COPD & Emphysema

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In chronic obstructive pulmonary disease (COPD), irreversible airway obstruction prevents air from leaving the lungs, mainly due to collapse at the distal terminal bronchioles. This phenomenon, known as air trapping, is influenced by key risk factors, the most important of which is cigarette smoking. Toxins such as those in cigarette smoke collect in the respiratory bronchioles, activating an inflammatory response that recruits neutrophils to the distal airways. COPD is broadly categorized into emphysema and chronic bronchitis.

Clinically, COPD presents with a range of symptoms such as progressive dyspnea, diffuse bilateral wheezing, and a productive cough in cases of chronic bronchitis. Additionally COPD results in distinctive pulmonary function test abnormalities: increased TLC and increased FRC are noted, alongside decreased FEV1/FVC ratio (<0.7) and low DLCO.

Emphysema primarily affects the distal airways including the alveolar sac, alveolar ducts, and respiratory bronchioles. It is characterized by permanent airway dilation and decreased elasticity, predominantly in the upper two-thirds of the lung in centriacinar emphysema, and throughout the respiratory unit in panacinar emphysema. Neutrophils produce elastase, which if uninhibited, results in increased compliance and damage to the distal airways. This damage is especially pronounced in the context of alpha-1 antitrypsin (AAT) deficiency, which leads to more widespread destruction, predominantly affecting the lower lobes of the lung. AAT deficiency also results in liver damage & cirrhosis due to non-secreted AAT accumulation in hepatocytes, and increased emphysema risk in smokers.

Emphysema manifests with a ‘classic emphysema pose’ where accessory muscles are used to help maintain pressure to inflate distal airways. Diagnostic findings in emphysema include hyperinflated lungs on CXR evidenced by a flat diaphragm, more than 10 posterior rib shadows, increased parenchymal radiolucency, and a lengthened cardiac silhouette. Emphysema can also present with pulsus paradoxus, distant heart sounds, and diminished lung sounds, as well as a low DLCO. Early in the course, hyperventilation maintains normal arterial oxygen levels but may result in respiratory alkalosis. Later in its progression, severe air trapping leads to increased CO2 retention, resulting in respiratory acidosis and a severe decrease in DLCO resulting in hypoxemia and cyanosis.

On the other hand, chronic bronchitis involves the proximal large airways, marked by mucus gland hypertrophy and hypersecretion in the trachea, bronchi, and bronchioles. Chronic bronchiolitis, as part of chronic bronchitis, causes goblet cell metaplasia and proliferation. Mucus hypersecretion causes mucus plugs in bronchioles that cause distal airway obstruction, increasing PaCO2 and causing respiratory acidosis, while the impaired oxygenation of alveoli results in hypoxemia and cyanosis.

Chronic hypoxemia in COPD results in pulmonary arterial hypertension due to hypoxic vasoconstriction, eventually causing right heart failure. Supplemental oxygen can be both beneficial and risky in COPD patients. While it can decrease the respiratory rate, it also inhibits firing of peripheral chemoreceptors like those in the aortic arch and carotid bodies, which sense decreases in PaO2, potentially causing respiratory failure.

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What mechanisms lead to irreversible airway obstruction in COPD, and how do they affect the distal airways?

Irreversible airway obstruction in COPD primarily results from exposure to respiratory irritants like cigarette smoke. These irritants trigger an inflammatory response, recruiting neutrophils to the distal airways. Neutrophils release elastase, an enzyme that degrades elastin, reducing airway elasticity and increasing compliance. This culminates in emphysema, characterized by permanent dilation of the distal airways.

How does alpha-1 antitrypsin (AAT) deficiency influence the development of COPD and emphysema?

Alpha-1 antitrypsin (AAT) deficiency allows for unchecked elastase activity by neutrophils, leading to accelerated destruction of the distal airways. This results in panacinar emphysema, affecting the entire respiratory unit and predominantly involving the lower lung lobes. AAT deficiency is also a risk factor for early-onset emphysema and can cause liver damage due to AAT accumulation in hepatocytes. Smoking increases the risk of emphysema in AAT deficiency as chemicals in cigarette smoke directly inhibit AAT.

What are the clinical manifestations of emphysema and how does it influence pulmonary function?

Emphysema typically presents with progressive dyspnea and diffuse bilateral wheezing, sometimes accompanied by weight loss. Physical examination may reveal hyperinflated lungs, distant heart sounds, and diminished lung sounds. Functionally, emphysema leads to increased total lung capacity (TLC) and functional residual capacity (FVC), while reducing forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). It also lowers the lung's diffusion capacity for carbon monoxide (DLCO), affecting gas exchange.

How does chronic bronchitis contribute to the pathophysiology and symptoms of COPD?

Chronic bronchitis is defined by a productive cough lasting for at least three consecutive months in two consecutive years. It primarily affects the proximal large airways and is characterized by mucus gland hypertrophy and hypersecretion. This results in mucus plug formation, obstructing the distal airways, trapping air, and limiting alveolar oxygenation. Early in its course, respiratory acidosis and cyanosis are observed due to the buildup of CO2 and subsequent increase in PaCO2 .

What complications are associated with the chronic hypoxemia often observed in patients with COPD?

Chronic hypoxemia in COPD leads to hypoxic vasoconstriction, leading to pulmonary arterial hypertension (PAH). Over time, the elevation in pulmonary arterial pressure can result in right heart failure, or cor pulmonale. Supplemental oxygen therapy, often used to alleviate hypoxemia, can paradoxically decrease respiratory rate by inhibiting peripheral chemoreceptors, potentially leading to respiratory failure.