Alveolar capillaries, endothelium

The Endothelium and Lymphatics The capillary endothelial surface of the lung is the largest in the body [131]. The alveolar-capillary endothelium has... 

More specifically, the blood-gas interface consists of the alveolar epithelium, capillary endothelium, and interstitium. The alveolar wall is made up of a single layer of flattened type I alveolar cells. The capillaries surrounding the alveoli also consist of a single layer of cells — endothelial cells. In between the alveolar epithelium and capillary endothelium is a very small amount of interstitium. Taken together, only 0.5 pm separates the air in the alveoli from the blood in the capillaries. The extreme thinness of the blood-gas interface further facilitates gas exchange by way of diffusion. 

Figure 11.1 Ultrastructure of the human lung alveolar barrier. The tissue specimen is obtained via lung resection surgery. (A) Section through a septal wall of an alveolus. The wall is lined by a thin cellular layer formed by alveolar epithelial type I cells (ATI). Connective tissues (ct) separate ATI cells from the capillary endothelium (en) within which an erythrocyte (er) and granulocyte (gc) can be seen. The minimal distance between the alveolar airspace (ai) and erythrocyte is about 800-900 nm. The endothelial nucleus is denoted as n. (B) Details of the lung alveolar epithelial and endothelial barriers. Numerous caveolae (arrows) are seen in the apical and basal plasma membranes of an ATI cell as well as endothelial cell (en) membranes. Caveolae may partake transport of some solutes (e.g., albumin). (C) ATII cells (ATII) are often localised in the comers of alveoli where septal walls branch off. (D) ATII cells are characterised by numerous multilamellar bodies (mlb) which contain components of surfactant. A mitochondrion is denoted as mi.

Barriers to pulmonary absorption of proteins and peptides include respiratory mucus, mucociliary clearance, pulmonary enzymes/proteases, alveolar lining layer, alveolar epithelium, basement membrane, macrophages and other cells [3, 18]. The molecular weight cutoff of tight junctions for alveolar type I cells is 0.6 nm, while endothelial junctions allow the passage of larger molecules (4-6 nm). In order to reach the bloodstream in the endothelial vasculature, proteins and peptides must cross this alveolar epithelium, the capillary endothelium, and the intervening extracellular matrix. 

Once a drug aerosol has made its way through the conducting airways to deposit in the deep lung, the major barriers to entering the body are the 0.15 pm layer of type I alveolar cells that are covered by a very thin layer of epithelial lining fluid consisting mainly of surfactant and the relatively permeable endothelium of the alveolar capillaries. Alveolar cells have so called... 

In the separation of alveolar air space and blood circulation, the alveolar epithelium is a more restrictive paracellular barrier than the capillary endothelium. About one-third of the alveolar epithelial cells are type I cells, but these cells make up approximately 95% of the cellular surface area. The remaining two-thirds of the alveolar epithelial cells that comprise the remaining 5% of the cellular surface area are the surfactant-producing cuboidal type II cells.43,45,52 Type I cells have thin cytoplasmic extensions and exhibit a large number of plasmalemmal invaginations called caveolae, which may play a role in macromolecular and protein transport across the blood-air barrier of the lung.44,45,58,59... 

Activated neutrophils and platelets adhere to the pulmonary capillary endothelium, initiating multiple inflammatory cascades with a release a variety of toxic substances. There is diffuse pulmonary endothelial cell injury, increased capillary permeability, and alveolar epithelial cell injury. Consequently, interstitial pulmonary edema occurs and gradually progresses to alveolar flooding and collapse. The end result is loss of functional alveolar volume, impaired pulmonary compliance, and profound hypoxemia. ... 

The diffusing capacity of the lung for carbon monoxide (CO) is a measure of the ability of the alveolar capillary membrane to transfer or conduct gases from the alveoli to the blood. This transport process is entirely a passive one brought about by diffusion. As described previously in Section 2.2, the barriers for diffusion consist of surfactant, alveolar epithelium, interstitital fluid, capillary endothelium, plasma, and the red blood cell membrane. 

When a person is exposed to a volatile organic solvent through inhalation, the solvent vapor diffuses very rapidly torough the alveolar membranes, fire connective tissues and the capillary endothelium and into fire red blood cells or plasma. With respiratory gases the whole process takes less than 0.3 seconds. This results in almost instantaneous equilibration between the concentration in alveolar air and in blood and, flierefore, the ratio of the solvent concentration in pulmonary blood to that in alveolar air should be approximately equal to the partition coefficient. As the exposure continues, the solvent concentration in the arterial blood exceeds that in the mixed venous blood. The partial pressures in alveolar air, arterial blood, venous blood and body tissues reach equilibrium at steady state. When the exposure stops, any unmetabolized solvent vapors are removed from the systemic circulation through pulmonary clearance. During that period the concentration in fire arterial blood is lower than in the mixed venous blood and the solvent concentration in alveolar air will depend on the pulmonary ventilation, the blood flow, the solubifity in blood and the concentration in the... 

Fig. 1. Sites of injury in the lungs of patients with ARDS. The capillary endothelium and the pulmonary alveolar epithelium are separate sites of injury, and the mechanisms of injury differ. PMNs migrate through each of these barriers as they enter the alveolar spaces.

Lymphocytes, monocytes, and platelets were frequently seen in the lumina of alveolar capillaries in specimens with alveolitis compared with nonalveolitis specimens (P <0.005). Adhesion between lymphocytes and monocytes and endothelium was frequently observed. Adhesion between infiltrating cells and endothelium was seen in 80% of specimens with alveolitis and in 43 % of specimens without alveohtis (Takemura et al. 1995). 

FIGURE 1. A transmission electron micrograph of lung tissue illustrating attenuated type 1 pneu-mocytes (arrowheads), type II pneumocyte (arrow), and a pulmonary alveolar macrophage (PAM), a = alveolus c = capillary asterisk = platelet double arrowheads = capillary endothelium. The blood-air barrier consists of the type I pneumocyte, capillary endothelium, and the basement membrane separating these two cells. 

In summary, IPF is a complex disorder that appears to occur in response to repetitive injury within the alveolar space that involves both inflammatory and noninflammatory components (Fig. 2). The AFC and adjacent endothelium are the major cells affected and initiate the release of cytokines followed by an intense immune response, which exacerbates alveolar-capillary BM damage. Without a normal BM, cellular communication (leukocyte to nonleukocyte) is altered, driving lung remodeling toward fibrosis. 

Three the alveolar epithelium, alveolar macrophages, and capillary endothelium... 

The epithelial Uning fluid of the lung is separated by the nonfenestrated capillary endothelium on one side and alveolar membrane on the other both are permeable to lipid-soluble antibiotics such as macrolides, quinolones, clindamycin, and trimethoprim-sulfamethoxazole, but relatively impermeable to water-soluble agents such as the aminoglycosides and P-lactams. However, the contribution of antibiotic transport of the water-soluble agents by polymor-... 

Capillary endothelial cells comprise 30-42% of cells in the alveolar region and comprise the walls of the extensive network of blood capillaries in the lung parenchyma. The endothelium forms a continuous, attenuated cell layer that transports respiratory gases, water, and solutes. However, it also forms a barrier to the leakage of excess water and macromolecules into the pulmonary interstitial space. Pulmonary endothelial cells, like type I cells, are vulnerable to injury from inhaled substances and substances in the systemic circulation. Injury to the endothelium results in fluid and protein leakage into the pulmonary interstitium and alveolar spaces, resulting in pulmonary edema. 

---