Extravasation blood capillaries

Many diseases result from the dysfunction of cells located outside the cardiovascular system. Thus, for a drug to exert its therapeutic effects, it must exit from the central circulation and interact with its extravascular-extraceUular or extravascular-intracellular target(s). This process of transvascular exchange is called extravasation, and it is governed by the permeability of blood capillary walls. The main biological features that control permeability of capillaries include the structure of the capillary wall under normal... 

Fig. 3 Scanning electron microscope images of blood vessels in normal tissues and blood vessels of tnmor. Normal capillary of the pancreas (A), colon (intestinal villi) (B), and liver (sinusoid) (C), and enlarged image of blood capillary of normal liver (D) are shown. (E) Metastatic tumor nodule (area ) in the normal liver is shown. (F) Tumor vessels at capillary level (larger magnification) and showing rough surface, and early phase of extravasating vessels (shown by arrows). No leakage of polymer is seen in normal tissues (A-D), whereas tumor-selective extravasation of polymer (by EPR effect) is seen clearly in the tumor nodule (E)...

The clinical scenario and the severity of the volume abnormality dictate monitoring parameters during fluid replacement therapy. These may include a subjective sense of thirst, mental status, skin turgor, orthostatic vital signs, pulse rate, weight changes, blood chemistries, fluid input and output, central venous pressure, pulmonary capillary wedge pressure, and cardiac output. Fluid replacement requires particular caution in patient populations at risk of fluid overload, such as those with renal failure, cardiac failure, hepatic failure, or the elderly. Other complications of IV fluid therapy include infiltration, infection, phlebitis, thrombophlebitis, and extravasation. 

There are differences in the ease of extravasation of macromolecules from the bloodstream into different tissues [14, 104, 105]. Capillaries in the liver, spleen, and bone marrow have incomplete basal membranes and are lined with endothelial cells which are not continuously arranged. Capillaries in the muscle have a somewhat tighter arrangement, and there is an almost impermeable barrier which isolates the central nervous system from circulating blood. The rate of glomerular filtration of macromolecules depends on their hydrodynamic radius, the threshold being approx. 45 A [106]. Structure of the macromolecule is of utmost importance, since shape, flexibility, and charge influence the penetration and possible readsorption in the tubular epithelia [100]. 

Polymeric micelles. When water-soluble polymers are conjugated with lipophilic, poorly water-soluble polymers, the resulting copolymers are amphiphilic and can be used to constitute spherical micelles.54 The sizes of the polymeric micelles range between 10 and 100 nm, which is ideal for preferential extravasation at the fenestrated capillary blood vessels. The polymeric micelles have a hydrophobic core consisting of the... 

There is an increased blood flow in brain tumors (ref. 589), and the blood-brain barrier is leaky in and around 9L tumors because the blood vessels associated with these (ref. 568), and other (ref. 565-567), tumors are fenestrated. This well-known leakiness of tumor capillaries, which in the case of brain tumors includes breaches in the blood-brain barrier (ref. 566,568 cf. Section 12.2), would allow extravasation of small particulate matter (cf. ref. 590-594) or LCM. Once in the tumor area, LCM remain there because of an affinity for tumor cell surface components (cf. ref. 531 see also Chapter 14). At least 4 different types of experimental tumors in rats (C6 glioma, 9L gliosarcoma, Novikoff hepatoma, and Walker-256 carcinosarcoma), as well as several spontaneous tumors in dogs (ref. 570), do interact with LCM in a preferential manner (cf. Chapters 12 and 13), suggesting that LCM affinity may be for tumor cells in general (ref. 531). 

Continuous capillaries are found in the skin, all types of muscle, mesenteries, and the central nervous system (blood-brain barrier). These capillaries are characterized by tight junctions between the endothelial cells and an uninterrupted basement membrane. The restrictive capacity of the capillary walls barely allows extravasation of macromolecules into the parenchyma of these tissues. 

The arrest of tumor cells in the capillary bed of secondary organs and their subsequent extravasation occur through interactions with the local microvascular endothelium and the subendothelial matrix. The specificity of these interactions, depending on the heterogeneity of both microvascular endothelial cells (EC) and tumor cells, may favor in a selective way the initial adhesive events in preferred metastatic sites, and may consequently facilitate metastatic dissemination to those organs (Blood and Zetter, 1990 Pauli et al., 1990 Rusciano and Burger, 1992), similarly to what happens... 

CARDIOVASCULAR SYSTEM Histamine characteristically causes dilation of resistance vessels, an increase in capillary permeability, and an overall fall in systemic blood pressure. In some vascular beds, histamine wdl constrict veins, contributing to the extravasation of fluid and edema formation upstream of the capUlaries and postcapiUary venules. 

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