Renal plasma flow

Explain how plasma clearance of para-aminohippuric acid is used to determine the effective renal plasma flow... 

A substance that fulfills these criteria is para-aminohippuric acid (PAH). All of the PAH not filtered at the glomerulus is secreted by the proximal tubule. The net effect is that all of the plasma flowing through the nephrons is completely cleared of PAH. It is important to note that about 10 to 15% of the total renal plasma flow supplies regions of the kidneys that are not involved with filtration or secretion. Consequently, this plasma cannot be cleared of PAH. Therefore, the plasma clearance of PAH provides a measurement of the effective renal plasma flow, that is, the volume of plasma that actually flows through the nephrons. The ERPF is normally about 625 ml/ min. (This value is based on a renal blood flow of about 1.1 1/min and a hematocrit of about 42.)... 

If the apparent plasma clearance (dose/area under the plasma concentration-time curve, equivalent to true clearance/fraction of dose absorbed) gives an implausibly high value of clearance (e.g., greater than hepatic and renal plasma flow), it is likely the bioavailability is low. However, this could be due to presystemic metabolism in addition to low absorption. 

Renal blood flow (RBF) is a function of renal plasma flow and the density of red blood cells. 

Angiotensin-converting enzyme (ACE) inhibitors such as captopril exert a long-term reno-protective effect. Among other effects, they lower systemic blood pressure and renal plasma flow and effectively reduce urinary protein excretion. Renal delivery of ACE-inhibitors may increase this efficacy and reduce extra-renal side-effects. Renal targeting of an ACE-in-hibitor can also be useful in clarifying the contribution of local ACE inhibition to these reno-protective effects. 

Reduced hepatic mass reduced hepatic blood flow. Often decreased metabolizing isoenzyme activity. PseudocapiUar-ization of hepatic sinusoids Reduced renal plasma flow reduced glomerular filtration rate, altered tubular transport function... 

Glomerular filtration rate Renal plasma flow... 

Elimination Reduced renal plasma flow Reduced glomerular filtration rate Decreased tubular secretion function Decreased renal elimination of drugs and metabolites marked interindividual variation... 

Typical 24 h indices Filtered Nan-Filtered Cl-Filtered HCO-3 Filtered Kn-Renal blood flow Renal plasma flow Glomerular filtrate Urinary volume... 

Renal function is depressed by opioids. It is believed that in humans this is chiefly due to decreased renal plasma flow. In addition, opioids have been found to have an antidiuretic effect in humans. Mechanisms may involve both the CNS and peripheral sites. Opioids also enhance renal tubular sodium reabsorption. The role of opioid-induced changes in antidiuretic hormone (ADH) release is controversial. Ureteral and bladder tone are increased by therapeutic doses of the opioid analgesics. Increased sphincter tone may precipitate urinary retention, especially in postoperative patients. Occasionally, ureteral colic caused by a renal calculus is made worse by opioid-induced increase in ureteral tone. 

Of 12 patients with ascites due to cirrhosis of the liver, who received subcutaneous octreotide 300 micrograms bd for 11 days, 11 had increased renal plasma flow and 10 had a reduced GFR (44). Creatinine concentrations did not change. The effects of octreotide on the kidneys have been variably reported in previous studies. In patients with cirrhosis the effects are likely to be affected by the activated renin-angiotensin-aldosterone system. 

To varying degrees, all inhaled anesthetics decrease glomerular filtration rate and effective renal plasma flow and increase filtration fraction. All the anesthetics tend to increase renal vascular resistance. Since renal blood flow decreases during general anesthesia in spite of well-maintained or even increased perfusion pressures, autoregulation of renal flow is probably impaired. 

Renal plasma flow and glomerular filtration rate are usually unaffected, but free water clearance may increase. Because most sodium is reabsorbed in the proximal renal tubules, spironolactone is relatively ineffective when administered alone. Concomitant administration of a diuretic which blocks re-absorption of sodium proximal to the distal portion of the nephron (such as a thiazide or loop diuretic) is required for maximum diuretic effects. When administered with other diuretics, spironolactone produces an additive or synergistic diuretic response and decreases potassium excretion caused by the other diuretic [65],... 

In the spontaneously hypertensive rat (SHR) SK F 82526 was inactive as a natriuretic, but was active as an antihypertensive agent. The weaker natriuretic activity of SK F 82526 compared to SK F 38393 was also seen in conscious dog renal clearance studies (27). SK F 82526 given 5 mg/kg p.o. increased renal plasma flow 81%, glomerular filtration rate 15%, but elevated sodium excretion only about half the amount observed with SK F 38393, and this in a somewhat delayed response. SK F 82526 when given in the drinking water at 200 mg/kg/day for 30 days in developing SHR blunted the onset of hypertension and also lowered blood pressure acutely in anesthetized SHR. It did not lower blood pressure in anesthetized Dahl salt sensitive hypertensive rats. 

As noted earlier, variation in kidney function can affect drug toxicity. Regardless of whether renal function is normalized to body weight or body surface area, it is lower in the neonate compared to the adult. As the infant matures, renal blood flow increases as a consequence of increased percent of the cardiac output going to the kidneys as well as decreased peripheral vascular resistance. Renal plasma flow increases approximately eight-fold within 1-2 years of birth. 

After 40 years of age, liver mass decreases at a rate of approximately 1 percent per year, in addition to a reduction in blood flow (40-50 percent), resulting in a diminished ability to metabolize drugs. However, since hepatic drug metabolism varies widely among individuals, there are no absolute age-related alterations in this regard. Cardiac output also decreases by approximately 1 percent per year beginning at 30 years of age and contributes to the decrease in hepatic blood flow. Glomerular filtration rate, renal plasma flow, and tubular secretory capacity also become reduced. 

Plasma clearance is expressed as the volume of plasma from which all drug appears to be removed in a given time, for example, as ml/min. Clearance equals the amount of renal plasma flow multiplied by the extraction ratio, and since these are normally invariant over time, clearance is constant. 

GFR is estimated by calculating the clearance of the freely-filtered tracer or endogenous substance. RPF estimated using PAH clearance is often designated effective renal plasma flow (ERPF). Renal plasma flow is converted to renal blood flow (RBF) by dividing ERPF by the plasma fraction of whole blood, as estimated from the hematocrit (Hct) ... 

Ronnhedh C, Jacquenod M, Mather LE (1996) Urineless estimation of the glomerular filtration rate and renal plasma flow in the rat. J Pharm Tox Methods 36 123-129 Sapirstein LG, Vidt DC, Mandell MJ, Hanusek G (1955) Volumes of distribution and clearances of intravenously injected creatinine in the dog. Am J Physiol 181 330-336 Sarkar SK, Holland GA, Lenkinski R et al. (1988) Renal imaging studies at 1.5 and 9.4 T effects of diuretics. Magn Reson. Med 7 117-124... 

Tucker et al. showed that both sudden severe physical exercise and longer sustained work on a treadmill during training decreases urinary riboflavin excretion during the experimental periods (12) The acute reduction in riboflavin excretion observed by these investigators was attributed to a reduction in renal plasma flow. In order to explain the long-term reduced excretion of the vitamin, they proposed that riboflavin was retained for incorporation into "new muscle tissue". The significance of this study is that if the hypotheses... 

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