Capillaries, permeability

The bioflavanoids (vitamin P complex) are substances which maintain the small blood vessel walls. The substances are widely distributed among plants, eg, all citms fmits, and have been used medicinally to decrease capillary permeability and fragility. 

Bradykinin is a nonapeptide enzymatically produced from kallidin in the blood, where it is a potent agent of arteriolar dilation and increased capillary permeability. 

The classical skin response to local release of histamine that results from contact with an allergen, irritant or following an insect bite. A central wheal develops as a direct result of local inflammation and the the oedema the follows the increased capillary permeability caused by histamine acting on HI-receptors on vascular-endothelial cells. 

In addition to the reports of uptake of intact small liposomes (SUV) by hepatocytes (Scherphof et al., 1983), there is some evidence of uptake of intravenously administered liposomes as intact structures by cells other than mononuclear phagocytes of the MPS. Recently, the integrity of the capillary endothelial barrier in several pathophysiological conditions was discussed (Bodor and Brewster, 1986). Several studies already indicated an increased capillary permeability during inflammation both in animals (Lopez-Berestein et al., 1984a) and in man (Morgan et al., 1985 Williams et al., 1987). 

As observed by Celus, a Roman physician during the first century A.D., the four cardinal signs characterize inflammation swelling, redness, heat, and pain. Swelling/edema occurs in response to the accumulation of fluids from damaged capillaries following injury. Increased fluid accumulation leads to increase capillary permeability. Histamine, produced and released by resident mast cells, also... 

Lipoxygenases catalyse the regio-specific and stereoselective oxygenation of unsaturated fatty acids. The mammalian enzymes have been detected in human platelets, lung, kidney, testes and white blood cells. The leukotrienes, derived from the enzymatic action of the enzyme on arachidonic acid, have effects on neutrophil migration and aggregation, release of lysosomal enzymes, capillary permeability, induction of pain and smooth muscle contraction (Salmon, 1986). 

The pathophysiologic mechanisms of portal hypertension and of cirrhosis itself are entwined with the mechanisms of ascites (Fig. 19-3). Cirrhotic changes and the subsequent decrease in synthetic function lead to a decrease in production of albumin (hypoalbuminemia). Albumin is the major intravascular protein involved in maintaining oncotic pressure in the vascular system low serum albumin levels and increased capillary permeability allow fluid to leak from the vascular space into body tissues. This can result in peripheral edema, ascites, and fluid in the pulmonary system. The obstruction of hepatic sinusoids and... 

Schnitzer JE. (1993). Update on the cellular and molecular basis of capillary permeability. Trends Cardiovasc Med 3 124-130. 

EM Renkin. Multiple pathway of capillary permeability. Circ Res 41 735-743, 1977. 

Increased capillary permeability may allow plasma proteins to leak into the interstitial spaces of a tissue. The presence of excess protein in these spaces causes an increase in interstitial fluid colloid osmotic pressure and pulls more fluid out of the capillaries. Mediators of inflammation such as histamine and bradykinin, which are active following tissue injury and during allergic reactions, increase capillary permeability and cause swelling. 

Histamine, which promotes bronchoconstriction as well as the vasodilation and increased capillary permeability that lead to inflammation... 

Figure 5. Continued. Phagocytosis is indicated by the release of the lysosomal enzyme, -glucuronidase. Increased alveolar/capillary permeability is indicated by the increase in protein in the lavage fluid. (Reproduced with permission from ref. 22. Copyright 1988 Academic.)...

The theoretical advantage of colloids is their prolonged intravascular retention time compared to crystalloid solutions. Isotonic crystalloid solutions have substantial interstitial distribution within minutes of IV administration, but colloids remain in the intravascular space for hours or days, depending on factors such as capillary permeability. However, even with intact capillary permeability, the colloid molecules eventually leak through capillary membranes. 

Symptom relief is caused in part by anticholinergic properties, which are responsible for the drying effect that reduces nasal, salivary, and lacrimal gland hypersecretion. Antihistamines antagonize increased capillary permeability, wheal-and-flare formation, and itching. 

The antiinflammatory mechanisms whereby corticosteroids exert their beneficial effect in COPD include reduction in capillary permeability to decrease mucus, inhibition of release of proteolytic enzymes from leukocytes, and inhibition of prostaglandins. 

The rate of absorption from an SC injection site may be retarded by immobilization of the limb, local cooling to cause vasoconstriction, or application of a tourniquet proximal to the injection site to block the superficial venous drainage and lymphatic flow. In small amounts, adrenergic stimulants, such as epinephrine, will constrict the local blood vessels and, therefore, slow systemic absorption. Conversely, cholinergic stimulants (such as methacholine) will induce very rapid systemic absorption subcutaneously. Other agents may also alter their own rate of absorption by affecting local blood supply or capillary permeability. 

Invasion of the tissues by an infective agent initiates an inflammatory response in the animal. This is non-specific and is mediated primarily by substances released from tissues that are damaged as a result of either trauma or the toxic effects of the infective agent. The major mediator is the vasoactive amine histamine, which causes an increased local blood flow and capillary permeability, resulting in local oedema. A major aspect of the inflammatory response is the involvement of large numbers of phagocytic cells, particularly the polymorphonuclear leucocytes. These are chemotactically attracted to the inflamed tissues and are mainly responsible for the elimination of particulate material. This often results in the destruction of many of these cells and the formation of pus. 

J. E. Schnitzer, P. Oh, E. Pinney, and J. Allard. Filipin-sensitive caveolae-mediated transport in endothelium reduced transcytosis, scavenger endocytosis, and capillary permeability of select macromolecules. J. Cell Biol. 127 1217-1232 (1994). 

Levitt, D.G., PKQuest capillary permeability limitation and plasma protein binding — application to human inulin, dicloxacillin and ceftriaxone pharmacokinetics, BMC Clin. Pharmacol., 2, 7,2002. 

Effects of different fractions obtained from LC after solvent partition of the crude extract on capillary permeability induced by acetic acid in mice are shown in Tables 8.1 and 8.2. 

An interesting report [54] of oxytetracycline levels in bronchial secretions has provided evidence that the drug often fails to reach therapeutic concentrations in sputum but that concurrent administration of bromhexine greatly increases its levels in such exudate. This property has been briefly alluded to above in connection with penetration of doxycycline into sinus secretions. The authors [54] attribute this higher antibiotic concentration in sputum to increased capillary permeability, without quoting authority. 

Leukotrienes increase capillary permeability and serve as chemotactic factors for neutrophil granulocytes. As "slow-reacting substances of anaphylaxis," they are involved in allergic reactions (p. 326) together with PG, they evoke the spectrum of characteristic inflammatory symptoms redness, heat, swelling, and pain. 

IgE-mediated allergic reactions (p. 72) involve mast cell release of histamine (p. 114) and production of other mediators (such as leukotrienes, p. 196). Resultant responses include relaxation of vascular smooth muscle, as evidenced locally by vasodilation (e.g., conjunctival congestion) or systemically by hypotension (as in anaphylactic shock) enhanced capillary permeability with transudation of fluid into tissues— swelling of conjunctiva and mucous membranes of the upper airways ( hay fever ), cutaneous wheal formation contraction of bronchial smooth muscle-bronchial asthma stimulation of intestinal smooth musde—diarrhea. 

---