Glucose proximal tubule reabsorption

Sodium SGLTl -dependent unidirectionai transporter Small intestine and kidney Active uptake of glucose from lumen of intestine and reabsorption of glucose in proximal tubule of kidney against a concentration gradient... 

Proximal tubule Cells of the PCT are responsible for bulk transport of solutes, with approximately 70-80% of the filtered load of sodium chloride (active processes) and water (passive, down the osmotic gradient established by sodium reabsorption) and essentially all of the amino acids, bicarbonate, glucose and potassium being reabsorbed in this region. 

At the proximal tubule, the concentrations of glucose, proteins, and amino acids decrease greatly due to reabsorption by active transport into the capillary blood. Na , K+, Cl , and HCOg" are also reabsorbed by active transport, although their concentrations vary minimally due to the large decrease in the water flow rate. 

The amount of phosphorus excreted in the urine vanes with the level of ingested phosphorus and factors influencing phosphorus availability and utilization. It has been shown that in the dog, when plasma phosphate is normal or low, over 99% of the filtered ion is reabsorbed, presumably in die upper part of the proximal tubule. Increased plasma concentrations of alanine, glycine, and glucose depress phosphate reabsorption. 

Uranium. About 50% of plasma uranium is bound, as the uranyl ion, to bicarbonate, which is filtered by the glomerulus. As a result of acidification in the proximal tubule, the bicarbonate complex dissociates, followed by reabsorption of the bicarbonate ion the released UO22"1" then becomes attached to the membrane of the proximal tubule cells. The resultant loss of cell function is evidenced by increased concentrations of glucose, amino acids, and proteins in the urine. 

Electrolyte imbalances K+, i Mg +, i Na+, i Cl, T uric acid reabsorption in the proximal tubules can precipitate gouty attacks. Other side effects include rash, T glucose, dizziness, photosensitivity, i BP, headache, T lipids. 

Figure 18-3 Site 1 The Na transport systems responsible for the reabsorption of Na and associated solutes in the proximal tubule. A. Transcellular reabsorption of Na THCOj, which is controlled by carbonic anhydrase (CA). Acetazolamide and other CA inhibitors block Na reabsorption by this route. B. Transcellular reabsorption of Na coupled to glucose, amino acids, and phosphate C Paracellular transport of Na /Cl. No commercially available agents inhibit Na reabsorption by routes B or C, Na"/K -ATPase is indicated by filled circles on the antiluminal membrane.

Since the kidneys are the main depot for cadmium, they are of greatest concern for cadmium toxicity. Cadmium interferes with the proximal tubule s reabsorption function. This leads to abnormal actions of uric acid, calcium, and phosphorus. Amino aciduria (amino acids in the urine) and glucosuria (glucose in the urine) result in later stages, proteinuria (protein in the urine) results. When this happens, it is assumed that there is a marked decrease in glomerular filtration. Long-term exposure to cadmium leads to anemia, which may result from cadmium interfering with iron absorption. 

The proximal tubule is the most metabolically active part of the nephron, facilitating the reabsorption of 60% to 80% of the glomerular filtrate volume—including 70% of the filtered load of sodium and chloride, most of the potassium, glucose, bicarbonate, phosphate, and sulfate—and secreting 90% of the hydrogen ion excreted by the kidney (Table 45-1). 

The glomerular filtrate containing virtually very little protein (approximately 30 mg/dl) enters the proximal tubule. Approximately 80% of the water and solute from the glomerular filtrate is reabsorbed in the proximal tubule as an isotonic solution. Solutes such as glucose and proteins are almost totally reabsorbed. Creatinine, in contrast, is not reabsorbed. Approximately 65% of the sodium in the glomerular filtrate is reabsorbed in the proximal tubule by active transport. The rate of reabsorption of sodium in the proximal tubule, however, is under the... 

To date, several small molecule biomarkers of renal toxicity have been described in the literature. Urine composition is considered to reflect kidney function and pathology. Thus, in the presence of proximal tubule damage, the relative concentrations of a number of metabolites (glucose, lactate, alanine, lysine, glutamine, glutamate, and valine) are markedly increased due to impaired reabsorption of those metabolites. An increase in the relative concentrations of those metabolites in urine is typically accompanied by a corresponding decrease in plasma levels [50,55],... 

In children with lead encephalopathy, a proximal tubule defect for glucose reabsorption (glycosuria without hyperglycemia) was first noted by McKhann in 1926 and aminoaciduria was described by Wilson et al. in 1953 [10,11]. The Fanconi syndrome (aminoaciduria, phosphaturia, and glycosuria) has been observed... 

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