L73-76 Pulmonary Pathology I-IV Flashcards
1
Q
Describe the lining of the trachea.
A
- Cartilage
- Mucosa (epithelium and submucosal glands)
- Transverse muscle bundles
- Longitudinal muscle bundles
2
Q
How do the trachea and bronchi differ?
A
Bronchial cartilage is discontinuous vs. Tracheal cartilage is continuous
3
Q
Describe the primary bronchial epithelium.
A
Pseudostratified ciliated columnar epithelium with some goblet cells (More ciliated than goblet normally)
4
Q
How do the tertiary bronchi and bronchioles differ?
A
Tertiary bronchi have cartilage and submucosal glands vs. Bronchioles lack cartilage and submucosal glands
5
Q
What types of cells line the bronchioles?
A
Ciliated and non-ciliated (clara) cells
6
Q
What are the types of cells in the alveoli?
A
- Type I (squamous pneumocytes): gas exchange
- Type II (granular pneumocytes): secrete surfactant
- Alveolar macrophages
- Endothelial cells (line blood vessels)
- Fibroblasts (structural support)
- Rare lymphocytes and mast cells
7
Q
The lungs develop from the ___.
A
Foregut
8
Q
What are the 4 common congenital lung abnormalities?
A
- Agenesis
- Hypoplasia
- Atresia and tracheoesophageal fistula
- Congenital Cystic Adenomatoid Malformation (CCAM/CPAM)
9
Q
Acute lung injury is a spectrum of bilateral pulmonary damage (epithelial and endothelial) which manifests as what three things?
A
- Acute onset dyspnea (may also be tachypnic)
- Hypoxemia (may lead to cyanosis)
- Development of bilateral pulmonary infiltrates in the absence of cardiac failure
10
Q
What are clinical causes of ALI?
A
A: Aspiration, acute pancreatitis, air/amniotic fluid embolism
R: Radiation
D: Drug overdose, DIC< drowning
S: Shock, sepsis, smoke inhalation
Also: pneumonia, trauma, fat embolism, inhalation injury, reperfusion injury, uremia
11
Q
If ALI is severe, it can progress to ___.
A
ARDS (Acute Respiratory Distress Syndrome)
12
Q
Describe the pathogenesis of ALI.
A
Injury occurs. Macrophages secrete IL-1, IL-8, TNF, leading to neutrophil margination, sequestration, and migration into the alveolus. Local tissue damage occurs, edema enters the alveoli, surfactant is inactivated, and hyaline membrane forms.
13
Q
How is ARDS treated?
A
Supportive care, treat underlying condition
14
Q
What are the phases of ARDS?
A
- Early exudative phase (acute)
- Subacute proliferative phase (organizing)
- Fibrotic phase (late)
15
Q
What is the primary histological finding in ARDS?
A
Diffuse alveolar damage
16
Q
What are some causes of respiratory distress syndrome in newborns?
A
- Fetal injury during delivery
- Aspiration
- Cord compression
- Excessive sedation of the mother
- Hyaline membrane disease/RDS (most common)
17
Q
What is the fundamental abnormality in respiratory distress syndrome?
A
Insufficient pulmonary surfactant production by immature lungs, resulting in failure of lungs to inflate after birth
18
Q
Surfactant, synthesized in ___ cells, can be secreted as early as ___ weeks, but is not produced in sufficient amounts until ___ weeks.
A
Type II pneumocytes; 20; 34
19
Q
Discuss how prematurity leads to hyaline membrane formation.
A
- Reduced surfactant synthesis, storage, and release
- Increased alveolar surface tension
- Atelectasis
- Uneven perfusion and hypoventilation
- Hypoxemia and CO2 retention
- Acidosis
- Pulmonary vasoconstriction
- Pulmonary hypoperfusion
- Endothelial and epithelial damage
- Plasma leak into alveoli
- Hyaline membrane formation
20
Q
What modulates surfactant synthesis?
A
- Glucocorticoids (increase production)
- Insulin (decrease production)
- Labor (induces production)
- Prolactin
- Thyroxine
- TGF-beta
21
Q
What is atelectasis?
A
Complete or partial collapse of a lung or lobe of a lung
22
Q
What are the three types of acquired atelectasis and where does the mediastinum shift?
A
- Resorption/obstruction - shifts toward affect lung
- Compression - shifts away from affect lung
- Contraction
23
Q
What can cause resorption/obstruction atelectasis?
A
Excessive secretions (asthma, COPD, bronchiectasis)
24
Q
What can cause compression atelectasis?
A
Effusions, tumors, CHF
25
What can cause contraction atelectasis?
Fibrosis
26
What is pneumothorax?
Air or gas in the pleural cavity that causes compression and atelectasis
27
Broadly, what is the problem in obstructive vs. restrictive lung diseases?
Obstructive: increased resistance to airflow due to obstruction at any level
Restrictive: reduced expansion of lung parenchyma with decrease in total lung capacity
28
What are the major pathologic features of asthma?
1. Chronic bronchial inflammation with eosinophils
2. Bronchial smooth muscle hyperreactivity
3. Increased mucus production
29
What are the symptoms of asthma?
Wheezing, breathlessness, chest tightness, cough
30
What is atopic asthma?
Immune-mediated, type I hypersensitivity reaction
Begins in childhood, triggered by environmental allergens
Family history of asthma, atopy
Positive skin and serum tests
31
What is non-atopic asthma?
Non-immune triggering mechanisms
Negative skin and serum tests
32
When should we suspect drug-induced asthma?
Patients with recurrent rhinitis and nasal polyps (particularly aspirin)
33
Describe the pathogenesis of asthma.
APC presents antigen to Th2 cells. These produce IL-3, IL-5, GM-CSF, which recruit eosinophils. These degranulate and lead to increased mucus production and smooth muscle hyperactivity.
IgE also binds to mast cells, creating memory.
34
Which chromosome has several susceptibility genes for asthma? What are the genes?
5q: IL-13 CD-14
Also 20q: ADAM 33
35
What is status asthmaticus?
Prolonged bout of asthma lasting for days, responding poorly to treatment
36
What can be seen on microscopy in asthma?
Curschmann spirals
37
What can be seen on histology in asthma?
Eosinophils
| Charcot Leydon Crystals (degranulated eosinophils)
38
What are the 2 types of COPD? Compare them briefly.
Chronic bronchitis: tends to affect larger airways, results in mucus hypersecretion and inflammation
Emphysema: tends to affect lower airways, lose elastic recoil due to destruction of septa
39
What is the clinical definition of chronic bronchitis?
Persistent productive cough for at least three consecutive months in at least two consecutive years
40
What is at risk for chronic bronchitis?
1. Smokers
2. Urban dwellers
3. Middle aged men
41
What are the 4 types of emphysema?
1. Centriacinar (centrilobular)
2. Panacinar (panlobular)
3. Distal acinar (paraseptal)
4. Irregular
42
Centriacinar emphysema:
1. Location
2. Population
3. Associations
1. Respiratory bronchioles, upper lobes
2. Male smokers
3. Chronic bronchitis, coal-workers pneumoconiosis
43
Panacinar emphysema:
1. Location
2. Associations
1. Lower lobes
| 2. Alpha-1-anti-trypsin deficiency
44
Distal acinar emphysema:
1. Location
2. Can lead to ___ in young adults
1. Along pleura and lobular septa, adjacent to areas of fibrosis, scarring, atelectasis
2. Spontaneous PT
45
Discuss the pathogenesis of emphysema.
Tobacco generates ROS. These inactivate antiproteases (functional alpha-1-AT deficiency). Neutrophils produce elastase that cannot be broken down. This causes tissue damage.
46
Discuss the gross lung appearance in emphysema.
Hyperinflated lungs with formation of bullae
47
Discuss the histologic appearance in emphysema.
Destruction of septal walls, loss of elastic recoil, destruction of vascular bed, cystically dilated spaces
48
Alpha-1-AT is encoded by codominantly expressed genes on chromosome ___.
14
49
Compare the age of bronchitis vs. emphysema.
40-45 vs. 50-75
50
Compare the dyspnea of bronchitis vs. emphysema.
Mild/late vs. Severe/early
51
Compare the cough of bronchitis vs. emphysema.
Early/copious sputum vs. Late/scanty sputum
52
Compare the frequency of infections of bronchitis vs. emphysema.
Common vs. Occasional
53
Compare the airway resistance of bronchitis vs. emphysema.
Increased vs. Normal/slightly increased
54
Compare the elastic recoil of bronchitis vs. emphysema.
Normal v. Low
55
Compare the CXR of bronchitis vs. emphysema.
Prominent vessels/large heart vs. Hyperinflation/small heart
56
Compare the appearance of bronchitis vs. emphysema.
Blue bloater (R heart failure, water weight gain) vs. Pink puffy (skinny, lanky)
57
What is bronchiectasis?
Permanent dilation of bronchi and bronchioles caused by destruction of the muscle and elastic tissue caused by chronic necrotizing inflammation
58
What are causes/predisoposing conditions of bronchiectasis?
1. Obstruction
2. Infection (TB, aspergillus)
3. Congenital/Hereditary (CF, Kartagener's, immunodeficiency)
4. Other (RA, Lupus, Graft vs. Host disease)
59
What are the 4 parts of Kartagener syndrome?
1. Sinusitis
2. Bronchiectasis
3. Situs inversus
4. Infertility
60
What causes Kartagener syndrome?
Primary ciliary dyskinesia caused by absence/shortening of dynein arms
61
What are the symptoms of restrictive/infiltrative lung disease?
1. Dyspnea
2. End inspiratory crackles
3. Hypoxia
62
What are the CXR findings of restrictive/infiltrative lung disease?
1. Nodules
2. Irregular lines
3. Ground glass shadows
63
What is the primary gross end stage pathology of restrictive/infiltrative lung disease?
Honeycomb lung
64
What is the common pathogenesis of infiltrative lung disease?
Inflammation and fibrosis of the interstitium
65
Sarcoidosis predominates in the ___ lobes of the lung.
Upper
66
What CXR abnormalities are seen in 90% of patients with sarcoidosis?
Bilateral hilar lymphadenopathy
67
What is seen on histology in sarcoidosis?
1. Non-caseating granulomas (rim of lymphocytes, found along lymphatic routes)
2. Multi-nucleated giant cells with cytoplasmic inclusions (Schaumann bodies, asteroid bodies)
68
Sarcoid granulomas may include this cell, seen on histology.
Epithelioid histiocytes (flip flop cell)
69
What are some lab abnormalities seen in sarcoidosis?
1. Elevated serum ACE
2. Hypercalcemia
3. Systemic immune abnormality markers
70
Why is hypercalcemia seen in sarcoidosis?
Granulomas promote conversion of 25-OH Vitamin D to 1,25-OH Vitamin D, which promotes absorption of calcium from the gut
71
What is the histologic pattern seen in idiopathic pulmonary fibrosis (IPF)?
Usual interstitial pneumonia
72
Describe the pathogenesis of idiopathic pulmonary fibrosis.
1. Repeated cycles of epithelial activation/injury
2. Abnormal epithelial repair
3. Fibroblastic proliferation
73
Describe the gross morphology of IPF.
1. Cobblestoning - pleural surface scarring
2. Firm, rubbery, white surface - fibrosis
3. Honeycombing (peripheral cysts)
74
What are the symptoms of IPF?
1. Dyspnea on exertion
2. Dry cough
3. Velcro crackles
75
What is a miscellaneous group of disorders characterized by the accumulation of dust in the lungs and the tissue reaction to its presence?
Pneumoconioses
76
What happens in anthracosis?
Smokers, urban dwellers, coal miners, etc. inhale carbon pigment, which is engulfed by macrophages
77
What is the difference between simple coal workers pneumoconiosis and progressive massive fibrosis?
In simple coal workers pneumoconiosis, accumulations of dust-laden macrophages lead to fibrosis. In progressive massive fibrosis, coal nodules coalesce, leading to fibrotic bulky black tissue masses - "black lung"
78
What is Caplan Syndrome?
Rheumatoid pneumoconiosis - form of coal worker pneumoconiosis associated with RA; cavitating nodules on radiology
79
In addition to fibrosis, what can asbestos cause?
Pleural effusions, pleural plaques, bronchgenic carcinoma, malignant mesothelioma, and laryngeal carcinoma
80
What is seen on histology in asbestosis?
Ferruginous bodies
81
Discuss the risks associated with asbestos exposure, lung cancer, malignant mesothelioma, and smoking.
Lung cancer: 5x increase risk for asbestos workers, 55x for those who also smoke
Malignant mesothelioma: 1000x increase for asbestos workers, no additional increase for those who also smoke
82
What is the most prevalent chronic world occupational disease?
Silicosis
83
What is seen on histology in silicosis?
1. Nodules with concentric hyalinzed collagen and a whorled appearance
2. Coalesced nodules
3. Progressive massive fibrosis
4. Fibrotic lesions in hilar lymph nodes, pleura
84
What happens to the lymph nodes in silicosis?
Eggshell calcification
85
Those who have silicosis are at increased risk for ___. Why?
TB - silica depresses cell-mediated immunity
86
What is the most common benign lung tumor and what is it?
Hamartoma; benign neoplasm with various disorganized mesenchymal tissues; contains clefts and cartilage
87
What are the dominant oncogenes involved in lung cancer?
C-MYC, KRAS, EGFR, c-Met, C-KIT
88
What are the tumor suppressor genes involved in lung cancer?
p53, RB1, p16, other genes on chromosome 3
89
Smokers tend to develop what kind of lung cancers and where?
Small cell and squamous cell carcinomas; central airway compartments (airway conducting system, proximal bronchus)
90
Non-smokers tend to develop what kind of lung cancers and where? What genes are involved?
Adenocarcinoma; terminal respiratory units (gas exchange system, distal parenchyma)
91
What gene is implicated in the development of adenocarcinoma in smokers? In non-smokers?
Smokers: KRAS
| Non-smokers: EGFR
92
What are the 4 common complaints involved with lung cancer?
1. Cough
2. Weight loss
3. Chest pain
4. Dyspnea
93
What are other clinical features of lung cancer?
1. Pneumonia, abscess
2. Pleural effusion
3. Pericardial tamponade
4. Hoarseness (recurrent laryngeal nerve)
5. Dysphagea
6. Diaphragm paralysis (phrenic nerve)
7. Rib destruction
94
What is SVC syndrome?
Facial swelling, cyanosis, dilation of veins in head and neck when SVC is involved in lung cancer
95
What are pancoast tumors?
Apical tumors
96
What can pancoast tumors cause?
1. Destruction of 1st/2nd rib
| 2. Horner syndrome
97
What are the symptom of Horner syndrome?
```
Ptosis
Anhidrosis
Miosis
Enopthalmos
Loss of ciliospinal reflex
```
98
What are 3 common paraneoplastic syndromes?
1. SIADH
2. Cushings
3. Calcitonin
99
What are some other systemic manifestations of lung cancer?
1. Eaton-Lambert
2. Sensory neuropathy
3. Acanthosis nigricans
4. Clubbing
100
What happens in Eaton-Lambert?
Muscle weakness due to autoantibodies against calcium channels
101
What cancer is Eaton-Lambert most commonly associated with?
Small cell carcinoma
102
What are the 2 types of lung carcinoma?
1. Small cell carcinoma (20%)
| 2. Non-small cell carcinoma (80%)
103
What are the 3 types of non-small cell carcinoma?
1. Squamous cell carcinoma (25-30%)
2. Adenocarcinoma (30-40%)
3. Large cell carcinoma (10-15%)
104
Squamous cell carcinoma is more common in ___ (men v. women) and is associated with ___. It tends to arise ___ (centrally vs. peripherally).
Men; smoking; centrally
105
What are some histologic features of squamous cell carcinoma?
Intercellular bridges and keratinization
106
Squamous cell carcinoma has a high frequency of ___ mutations.
p53 (rarely EGFR and KRAS)
107
Adenocarcinoma is more common in ___ (men v. women) and is less associated with smoking. It tends to arise ___ (centrally vs. peripherally).
Women; peripherally
108
Describe the gross mass in adenocarcinoma.
Spiculated mass and central scarring
109
What are the three precursor lesions in adenocarcinoma?
1. Atypical Adenomatous Hyperplasia (AAH)
2. Adenocarcinoma in situ (AIS)
3. Minimally invasive adenocarcinoma
110
Describe the AAH lesions.
1. Well-demarcated focus
2. <5 mm
3. Lined by cuboidal to low columnar epithelium
111
Describe the AIS lesions.
1. 3cm or less
2. Grow along pre-existing structures
3. Preservation of alveolar architecture
4. No invasion
112
Describe the MIA lesions.
1. 3cm or less AND
2. Invasive focus <5 mm
3. No invasion into pleura, lymphatics, or blood vessels
113
Adenocarcinomas are often ___ positive and 80% contain ___.
TTF-1; mucin
114
What happens in the EGFR mutations?
Mutations occur in the kinase receptor of the tyrosine kinase domain resulting in constitutive activation
115
What is the targeted therapy available for EGFR mutations?
Erlotinib
116
What is the targeted therapy available for ALK mutations/gene fusions?
Crizotinib
117
What is the targeted therapy available for KRAS mutations?
No specific targeted therapy
118
Describe small cell carcinoma on histology.
Oat cells, densely packed small blue tumor, scant cytoplasm, finely dispersed chromatin, high mitotic activity, necrosis
119
What 2 genes are inactivated in 100% of cases of small cell carcinoma?
p53 and RB
120
Where does mesothelioma originate from?
Pleura (mesothelial cells)
121
Which tumor suppressor genes are involved in mesothelioma?
p16/CDKN2A
| NF2
122
What are the 2 histologic types of mesothelioma?
1. Epithelioid
| 2. Sarcomatoid
123
What is seen on EM in mesothelioma?
Microvilli
