Chapter 15: The lung
The respiratory system develops from the ventral wall of foregut; to lateral lung buds develop from the midline trachea, which eventually divide in to the bronchi. Each bronchus sequentially bifucate into progressively smaller airways, which have double arterial supply from the pulmonary and bronchial arteries. The right mainstem bronchus is more vertically in line with the trachea and as a consequence aspirated foreign bodies more frequently enter the right lung.
They subsequent, smaller branches of the bronchi without cartilage and submucosal glands are defined as bronchioles, which branch further into terminal bronchioles. Just distal are the acini, which are composed of:
Respritory bronchioles:
Alveolar ducts:
Alceolar sacs:
Clusters of 3-5 acini (and their terminal bronchioles) is call ad lobule.
The components of the conductive respiratory tree: larynx, trachea, and bronchioles—are lined with pseudostratified, columnar, ciliated epithelium. (The most superficial cellular layer of the vocal folds is squamous epithelium.)
Congenital disorders are rare but nonetheless are important to consider:
Pulmonary hypoplasia: compression of lungs during development such as a diaphragmatic hernia or oligohydraminos can lead to reduced weight, volume, and acini in either lung.
Foregut cysts: ectopic detachments of the foregut that are bronchogenic, esophageal or enteric (in order of frequency) during embryogenesis most frequently in the hilum. They are typically found incidentally or present due to compression of nearby structures.
Pulmonary sequestration: areas of the lung that have either lack connection to conducting airways or have abnormal blood supply from the aorta (or its branches). They can be extralobar presenting as masses often in infancy or intralobar later in adolescence due to recurrent infections or bronchiectasis.
Less common congenital disorders include atresia, stenosis, tracheoesophageal fistulas, vascular abnormalities, and congenital malformations, and congenital lobar overinflation (emphysema).
Atelectasis refers to either incomplete expansion of the lung parenchyma, in case of a neonate, or collapse of previously inflated lung parenchyma. There are three main types:
Resorption atelectasis: The remaining air behind an obstruction (e.g. a mucus plug, exudates, foreign bodies, tumors) is still absorbed causing collapse of the tissue.
Compression atelectasis: Large volumes of fluid, air, tumor, etc. in the plural cavity compresses air out of the lung parenchyma and shifts the mediastinum away from the affected lung.
Contraction atelectasis: Fibrosis of the lung prevents expansion of the tissue to be filled by air. Only this type of atelectasis is reversible.
Pulmonary edema is defined as accumulation of interstitial fluid in the alveolar space and is a consequence of hemodynamic dysfunction, cardiogenic, or is microvascular injury. Idopathic edema is associated with high altitude or may be neurogenic as in the case of CNS trauma.
Increased hydrostatic pressure—commonly associated with leftsided congestive heart failure, volume overload, or pulmonary vein obstruction—causes fluid to begin to accumulate first in the lower lobes where it will be the highest. Fine pale-pink granules will can be seen in the transudate on a pictomicrograph along with hemosiderin-laden macrophages may be present. The latter are become so abundant in chronic congestion, that they lungs appear brown on gross examination (brown induration) and become predisposed to infection.
Decreased oncotic pressure from hypalbuminemia, nephrotic syndrome, liver disease, or enteropathies that result in a loss of protein prevents fluid resorption.
Primary injury to endothelium or secondary injury due to injury of the alveolar cells promotes inflammation and subsequently leakage of exudate into the interstitial spaces; perhaps subsequently into to the alveloi. In the case of injury due to infection—i.e. pneumonia—edema tends to be localized and is not a major contributor to the presentation. However, in cases of diffuse injury edema is a central component of acute respritory distress syndrome, a potentially fatal condition.
Acute lung injury is defined by bilateral infiltrates and significant hypoxemia without cardiac failure and are characterized by increased pulmonary vascular permeability, edema, and cell death associated with inflammation: diffuse alveolar damage is seen histologically. Acute lung injury can progress into acute respiratory distress syndrome.
Pathogenesis. Injury to pneumocytes and pulmonary endothelium sets off a positive feedback reaction of inflammation.
Endothelial cell actiation occurs as a result of injury or secondary to activated macrophages, which release factors such as TNF. Circulating inflammatory mediators may also play a role in expression of adhesion molecules, procoagulants, and chemokines.
Neutophils adhere to activated endothelium and release proteases, reactive oxidizing speces, and cytokines notably macrophage migration inhibitory factor and consequently promotes the ongoing inflammatory response, which can damage and activate more endothelial tissue.
Necrosis and damage of type 2 pneumocytes leads to decreased and dysfunctional release of surfactant as the inflammatory causes fluid accumulation in the alveoli due to inflammation and leaky endothelium. The protein rich edema and cellular debris form hyaline membranes a characterising feature of acute lung injury and distress syndrome.
Injury is resolved as the debris is cleared and macrophages being to release TGF-β and PDGF stimulating fibroblast proliferation and collagen deposition. Bronchiolar stem cells and uninjured endothelium proliferate and replace dead cells.
Clinical Course. Individuals with acute lung injury tend to already be hospitalized for its underlying cause. Its presentation includes profound dyspnea; tachypnea; refractory hypoxemia, cyanosis, and respiratory failure. Diffuse bilateral infiltrates will be seen on a chest radiography. Respiratory acidosis may develop. Regions of the lung collapse, consolidate, or lose compliance due to surfactant dysfunction. These poorly ventilated regions continue to be perfused leading to ventilation/perfusion mismathc.
Acute interstitial pneumonia, sometimes called idiopathic acute lung injury/respiratory distress syndrome, is used to describe the presentation of acute lung injury or distress syndrome without a know etiology.
Occlusions of the large arteries of the lung are almost always embolic, thrombotic, and originate in the deep veins of the lower extremities—pulmonary thromboses develop only in disease states of the lungs (e.g. pulmonary hypertension, [pulmonary atherosclerosis], and heart failure)
Pathogenesis. Individuals experiencing a pulmonary embolism typically have some primary predisposing condition: [Factor 5 Leiden], [anitphopholipid syndrome], or prothrombin mutations—or a secondary predisposing condition: obesity, recent surgery, cancer, oral contraceptive use, central venous lines, and those mentioned previously. Non-thrombotic emboli are rare; fat emboli from broken bones or injection of air are two examples.
Depending on the size, number, and location of emboli, respiratory comprimse due to a lack of nonperfusion but ventilated portions of the lungs and hemodynamic compromise due to increased vascular resistance can cause death or acute cor pulmonale (right sided heart failure).
Clincical Course. Presentation, prognosis, and treatment of pulmonary emboli differ widely based on the size of the embolism. Large or “massive” pulmonary emboli—blockage of the pulmonary artery that results in right ventricle dilation and sustained systolic blood pressure < 90mmHg—is one a cause of instantaneous death. Electromechanical dissociation of the heart, prescience of a heart rhythm on electrocardiogram without a palpable pulse is one finding. In contrast, smaller emboli may be entirely asymptomatic or with transient chest pain and cough. They are often resolved with contraction and fibrinolysis.
More severe dyspnea, tachypnea, fever, chest pain, coucgh, and hemoptysis can be seen when emboli result in infarction of pulmonary parenchyma. This occurs in about 10% of cases and most often affects the lower lobes. Infarcted tissues also has the potential for be come infected, a septic infact, which can develop into an abscess predicating an intense inflammatory response and neutrophilic infiltration.
Diagnosis is most frequently made based off of computed tomography of the chest if simple chest radiograph is inconclusive. Infrequently, ventilation/perfusion scans are used or pulmonary angiography when other methods are contraindicated.
Pulmonary hypertension is defined as a mean pulmonary artery pressure ≥ 25mmHg. Pulmonary hypertension is further classified as:
Pulmonary arterial hypertension (due to hypertrophy or hyperplasia of the small muscular arteries)
Pulmonary hypertension secondary to left heart failure
Pulmonary hypertension secondary to disorders of the parenchyma or hypoxemia
Chronic thromboembolic pulmonary hypertension
Multifactorial pulmonary hypertension
Pathogensis. The etiology of pulmonary hypertension is most often mechanical cardiopulmonary dysfunction resulting in increased: pulmonary blood flow, pulmonary vascular resistance, or left heart resistance. Examples of common causes of pulmonary hypertension:
Chronic obstructive or intestitial lung disease destroy alveolar capillaries increases pulmonary vascular resistance—a group 3 disorder.
Congenital or aquired heart diseases: Mitral stenosis or aortic stenosis increase left atrial pressure and subsequently the pulmonary vascular pressure—a group 2 disorder.
Recurret thromboemboli reduce the cross sectional are of the pulmonary vasculature, which increases resistance—a group 4 disorder.
Autoimmune disorders such as systemic sclerosis, that involve the pulmonary vasculature, increase resistance—a group 1 disorder.
Obstructive sleep apnea just like other diseases that cause hypoxemia is another example of group 3 causes of pulmonary hypertension.
Primary pulmonary hypertension is an autosomal dominant, low penetrant disorder caused by a pathogenic variant of BMPR2 causing a loss-of-function to bone morphogenetic receptor 2, part of the TGF-β family of receptors. In addition to bone growth, BMPR2 plays an important role in embryogensis, apoptosis, proliferation, and differentiation. Haploinsufficy of BMPR2 leads to hyperplasia of the tunica intima and media.
Clinical features. Along with those of the primary disease, individuals with pulmonary hypertension of all types present with signs and symptoms: dyspnea, fatigue, and pseudoangina. Advanced stages of the disease are characterized by respiratory distress syndrome, cyanosis, right ventricular hypertrophy, decompensated cor pulmonale, end non-embolic pulmonary thrombosis. Treatment is of the underlying disease, vasodilators for group 1 type, or lung transplant.
Two interstitial lung disorders and a set of disorders associated with vasculitis can cause pulmonary hemorrhage and hence are named pulmonary hemorrhage syndromes.
Autoantibodies against the noncollagenous domain of the α3 chain of collagen IV results in inflammatory destruction of basement membrane of the renal glomeruli and pulmonary alveoli causing rapidly progressive glomerulonerphritis and necrotizing hemorrhagic interstitial pneumonitis. Though the disease is rare it most often affects adolescents and those in the second decade of life.
Pathogenesis. The disease is described in greater detail in Chapter 20: The kidney ). It is presumed to be due to environmental exposure: viral infection, hydrocarbon solvents, or inhaled tobacco smoke. HLA subtypes HLA-DRB 1501 and 1502 are a marker for predisposition.
Clinical features. The classic clinical case begins with hemoptysis and radiographs of focal pulmonary consolidations before signs and symptoms of glomerulonephritis and rapidly progressive renal failure—death is usually due to uremia. The disease can be well treated and managed with plasmapheresis to remove circulating anti-basement membrane antibodies.
Evident from its name, idiopathic pulmonary hemosiderosis is a disorder of unknown etiology that causes intermittent, diffuse alveolar hemorrhage. The disease is characterized insidious progression of a productive cough, hemoptysis, and anemia. The presentation in the lungs is similar to that of goodpasture syndrome but lacks anti-basement membrane antibodies and involvement of the kidneys.
The fact that the individuals seem to develop additional autoimmune disorders and that idiopathic pulmonary hemosiderosis can be managed by long term immunosuppression combined with prednisone or azathioprine suggests and immunologic etiology,
Polyangiitis with granulomatosis is an autoimmune disorder that affects the upper respirtory tact and lungs. A transbronchial biopsy is usually needed for a positive diagnosis capillaritis and scatter poorly formed granulomas. See chapter 11 for more discussion.