There are several points that show the unique character of pulmonary circulation:
All the blood in the body passes via the pulmonary artery to the pulmonary capillary bed The chest cavity is usually at a negative pressure The pulmonary capillary is very small (smaller than erythrocytes: diameter is less than 8 m The pulmonary circulation is at a lower pressure than systemic circulation (normal mean pulmonary artery pressure is 9 to 16mmHg) The alveolar macrophage stimulates pulmonary endothelial cells
The pulmonary endothelial cells are easily activated because of endotoxin or bacterial stimulation from the airways Pulmonary vascular blood is provided from two sources: the pulmonary artery and bronchial arteries, a branch of the systemic arterial system
Because of these unique circulation systems, the lung easily becomes a target organ for systemic inflammation. Endotoxins or bacteria stimulate pulmonary endothelial cells to express adhesion molecules such as P-and E-selectin and intercellular adhesion molecule-1 (ICAM-1). Since the neutrophils are also activated to express those ligands such as P-selectin glycoprotein ligand-1 (PSGL-1), CD11b/ CD18, or L-selectin, activated neutrophils accumulate in the lung. Activated neutrophils starts rolling and sticking on the surfaces of endothelial cells. While the neutrophils are rolling, they release neutrophil elastase and reactive oxygen species (ROS). Those inflammatory mediators injure the endothelial cells and the vascular permeability increases. The changes in pulmonary microvascular permeability may result in interstitial edema as well as alveolar flooding, leading to serious problems with gas exchange.
There is another mechanism of neutrophil accumulation to the lung: the adhesion molecule-independent accumulation. When the neutrophils are activated by cytokines or platelet activating factor, intracellular calcium levels markedly increase via G protein-coupled receptors, serine/ threonine kinase, Akt, and phosphatidylinositol 3-kinases (PI3), which results in F-actin activation. As a consequence, cell deformability decreases significantly. Since the diameter of the neutrophil (approximately 12 m) is greater than that of the pulmonary capillary, the stiffened neutrophils are stopped in the pulmonary microcirculation. This is an adhesion molecule-independent white cell accumulation in the lung, and it also causes lung injury because of perfusion disturbances.
Selectins may play a role in this process of neutrophil activation as well as cellular adhesion. We have reported that some activated neutrophils escape from the lung into aortic blood following acute lung injury induced by smoke inhalation. Activation of these cells was prevented by treatment with an antibody to L-selectin.
Activation of Akt/PI3 also inhibits neutrophil apoptosis by increasing transcription of the anti-apoptotic proteins Mcl-1 and Bcl-2, and also inhibiting caspase-9, a cell death protein. Without apoptosis the life of the neutrophils is prolonged, thus increasing the duration of the inflammatory process.
In terms of bronchial circulation, the adherence process may play a more important role since these systemic capillaries are larger and there is a better defined venular area. During the passage of neutrophils through this systemic circuit, they may become activated and the cells then pass on into bronchial venous drainage to lodge in the pulmonary microvasculature.
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.