bronchiectasis
Atelectasis is a reversible disorder, except in cases caused by what?
Contraction atelectasis
What are the 3 main types of acquired atelectasis and what is each caused by?
- Resorption due to complete obstruction of airway (mucus plugs)
- Compression due to accumulation of material or air within pleural cavity (i.e., transudate/exudate/blood or pneumothorax)
- Contraction due to fibrosis or restrictive processes in pleura preventing full lung expansion
Which type of acquired atelectasis causes the mediastinum/trachea to shift toward the affected lung; which type causes a shift away?
- Resorption —> mediastinum shifts toward affected lung
- Compression –> mediastinum shifts away from affected lung
Which type of acquired atelectasia occurs in the setting of asbestosis?
Contraction atelectasis
Hemodynamic pulmonary edema is due to an increase in what; most commonly occuring in what setting?
↑ hydrostatic pressure –> left-sided CHF
What is the histological appearance of of the alveolar capillaries in hemodynamic pulmonary edema?
Engorged, and an intra-alveolar transudate appears as finely granular pale PINK material
Where does fluid accumulate initially in pulmonary edema due to hydrostatic pressure being greatest in these sites (dependent edema)?
Basal regions of the lower lobes
List 4 causes of decreased oncotic pressure, which cause “leaking out” and pulmonary edema?
- Hypoalbuminemia
- Nephrotic syndrome
- Liver disease
- Protein-losing enteropathies
List some of the etiologies which can cause direct injury to the alveolar wall leading to pulmonary edema?
- Infections: bacterial pneumonia
- Inhaled gases: high [O2] and smoke
- Liquid aspiration: gastric contents; near drowing
- Radiation
What are 2 causes of pulmonary edema of undetermined origin?
- High altitude
- Neurogenic (CNS trauma)
In long-standing pulmonary congestion (i.e., mitral stenosis), hemosiderin-laded macrophages are abundant, and what is the gross morphology of the lungs?
Soggy lungs become firm and brown (brown induration)
When the edema associated with pneumonia fails to stay localized and instead becomes diffuse alveolar edema what fatal condition may this lead to?
ARDS
Acute lung injury (aka noncardiogenic pulmonary edema) is characterized by the abrupt onset of significant _________ and __________ in the absence of __________.
Acute lung injury (aka noncardiogenic pulmonary edema) is characterized by the abrupt onset of significant hypoxemia and bilateral pulmonary infiltrates in the absence of cardiac failure.
The histologic manifestation of both ALI and ARDS is what?
Diffuse alveolar damage (DAD)
What is an important early event in the pathogenesis of ALI/ARDS?
Endothelial activation
Following endothelial activation in ALI/ARDS there is adhesion and extravastion of which immune cells and what is the result?
- Neutrophils
- Degranulate and release proteases, ROS, and cytokines
Which factor is released inside of alveoli during ALI/ARDS that acts to sustain the ongoing pro-inflammatory response leading to more endothelial injury and local thrombosis?
Macrophage migration inhibitory factor (MIF)
The thickened protein-rich edema fluid + debris from dead alveolar cells accumulate in ALI/ARDS, and lead to the formation of what?
HYALINE membranes
If there is resolution of the injury in ARDS/ALI, what factors are released from macrophages which stimulate fibroblast growth and collagen deposition leading to fibrosis of alveolar walls?
- TGF-β
- PDGF
Following the fibroproliferative phase in ARDS, what 2 pathways may ensue and the result of each?
- Resolution –> restoration of normal cellular structure and function
- Fibrosis –> destruction and distortion of normal cellular structure –> IRREVERSIBLE
ALI/ARDS is more common and associated with a worse prognosis in whom?
Chronic smokers and alcoholics
During the acute stage of ALI/ARDS what is seen morphologically in the lungs?
- Lungs are heavy, firm, red, and boggy
- Exhibit congestion, interstitial and intra-alveolar edema, inflammation, fibrin deposition, and DAD
- Alveolar walls become lined with waxy hyaline membranes
In the organizing stage of ALI/ARDS what are the type 2 pneumocytes doing and what begins to form?
- Type 2 pneumocytes are proliferating
- Granulation tissue forms in the alveolar walls and spaces
Fatal cases of ALI/ARDS often have superimposed?
Bronchopneumonia
What is seen on radiographic imaging of patient with ALI?
Diffuse bilateral infiltrates
Pt’s with ALI will have what sx’s?
- Profound dyspnea and tachypnea
- Followed by ↑ cyanosis and hypoxemia
Why may the hypoxemia associated with ALI/ARDS be refractory to O2 therapy; what acid-base disturbance may develop?
Due to ventilation perfusion mismatching and respiratory acidosis may develop
What is the cause of the ventilation perfusion mismatch and hypoxemia in ALI/ARDS?
- Poorly aerated regions continue to be perfused
- Perfusion = normal; but ventilation = decreased
ARDS is a diagnosis of exclusion using the criteria which can be remembered with mnemonic A.R.D.S.
- Abnormal CXR (bilateral lung opacities)
- Respiratory failure within 1 week of alveolar insult (ABRUPT)
- Decreased PaO2/FiO2 ≤200 = hypoxia
- Symptoms of respiratory failure are NOT due to HF/fluid overload
The causes of ARDS may be remembered with “SPARTAS.”
- Sepsis
- Pancreatitis/Pneumonia
- Aspiration
- uRemia
- Trauma
- Amniotic fluid embolism
- Shock
Neonatal respiratory distress syndrome is associated with what underlying risk factors?
- Pre-term infant
- Male gender
- Maternal diabetes
- Delivery by C-section
What is the characteristic finding on CXR of infants w/ neonatal respiratory distress syndrome?
“Ground-glass” picture
What plays a particularly important role in the synthesis of surfactant?
Glucocorticoids
Analysis of what in the amniotic fluid provides a good estimate of the level of surfactant in the alveolar lining?
Phospholipids
Oxygen is required in neonates affected by neonatal respiratory distress syndrome, but what are 2 complications which may arise?
- Retrolental fibroplasia (aka retinopathy of prematurity)
- Bronchopulmonary dysplasia
Infants that recover from RDS are also at increased risk for developing what 3 complications associated with preterm birth?
- PDA
- Intraventricular hemorrhage
- Necrotizing enterocolitis
What is the term used to describe widespread ALI of unknown etiology associated with a rapidly progressive clinical course?
Acute interstitial pneumonia (aka idiopathic ALI-DAD)
What is the typical presentation of someone with Acute Interstitial Pneumonia?
Pt presents w/ ARF following an illness of <3 weeks duration that resembles a URI
When do most deaths associated with Acute Interstitial Pneumonia occur?
Within 1-2 months
The radiographic and pathologic features of acute interstitial pneumonia are identical to what?
Organizing stage of ALI
Which 2 obstructive lung diseases are grouped together and referred to as COPD?
- Chronic bronchitis
- Emphysema
Asthma is distinguished from chronic bronchitis and emphysema by the presence of what feature?
Reversible bronchospasm
Which obstructive lung disease is charactetrized by irreversible enlargement of the airspace distal to the terminal bronchioles, accompanied by destruction of the walls without fibrosis?
Emphysema
Of the 4 major types of emphysema which 2 cause clinically significant airflow obstruction; which is most common?
- Centriacinar (centrilobular) = most common = Upper lungs
- Panacinar (panlobular) = Lower zones
Where are lesions of centriacinar (centrilobular) emphysema most commonly seen and most severe?
Upper lobes, in the apical segments
Centriacinar (centrilobular) emphysema occurs predominantly in whom and is often associated with what other lung disorder?
Heavy smokers, often in assoc. w/ chronic bronchitis (COPD)
Panacinar (panlobular) emphysema occurs most commonly where in the lungs and is associated with what underlying abnormality?
- Lower zone and anterior margins of lung, usually most severe at bases
- Associated w/ α1-antitrypsin deficiency
*Image on right*
Which type of emphysema most likely underlies many cases of spontaneous pneumothorax in young adults?
Distal acinar (paraseptal) emphysema
What are some of the inflammatory mediators released by macrophages and resident epithelial cells which influence the development of emphysema?
- Leukotriene B4
- IL-8
- TNF
The pathogenesis of emphysema is related to an imbalance between which factors?
Proteases (i.e., elastase) and anti-proteases (α<strong>1</strong>-antitrypsin)
Which gene related to protection from oxidatie stress may be mutated in emphysema and other smoking-related lung diseases?
NRF2
α1-antitrypsin is encoded by which locus and on what chromosome?
Proteinase inhibitor (Pi) on chromosome 14
Loss of elastic tissue in the walls of alveoli in emphysema causes respiratory bronchioles to do what during expiration?
Collapse —> functional airflow obstruction
What are 3 inflammatory changes seen in the small airways of pt with emphysema and even young smokers that narrow the bronchiolar lumen and contribute to obstruction?
- Goblet cell hyperplasia –> mucus plugging of lumen
- Inflammatory infiltrate in bronchial walls w/ neutrophils, macrophages, B cells, and T cells
- Thickening of the bronchiolar wall due to smooth m. hypertrophy and peribronchial fibrosis
What is the characterisitc gross morphology seen in advanced emphysema?
- Enlarged lungs which often overlap the heart
- Large alveoli seen on cut surface of fixed lungs
Microscopically, in emphysema, the large alveoli are separated by what and have fibrosis where?
Thin septa w/ only focal centriacinar fibrosis
Which sx of emphysema typically appears first and what are some other associated sx’s that may be present?
- Dyspnea that’s progressive
- Cough or wheezing may be present, easily confused w/ asthma
- Weight loss is common; may be severe enough as to suggest cancer
What value and test is the key to diagnosis of emphysema?
Impaired expiratory airflow, best measured w/ spirometry
Development of what associated w/ 2’ HTN is an indicator of poor prognosis in pt w/ emphysema?
Cor pulmonale and eventual CHF, related to 2’ pulmonary HTN
How will a CXR of predominant bronchitis differ from predominant emphysema?
- Bronchitis = prominent vessels; large heart
- Emphysema = hyperinflation; small heart
Obstructive overinflation is commonly caused by what; why is the form of emphysema significant?
- Tumor or foreign object
- Can be life-threatening emergency, due to affected portion distending and compressinf remaining lung
What is a complication which may arise w/ Bullous Emphysema?
Rupture of bullae –> pneumothorax
What is the primary or initiating factor in the pathogenesis of chronic bronchitis?
Exposure to noxious or irritating inhaled substances such as tobacco smoke and dust from grain, cotton, and silica
What is the earliest feature seen in the pathogenesis of Chronic Bronchitis; over time there is a marked increase in what cell type?
- Mucus hypersecretion
- Assoc. w/ hypertrophy of the submucosal glands in trachea and bronchi
- With time there is marked ↑ in goblet cells in small airways
What is the role of infection in Chronic Bronchitis?
- Significant in maintaining the pathologic state
- Critical in producing acute exacerbation
What are the characteristic gross morphological features of chronic bronchitis; enlargement of what?
- Mild inflammation of airways (predominantly lymphocytes)
- Enlargement of the mucus-secreting glands of the trachea and bronchi
Althought the number of goblet cells increase slightly in Chronic Bronchitis what is the major change seen?
Size of mucous glands (hyperplasia)
The increase in size of the mucous glands in chronic bronchitis can be assessed via what ratio?
Ratio of thickness of mucous gland layer to the thickness of the wall btw the epithelium and cartilage (Reid index)
What morphological changes may the epithelium exhibit in Chronic Bronchitis and may lead to what complication?
Squamous metaplasia and dysplasia –> carcinoma
In the most severe cases of Chronic Bronchitis, there may be obliteration of the lumen due to fibrosis and this is known as?
Bronchiolitis obliterans
Long-standing severe chronic bronchitis commonly leads to what (cause of death)?
Cor pulmonale –> HF
Early-onset allergic asthma is associated with inflammation due to what type of T cells and has good response to what tx?
- TH2 helper T cell inflammation
- Responds well to corticosteroids
Respiratory infections due to what are common triggers of non-atopic asthma and may act in synergy with enviornmental allergens to cause atopic asthma?
Viruses (i.e., rhinovirus, parainfluenza, and respiratory syncytial virus)
Non-atopic asthma attacks may be triggered by seemingly innocuous events, such as what?
- Exposure to cold
- Exercise
Aspirin-sensitive asthma occurs most commonly in pt’s with what underlying disorders?
Recurrent rhinitis and nasal polyps
Pt’s with aspirin-sensitive asthma suffer from what sx’s during an attack?
- Asthmatic attacks
AND
- Urticaria (aka hives)
Describe how aspirin inhibiting cyclooxygenase plays a role in the pathogenesis of aspirin-sensitive asthma?
Leads to rapid ↓ in PGE2, which normally inhibit leukotrienes B4, C4, D4, and E4
As asthma progresses and becomes more severe, there is ↑ local secretion of growth factors, which induce what 5 changes?
- Mucus gland hypertrophy
- Smooth m. proliferation
- Angiogenesis
- Fibrosis
- Nerve proliferation
A fundamental abnormality in the pathogenesis of asthma is an exaggerated response by which immune cells to normally harmless enviornmental allergens?
TH2 response
What is the role of IL-4, IL-5, and IL-13 released from TH2 cells in asthmatic patients?
- IL-4 stimulates class switching to IgE
- IL-5 activates eosinophils
- IL-13 stimulates mucus secretion and IgE production by B cells
Other than TH2 cells what other type of T cell is seen in the late-phase reaction of asthma and what is it’s function?
TH17 produce IL-17 –> recruit neutrophils
The bronchoconstriction characteristic of the early phase (immediate hypersensitivity) of asthma is triggered by what?
Direct stimulation of Vagal (parasympathetic)receptors by reflexes triggered via mediators produced bymast cells and other immune cells
Which 2 types of mediators play a clear role in the bronchospasm, increased vascular permeability, and airway smooth muscle constriction seen in asthma?
- Leukotrienes C4, D4, E4
- ACh released from intrapulmonary parasympathetic nerves
Which factors released from eosinophils in the late phase reaction of asthma cause damage to the epithelium?
- Major basic protein
- Esoinophil cationic protein
Leukotrienes C4, D4, E4 are responsible for what 3 pathogenic processes in asthma?
- Bronchoconstriction
- Mucus secretion
- ↑ vascular permeability
There is an increased incidence of what 2 other allergic disorders in those with atopic asthma?
- Allergic rhinitis
- Eczema
One susceptibility locus for asthma is located on what chromosome; near the gene cluster encoding what cytokines?
- Chromosome 5q
- IL-3, IL-4, IL-5, IL-9 and IL-13 + IL-4 receptor
Polymorphisms in which interleukin gene have the strongest and most consistent associations w/ asthma or allergic disease?
IL13 gene
Polymorphisms in which gene encoding a metalloproteinase, may be linked to ↑ proliferation of bronchial smooth m. cells and fibroblasts –> bronchial hyperreactivity and subepithelial fibrosis?
ADAM33
Variants of which interleukin receptor gene is associated w/ atopy, elevated total serum IgE and asthma?
IL-4 receptor gene variants
Increased serum levels and lung expression of which chitinase-like glycoprotein is correlated w/ disease severity, airway remodeling, and decreased pulmonary function in asthmatics?
YKL-40
What is the most striking gross finding in pt’s dying of acute severe asthma (status asthmaticus)?
Occlusion of bronchi and bronchioles by thick, tenacious mucus plugs, which often contain shed epithelium
The idea that microbial exposure during early development reduces the later incidence of allergic (and some autoimmune) diseases has been known as what?
Hygiene hypothesis
What are 2 characteristic findings in the sputum or bronchoalveolar lavage specimens in a pt w/ severe asthma?
- Curschmann spirals = Coiled mucus plus
- Numerous eosinophils and Charcot-Leyden crystals composed of an eosinophil protein called galectin-10
The characteristic histologic finding of “airway remodeling” in pt w/ asthma includes what 5 major changes?
- Thickening of airway wall
- Sub-basement membrane FIBROSIS
- ↑ vascularity
- ↑ in size of submucosal glands and # of goblet cells
- Hypertrophy and hyperplasia of the bronchial wall muscle
What are the 4 contributors to chronic irreversible airway obstruction in asthma?
- Muscular bronchoconstriction
- Acute edema
- Mucus plugging
- Airway remodeling
What are the cardinal sx’s of asthma?
- Chest tightness
- Dyspnea
- Wheezing
- Cough (with or w/o sputum production)
Chronic irreversible airway obstruction will show a decreased response to what?
Therapeutic agents –> Bronchodilators and/or Corticosteroids
Disorder in which destruction of smooth muscle and elastic tissue by chronic necrotizing infections leads to permanent dilation of bronchi and bronchioles
Bronchiectasis
List congenital or hereditary conditions which may lead to Bronchiectasis?
- Cystic Fibrosis
- Intralobar sequestration
- Primary ciliary dyskinesia
- Kartagener syndromes
Many cases of Bronchiectasis lack any association with another disease process and therefore are what?
Idiopathic
What are the 2 major conditions associated with Bronchiectasis and are often both necessary for its development?
- Obstruction
- Infection
Which 3 organisms are the most common causes of lung infection in pt with CF?
- Staphylococcus aureus
- Haemophilus influenzae
- Pseudomonas aeruginosa
Which autoimmune disorders and other conditions are associated w/ developing Bronchiectasis?
- Rheumatoid Arthritis
- SLE
- IBD
- COPD
- Post-transplantation
In CF the primary defect in ion transport leads to defective what in the lungs?
- Mucociliary action + airway obstruction by thick viscous secretions
- Sets stage for chronic bacterial infections
Primary ciliary dyskinesia is due to mutations in what?
Ciliary motor proteins (i.e., Dynein arm of microtubules)
Half of the pt’s with primary ciliary dyskinesia have what syndrome and what is the triad of this syndrome?
- Kartagener syndrome
- Marked by situs inversus + bronchiectasis + sinusitis
Males with Kartagener Syndrome tend to be what?
Infertile, as result of sperm dysmotility
Allergic bronchopulmonary aspergillosis occurs in what 2 underlying conditions?
- Asthma
- Cystic Fibrosis
Which stain can be used to demonstrate Aspergillus and what is seen?
- Silver stain
- Aggregates of fungal hyphae
What are characteristic findings in the seurm of someone with Allergic Bronchopulmonary Aspergillosis?
High serum IgE and serum Abs to Aspergillus
Bronchiectasis usually affects which lobes of the lung, particularly which air passages, and is most severe where?
- Lower lobes bilaterally
- Particularly air passages that are vertical
- Most severe in the more distal bronchi and bronchioles
Which lung disease will have dilated airways, sometimes up to 4x normal size?
Bronchiectasis
What are the signs/sx’s of Bronchiectasis?
- Severe, persistent cough w/ foul smelling, sometimes bloody sputum
- Dyspnea and orthopnea in severe cases
- Occasionaly hemoptysis, which can be massive!
What are 3 potential complications of Bronchiectasis?
- Cor pulmonale
- Brain abscess
- Amyloidosis
