Glomerulus renal physiology

Due to the metabolic stability, low molecular weight and absence of ionization at physiological pH, fluconazole has to rely on renal clearance as its major clearance mechanism. The compound has a log P or D7 4 value of 0.5, which means following filtration at the glomerulus a substantial proportion (80 %) of the compound in the filtrate will undergo tubular reabsorption. The resultant low rate of renal clearance gives fluconazole a 30-h half-life in man and is consequently suitable for once-a-day administration. 

Oxalate is excreted primarily by the kidney. Oxalate is freely filtered at the glomerulus, where its concentration is normally 1 5 pM. One of the few physiologic functions of oxalate occurs in the proximal tubule where it plays a role in transcellular reabsorption of chloride (mainly present as sodium chloride). Cl entry across the apical membrane is mediated by Cl /oxalate exchange (oxalate is recycled from the tubular lumen to the cell by oxalate/ sulfate exchange, in parallel with Na /sulfate cotransport) [4]. Early studies of renal oxalate clearance using radio-labeled oxalate showed secretion in almost all subjects studied. More recent studies using direct measurement of serum and urine... 

Most of the clinical laboratory information used to assess kidney function is derived from or related to measurement of the clearance of some substance by the kidneys. The renal clearance of a substance is defined as the volume of plasma from which the substance is completely cleared by the kidneys per unit of time. Provided a substance S is in stable concentration in the plasma is physiologically inert freely filtered at the glomerulus and neither secreted, reabsorbed, synthesized, nor metabolized by the kidney, then the amount of that substance filtered at the glomerulus is equal to the amount excreted in the urine (i.e., the amount of S entering the kidney must exactly equal the amount leaving it). The amount of S filtered at the glomerulus = GFR multiplied by plasma S concentration GFR X PS. The amount of S excreted equals the urine S concentration (US) multiplied by the urinary flow rate (V, volume excreted per unit time). 

Under normal physiological conditions, the usual daily dietary intake of 5 to 10 mg of Al is completely excreted. This excretion is accomplished by avid filtration of Al from the blood by the glomerulus of the kidney. Patients in renal failure lose this ability and are candidates for Al toxicity. The dialysis process is not highly effective at eliminating Al and can be a significant source of exposure. Furthermore, it is a common practice to administer Al-based gels orally... 

Besides intestinal absorption, another important determinant of bioavailability is secondary active transport of ascorbate in the kidney. Most AA circulates in the blood in the form of the ascorbate anion. The ascorbate in the blood plasma is freely filtered at the renal glomerulus, but much of it is reabsorbed in the proximal tubule. Ascorbate uptake across the luminal membranes of renal proximal tubule cells occurs through sodium-ascorbate cotransport. The amount of ascorbate lost in the urine rises when the plasma ascorbate concentration exceeds the renal threshold. Above this threshold the tubular reabsorptive capacity is overwhelmed. The renal threshold for AA is reported to be slightly higher in men than in women (plasma ascorbate concentrations of 86 and 71 pM, respectively), but the underlying mechanism and physiological importance of this difference are unknown (Oreopoulos etal., 1993). 

FIGURE 6.4 Elimination of foreign chemicals by the kidney. Chemicals that have been taken up into the bloodstream are filtered at the glomerulus and enter the renal tubule with the glomerular filtrate. Once in the renal tubule, some chemicals tend to stay in the tubule and be excreted in urine, while others tend to diffuse out of the renal tubule and be reabsorbed into the bloodstream. The electrical polarity of the foreign chemical plays an important role in determining whether the chemical is excreted or reabsorbed. (Reprinted with permission from David Shier, Jackie Butler and Ricki Lewis, Hole s Human Anatomy and Physiology, 7th ed. [Dubuque Wm. C. Brown, 1996], 811.)... 

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