CPR1 - Pathology {4.06-4.07,5.07-5.08}

How does the WHO define Chronic Obstructive Pulmonary Disease (COPD)?

A common, preventable, and treatable disease characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities caused by exposure to noxious particles or gases.

In the last two decades, which gender has seen an increased incidence of COPD, possibly due to increased cigarette smoking?

Women

What percentage of never-smokers with COPD are women?

80%

What is the defining characteristic of emphysema regarding the location of airspace enlargement?

Airspaces distal to the terminal bronchioles.

The destruction of alveolar walls in emphysema leads to airflow obstruction primarily through the loss of _____.

Elastic recoil

What gross morphologic structures are formed when adjacent alveoli fuse in emphysema?

Blebs or bullae

Which type of emphysema specifically involves the respiratory bronchioles (central/proximal acinus) and is most common in smokers?

Centriacinar (centrilobular) emphysema

Panacinar (panlobular) emphysema is characteristically associated with a deficiency in _____.

α1-antitrypsin

Which type of emphysema involves the distal acinus and subpleural regions and is a recognized cause of spontaneous pneumothorax?

Paraseptal (distal acinar) emphysema

Irregular emphysema is usually associated with focal areas of the acinus and often occurs following _____.

Infection or scarring

What is the primary etiology for more than 95% of clinically significant centrilobular emphysema cases?

Heavy cigarette smoking

On which chromosome is the SERPINA1 gene, responsible for encoding α1-antitrypsin, located?

Chromosome 14

What is the physiological role of α1-antitrypsin in the lungs?

It acts as a protease inhibitor for the elastase enzyme.

During emphysema pathogenesis, nicotine and reactive oxygen species attract which inflammatory cells to the alveolar spaces?

Neutrophils

What specific proteases are released by activated neutrophils that damage alveolar walls in emphysema?

Elastase and proteinase 3

How does oxidative damage from tobacco smoke affect α1-antitrypsin?

It leads to the inactivation of α1-antitrypsin.

Approximately what percentage of emphysema patients have a genetic deficiency of α1-antitrypsin (homozygous PiZZ)?

1%

Besides elastases, what other protein group's imbalance contributes to matrix destruction in emphysema?

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs).

Term: Bulla

Definition: An air-containing space measuring >1 cm, surrounded by a thin wall <1 mm thick.

Term: Bleb

Definition: A small gas-containing space within the visceral pleural surface measuring <1 cm.

In addition to tobacco smoke, paraseptal emphysema is associated with which genetic connective tissue disorders?

Marfan and Ehlers-Danlos syndromes

The clinical phenotype of emphysema, characterized by a thin build and hyperinflated chest without cyanosis, is known as a _____.

Pink puffer

Why is there little ventilation/perfusion (V/Q) mismatch in classic emphysema?

Because both the airspaces and the associated capillaries are destroyed together.

What is the typical FEV1/FVC ratio finding in pulmonary function testing for COPD?

<0.70

What radiographic sign describes the increased AP diameter of the thorax seen in advanced emphysema?

Barrel Chest

Why does the heart appear 'small and narrow' on a radiograph of a patient with advanced emphysema?

It is the result of the downward push of the diaphragm by hyperinflated lungs.

What is the clinical definition of Chronic Bronchitis?

A productive cough on most days for ≥ 3 months in each of 2 consecutive years without other causes.

What are the three primary types of inflammatory cells recruited in the pathogenesis of chronic bronchitis?

CD8+ T lymphocytes, macrophages, and neutrophils.

In chronic bronchitis, proteases released by neutrophils stimulate the hypertrophy of which large-airway structure?

Submucosal mucous glands

What epithelial change in the bronchi results in marked increases in mucin secretion during chronic bronchitis?

Goblet cell hyperplasia

Term: Reid Index

Definition: The ratio of bronchial gland thickness to the total thickness of the bronchial wall (submucosa).

What precancerous epithelial change occurs in chronic bronchitis as a result of direct tobacco smoke damage?

Squamous metaplasia

The clinical phenotype of chronic bronchitis, characterized by cyanosis and peripheral edema, is known as a _____.

Blue bloater

What is the primary cause of cyanosis in 'blue bloaters' with chronic bronchitis?

Hypoxemia

Cor pulmonale refers to heart failure of which specific chamber as a complication of chronic lung disease?

Right ventricle

How does the diffusing capacity of the lungs for carbon monoxide typically differ between emphysema and chronic bronchitis?

It is decreased in emphysema and usually normal in chronic bronchitis.

Which COPD phenotype is more commonly associated with early-onset dyspnea?

Emphysema (Pink puffer)

What is the characteristic feature of airway narrowing in asthma compared to other COPD conditions?

It is episodic and reversible.

Approximately 70% of asthma cases are classified as 'extrinsic' or 'atopic,' meaning they are mediated by which antibody?

IgE

Atopic asthma is primarily driven by which type of T-helper cell immune response?

Th2-mediated

List three microscopic findings in the airway mucus of an asthmatic patient.

Curschmann spirals, Creola bodies, and Charcot-Leyden crystals.

From which cell type's granules are Charcot-Leyden crystals derived in asthma?

Eosinophils

What microscopic change to the bronchial basement membrane is characteristic of asthma histology?

Thickening

What is the term for a life-threatening, acute asthmatic episode that fails to respond to standard treatments?

Status Asthmaticus

How is bronchiectasis defined pathologically?

Irreversible dilation of bronchi caused by destruction of bronchial wall muscle and elastic tissue.

What is the most common inherited cause of bronchiectasis?

Cystic fibrosis

What clinical triad defines Kartagener Syndrome?

Situs inversus, sinusitis, and bronchiectasis.

Primary Ciliary Dyskinesia (PCD) is caused by ultrastructural defects in cilia and _____.

Sperm tails

What specific ultrastructural component is characteristically absent in the cilia of patients with Kartagener syndrome?

Dynein arms

What is the fundamental 'vicious cycle' in the pathogenesis of bronchiectasis?

Obstruction → impaired clearance → infection → inflammation → destruction → airway dilation.

In bronchiectasis, how much larger can the affected airways become compared to their normal size?

Up to four times

What is the likely diagnosis for a patient presenting with male infertility, recurrent sinusitis, and chronic bronchiectasis?

Primary Ciliary Dyskinesia (PCD)

Centrilobular emphysema typically shows a regional predominance in which part of the lungs?

Upper lobes

Panacinar emphysema typically shows a regional predominance in which part of the lungs?

Lower lobes

What inflammatory cell type is characteristically found in the bronchial wall infiltrates of an asthmatic patient?

Eosinophils

Name the four broad clinical categories of restrictive lung disease based on origin.

Chest wall disorders, pleural diseases, neuromuscular disorders, and interstitial lung diseases.

What is an example of a neuromuscular disorder that can cause restrictive lung disease?

Guillain-Barre syndrome.

In the United States, what percentage of specific interstitial lung diseases is attributed to Sarcoidosis?

20%.

Which major category of chronic interstitial lung disease includes Sarcoidosis and Hypersensitivity pneumonitis?

Granulomatous diseases.

Hypersensitivity pneumonitis is a diffuse granulomatous interstitial lung disease caused by the inhalation of _____.

Antigenic particles (e.g., microbes, animal proteins, chemicals).

What is the causative agent of 'Farmer's lung'?

Micropolyspora faeni from moldy hay.

The condition 'Bagassosis' is caused by exposure to which organism found in sugar cane?

Thermoactinomyces sacchari.

What are the three components of the classic microscopic triad for Hypersensitivity Pneumonitis?

Bronchiolitis obliterans, lymphocytic interstitial infiltrate, and poorly formed nonnecrotizing granulomas.

How do the granulomas of Hypersensitivity Pneumonitis differ from those of Sarcoidosis?

They are loosely organized and ill-defined, whereas sarcoidosis granulomas are tightly organized.

What term describes the fibroblastic plugs in alveolar sacs often seen in Hypersensitivity Pneumonitis?

Masson bodies.

How long after exposure do peak symptoms of acute Hypersensitivity Pneumonitis typically appear?

3 to 6 hours.

Define Sarcoidosis.

A systemic disease characterized by nonnecrotizing/noncaseating epithelioid granulomas in multiple organs.

What is the peak incidence age range for Sarcoidosis?

20 to 29 years.

Which serum enzyme is frequently elevated in patients with Sarcoidosis?

Angiotensin Converting Enzyme (ACE).

What are the three components of the triad known as Löfgren syndrome?

Erythema nodosum, bilateral hilar lymphadenopathy, and polyarthralgia.

What clinical features constitute Heerfordt syndrome?

Uveitis, parotitis, fever, and facial nerve palsy.

What is the characteristic radiologic finding of stage II Sarcoidosis?

Bilateral hilar lymphadenopathy and profuse bilateral pulmonary micronodules.

Describe the clinical appearance of Lupus pernio in Sarcoidosis.

Chronic cutaneous induration and purple discoloration of the central face and hands.

Where are Sarcoid granulomas typically distributed within the lung parenchyma?

Along bronchovascular bundles and interlobular septa.

What are the star-shaped crystals found within multinucleated giant cells in Sarcoidosis called?

Asteroid bodies.

What are Schaumann bodies?

Small lamellar calcifications found within granulomas in Sarcoidosis.

Define Idiopathic Pulmonary Fibrosis (IPF).

A pattern of lung damage characterized by diffuse interstitial inflammation and extensive fibrosis leading to 'honeycomb' lung.

What are the two primary antifibrotic drugs used to decrease the rate of progression in IPF?

Pirfenidone and Nintedanib.

Which specific pathway is most likely involved in the development of fibrosis in IPF?

TGF-β pathways.

In the context of IPF, what does 'temporal heterogeneity' mean?

Lesions representing different stages of disease progression coexist simultaneously in the lung.

In the context of IPF, what does 'geographic heterogeneity' mean?

The presence of abnormal, fibrotic lung tissue mixed with areas of normal lung parenchyma.

Where does fibrosis typically begin in a patient with Idiopathic Pulmonary Fibrosis?

The lower lobes, specifically subpleural and paraseptal regions.

What microscopic finding in IPF is characterized by massive dilatation of air spaces and thickened walls?

Honeycombing.

Define Pneumoconiosis.

A pulmonary disease resulting from the inhalation of mineral dust.

Asbestos exposure is a multiplicative risk factor for which type of malignancy?

Lung carcinoma.

What is the primary location for pleural plaques in asbestosis-related disease?

Parietal and diaphragmatic pleura.

What are 'asbestos bodies'?

Asbestos fibers coated with an iron-containing proteinaceous material (ferruginous bodies).

What is the latency period for the development of asbestosis?

20 to 30 years.

Which occupational group is at high risk for Silicosis?

Sandblasters and silica miners.

Silicosis primarily affects which zone of the lungs?

Upper lung zones.

Silicosis is associated with an increased risk of which specific infectious disease?

Tuberculosis.

What is the difference between Anthracosis and Coal Workers Pneumoconiosis (CWP)?

Anthracosis is a clinically insignificant collection of carbon macrophages, while CWP involves fibrotic nodules.

What characterizes 'complicated' Coal Workers Pneumoconiosis (Black Lung)?

Nodular lesions 2.0 cm or greater in size and significant respiratory impairment.

What is Caplan syndrome?

The coexistence of Rheumatoid Arthritis nodules and Pneumoconiosis.

According to the American Thoracic Society, what is a necessary criterion for diagnosing asbestosis besides structural pathology?

Evidence of causation documented by occupational and exposure history.

What is the median survival time for a patient with IPF who does not receive a transplant?

3 years.

Why is Sarcoidosis considered a 'diagnosis of exclusion'?

Clinicians must rule out other causes of granulomatous disease before confirming the diagnosis.

Panacinar (panlobular) emphysema is characteristically associated with what morphological changes?

Uniform enlargement of the entire acinus

How is pneumonia defined pathologically?

Infection, inflammation, and consolidation of the lung parenchyma.

What is the process of consolidation in pneumonia?

Solidification of pulmonary tissue caused by alveolar inflammatory exudate.