Tissue fluid, volume

In 1971, Hiatt et al. found that polyethylene oxide (PEO) of molecular weight about 100000 prevented the adsorption of rabies virus to porous glass with an average pore diameter of 1250 A. The support was modified by passage of one void volume of 0.4% solution of the polymer in water, followed by 5 or more volumes of distilled water or buffered salt solution. The virus was effectively purified from the admixtures of brain tissue fluid by means of size-exclusion chromatography on the modified glass column [28]. 

A common practice is to fix tissues in a small volume of fluid, much to the detriment of quality. If the fluid volume of the fixative is not adequate, water from the specimen will reduce its concentration sufficiently to slow diffusion. A ratio of 20 1 in the volume of fixative to the volume of the specimen will prevent that from happening. 

Some physiological volumes are known or have been estimated. Over two decades ago, Oie and Tozer proposed a relationship between the volume of distribution of a drug and its extent of plasma and tissue binding, using various fixed values for plasma and extracellular fluid volumes [1], This equation has been utilized in some methods used for prediction of steady-state VD, which will be discussed later ... 

Hypertension is a well known contributor to a number of diseases, but hypotension can be equally dangerous as tissues rely upon pressure to maintain a constant delivery of nutrients via the micro-circulation of fluid around individual cells. As pressure and volume are interdependent, blood pressure is controlled by either changing the internal diameter of the vessels (vasoconstriction or vasodilation) or by increasing the fluid volume contained within the vasculature. 

Reabsorption of water is a fundamental function of the kidney because loss of fluid volume and reduction in blood pressure (hypotension) would have devastating consequences on all other tissues, possibly leading to severe metabolic disruption or even death. Blood pressure is monitored by the kidney and regulated by secretion of a proteolytic enzyme called renin, which initiates a cascade involving angiotensin and aldosterone to restore blood volume. 

Ehrhardt C, Kneuer C, Fiegel J, Hanes J, Schaefer UF, Kim KJ, Lehr CM (2002) Influence of apical fluid volume on the development of functional intercellular junctions in the human epithelial cell line 16HBE14o- Implications for the use of this cell line as an in vitro model for bronchial drug absorption studies. Cell Tissue Res 308(3) 391-400. 

Mobilization of edemas (A) In edema there is swelling of tissues due to accumulation of fluid, chiefly in the extracellular (interstitial) space. When a diuretic is given, increased renal excretion of Na and H2O causes a reduction in plasma volume with hemoconcentra-tion. As a result, plasma protein concentration rises along with oncotic pressure. As the latter operates to attract water, fluid will shift from interstitium into the capillary bed. The fluid content of tissues thus falls and the edemas recede. The decrease in plasma volume and interstitial volume means a diminution of the extracellular fluid volume (EFV). Depending on the condition, use is made of thiazides, loop diuretics, aldosterone antagonists, and osmotic diuretics. 

In the Hornsey (1956) procedure, the sample was minced thoroughly, and a 10 g sample was mixed in a tall beaker (to prevent undue evaporation) with 10 ml of a solution of 40 ml acetone and 3 ml water. Total fluid volume was 50 ml, including the 7 ml water in the sample. This procedure was preferred over dilution of sample to 50 ml final volume, since calculations were simplified and correction for the volume of insoluble meat tissues was avoided. Later workers have modified the procedure, using smaller samples and less solvent. Pearson and Tauber (1984) used a 2 g sample and capped test tubes to prevent acetone evaporation, and Carpenter and Clark (1995) used 5 g samples. 

Diffusion in the interstitial space is closely related to the volume fraction of space that is available to fluid and solute transport in tissues. The volume fraction of tumor interstitial fluid space varies from 15% in human gliomas up to 60% in a rat fibrosarcoma 4956 (Jain, 1987). The available volume fraction (KAV) of solutes is a measure of the steady state ratio of drag concentrations between tissues and the plasma (Krol et al., 1999). Thus, drug and gene delivery can be significantly improved through increasing KAV. In ex vivo experiments, KAV determines the ratio of concentrations between tissues and external solutions at the equilibrium state. KAV has been studied extensively in normal tissues but poorly in tumor tissues (Table 20.1) (Krol el al., 1999). KAV depends on the size of solutes and the dependence is determined by both the size and the connectedness of pores (Yuan et al., 2001). 

It has also been suggested that certain diuretics such as spironolactone (Aldactone) might be especially helpful in heart failure.14,42 Spironolactone blocks aldosterone receptors in the kidneys and other tissues, thereby producing a diuretic effect as well as preventing adverse cardiovascular changes associated with excess aldosterone production. Future studies will help clarify whether spironolactone should be used preferentially in heart failure because of its ability to reduce fluid volume and protect against aldosterone-induced damage.53... 

The one-compartment model of distribution assumes that an administered drug is homogeneously distributed throughout the tissue fluids of the body. For instance, ethyl alcohol distributes uniformly throughout the body, and therefore any body fluid may be used to assess its concentration. The two-compartment model of distribution involves two or multiple central or peripheral compartments. The central compartment includes the blood and extracellular fluid volumes of the highly perfused organs (i.e., the brain, heart, liver, and kidney, which receive three fourths of the cardiac output) the peripheral compartment consists of relatively less perfused tissues such as muscle, skin, and fat deposits. When distributive equilibrium has occurred completely, the concentration of drug in the body will be uniform. 

Drugs that show extensive tissue binding are said to have an apparent volume of distribution many times the total body size. For example, digoxin (see Chapter 35), which binds to plasma protein to the extent of 23%, has an apparent volume of distribution of 8 1/kg. The volume of distribution of drugs that do not bind to plasma or tissue proteins varies between the extracellular fluid volume (16 liters) and the total body water (42 liters). Insulin, sodium, and iodine are confined to the extracellular water, whereas caffeine and ethanol are distributed in the total body water. 

Therefore, Vd is the apparent fluid volume, usually expressed in milliliters or liters, in which the drug is dissolved. Values of Vd compatible with the known volume of a body compartment may suggest that the drug is confined to that compartment. Values of Vd greater than the total body volume of water indicate that the drug is concentrated in a tissue compartment. 

Metal Matrix Concentrations in tissues/fluids /imol l 1 Reference Therapeutic levels levels ETA-AAS sensitivity (Pg/0.0044 A) Volume required for analysisb (pl/0.0044 A)... 

Because of its powerful action in the kidney, torasemide can rapidly deplete extracellular fluid volume and mobilize tissue oedema, particularly from the lung. This both improves the patient s breathing and improves their ability to exercise. 

The term oedema (ro oihruta = the swelling) describes an increase in the extracellular fluid volume as a result of isotonic hyperhydration. Oedema is a symptom with multiple causes, yet not an illness. The term anasarca refers to a massive, generalized soaking of the subcutaneous tissue ( tissue dropsy ), (s. fig. 16.2)... 

Ca2+) from EDTA in accordance with its 107-fold greater affinity for the chelate. Free lead ions are removed from the blood and tissues (directly from bone and indirectly from parenchymatous organs) as the soluble lead chelate formed is rapidly excreted by glomerular filtration. Because of its ionic character, it is unlikely that CaNa2EDTA significantly penetrates cells the apparent volume of distribution is numerically similar to the extracellular fluid volume. 

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