Week 6 Flashcards
Histologically, what differentiates a bronchus from a bronchiole?
- Bronchus has cartilage chips, bronchiole does not
- Bronchus has goblet cells, bronchiole does not
- Bronchus has no smooth muscle, bronchiole does
Diffuse Alveolar Damage definition
- the pathologic sequence of events that follows severe [acute lung injury] caused by any one of a variety of toxic insults.
- Typically occurs in the context of acute respiratory distress syndrome
What does the “diffuse” mean in Diffuse Alveolar Damage?
- All parts of the alveolus are involved (epithelium, endothelium, and interstitial space)
What is the pathogenesis of DAD?
- **Occurs in the context of acute lung injury**
What is the main defining feature of DAD histologically?
- hyaline membranes
- (plus thickening of the interstitial septa)
Characteristics of organizing DAD
-
Alveolar collapse
- Due to epithelial necrosis –> type 2 pneumocytes die –> decreased surfactant
- pneumocyte hyperplasia
- In an attempt to repair the damage
- fibrosis
Acute vs. Organizing DAD
- Hyaline membranes peak in acute phase
- pneumocyte hyperplasia + interstitial fibrosis peak during organizing phase
Ultimate result of DAD
- Impaired gas exchange due to thickened interstitium
- V/Q mismatch –> hypoxemia and respiratory failure
Most common organism responsible for community-acquired pneumonia
Strep Pneumoniae
Common organism causing community-acquired pneumonia in alcoholics
klebsiella
Most common organism causing community-acquired pneumonia in COPD
H. influenzae
Bacterial pneumonia syndromes
- community-acquired
- aspiration pneumonia
- healthcare setting
two patterns of bacterial pneumonia on gross anatomy)
- bronchopneumonia
- patches affected
- lobar pneumonia
- whole lobe is affected
- **Both have the same appearance under the microscope
Microscopic appearance of bacterial pneumonia
- Septa are relatively normal (i.e. thin)
- Contrasted with DAD where the septa are thickened
- Air spaces are filled with pus
- fibrin
- neutrophils
Complications of pneumonia
- Abscess formation
- Empyema
- spread of infection within pleural cavity
- Systemic bacteremia
- “Metastatic” abscesses
- Endocarditis
- Meningitis
- Suppurative arthritis
Definition of a lung abscess
- Local suppurative process resulting in tissue necrosis
Causes of lung abscess
- Aspiration
- Pneumonia
- others
appearance of lung abscess histologically
- Central area of necrosis
- Often blue
- Can be pink in cases of acellular necrosis
- Organizing fibroblasts/myofibroblasts around it
- Pink
Defining feature of granulomatous pneumonia
- Produce granulomas
Bacterial pneumonia vs. granulomatous pneumonia
- Bacterial –> suppurative inflammation
- Granulomatous –> granulomatous inflammation
Causes of granulomatous pneumonia
- TB
- Fungal
- Histoplasma capsulatam
- coccidiodes immitis
- blastomyces dermatidis
microscopic appearance of non-necrotizing granuloma
- Granuloma = multinucleated giant cells + macrophages
microscopic appearance of necrotizing granuloma
- Giant cells characterize granloma
- Blue area = necrosis
appearance of hypocellular necrotizing granuloma
- red = multinucleated giant cell
Can you see necrotizing and non-necrotizing granulomas together?
Yes
Tuberculosis buzzword
- Caseous necrosis
Tuberculosis histology
- Acid-Fast stain to see the mycobacterium
- TB causes granulomatous pneumonia
Stain used for fungal organisms
Silver stain (GMS stain)
Histoplasmosis
- Fungal cause of granulomatous pneumonia
- Organisms appear black on silver stain
- “Ovoid structures” with “narrow based budding”
- We do see this in michigan b/c it’s endemic to ohio and mississippi river valley
Blastomyces dermatidis
- Fungal cause of granulomatous pneumonia
- Double-contoured wall = “railroad tracks” appearance
- Broad based budding
cocciciomycosis
- Fungal organism causing granulomatous pneumonia
- Complex internal structure due to endospores
- Best seen on GMS stain
pneumocystis pneumonia
- An opportunistic form of pneumonia
- Classically seen in HIV patients w/ low CD4 count or recent transplants
CXR of pneumocystic pneumonia
- diffuse bilateral infiltrates
histology of pneumocystic pneumonia
- Alveolar spaces filled with pink and bubbly exudate
- Often described as “frothy” exudate
Two broad categories of lung cancer
- Small cell
- Non-small cell
- Adenocarcinoma
- Squamous cell carcinoma
Adenocarcinoma characterization
- Adenocarcinomas are characterized by:
- gland formation
- mucin production
- and/or expression of pneumocyte markers (TTF-1, napsin A).
pneumocyte markers for adenocarcinoma
- TTF-1
- Napsin A
microscopic appearance of gland formation
- adenocarcinoma
Microscopic appearance of mucin production
- adenocarcinoma
Adenocarcinoma is found in proximal/distal lung tissue?
- distal
- i.e. peripheral
adenocarcinoma in situ definition
- this is pre-invasive
- Can be mucinous or non-mucinous. Mucinous is quite rare
histologic hallmark of adenocarcinoma in situ
- tumor cells line the alveolar septa
- See slides 87 and 88
Squamous cell carcinoma characterization
- Squamous cell carcinoma is defined by the presence of:
- keratinization
- intercellular bridges
- and/or expression of squamous markers (cytokeratin 5/6, p63/p40).
Squamous cell markers
- cytokeratin 5/6
- p63
- p40
Squamous cell carcinoma tends to affect the distal/proximal airways?
- proximal
- ex: tumor in the trachea
histologic appearance of squamous cell carcinoma
- islands of tumor cells
- Distinguished from adenocarcinomas glands
Distinguishing feature of small cell carcinoma and carcinoid tumors
- They express the same neuroendocrine markers (CD56, chromogranin, synaptophysin)
Neuroendocrine markers of small cell carcinoma and carcinoid tumors
- CD56
- chromogranin
- synaptophysin
Small cell carcinoma characteristics
- Fine nuclear chromatin
- (“salt & pepper”)
- Scant cytoplasm
- Nuclear molding
- i.e. cobblestone appearance
- High mitotic count
- Necrosis
small cell carcinoma is found in more distal/proximal lung?
proximal, like the trachea
Carcinoid tumors vs. small cell carcinoma
- Both have the salt and pepper chromatin
- Carcinoid tumors do NOT show nuclear molding
- Carcinoid tumors have much lower mitotic activity
Malignant mesothelioma is caused by what?
- asbestos exposure
Significant symptom for malignant mesothelioma
- Bloody cough
Symptoms for malignant mesothelioma
- Cough (bloody)
- chest pain
- dyspnea
- pleural effusion
Key pathologic/morphologic finding in mesothelioma
- Thickening of the pleura
- both viscearl and parietal show tumors
Embryonic period of lung development
less than 6 weeks
pseudoglandular phase of lung development
7 - 16 weeks
At what stage do most congenital abnormalities in lung differentiation occur?
Pseudoglandular phase (7 - 16 weeks)
Canalicular Phase
- 16 - 24 weeks
Development in canalicular phase
- Gas exchange is possible AT THE END of this stage
- Gas exchange possible at the end of this stage, but it’s very limited b/c alveolar walls are thick, there aren’t enough aveoli, and surfactant is limited.
Saccular phase of lung development
24 - 36 weeks
Key events in saccular phase
- Surfactant production increases
- Babies can breathe on their own pretty well by the end of this phase
- Interstitium thins –> gas exchange more efficient
Alveolar phase
36 weeks onward (maybe up until 2 years)
Key events in alveolar phase
The number of alveoli multiplies exponentially
Main ingredient in surfactant
dipalmitoyl phsphatidylcholine
Cause of respiratory distress syndrome
- Lack of surfactant (primarily)
- Also structural immaturity of the lungs
At what age is a preterm baby viable?
24 weeks (end of canalicular phase)
Nearly all babies born before ____ weeks develop RDS
28 weeks
Treatment for RDS
- Mechanical ventilation
- CPAP
- exogenous surfactant
- Steroids for mother (if baby still inside)
Bronchopulmonary dysplasia
- Chronic lung disease resulting from tx of RDS
- exogenous surfactant
- mechanical ventilation
- Arrested alveolar development and asthma-like symptoms
pulmonary hypoplasia
- Another term for hypoalveolarization, or delayed lung development