Renal system composition

The term clearance is used here in the sense of total body clearance and is analogous to the term renal clearance. The body as a whole is regarded as acting as a xenobiotic-eliminating system, where the rate of elimination divided by the average plasma concentration of the compound is the total body clearance. Here clearance is calculated (25) by dividing the administered dose of the substance by the area under the plasma concentrationtime curve produced by that dose. This pharmacokinetic parameter, as well as others presented in this publication, was calculated by the use of the MLAB on-line computer system established at the National Institutes of Health by Knott and Reece (26). Similar to t the total clearance is a composite of the individual clearances of the material by the various tissues of the body. 

Biological issues (i) Mg bioavailabihty, metabolism and physiology . (ii) Cell proliferation and differentiation , (iii) Animal husbandry. (iv) Magnesium in blood . (v) Genetic regulation , (vi) Mineral phase composition of bone and teeth . (vii) Brain and nervous system , (viii) Renal handling of magnesium . 

The other approach is indirect, namely, to measure not enzymes as such, but their physiological biochemical efficacy. This can be achieved by oral administration of a composite test substance, which is hydrolyzed ( digested ) into its components exclusively by a specific pancreatic enzyme and subsequently absorbed and eliminated by the renal or the respiratory system. Ideally, the urinary excretion/respiratory exhalation of a metabolite of the test substance is proportional to its hydrolysis in the small intestine, which in turn is directly dependent on the quantity of pancreatic enzymes present. 

The effects of CPH-treatment of rats (1200 mg/ kg/d for 3d) on the polypeptide composition of renal brush border from the proximal tubule cells enzymatic activities and transport systems of the brush border membrane vesicles (BBMV) were investigated [77]. The results of these studies showed that CPH-treatment induces a 20-30% decrease in the specific activities of renal brush border enzymes leucine aminopeptidase and D-glutamyltransferase. SDS-gel electrophoresis showed that CPH-treatment induced a decrease of the intensity of 3 brush border polypeptides of molecular weights of 72,000, 58,000 and 39,000 [77]. 

Amino acids that enter the blood are transported across cell membranes of the various tissues principally by Na -dependent cotransporters and, to a lesser extent, by facilitated transporters (Table 37.1). In this respect, amino acid transport differs from glucose transport, which is Na -dependent transport in the intestinal and renal epithelium but facilitated transport in other cell types. The Na dependence of amino acid transport in liver, muscle, and other tissues allows these cells to concentrate amino acids from the blood. These transport proteins have a different genetic basis, amino acid composition, and somewhat different specificity than those in the luminal membrane of intestinal epithelia. They also differ somewhat between tissues. For instance, the N system for glntamine nptake is present in the liver bnt either not present in other tissues or present as an isoform with different properties. There is also some overlap in specificity of the transport proteins, with most amino acids being transported by more than one carrier. 

Approximately 10% of the human population (with regional differences indicating both genetic and environmental factors [33]) is affected by the formation of stones or calculi in the urinary tract. Urolithiasis is not only a painful condition, but also causes annual costs to the health system in the order of billions of dollars in the USA alone [34, 35]. Based on their composition, structure and location in the urinary tract, renal stones have been classified into 11 groups and their formation mechanisms have been discussed together with alterations in urinary parameters and metabolic risk factors for renal lithiasis [35]. Approximately 70% of these stones contain calcium oxalate monohydrate (COM) and dihydrate as major components, while other calculi are composed of ammonium magnesium phosphate (struvite), calcium phosphates (hydroxyapatite and brushite), uric acid and urates, cystine and xanthine. An accurate knowledge of the solubilities of these substances is necessary to understand the cause of renal or bladder calculi formation and find ways towards its prevention and treatment [36]. 

The explanation for the changes in extracellular hydrogen and potassium ions occurring in parallel hinges on the principle of electroneutrality. This is a constraint which applies to all systems, animate and inanimate. Despite the fact that, in the context of acid-base physiology, the principle has been applied to the kidney, the whole argument depends on the physics of the system and is independent of the details of renal mechanisms. Whatever mechanism were operating for the maintenance of ionic composition of the extracellular fluid, it would necessarily incorporate the principle of electroneutrality. 

As Barcroft has shown, the freedom of human life, as expressed in repose and action, requires constancy in the composition of the blood and the cerebro-spinal fluid, while the stability of the internal environment as a whole requires inter-dependent mechanisms for storage, distribution and removal of solutes. Transitory changes in the blood due to metabolic activity are compensated for by si)ecially adapted systems for neutralisation, detoxication, and pulmonary and renal excretion, and form part of the routine physiological activities of life. Excessive changes in the blood composition are the result of pathological processes, resulting in abnormal metabolism or in defective compensation and excretory dysfunction. 

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