Normal Respiratory Microanatomy Conducting Portion- tubular passageways that serve to warm or cool, humidify and clean air Nasal Cavities • Vestibular region has a lightly keratinized, stratified squamous epithelium with coarse hairs (vibrissae) and sebaceous glands. The vibrissae act as coarse filters and are richly supplied with nerve endings. • Respiratory region has a ciliated pseudostratified columnar epithelium (respiratory epithelium) with numerous goblet cells o Cell types: Goblet Ciliated- projections to snag mucus flow Brush- innervated by CN V (unknown secretory or sensory function) Basal- stem cells EEC (enteroendocrine)- hormone secreting; origin of oat cell carcinomas • Mucus moistens air and traps particles, while cilia beat towards pharynx causing about one pint of mucus to be swallowed per day • Turbinate bones on lateral walls help make airflow more turbulent • Swell bodies are venous cavernous plexuses which function for heat exchange and alternate left to right every half-hour • Vessels have intimal cushions so when the tunica media relaxes, the vessel opens (erectile characteristic similar to that of the penis) • Blood supply is arranged in redundant loops (counter-current system) • Olfactory region has an epithelium similar to respiratory epithelium but lacking goblet cells. The glands associated with olfactory epithelium produce only serous fluid, no mucous. o Olfactory cells are bipolar neurons that are structurally but not functionally identical; they have non-motile cilia that increase surface area o Basal cells may be stem cells for olfactory cells (do replace other cells) o Sustentacular cells form mesaxons around the olfactory cell axons (function similarly to glial cells) and are also secretory o Brush cells are rich in microvilli and serve an unknown function (probably sensory) Paranasal Sinuses (Frontal, Sphenoidal, Ethmoidal, Maxillary) • Epithelium is similar to respiratory epithelium but with fewer cilia, fewer goblet cells and relatively few glands • Compromised drainage of the sinuses causes congestion and irritation of nerve endings within the lamina propria o Can be treated with drugs like epinephrine that constrict vessels, decrease blood flow, reduce swelling and allow drainage Trachea • Lined with respiratory epithelium, with cilia beating up toward pharynx • Abundant serous and mucous glands within the submucosa • Has 16-20 C-shaped rings of cartilage in the adventitia, all of which open posteriorly Bronchi • Identical to trachea, except hyaline cartilage is arranged in plates • Picture shows small portions of hyaline cartilage (on left and right edges of picture), substantial glandular tissue, and bands of smooth muscle just beneath the lamina propria Bronchioles • Encircled by a complete layer of smooth muscle, which plays an important role in regulating the diameter of the bronchiole o This is the smooth muscle that spasms in asthmatics • Lined by ciliated simple columnar epithelium • Contain sparse glands in the submucosa Respiratory Portion- segments of the respiratory tract in which gas exchange occurs Respiratory Bronchioles • Can be differentiated from terminal bronchiole (also pictured) by the openings of alveoli • Lined by ciliated simple cuboidal and simple squamous epithelium • Contain no glands Type II Alveoli cell • Lined by simple squamous epithelium • Type I cells cover about 95% of the alveolar surface o Not mitotically capable o Can share basal lamina with capillary, creating thinnest part of the respiratory minimal barrier (type I cell, basal lamina, endothelial cell) Dust cell • Type II cells cover about 5% of the alveolar surface (bulge) o Are mitotically capable (reserve for Type I and II cells) o Produce and release surfactant, which decreases alveolar surface tension Surfactant is first produced by the fetus at about 24 weeks gestation Surfactant increases with ventilation and is stimulated by corticosteroids • Alveolar macrophages (dust cells) are monocyte-derived cells that phagocytose debris and surfactant • Interalveolar wall contains collagen for support and to limit expansion and elastic fibers to accommodate inspiration Gas exchange first occurs at the respiratory bronchioles due to the appearance of alveoli (arrows). Conducting Respiratory Respiratory Minimal Barrier Chronic Obstructive Pulmonary Disease A disease state characterized by progressive development of airflow limitation that is not fully reversible and usually results from an abnormal response of the lungs to noxious particles or gases Prevalence • 16 million people in the U.S. have COPD • Rare in people under 40 years old • WHO predicts that by 2020, COPD will rise from 6th to 3rd place worldwide as the most common cause of death Etiology • Important contributing factors to the genesis of COPD are cigarette smoking and air pollution • Four major conditions cause COPD o Emphysema o Chronic bronchitis/bronchiolitis o Asthma o Bronchiectasis Clinical Findings • Patients with COPD often have overlapping symptoms of chronic bronchitis, chronic asthma and emphysema • Cough with mucoid to mucopurulent sputum • Dyspnea, first on exertion and later in the disease at rest • Prolonged expiration, with or without wheezes • Decreased breath sounds Normal chest x-ray (left) and chest x-ray of COPD • Hyperresonance to percussion (right) showing flat, depressed diaphragms and long, narrow heart shadow • FVC, FEV1 and FEV1/FVC are all decreased • TLC, RV and RV/TLC are all increased • Hypoxemia and hypercapnia can occur later in the disease (when FEV1 falls below 1.0 L) • Chest x-ray shows hyperinflation with flat, depressed diaphragms, a long and narrow heart shadow, and increased space behind the sternum Complications • Hypoxic pulmonary hypertension • Right heart failure (cor pulmonale) Lateral chest x-ray • Frequent intercurrent respiratory tract infections (>2 per year) showing increased space behind the sternum • Weight loss and loss of appetite • Respiratory failure with severe hypoxemia, hypercapnia, and respiratory acidosis Management • Smoking cessation • Oxygen therapy • Bronchodilators (mainly inhaled) • Steroids (for acute episodes) • Antibiotics • Mechanical ventilation • Surgery (LVRS, transplantation) Emphysema A condition of the lung characterized by abnormal permanent enlargement of the airspaces distal to the terminal bronchiole, accompanied by the destruction of their walls and without obvious fibrosis Pathogenesis • Hypothesis is that alveolar wall destruction is due to an imbalance between proteases (especially elastase) and antiproteases (especially α1-antitrypsin) o Low serum levels of the protease inhibiter (Pi) α1- antitrypsin lead to the development of emphysema 90% of the population has the normal phenotype PiMM In emphysema, alveolar walls are Indiviudals with the PiZZ phenotype are at destroyed and air spaces are dilated high risk for developing emphysema o Smokers have increased numbers of PMNs in their alveoli These PMNs secrete free radicals that inhibit α1-antitrypsin Oxidants in cigarette smoke also inhibit α1-antitrypsin Panacinar Emphysema (panlobular emphysema) • Dilation and destruction of entire acini • Characterized by multiple small cystic spaces which, on cut section, give the lung a ragged fishnet appearance • Lesions tend to be in the lower and anterior zones of the lung bilaterally • This form is quite common, especially in older adults • Noxious environmental factors facilitate panacinar emphysema Panacinar emphysema, showing destruction of • This form is also seen with α1-antitrypsin deficiency most of the lung lobule Centriacinar Emphysema (proximal acinar emphysema) • Most common form of emphysema (strongly linked to cigarette smoking) • Dilation and destruction primarily involving the proximal portion of the acinus (respiratory bronchioles) • Characterized by spotty, multifocal, cystic spaces with interstitial deposits of anthracotic pigment • Lesions tend to be more prominent in the upper lobes Paraseptal Emphysema (distal acinar emphysema) • Dilation and destruction primarily involving the peripheral portion of the acinus (distal alveolar ducts and sacs) Centriacinar emphysema, • Cystic or bullous lesions are most common in the apices, anterior showing diseased spots surrounded by spared acinic margins of upper lobes, and diaphragmatic surfaces of lower lobes tissues o A bulla is a dilation of an air space that is 1cm or greater • Since distal acini attach to relatively rigid structures (pleura or septa) a shearing effect is facilitated under stress o This can cause leakage of air from the lung airways into the interstitium and pleura, creating subpleural collections of air (“blebs”) which are prone to rupture Pleural bleb Bullous disease of the lung, a cyst-like enlargement of the airspace that can be a manifestation of paraseptal emphysema Chronic Bronchitis A clinical diagnosis requiring a chronic cough that produces sputum for 3 months or more in at least 2 consecutive years, without any other disease that could account for this symptom Etiology • Smoking is a major etiological factor o Only 5-10% of chronic bronchitis cases occur in non-smokers • Environmental factors such as pollution can play a role in causing chronic bronchitis • Weather conditions and infectious agents can also contribute to chronic bronchitis Clinical Findings • Chronic cough that produces sputum • Bronchitis is especially likely to cause right ventricular hypertrophy and lung congestion (“blue bloater” syndrome and cor pulmonale) Pathogenesis • Inflammatory