Chapter 15: The Lung - Congenital through Obstructive Flashcards
(127 cards)
1
Q
Except for the vocal cords, the entire respiratory tree is lined by what type of epithelium?
A
Pseudostratified, tall, columnar, ciliated epithelium
2
Q
Bronchia mucosa contains population of neuroendocrine cells with neurosecretory granules containing which factors?
A
- Serotonin
- Calcitonin
- Gastrin-releasing peptide (bombesin)
3
Q
Numerous mucus-secreting goblet cells and submucosal glands are dispersed throughout the walls of which parts of the respiratory tree?
A
- Trachea
- Bronchi
- NOT the bronchioles
4
Q
What are 2 functions of the Type 2 pneumocytes of the alveolar epithelium?
A
- Produce surfactant
- Repair of alveolar epithelium by giving rise to type 1 pneumocytes
5
Q
Pulmonary hypoplasia occurs in utero and what are 2 major causes?
A
- Congenital diaphragmatic hernia
- Oligohydramnios
6
Q
Foregut cysts are most often located where in the lungs and which classification/type is most common?
Treatment?
A
- Hilum or middle mediastinum
- Bronchogenic = most common
- Excision = curative!
7
Q
Pulmonary sequestration refers to a discrete area of lung with what 2 features?
A
- Lacks any connection to the airway system
- Has abnormal blood supply arising from aorta or its branches
8
Q
Congenital pulmonary adenomatoid malformations (CPAM/CCAM) are caused by what?
A
“Arrested development” of pulmonary tissue –> formation of intrapulmonary cystic masses WITH connection to tracheobronchial airways and pulmonary vasculature
9
Q
Via which imaging modality can congenital pulmonary adenomatoid malformations be detected?
A
Fetal ultrasound
10
Q
Congenital pulmonary adenomatoid malformations can be deadly due to what complications?
A
- Hydrops or pulmonary hypoplasia
- Can get infected later in life
11
Q
Extralobar pulmonary sequestrations most commonly come to attention in infants how?
A
- As mass lesions
- Associated w/ other congenital anomalies
12
Q
When do intralobal pulmonary sequestrations typically present and are often due to what?
A
- Older children/adults
- Due to recurrent localized infection or bronchiectasis
13
Q
Atelectasis is a reversible disorder, except in cases caused by what?
A
Contraction atelectasis
14
Q
What are the 3 main types of acquired atelectasis and what is each caused by?
A
- 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
15
Q
Which type of acquired atelectasis causes the mediastinum/trachea to shift toward the affected lung; which type causes a shift away?
A
- Resorption —> mediastinum shifts toward affected lung
- Compression –> mediastinum shifts away from affected lung
16
Q
Which type of acquired atelectasia occurs in the setting of asbestosis?
A
Contraction atelectasis
17
Q
Hemodynamic pulmonary edema is due to an increase in what; most commonly occuring in what setting?
A
↑ hydrostatic pressure –> left-sided CHF
18
Q
What is the histological appearance of of the alveolar capillaries in hemodynamic pulmonary edema?
A
Engorged, and an intra-alveolar transudate appears as finely granular pale PINK material
19
Q
Where does fluid accumulate initially in pulmonary edema due to hydrostatic pressure being greatest in these sites (dependent edema)?
A
Basal regions of the lower lobes
20
Q
List 4 causes of decreased oncotic pressure, which cause “leaking out” and pulmonary edema?
A
- Hypoalbuminemia
- Nephrotic syndrome
- Liver disease
- Protein-losing enteropathies
21
Q
List some of the etiologies which can cause direct injury to the alveolar wall leading to pulmonary edema?
A
- Infections: bacterial pneumonia
- Inhaled gases: high [O2] and smoke
- Liquid aspiration: gastric contents; near drowing
- Radiation
22
Q
What are 2 causes of pulmonary edema of undetermined origin?
A
- High altitude
- Neurogenic (CNS trauma)
23
Q
In long-standing pulmonary congestion (i.e., mitral stenosis), hemosiderin-laded macrophages are abundant, and what is the gross morphology of the lungs?
A
Soggy lungs become firm and brown (brown induration)
24
Q
When the edema associated with pneumonia fails to stay localized and instead becomes diffuse alveolar edema what fatal condition may this lead to?
A
ARDS
25
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**.
26
The histologic manifestation of both ALI and ARDS is what?
**Diffuse alveolar damage (DAD)**
27
What is an important early event in the pathogenesis of ALI/ARDS?
**Endothelial activation**
28
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**
29
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**)
30
The thickened protein-rich edema fluid + debris from dead alveolar cells accumulate in ALI/ARDS, and lead to the formation of what?
**HYALINE** **membranes**
31
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
32
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**
33
ALI/ARDS is more common and associated with a worse prognosis in whom?
**Chronic smokers** and **alcoholics**
34
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**
35
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**
36
Fatal cases of ALI/ARDS often have superimposed?
Bronchopneumonia
37
What is seen on radiographic imaging of patient with ALI?
**Diffuse bilateral infiltrates**
38
Pt's with ALI will have what sx's?
- **Profound dyspnea** and **tachypnea**
- Followed by ↑ **cyanosis** and **hypoxemia**
39
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
40
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**
41
ARDS is a diagnosis of exclusion using the criteria which can be remembered with mnemonic **A.R.D.S**.
- **A**bnormal CXR (**bilateral lung opacities**)
- **R**espiratory failure within 1 week of alveolar insult (**ABRUPT**)
- **D**ecreased PaO2/FiO2 ≤200 = **hypoxia**
- **S**ymptoms of respiratory failure are **NOT due to HF/fluid overload**
42
The causes of ARDS may be remembered with "SPARTAS."
- **S**epsis
- **P**ancreatitis/**P**neumonia
- **A**spiration
**-** u**R**emia
- **T**rauma
- **A**mniotic fluid embolism
- **S**hock
43
Neonatal respiratory distress syndrome is associated with what underlying risk factors?
- **Pre-term** infant
- **Male** gender
- **Maternal diabetes**
- Delivery by **C-section**
44
What is the characteristic finding on CXR of infants w/ neonatal respiratory distress syndrome?
**"Ground-glass"** picture
45
What plays a particularly important role in the synthesis of surfactant?
Glucocorticoids
46
Analysis of what in the amniotic fluid provides a good estimate of the level of surfactant in the alveolar lining?
Phospholipids
47
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**
48
Infants that recover from RDS are also at increased risk for developing what 3 complications associated with preterm birth?
- **PDA**
- **Intraventricular hemorrhage**
- **Necrotizing enterocolitis**
49
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**)
50
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**
51
When do most deaths associated with Acute Interstitial Pneumonia occur?
Within **1-2 months**
52
The radiographic and pathologic features of acute interstitial pneumonia are identical to what?
**Organizing** stage of **ALI**
53
Which 2 obstructive lung diseases are grouped together and referred to as COPD?
- **Chronic bronchitis**
- **Emphysema**
54
Asthma is distinguished from chronic bronchitis and emphysema by the presence of what feature?
**Reversible bronchospasm**
55
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
56
Of the 4 major types of emphysema which 2 cause clinically significant airflow obstruction; which is **most common**?
1. **Centriacinar** (**centrilobular**) = **most common** = **Upper lungs**
2. **Panacinar** (**panlobular**) = **Lower zones**
57
Where are lesions of centriacinar (centrilobular) emphysema most commonly seen and most severe?
**Upper lobes**, in the **apical** segments
58
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**)
59
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\***
60
Which type of emphysema most likely underlies many cases of spontaneous pneumothorax in young adults?
**Distal** acinar (**paraseptal**) emphysema
61
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**
62
The pathogenesis of emphysema is related to an imbalance between which factors?
**Proteases** (i.e., **elastase**) and **anti-proteases** (α1**-antitrypsin**)
63
Which gene related to protection from oxidatie stress may be mutated in emphysema and other smoking-related lung diseases?
***NRF2***
64
α1-antitrypsin is encoded by which locus and on what chromosome?
**Proteinase inhibitor** (***Pi****)* on **chromosome 14**
65
Loss of elastic tissue in the walls of alveoli in emphysema causes respiratory bronchioles to do what during expiration?
**Collapse** ---\> **functional airflow obstruction**
66
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**
67
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
68
Microscopically, in emphysema, the large alveoli are separated by what and have fibrosis where?
**Thin septa** w/ only **focal centriacinar fibrosis**
69
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
70
What value and test is the key to diagnosis of emphysema?
**Impaired** expiratory airflow, best measured w/ **spirometry**
71
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**
72
How will a CXR of predominant bronchitis differ from predominant emphysema?
- **Bronchitis** = prominent vessels; **large heart**
- **Emphysema** = **hyperinflation**; **small heart**
73
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
74
What is a complication which may arise w/ Bullous Emphysema?
**Rupture** of bullae --\> **pneumothorax**
75
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**
76
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
77
What is the role of infection in Chronic Bronchitis?
- Significant in **maintaining** the pathologic state
- **Critical** in producing **acute exacerbation**
78
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**
79
Althought the number of goblet cells increase slightly in Chronic Bronchitis what is the major change seen?
**Size** of **mucous glands** (**hyperplasia**)
80
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**)
81
What morphological changes may the epithelium exhibit in Chronic Bronchitis and may lead to what complication?
**Squamous metaplasia** and **dysplasia --\> carcinoma**
82
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**
83
Long-standing severe chronic bronchitis commonly leads to what (cause of death)?
**Cor pulmonale** --\> **HF**
84
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**
85
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)
86
Non-atopic asthma attacks may be triggered by seemingly innocuous events, such as what?
- Exposure to **cold**
- Exercise
87
Aspirin-sensitive asthma occurs most commonly in pt's with what underlying disorders?
**Recurrent rhinitis** and **nasal polyps**
88
Pt's with aspirin-sensitive asthma suffer from what sx's during an attack?
- **Asthmatic attacks**
AND
- **Urticaria** (aka **hives**)
89
Describe how aspirin inhibiting cyclooxygenase plays a role in the pathogenesis of aspirin-sensitive asthma?
Leads to r**apid ↓ in PGE2**, which normally inhibit **leukotrienes B4, C4, D4, and E4**
90
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**
91
A fundamental abnormality in the pathogenesis of asthma is an exaggerated response by which immune cells to normally harmless enviornmental allergens?
**TH2 response**
92
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
93
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**
94
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 by**mast cells** and other immune cells
95
Which 2 types of mediators play a clear role in the bronchospasm, increased vascular permeability, and airway smooth muscle constriction seen in asthma?
1. **Leukotrienes C4, D4, E4**
2. **ACh** released from **intrapulmonary parasympathetic** nerves
96
Which factors released from eosinophils in the late phase reaction of asthma cause damage to the epithelium?
- **Major basic protein**
- **Esoinophil cationic protein**
97
Leukotrienes C4, D4, E4 are responsible for what 3 pathogenic processes in asthma?
- **Bronchoconstriction**
- **Mucus secretion**
- ↑ **vascular permeability**
98
There is an increased incidence of what 2 other allergic disorders in those with atopic asthma?
- Allergic rhinitis
- Eczema
99
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**
100
Polymorphisms in which interleukin gene have the **strongest** and most consistent associations w/ asthma or allergic disease?
***IL13 gene***
101
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**
102
Variants of which interleukin receptor gene is associated w/ atopy, elevated total serum IgE and asthma?
**IL-4 receptor gene variants**
103
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**
104
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**
105
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**
106
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**
107
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**
108
What are the 4 contributors to chronic **irreversible** airway obstruction in asthma?
- **Muscular bronchoconstriction**
- **Acute edema**
- **Mucus plugging**
- **Airway remodeling**
109
What are the cardinal sx's of asthma?
- Chest tightness
- Dyspnea
- Wheezing
- Cough (with or w/o sputum production)
110
Chronic irreversible airway obstruction will show a decreased response to what?
**Therapeutic agents** --\> **Bronchodilators** and/or **Corticosteroids**
111
Disorder in which destruction of smooth muscle and elastic tissue by chronic **necrotizing** infections leads to permanent dilation of bronchi and bronchioles
Bronchiectasis
112
List congenital or hereditary conditions which may lead to Bronchiectasis?
- Cystic Fibrosis
- Intralobar sequestration
- Primary ciliary dyskinesia
- Kartagener syndromes
113
Many cases of Bronchiectasis lack any association with another disease process and therefore are what?
Idiopathic
114
What are the 2 major conditions associated with Bronchiectasis and are often both necessary for its development?
- Obstruction
- Infection
115
Which 3 organisms are the most common causes of lung infection in pt with CF?
- *Staphylococcus aureus*
- *Haemophilus influenzae*
- *Pseudomonas aeruginosa*
116
Which autoimmune disorders and other conditions are associated w/ developing Bronchiectasis?
- Rheumatoid Arthritis
- SLE
- IBD
- COPD
- Post-transplantation
117
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**
118
Primary ciliary dyskinesia is due to mutations in what?
Ciliary motor proteins (i.e., **Dynein arm** of **microtubules**)
119
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**
120
Males with Kartagener Syndrome tend to be what?
**Infertile**, as result of **sperm dysmotility**
121
Allergic bronchopulmonary aspergillosis occurs in what 2 underlying conditions?
- Asthma
- Cystic Fibrosis
122
Which stain can be used to demonstrate Aspergillus and what is seen?
- **Silver stain**
- Aggregates of **fungal hyphae**
123
What are characteristic findings in the seurm of someone with Allergic Bronchopulmonary Aspergillosis?
**High serum IgE** and serum **Abs** to ***Aspergillus***
124
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**
125
Which lung disease will have **dilated** airways, sometimes up to **4x** normal size?
Bronchiectasis
126
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!
127
What are 3 potential complications of Bronchiectasis?
- Cor pulmonale
- Brain abscess
- Amyloidosis
