The sinusoids are unique exchange vessels composed of specialized nonparenchymal cells that exhibit structural and functional heterogeneity.
The structure of the sinusoid is illustrated in Figure 3. The endothelial cells are highly fenestrated and lack a supporting basal lamina. The fenestrae are organized in clusters known as sieve plates. As a result, there is continuity between the plasma in the sinusoid lumen and the perisinu-soidal space (of Disse). The sinusoidal endothelial cells contain numerous endosomes and scavenge a number of substances including breakdown products of connective tissue. They also are the source of several cytokines, eicosanoids, nitric oxide, and endothelins.
Stellate cells (fat-storing cells of Ito) lie external to the endothelium in the space of Disse. They are pericytes that frequently contain lipid droplets serving as storage sites for vitamin A. Multiple cytoplasmic projections of these cells surround and embrace the abluminal surfaces of the endothelial cells. When activated, these cells produce collagen and become contractile. As a result, they are thought to play a role in the regulation of sinusoidal blood flow.
Kupffer cells are attached to the luminal surfaces of the endothelium. These are highly phagocytic, specialized fixed
macrophages of the liver and contain numerous lysosomes and phagosomes. Kupffer cells are involved in a number of host defense mechanisms and immune functions and are the source of a number of cytokines, eicosanoids, free radicals, and nitric oxide.
The organization of the sinusoid network exhibits heterogeneity. Near portal venules and hepatic arterioles, sinusoids
are arranged in interconnecting polygonal networks; farther away from the portal venules the sinusoids become organized as parallel vessels that terminate in central venules (terminal hepatic venules). Short intersinusoidal sinusoids connect adjacent parallel sinusoids. Figure 4 is a microvas-cular cast illustrating these regional differences.
In the periportal area, the volume of liver occupied by sinusoids is greater than that surrounding central venules. However, because of the smaller size and anastomotic nature of the periportal sinusoids, the surface available for exchange in this area (surface/volume ratio) is greater than in centrilobular sinusoids. The size and pattern of distribution of endothelial fenestrae differs along the length of the sinusoid. At the portal end, the fenestrae are larger but comprise less of the endothelial surface area than they do in the pericentral region. The functional significance of these regional differences is unclear but relates to the functional metabolic heterogeneity that has been demonstrated for hepatocytes in different regions of the lobule. This, in turn, may depend on the recognized portal-to-central intralobular oxygen gradient and the unique microcirculation in the liver.
Morphologic Sites for Regulating the Hepatic Microcirculation
There are several potential morphological sites for regulating blood flow through the sinusoids. These include the various segments of the afferent portal venules and hepatic arterioles, the sinusoids themselves, and central and hepatic venules. These vessels contain several potentially contractile cells—smooth muscle cells in arterioles and venules, and in sinusoids, endothelial, stellate, and Kupffer cells.
Portal venules and central venules contain limited amounts of smooth muscle in their walls relative to their luminal size, but nevertheless are contractile and respond to pharmacologic agents. Hepatic arterioles are more responsive because of a complete investment of smooth muscle and relatively small lumens. The principal site of regulation of blood flow through the sinusoids, however, is thought to reside in the sinusoid itself, where the major blood pressure drop occurs in the liver.
The sinusoidal lining cells are responsive to a wide variety of pharmacodynamic substances. By contracting (or swelling), they may selectively reduce the patency of the sinusoid lumen, thereby altering the rate and distribution of blood flow. The relative roles of Kupffer versus endothelial cells in this process are not yet resolved, but both appear to be involved. The participation of perisinusoidal, stellate cells (fat-storing, Ito cells) in regulating sinusoidal diameter also has been reported. All three cell types contain filaments, tubules, and contractile proteins suggestive of contractile activity.
Because of these structures, blood flow through individual sinusoids is variable. At sites where the lumen is narrowed by the bulging, nuclear regions of sinusoidal lining cells, flow may be impeded by leukocytes that transiently plug the vessel and obstruct flow. Transient leukocyte plugging is more frequent in the periportal sinusoids, which are narrower and more tortuous than those in the centrilobular region. The more plastic erythrocytes usually flow easily through such sites unless the lumen is reduced to near zero. Some sinusoids, however, may act as thoroughfare channels and have relative constant rates of blood flow, while others have more intermittent flow. This may depend on not only the distribution of intrasinusoidal sphincter cells but also on the distribution of arterio-sinus twigs (AST) and the contribution of arterial blood flowing to individual sinusoids. For example, arterial blood flowing into an individual sinusoid through a dilated AST may increase the rate of sinusoidal blood flow. Because of the delivery of arterial blood at higher pressure, some arterial blood may even reverse the entry of portal blood into the sinusoids. As a result, the AST in concert with the initial segment of the sinusoid in which it terminates may form a "functional" arterio-portal anastomosis so that arterial blood is delivered into the portal venules. In the anesthetized, healthy animal, however, terminal branches of the hepatic arteriole containing flow are seen infrequently so that most blood delivered to the sinusoids is derived from the portal venules. Consistent with this is the in vivo microscopic observation that the velocity of flow in sinusoids and portal and central venules located near the capsule of the liver is not significantly altered by hepatic artery occlusion in healthy anesthetized rats. However, arterial inflow to the sinusoids may be more significant in regions near the hepatic hilum.
The frequency distribution of the wide variations in blood flow in the sinusoids exhibits a polymodal pattern composed of several Gaussian distributions. These wide variations in flow are due to the structural features previously described for sinusoids and also are due to intermittent arterial inflow into the sinusoids. Blood pressures in portal and central venules have been measured to be about 6 to
7cmH2O and 1.5 to 3.0cmH2O, respectively. Arterial blood enters the sinusoid at pressures ranging from 12 to
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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.