Lung Path 2 - Obstructive (Singh) Flashcards by Monika Eszterhazy

What are the four obstructive lung diseases?

Emphysema

Chronic bronchitis

Asthma

Bronchiectasis

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Which 2 obstructive lung diseases are grouped together and referred to as COPD?

Chronic bronchitis
Emphysema

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What are the PFT characteristics of obstructive lung diseases?

Characterized by AIR TRAPPING

Decreased flow

Decreased FEV1

LOW FEB1/FVC ration

TLC increased (d/2 inabilty to exhale)

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What are the 3 inflammatory changes seen in the chronic bronchitis… or any other 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

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What are the complications of chronic bronchitis?

Bronchiectasis

Squamous metaplasia –> dysplasia –> carcinoma

Death from respiratory infection

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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

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Of the various types of emphysema, which 2 cause clinically significant airflow obstruction; which is most common?

Centriacinar (centrilobular) = most common = Upper lungs
Panacinar (panlobular) = Lower zones

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Where are lesions of centriacinar (centrilobular) emphysema most commonly seen and most severe?

Upper lobes, in the apical segments

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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)

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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*

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Which type of emphysema most likely underlies many cases of spontaneous pneumothorax in young adults?

Distal acinar (paraseptal) emphysema

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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

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The pathogenesis of emphysema is related to an imbalance between which factors?

Neutrophil elastase (protease) and anti-proteases (α_{<strong>1</strong>}-antitrypsin)

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Which gene related to protection from oxidatie stress may be mutated in emphysema and other smoking-related lung diseases?

NRF2

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α₁-antitrypsin is encoded by which locus and on what chromosome?

Proteinase inhibitor (Pi) on chromosome 14

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Loss of elastic tissue in the walls of alveoli in emphysema causes respiratory bronchioles to do what during expiration?

Collapse —> functional airflow obstruction

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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

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Microscopically, in emphysema, the large alveoli are separated by what and have fibrosis where?

Thin septa w/ only focal centriacinar fibrosis

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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

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What value and test is the key to diagnosis of emphysema?

Impaired expiratory airflow, best measured w/ spirometry

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What develops in association with secondary HTN, which is also an indicator of poor prognosis in pt w/ emphysema?

Cor pulmonale and eventual CHF, related to 2’ pulmonary HTN

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How will a CXR of predominant bronchitis differ from predominant emphysema?

Bronchitis = prominent vessels; large heart
Emphysema = hyperinflation; small heart

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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

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What is a complication which may arise w/ Bullous Emphysema?

Rupture of bullae –> pneumothorax

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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 lymphocyte infiltrates**) - **Enlargement** of the **mucus-secreting glands** of the **trachea** and **bronchi**

Although the number of goblet cells increase slightly in Chronic Bronchitis, what is the major change seen?

**mucous gland** **hyperplasia** --\> leads to epithelum damage in the airways

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? Why is it concerning?

**Squamous metaplasia** (primed for proliferation and growth) --\> **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** (RVF) --\> **HF**

Asthma is distinguished from chronic bronchitis and emphysema by the presence of what feature?

**Reversible bronchospasm**

Early-onset allergic asthma is associated with inflammation due to what type of T cells and has good response to what tx?

- **T_H2 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 typical asthma attack sx's during an attack... What is different about their clinical presenation?

- Asthmatic attacks and Urticaria (aka hives) during an attach **_Samter's Triad_** - ASA sensitivity - nasoplyps - recurrent rhinositis

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**

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?

**T_H2 response**

What is the role of IL-4, IL-5, and IL-13 released from T_H2 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 T_H2 cells what other type of T cell is seen in the late-phase reaction of asthma and what is it's function?

**T_H17** 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 by**mast 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?

1. **Leukotrienes C₄, D₄, E₄** 2. **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**

What are the 2 major conditions associated with Bronchiectasis and are often both necessary for its development?

- Obstruction - Infection

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

What are some acquired conditions that may lead to necrotizing inflammatory response (bronchiectasis)?

Allergic Bronchopulmonary Aspergillosis (ABPA) and Tuberculosis (chronic infection)

Many cases of Bronchiectasis lack any association with another disease process and therefore are what?

Idiopathic

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

How do you diagnoze Chronic Bronchitis?

Persistent cough with sputum production for 3months out of 2 consecutive years. Pathophysiologic findings will include mucus gland hyperplasia with damage to airway epithelium