Kidneys reabsorption from

Increasing calcium reabsorption from the proximal tubules in the kidney... 

The excretion of water soluble waste via the kidneys requires filtration followed by selective reabsorption from and secretion into the renal tubules. Regulation of normal blood pH within very strict limits due to proton secretion and bicarbonate reabsorption is a major role of the kidney. 

There are several efflux pumps which may affect absorption, blood-brain-barrier penetration, and reabsorption from kidney microtubules. The most commonly tested efflux pump in early drug discovery is the P-glycoprotein. Assays to identify P-glycoprotein substrates or inhibitors can be run using a variety of cell lines. 

Kidney medulla From the metabolic point of view the kidney is virtually two organs, the cortex and the medulla. The cortex contains the glomeruli, through which the blood is filtered, the proximal tubules and part of the distal tubules, from which ions and molecules are reabsorbed. The cortex is well supplied with blood so that ATP is generated by the oxidation of fuels. The medulla is metabolically quite different. Here the ATP is required for the reabsorption of ions from the loop of Henle. Some ATP is generated by anaerobic glycolysis, since the supply of blood, and therefore of oxygen, to the medulla is much poorer than to the cortex. This reflects control of the uptake of water and Na+ ions into the blood by the counter current mechanism. This depends on a slow flow of the blood in the capillaries. 

A second form of diabetes is also recognized diabetes insipidus, which is caused by a deficiency of the pituitary hormone, vasopressin. Vasopressin promotes water reabsorption from the kidney, hence a deficiency also induces S5anptoms of excessive urination and thirst. A key diagnostic difference between the common diabetes meUitus and the rare diabetes insipidus, is the absence of glucose in the urine in the latter case. Until a few decades ago, a popular way to differentiate between the two diseases was to taste the patient s urine to see if it was sweet. 

It increases the excretion of uric acid (by inhibiting its reabsorption from kidney tubules) and hence causes reduced serum levels of uric acid. 

Thiazides inhibit NaCI reabsorption from the luminal side of epithelial cells in the DCT by blocking the Na+/Q transporter (NCC). In contrast to the situation in the TAL, in which loop diuretics inhibit Ca2+ reabsorption, thiazides actually enhance Ca2+ reabsorption. This enhancement has been postulated to result from effects in both the proximal and distal convoluted tubules. In the proximal tubule, thiazide-induced volume depletion leads to enhanced Na+ and passive Ca2+ reabsorption. In the DCT, lowering of intracellular Na+ by thiazide-induced blockade of Na+ entry enhances Na+/Ca2+ exchange in the basolateral membrane (Figure 15-4), and increases overall reabsorption of Ca2+. Although thiazides rarely cause hypercalcemia as the result of this enhanced reabsorption, they can unmask hypercalcemia due to other causes (eg, hyperparathyroidism, carcinoma, sarcoidosis). Thiazides are useful in the treatment of kidney stones caused by hypercalciuria. 

The nephrotoxicity of bromobenzene (see chap. 7) and possibly 4-aminophenol is also believed to be due to the cysteine conjugates of the quinone or quinoneimine, respectively. Biliary excretion and reabsorption from the gut and delivery to the kidney is a crucial part of this process as it is with hexachlorobutadiene (chap. 7). 

Since chemicals are primarily metabolized in enzyme-rich tissues such as the liver and kidney, the extent of metabolism depends on the exposure of these various tissues to the chemical (i.e., for an oral route on the extent of intestinal absorption). The intestinal absorption into the systemic circulation and absorption into or out of other tissues may be influenced by carrier or reflux enzymes (e.g., P-glycoprotein enzymes in the intestinal wall that capture and return chemicals to the intestinal lumen). Similarly, there are carrier enzymes involved in transporting chemicals into the bile that have a marked specificity. The extent of metabolism and proportion of second and third generation metabolites increases with the time in contact with important organs such as the liver. This may be enhanced by reabsorption from the gut after excretion in the bile, which may be subsequent to metabolism (e.g., hydrolysis of glucuronides in the gut). 

The enzyme carbonic anhydrase facilitates the reaction between carbon dioxide and water to form carbonic acid, which then breaks down to hydrogen (H" ) and bicarbonate (HCOj") ions. This process is fundamental to the production of either acid or alkaline secretions and high concentrations of carbonic anhydrase are present in the gastric mucosa, pancreas, eye and kidney. Because the number of available to exchange with Na" in the proximal tubule is reduced, sodium loss and diuresis occur. But HCOg reabsorption from the tubule is also reduced, and its loss in the urine leads within days to metabolic acidosis, which attenuates the diuretic... 

Diuretics inhibit sodium and water reabsorption from the kidney tubules, resulting in diuresis (increased urine flow), lower blood pressure, and a decrease in peripheral and pulmonary edema. 

The kidneys receive a large blood flow (approximately a quarter of the total cardiac output of 5 litres per minute) and from this volume of blood approximately 170 litres of filtrate are produced every day Clearly, the body would quickly become dehydrated if this volume of fluid were lost to the sewage system, so most of it is reabsorbed from the kidney tubule and returned to the bloodstream. Small molecules that are dissolved in the glomerular filtrate are also reabsorbed back into the bloodstream, either by passive diffusion (which obeys Fick s law) or by the utilisation of energy in an active transport process similar to the mechanisms for gut absorption discussed previously. It should be realised that reabsorption from the glomerular filtrate and return to the bloodstream are involved in the duration of action of many drugs, and a drug molecule may be filtered and reabsorbed many times before it is finally excreted from the body. 

The vascular subcompartment equation of liver includes two terms for plasma flow, corresponding to the systemic and enterohepatic circulations. The vascular subcompartment equations of the kidney and liver include additional terms to account for urine excretion and secretion into the common bile duct from the liver. Terms for intestinal reabsorption from the gut lumen and for fecal excretion are also included. 

The sulfones are distributed throughout total body water and are present in all tissues. They are retained in skin and muscle and especially in liver and kidney. The sulfones persist in the circulation for a long time because of reabsorption from the bile periodic interruption of treatment is advisable for this reason. Dapsone is acetylated in the liver by the same enzyme that acetylates isoniazid. Daily administration of50-100 mg results in serum levels exceeding the usual minimal inhibitory concentrations, even in rapid acetylators, in whom the serum t of dapsone is shorter than usual. 

Xenobiotics and their metabolites can be eliminated from the body by several routes including urine, feces, and exhaled air. The primary organ systems involved in excretion are, therefore, the kidney and the gastrointestinal and respiratory systems. Xenobiotics are removed in the kidney by passive filtration of the blood or active secretion by carriers into the forming urine selective reabsorption from the forming urine may also occur. Fat-soluble compounds are more likely to be reabsorbed than those that are water soluble. Measurements of xenobiotics and their metabolites in the urine are often used as biomarkers of exposure, but in reality the amount of a compound or metabolite excreted in the urine is only a proportion of the absorbed compound. In the absence of a thorough understanding of the processes involved, this approach needs to be carefully evaluated. 

The posterior pituitary gland secretes antidiuretic hormone (ADH) and oxytocin. ADH is a vasopressin. Ox5docin is released to start labor contractions. ADH promotes water reabsorption from the renal tubules to maintain water balance in the body s fluids. A deficiency of ADH, called diabetes insipidus (Dl), causes the kidneys to excrete large amounts of water. This leads to severe fluid volume deficit and electrol5de imbalances. 

Fluid balance in the body is maintained or restored primarily by variations in urine output. Normally, this amounts to about 1400 mL/day, but the total excretion fluctuates according to water intake. The primary factor that controls urine production is the rate of water reabsorption from the renal tubules in the kidneys. This rate is regulated chiefly by the pituitary hormone vasopressin and by the adrenal cortex hormone aldosterone. 

In addition to increasing intestinal absorption of calcium, 1,25-dihydroxycholecalciferol increases the absorption of phosphorus from the intestine and also enhances calcium and phosphorus reabsorption from the kidney and bone. 

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