Pulm Path Pt 1 Flashcards
What are capillaries associated with in normal alveolar structure?
endothelium
What is the basement membrane associated with in normal alveolar structure?
interstitium
What do Type 1 pneumocytes do?
facilitate gas exchange
What do Type 2 pneumocytes do?
produce surfactant and replace Type 1 pneumocytes (are modified stem cells)
What do alveolar pores (of Kohn) do?
allow aeration but also bacteria/cells/exudate to travel between alveoli
What causes pulmonary hypoplasia?
- reduced pace in thoracic cavity (diaphragmatic hernia)
- impaired ability to inhale (oligohydramnios/renal agenesis/chest wall motion disorders)
What is a foregut cyst?
- detached outpourings of foregut, seen along hilum and mediastinum
- can be respiratory, esophageal, or gastroenteric
What are the complications of a foregut cyst?
rupture, infection, or airway compression
What is Congenital Pulmonary/Cystic Adenomatoid Malformation (CPAM/CCAM)?
“arrested development” of pulmonary tissue with the formation of intrapulmonary cystic masses
Can CPAM/CCAM be detected on fetal US?
yes
Why is CPAM/CCAM deadly?
due to hydrops or pulmonary hypoplasia
- can also get infected later in life
What are pulmonary sequestrations?
nonfunctioning lung tissue that forms an accessory lung bud
- typically in the region of lower left lobe
What are pulmonary sequestrations characterized by?
- lack of connection to the tracheobronchial tree
- independent (systemic) arterial supply
What determines if a pulmonary sequestration is intralobar or extralobar?
depends on whether the budding occurs before or after the pleura is established
What makes intralobar pulmonary sequestration (ILS) susceptible to infection and abscess formation?
lack of airway perfusion
- may present in older children and adults
When does extralobar pulmonary sequestration (ELS) usually present?
after birth with other congenital anomalies
- come to attention as mass lesions in the chest or abdomen
Which type of pulmonary sequestration has independent vessels, pleura and possibly airways?
extralobar (ELS)
- no connection to pulmonary vasculature or tracheobronchial tree
What are the 3 types of atelectasis discusses?
- resorption
- compression
- contraction
What is resorption atelectasis?
airway obstruction with gradual resorption of air
- reduces lung expansion
What is compression atelectasis?
accumulated material in the pleural cavity compresses the lung parenchyma
- not a direct lung issue
What is contraction atelectasis?
fibrotic or other innate restrictive process in the pleura or peripheral lung
- restricts lung expansion
What is pulmonary edema?
interstitial fluid (proteinaceous material) accumulates in alveolar spaces
What are the examples given of “pushing out” pulmonary edema?
- left sided heart failure
- volume overload
- pulmonary vein obstruction
What are the examples given of “leaking out” pulmonary edema?
- hypoalbuminemia
- nephrotic syndrome
- liver disease
What types of injury to alveolar wall can cause pulmonary edema?
- bacterial pneumonia
- sepsis
- smoke inhalation
- aspiration
What are the two physiologic mechanisms behind pulmonary edema?
- increased hydrostatic pressure -> forces fluid out
2. decreased oncotic pressure -> loses fluid through equilibrium across a semipermeable membrane
What is acute lung injury (ALI)?
acute onset, hypoxemia, bilateral infiltrates
- no evidence of cardiac failure
What is acute respiratory distress syndrome (ARDS)?
worsening hypoxemia
What is diffuse alveolar damage (DAD)?
the histologic manifestation of ARDS
- what pathologists diagnose, NOT physicians!
Which respiratory disorder presents with abrupt onset of symptoms, hypoxemia, bilateral infiltrates, and is non-cardiac in nature?
ARDS
What is the mechanism behind ARDS?
- endothelial activation
- adhesion/extravasion of neutrophils
- accumulation of intraalveolar fluid, formation of hyaline membranes
- resolution of injury
What makes up a hyaline membrane?
edema + fibrin + cell debris (dead cells) -> forms a sticky hyaline membrane
What leads to a decreased PaO2/FiO2 ratio?
decreased aeration -> ventilation-perfusion mismatch
What are the stages of progression of ARDS?
- exudative
- proliferative
- fibrotic
What can be seen in the exudative stage of ARDS?
edema, hyaline membranes, neutrophils
What can be seen in the proliferative stage of ARDS?
fibroblast proliferation, organizing pneumonia, early fibrosis
What can be seen in the fibrotic stage of ARDS?
extensive fibrosis, loss of normal alveolar architechture
What are the 2 possible pathways after the fibroproliferative phase of ARDS?
- resolution: restoration of normal cellular structure/function
- fibrosis: destruction and distortion of normal cellular structure -> IRREVERSIBLE
What is the difference between ARDS and acute interstitial pneumonia (AIP)?
AIP has same clinical presentation and histology as ARDS
** BUT CANNOT BE ATTRIBUTED TO A SPECIFIC CAUSE/ETIOLOGY**
What type of lung disease would you see:
- volume restriction
- normal FEV1/FVC ratio
- FVC reduced
restrictive
What type of lung disease would you see:
- decreased flow
- low FEV1/FVC ratio
obstructive
What is the most common cause of COPD/chronic bronchitis
smoking
What does the airway of someone with chronic bronchitis look like?
- increased mucus (and extra goblet cells)
- damaged cilia
- thickened smooth muscle (narrowed lumen)
How do physicians make the diagnosis of chronic bronchitis?
persistent cough with productive sputum for ** 3 months out of 2 consecutive years**
What is the predominant pathophysiologic mechanism of chronic bronchitis?
mucus glad hyperplasia -> damage to airway epithelium
What are the complications of chronic bronchitis?
- *squamous metaplasia** -> dysplasia -> carcinoma
- bronchiectasis (bronchi walls thickened d/t inflammation and infection)
- death from respiratory infection
Why is emphysema considered an obstructive disease?
because chronic bronchitis has left the bronchiole ducts narrowed/compressed -> ducts feeding into alveoli are obstructed
Pt presents with enlarged lungs and flattened diaphragm on CXR, “barrel chest”, reduced FEV1/FVC ratio
- severa/painful dyspnea
emphysema
What is the clinicoradiographic/pathologic diagnosis of emphysema?
permanent enlargement and destruction of airspaces distal to the terminal bronchiole
What can a deficiency in alpha-1 antitrypsin lead to?
emphysema
What does a1-antitrypsin do in the lungs?
it coats the lungs, and inhibits neutrophil elastase
-when left uninhibited, neutrophil elastase can cause lung damage
Where is a1-antitrypsin synthesized?
liver
- secreted into bloodstream to inhibit neutrophil elastase
What does neutrophil elastase do?
produced by WBC to break down harmful bacteria
- potentially damaging to lungs if left uninhibited
What are the 4 types of emphysema discussed?
- a1-antitrypsin deficiency
- COPD
- spontaneous
- localized
What is panacinar/panlobular swelling?
widespread swelling throughout
What is centroacinar/centrilobular swelling?
starts in the central part of the lung, alveoli are spared
What gene encodes a1-antitrypsin?
Pi gene (proteinase inhibitor) on xsome 14
What is the primary means of diagnosis for a1-AT def?
serum testing
- often diagnosed as adult
What are the 3 components of asthma?
- recurrent airway obstruction with a reversible component
- airway hyper-responsiveness
- airway inflammation
What is considered atopic (extrinsic) “classic” asthma?
- 2/3 of patients
- any age, typically children
- family hx of asthma
- ** elevated IgE levels (Type 1 hypersensitivity)**
- variety of allergen triggers
What cell types are seen in Type 1 hypersensitivity?
eosinophils, mast cells, lymphocytes
What is considered non-atopic (intrinsic) asthma?
- 1/3 of patients
- often older** patients
- typically normal IgE levels
- triggers include cold, exercise, infection
What cell types are seen in non-atopic asthma?
T lymphocytes, neutrophils
What immune response is seen in the immediate phase of an asthma attack?
bronchoconstriction, increase in mucus secretion, increase in vascular permeability
What is the immunologic mechanism behind an asthma attack?
antigen/allergen stimulates Th2 cell -> IgE activation -> mast cell activation -> eosinophil recruitment
What response does an increase in leukotrienes C/D/E, histamine, prostaglandin D and ACh cause?
bronchoconstriction
What does an increase in leukotrienes C/D/E cause?
mucus secretion and increased vascular permeability
What does an increase in interleukins case?
recruitment of inflammatory cells
What is status asthmaticus?
when asthma attacks follow each other without pause, potentially fatal
What is aspirin-sensitive asthma?
associated with nasal polyps and recurrent rhinitis (Samter’s triad)**
- a unique sensitivity to aspirin
- cross reacts with other NSAIDs
NOTE: COX 1/2 pathway inhibited by aspirin! Leave leukotrienes C/D/E in excess -> bronchospasm
What is bronchiectasis?
necrotizing inflammatory response
- the end stage process of multiple infections/obstructions
What are the examples given where bronchiectasis is seen?
- allergic bronchopulmonary aspergillosis (ABPA)
- cystic fibrosis
- chronic infection (Tb)
- primary ciliary dyskinesia
What is Kartagener’s syndrome?
primary ciliary dyskinesia
- dysfunction of dynein arm of microtubules
What is the triad seen in Kartagener’s syndrome?
- sinusitis
- bronchiectasis
- situs inversus (visceral organs are reversed)
NOTE: often male infertility involved
What is primary ciliary dyskinesia?
immobility of cilia and flagella due to microtubule defect
What is allergic bronchopulmonary asperigillosis (ABPA)?
exaggerated hypersensitivity response to Aspergillus infection overlying chronic lung disease
Pt presents with a background of asthma or cystic fibrosis, increased IgE on serum testing, positive skin test, thick mucus in bronchi
allergic bronchopulmonary aspergillosis
What is fungal hyphae a characteristic of?
Aspergillus
- leads to bronchiectasis over time
What stain demonstrates aggregates of fungal hyphae?
silver stain
What is pneumoconiosis?
reaction by the lungs to inhaled mineral or organic dust
- occupational exposure***
- air pollution
NOTE: exaggerated response in some individuals indicates a possible genetic component
What makes pneumoconiosis worse?
- exposure is high and repetitive
- size of particles is small
- smoking (impaired ciliary clearance)
What is Coal worker’s pneumoconiosis?
disease due to inhaled coal dust, with a spectrum of disease
- anthracosis
- coal macules/nodules
- progressive massive fibrosis
What is silicosis?
disease resulting from inhales silicon dioxide
- mining/quarry work
- concrete repair/demolition
NOTE: has insidious onset, it can progress after exposure is no longer present
What can silicosis progress to?
massive pulmonary fibrosis
- also a two-fold risk of developing cancer
What presents as dense collagenous nodules on histo slides, and eggshell calcifications on CXR?
silicosis
What is asbestosis?
interstitial and pleural disease resulting from inhalation of asbestos fibers
- isulation workers
- shipyard workers
- paper mill workers
- oil or chemical refinery workers
What are the disease manifestations of asbestosis?
- pleura: fibrosis/fibrous plaques, effusions, mesothelioma
- lung: interstitial fibrosis, carcinoma
- extrapulmonary neoplasms
When do you see feruginous bodies on a histo slide and “candlewax drippings” grossly?
asbestosis
What is mesothelioma associated with?
asbestos exposure
- may occur decades after exposure
- lifetime exposure risk as high as 10%
