Intercellular sealing

Numerous variations in the microvasculature bed (i.e., arterioles, capillaries, and venules) exist, which can affect permeability. For example, venular portions of the capillaries have thin endothelial cells (170 nm), with frequent interendothelial discontinuities. The gap in about 30% venular junctions is about 6 nm. Arterioles, in contrast, have endothelial cells that are linked by the tight junctions and communicating junctions, whereas the capillary endothelium contains only occluding junctions. Communicating gaps are small and rare in muscular venules and are absent in capillaries and pericytic venules. Endothelial cells in capillaries have more vesicles than those in arterioles (1000/pm vs. 190/pm ). The intercellular sealing is strong in arterioles, weU developed in capillaries, and particularly loose in venules. Furthermore, capillaries and venules have more transendothelial channels. 

The hepatocyte secretes biliary fluid into the bile canaliculi (dark green), tubular intercellular clefts that are sealed off from the blood spaces by tight junctions. Secretory activity in the hepatocytes results in movement of fluid towards the canalicular space (A). The hepatocyte has an abundance of enzymes carrying out metabolic functions. These are localized in part in mitochondria, in part on the membranes of the rough (rER) or smooth (sER) endoplasmic reticulum. 

Major differences between a general (nonneural) and brain capillary. In the brain capillary, the Intercellular clefts are sealed shut by tight Junctions. There are also reduced pinocytosis and no fenestrae. Exchange of compounds between the circulation and the brain must take place in the cells of the capillary wall, the major barriers of which are the inner and outer plasma membranes of the capillary endothelial cells. (Reprinted with permission from Oldendorf WA. Permeability of the blood-brain barrier. In Tower DB [ed.]. The Nervous System. Vol. 1 New York Raven, 1975.)... 

With sublingual or buccal application, the drug encounters the nonkeratinized, multilayered squamous epithelium of the oral mucosa. Here, the cells establish punctate contacts with each other in the form of des-mosomes (not shown) however, these do not seal the intercellular clefts. Instead, the cells have the property of sequestering polar lipids that assemble into layers within the extracellular space (semicircular inset, center right). In this manner, a continuous phospholipid barrier arises also inside squamous epithelia, although at an extracellular location, unlike that of intestinal epithelia. A similar barrier principle operates in the multilayered keratinized squamous epithelium of the skin. 

Active spread of microorganisms through normal subepithelial tissues is difficult in that the gel-like nature of the intercellular materials physically inhibits bacterial movement. Induced death and lysis of the tissue cells produces, in addition, a highly viscous fluid, partly due to undenatured DNA. Physical damage, such as wounds, rapidly seal with fibrin... 

Towards the end of the last century, Ehrlich injected the dye trypan blue intravenously and found that it entered all tissue except the central nervous system. Conversely, when he injected this dye into the cerebrospinal fluid, the brain was stained rapidly, but none of the dye entered the bloodstream. Diffusion of drugs from the blood to the brain is more restrictive than elsewhere. This barrier (known as the blood-brain barrier) is capillary endothelium in which intercellular clefts are more tightly sealed and the cell overlap is tighter than in other parts of the body (Rapo-port, 1976). This barrier is unusually permeable to lipids, but particularly impermeable to ions. When the barrier membranes are inflamed, however, a wider range of substances can pass through. 

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