Interstitial compartment

Inflammation. Figure 1 Sequence of events in the recruitment of leukocytes in postcapillary venules adjacent to injured tissue. At the site of lesion, diverse reactive substances stimulate the endothelium to produce inflammatory cytokines, chemoattractants and other inflammatory mediators. The cytokine-activated endothelium expresses adhesion molecules that lead to the low affinity interactions between leukocytes and endothelium, which is mediated by selectins and described as rolling. Subsequently integrins mediate the firm adhesion of leukocytes, which allows emigration of the cells from venules into the interstitial compartment. Activated mast cells, PMNs and macrophages secrete cytokines (TNFa), lipid mediators (LTB4) and other inflammatory players (histamine, NO). 

This compartment contains about one-third of total body water and is distributed between the plasma and interstitial compartments. The extracellular fluid is a delivery system. It brings to the cells nutrients (eg, glucose, fatty acids, amino acids), oxygen, various ions and trace minerals, and a variety of regulatory molecules (hormones) that coordinate the functions of widely separated cells. Extracellular fluid removes COj, waste... 

Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are members of a family of so-called natriuretic peptides, synthesized predominantly in the cardiac atrium, ventricle, and vascular endothelial cells, respectively (G13, Y2). ANP is a 28-amino-acid polypeptide hormone released into the circulation in response to atrial stretch (L3). ANP acts (Fig. 8) on the kidney to increase sodium excretion and glomerular filtration rate (GFR), to antagonize renal vasoconstriction, and to inhibit renin secretion (Ml). In the cardiovascular system, ANP antagonizes vasoconstriction and shifts fluid from the intravascular to the interstitial compartment (G14). In the adrenal cortex, ANP is a powerful inhibitor of aldosterone synthesis (E6, N3). At the hypothalamic level, ANP inhibits vasopressin secretion (S3). It has been shown that some of the effects of ANP are mediated via a newly discovered hormone, called adreno-medullin, controlling fluid and electrolyte homeostasis (S8). The diuretic and blood pressure-lowering effect of ANP may be partially due to adrenomedullin (V5). 

Butler, T.P., Grantham, F.H. and Gullino, P.M. (1975) Bulk transfer of fluid in the interstitial compartment of mammary tumours. Cancer Res., 35, 3084-3088. 

Alpha 1- antitrypsin (alA) Treatment of alA deficiency Sheep Aerosol Aerosolized alA able to pass through alveolar epithelium and gain access to interstitial compartment of lung [107]... 

Two-photon microscopy can be utilized to quantify microvascular flow rates within the kidney. Infusion of a nonfilterable intravenous fluorescent dye results in intravascular cells appearing as dark objects. Endothelial cell dysfunction within the microvasculature can be observed and quantified using the infusion of variously sized, differently colored dextrans or proteins. Movement of these molecules out of the microvasculature and accumulation within the interstitial compartment are readily observed during injury or disease. 

Plasma proteins are polyionic at pH 7.4 and cannot diffuse across membranes. The normal difference in concentrations of diffusible ions between the plasma and interstitial compartments is due to the presence of nondiffusible protein in plasma, shown in Table 1-5. 

Movements of water are due mainly to osmosis and filtration. In osmosis, water moves to the area of highest solute concentration. Thus, active movement of salts into an area creates a concentration gradient down which water flows passively. In filtration, hydrostatie pressure in arterial blood moves water and nonprotein solutes through specialized membranes to produce an almost protein-free filtrate This process occurs in formation of the renal glomerular filtrate. Filtration also accounts for movement of water from the vascular space into the interstitial compartment, which is opposed by the osmotic (oncotic) pressure of plasma proteins. 

Based on the administration of 1 L of each solution which may not be an appropriate amount for clinical use) numbers are approximations arrows indicate direction of fluid shift and plus signs Indicate fluid retention In that compartment. After distribution, 60% of albumin (and associated fluid) Is In Interstitial compartment and 40% Is In Intravascular compartment. 

It will also be appreciated that as fluid begins to leak from capillaries the pressure in the interstitial compartment rises rapidly and this will oppose the fluid leakage. 

Two major observations made during the low dose studies and post-treatment recovery, are that aminoglycosides induce (a) a dramatic increase in tubular cell turnover, and, (b) a marked prohferation in the cortical interstitial compartment [98,129]. The first phe-... 

Hyponatraemia due to water overload without a decrease in total body sodium is the commonest biochemical disturbance encountered in clinical practice. Further consideration of hyponatraemia of this type, and its treatment, depends on whether the patient has oedema or not. Oedema is an accumulation of fluid in the interstitial compartment. It is readily diag-iK)sed by looking for pitting in the lower extremities of ambulant patients (Fig. 3) or in the sacral area of recumbent patients. 

If the organ is reasonably well perfused (i.e., the flow-limited conditions are not satisfied), the full physiological pharmacokinetic treatment may be reduced by assuming the organ is membrane limited. Here, the limitation on transport is assumed to occur at either the capillary membrane separating the vascular and interstitial compartments or the plasma membranes separating the interstitial and intracellular compartments. For example, when the net flux between the interstitial and intracellular compartments is much slower than the net flux between the vascular and interstitial compartments and the plasma flow rate, the three-compartment model can be reduced to a two-compartment model ... 

About one liter of fluid per hour can be removed by ultraliltration hemodialysis and about 300 ml/hr by peritoneal dialysis using hypertonic dialysate. Such a rate of fluid removal from the intravascular space may be faster than the rate at which fluid can be replaced from the interstitial compartment, and hypotension may develop. Symptoms of hypotension may include seizures which, although actually due to cerebrovascular insufficiency, may be mistaken for DDS, particularly in diabetic subjects. 

Each of these methods samples only cells and soluble inflammatory products in the airspaces. Cells in the vascular and interstitial compartments are not recoverable, and there has been debate about whether adherence characteristics of air space cells modify cellular recovery. Neither method is likely to recover proteins that precipitate in the airspaces, and neither can sample precisely inflammatory products such as chemokines that bind to glycosaminoglycans and other structures in the lungs. Nevertheless, the measurements of cell populations and inflammatory products in BAL and edema fluid provide an estimate of the amounts that are actually present in the air space compartment of the lungs. The inability to accurately sample the total concentrations of specific inflammatory products in the lungs may account for some of the variability seen in clinical studies, and some of the difficulties that have been encountered in correlating BAL and edema fluid findings with clinical variables. 

The interstitial compartment of solid tumors is signfi-cantly different from that of most normal tissues (Vaupel and Mueller-Klieser 1983). In general, the tumor interstitial space is characterized by... 

Exported H -ions from the intracellular space to the interstitial compartment promote extracellular acidification. The latter, together with a HIF-la-induced upreg-ulation of the membrane-bound ectoenzyme carbonic anhydrase (CA IX), finally leads to buffering of the exported protons by extracellular bicarbonate causing a bicarbonate depletion and an intensified CO2 release, both characteric features of the tumor pathophysiome (Fig. 4.22) (Gulling etal. 1965 Gulling 1970, 1975 Vaupel 2008). 

As already outhned in Chap. 4, the interstitial compartment of tumors is significantly different from that of normal tissues. As a result of (a) vessel leakiness, (b) lack of functional lymphatics, (c) interstitial fibrosis and (d) contraction of the interstitial matrix mediated by stromal fibroblasts, most solid tumors have an... 

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