Blood capillaries endothelium

The structure of the blood capillary wall is complex and varies in different organs and tissues. It consists of a single layer of endothelial cells joined together by intercellular junctions. Each endothelial cell, on an average, is 20-40 pm long, 10-15 pm wide, and 0.1-0.5 pm thick, and contains 10,000-15,000 uniform, spherical vesicles called plasmalemmal vesicles. These vesicles range in size between 60 and 80 nm in diameter. About 70% of these vesicles open on the luminal side of the endothelial surface, and the remaining open within the cytoplasm. Plasmalemmal vesicles are believed to be involved in the pinocytic transport of substances across the endothelium. The transition time of pinocytic vesicles across the cell is... 

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. 

Lipoprotein (LPLase) is required for the metabolism of both chylomicrons and VLDL. This enzyme is induced by insulin and transported to the luminal surface of capillary endothelium where it is in direct contact with the blood. Lipoprotein lipase hydrolyzes the fiitty adds from triglycerides carried by ch)4oinicrons and VLDL and is activated by apoC-II. 

ICAM-1 An adhesion protein of the capillary endothelium. Its synthesis is increased following stimulation by TNF-a. It is related in the blood and CSF as soluble ICAM-1 (sICAM-1). The brain capillaries are rich in ICAM-1, and even a single lesion visible by magnetic resonance imaging results in elevated serum concentrations. 

Because the underlying problem in Parkinson disease is a deficiency of dopamine in the basal ganglia, simple substitution of this chemical would seem to be a logical course of action. However, dopamine does not cross the blood-brain barrier. Administration of dopamine either orally or parenterally will therefore be ineffective because it will be unable to cross from the systemic circulation into the brain where it is needed. Fortunately, the immediate precursor to dopamine, dihydroxyphenylalanine (dopa Fig. 10-2), crosses the blood-brain barrier quite readily. Dopa, or more specifically levodopa (the L-isomer of dopa), is able to cross the brain capillary endothelium through... 

G. E Made. Transport in quanta across the endothelium of blood capillaries. Anat Rec. 756 254(1960). 

The distribution of drugs depends on both the physicochemical properties of the drug molecules and the composition of tissue membranes. These factors can either result in a uniform or uneven distribution of dmgs into the various body compartments and fluids. In the extreme, distribution may tend toward an accumulation of drugs in particular tissues or to an almost complete exclusion of the drag from a particular compartment in a defined length of time. One unique compartment that has to be considered in this respect is the brain, which is separated from the capillary system of the blood by the blood-brain barrier, whose membrane has a special structure. It consists of a cerebral capillary network formed by a capillary endothelium that consists of a cell layer with continuous compact intercellular junctions. It has no pores, but special cells, astrocytes, which support the stability of the tissues, are situated at the bases of the endothelial membrane separating the brain and CSF from the blood. The astrocytes form an envelope around the capillaries. 

Similar to the ocular route, CNS delivery is concerned with localized drag delivery, in this case to the central nervous system, rather than achieving the systemic delivery of a drag. The primary challenge here is to penetrate the permeability barrier comprising the brain capillary endothelium, known as the Blood-Brain-Barrier (BBB). Various methods are under investigation, as described in Chapter 13. 

Figure 5.1 Schematic illustration of the structure of the wall of different classes of blood capillaries. (1) Continuous capillary (as found in the general circulation). The endothelium is continuous with tight junctions between adjacent endothelial cells. The subendothehal basement membrane is also continuous. (2) Fenestrated capillary (as found in exocrine glands and the pancreas). The endothelium exhibits a series of fenestrae which are sealed by a membranous diaphragm. The subendothehal basement membrane is continuous. (3) Discontinuous (sinusoidal) capillary (as found in the liver, spleen and bone marrow). The overlying endothelium contains numerous gaps of varying size. The subendothehal basement is either absent (hver) or present as a fragmented interrupted structure (spleen, bone marrow)...

Blood capillaries in the brain are structurally different from the blood capillaries in other tissues these structural differences result in a permeability barrier between the blood within brain capillaries and the extracellular fluid in brain tissue. This permeability barrier, comprising the brain capillary endothelium, is known as the Blood-Brain Barrier (BBB). 

The brain capillary endothelium comprises the lumenal and ablumenal membranes of capillaries, which are separated by approximately 300 ran of endothelial cytoplasm (Figure 13.2). The structural differences between brain capillary endothelium and non-brain capillary endothelium are associated with the endothelial tight junctions. The non-brain capillaries have fenestrations (openings) between the endothelial cells through which solutes can move readily via passive diffusion. In brain capillaries, the endothelium has epithelial-like tight junctions which preclude movement via paracellular diffusion pathways. There is also minimal pinocytosis across brain capillary endothelim, which further limits transport of moieties from blood to brain. 

Biodistribution of plasmid to either extracellular or intracellular targets is dependent on the structure of capillary walls, (patho)physiological conditions, the rate of blood and lymph supply, the physicochemical properties of plasmid and its carrier molecules. The fate of plasmid after in vivo administration is illustrated in Figure 14.4. The blood capillary walls are comprised of four layers, namely plasma-endothelial interface, endothelium, basal lamina, and adventia. Macromolecules can cross the endothelial barrier ... 

Consider two examples. First, in the brain capillary endothelium, luminal expression of the ATP-driven drug efflux pump, p-glycoprotein, provides a formidable barrier to drug penetration from blood to brain (Figure 15.2). This is best seen in... 

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. 

Figure 29.3. (A) Glomerular capillaries are positioned between two arterioles that regulate hydrostatic pressure and blood flow through the capillaries, thereby controlling glomerular filtration rate. (B) The glomerular basement membrane consists of three layers the capillary endothelium, the capillary basement membrane, and podocytes from epithelial cells of Bowman s capsule. The capillary basement membrane also contains three layers the lamina rara interna (blood side), lamina densa, and lamina rara externa (epithelial side). (From Guyton, A. C., and Hall, J. E. Textbook of Medical Physiology, 11th ed. Elsevier Saunders Company, Philadelphia, 2006. Reproduced with permission.)...

Transporters are critical in the function of capillary endothelium, where they contribute to the blood-brain, blood-germinal epithelium (blood-testis and blood-ovary), and blood-placental barriers. Endothelial cells in each of these tissues express high levels of MDR-1. The existence of a blood-brain barrier is well established and is thought to arise... 

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