COPD PDF

# CHRONIC OBSTRUCTIVE PULMONARY DISEASE ## I. BASIC PRINCIPLES - **Group of diseases characterized by airway obstruction; lung does not empty, and air is trapped.** - **Volume of air that can be forcefully expired is decreased (↓FVC), especially during the first second of expiration (↓↓FEV₁);...

# CHRONIC OBSTRUCTIVE PULMONARY DISEASE ## I. BASIC PRINCIPLES - **Group of diseases characterized by airway obstruction; lung does not empty, and air is trapped.** - **Volume of air that can be forcefully expired is decreased (↓FVC), especially during the first second of expiration (↓↓FEV₁); results in ↓FEV₁:FVC ratio.** - **Total lung capacity (TLC) is usually increased due to air trapping.** ## II. CHRONIC BRONCHITIS - **Chronic productive cough lasting at least 3 months over a minimum of 2 years; highly associated with smoking** - **Characterized by hypertrophy of bronchial mucous glands (Fig. 9.7)** - **Leads to increased thickness of mucus glands relative to bronchial wall thickness (Reid index increases to >50%, normal is <40%).** ### Clinical features - **Productive cough due to excessive mucus production** - **Cyanosis ('blue bloaters') - Mucus plugs trap carbon dioxide; ↑Paco₂ and ↓Pao₂** - **Increased risk of infection and cor pulmonale** ## III. EMPHYSEMA - **Destruction of alveolar air sacs (Fig. 9.8)** - **Loss of elastic recoil and collapse of airways during exhalation results in obstruction and air trapping.** - **Due to imbalance of proteases and antiproteases** - **Inflammation in the lung normally leads to release of proteases by neutrophils and macrophages.** - **α₁-antitrypsin (A1AT) neutralizes proteases.** - **Excessive inflammation or lack of A1AT leads to destruction of the alveolar air sacs.** - **Smoking is the most common cause of emphysema.** - **Pollutants in smoke lead to excessive inflammation and protease-mediated damage.** - **Results in centriacinar emphysema that is most severe in the upper lobes** - **A1AT deficiency is a rare cause of emphysema.** - **Lack of antiprotease leaves the air sacs vulnerable to protease-mediated damage.** - **Results in panacinar emphysema that is most severe in the lower lobes** - **Liver cirrhosis may also be present.** - **Mutant A1AT accumulates in the endoplasmic reticulum of hepatocytes, resulting in liver damage..** - **Biopsy reveals pink, PAS-positive globules in hepatocytes (Fig. 9.9.).** - **Disease severity is based on the degree of A1AT deficiency.** - **PiM is the normal allele; two copies are usually expressed (PiMM).** - **PiZ is the most common clinically relevant mutation; results in significantly low levels of circulating A1AT** - **PiMZ heterozygotes are usually asymptomatic with decreased circulating levels of A1AT however, significant risk for emphysema with smoking exists..** - **PiZZ homozygotes are at significant risk for panacinar emphysema and cirrhosis.** ### Clinical features of emphysema include: - **Dyspnea and cough with minimal sputum** - **Prolonged expiration with pursed lips ('pink-puffer')** - **Weight loss** - **Increased anterior-posterior diameter of chest ('barrel-chest,' Fig. 9.10)** - **Hypoxemia (due to destruction of capillaries in the alveolar sac) and cor pulmonale are late complications.** ## IV. ASTHMA - **Reversible airway bronchoconstriction, most often due to allergic stimuli (atopic asthma)** - **Presents in childhood; often associated with allergic rhinitis, eczema, and a family history of atopy** ### Pathogenesis (type I hypersensitivity) - Allergens induce TH2 phenotype in CD4+ T cells of genetically susceptible individuals. - T2 cells secrete IL-4 (mediates class switch to IgE), IL-5 (attracts eosinophils), and IL-10 (stimulates T2 cells and inhibits T1). - Reexposure to allergen leads to IgE-mediated activation of mast cells. - **Release of preformed histamine granules and generation of leukotrienes C4, D4, and E4 lead to bronchoconstriction, inflammation, and edema (early-phase reaction).** - **Inflammation, especially major basic protein derived from eosinophils, damages cells and perpetuates bronchoconstriction (late-phase reaction).** ### Clinical features are episodic and related to allergen exposure. - **Dyspnea and wheezing** - **Productive cough, classically with spiral-shaped mucus plugs (Curschmann spirals) and eosinophil-derived crystals (Charcot-Leyden crystals, Fig. 9.11).** - **Severe, unrelenting attack can result in status asthmaticus and death.** - **Asthma may also arise from nonallergic causes (non-atopic asthma) such as exercise, viral infection, aspirin (e.g., aspirin intolerant asthma), and occupational exposures.** ## V. BRONCHIECTASIS - **Permanent dilatation of bronchi (Fig. 9.12); loss of airway tone results in air trapping.** - **Due to severe inflammation with damage to airway walls. Causes include:** - **Cystic fibrosis** - **Primary ciliary dyskinesia - inherited defect of the dynein arm, which is necessary for ciliary movement. Associated with sinusitis, infertility (poor motility of sperm), and situs inversus (position of major organs is reversed, e.g., heart is on right side of thorax), which is called Kartagener syndrome** - **Tumor or foreign body (localized bronchiectasis)** - **Necrotizing infection (localized bronchiectasis)** - **Allergic bronchopulmonary aspergillosis - Hypersensitivity reaction to Aspergillus leads to chronic inflammatory damage; usually seen in individuals with asthma or cystic fibrosis** ### Clinical features: - **Cough, dyspnea, and foul-smelling sputum** - **Complications include hypoxemia with cor pulmonale and secondary (AA) amyloidosis.**