1 III-: RENAL CIRCULATION 



I481 



The method yields an average of 3.2 ml per min 

 per g kidney weight in anesthetized dogs (58) and in 

 man (68). Comparison of this method with a direct 

 method ( bubble flowmeter) in the do? under various 

 physiological conditions shows that the two yield 

 flow values which are not significantly different (58). 

 An obvious advantage is that the nitrous oxide method 

 can be employed during conditions of anuria. A 

 similar application using radioactive krypton (Kr 85 ) 

 has been employed during anuria (40). 



Critique of the Clearance .Method 



CRITERIA FOR APPLICATION OF CLEARANCE. Some of the 



criteria which must be met in order for the clearance 

 of a substance such as Diodrast or PAH to measure 

 accurately renal plasma flow are: a) change of volume 

 of blood in passage is negligible (i.e., urine and lymph 

 flow not excessive), b) concentration of substance in 

 blood is constant, or the rate of change of concentra- 

 tion is uniform for midpoint collection, <) rate of 

 urine flow should be sufficiently large and constant 

 so that it may be representative of the urine in the 

 nephrons, d) the substance should not be formed or 

 altered in the kidney, e) all blood in the renal vein 

 should pass through the kidney (and not enter via 

 shunts). 



FACTORS WHICH MIGHT INVALIDATE THE CLEARANCE 



method, a) Oliguria or marked fluctuations in urine 

 flow such as might accompany rapid changes in blood 

 pressure. If there is stagnation, or rapid fluctuation 

 of the urine flow in the nephrons, the collected sample 

 will not reflect the true excretion, and the midpoint 

 plasma sample will lack validity. b) Rapid changes in 

 plasma concentration, preventing establishment of 

 equilibrium among blood, interstitial fluid, tubular 

 cells, and tubular urine, c) Renal storage of substance 

 in tubular cells or interstitial fluid, d) Storage of sub- 

 stance in the erythrocytes in excess of the plasma 

 concentration, so that its simple outward diffusion 

 through the plasma adds appreciably to the amount 

 actually carried by the plasma leading to an errone- 

 ous plasma flow figure, e) Impairment of the PAH 

 tubular transfer mechanism, leading to an erroneously 

 low plasma flow figure. 



ADEQUACY OF C d AND C PAH AS MEASUREMENT OF RENAL 



plasma flow. Under stabilized conditions that fulfill 

 the criteria explained previously, good correspond- 

 ence of clearance to direct methods is obtained. 

 Selkurt (269) found that BF PAH averaged 91 per cent 



of the simultaneously measured direct blood flow 

 (venous outflow method). The difference was at- 

 tributable to incomplete extraction of PAH. Conn 

 & Markley (57) compared renal blood flow in anes- 

 thetized dogs as measured indirectly by the Fick 

 principle (PAH clearance) to blood flow measured 

 directly by bubble flowmeter. The ratio of indirect 

 to direct values averaged 1.025. Employment of the 

 Fick principle corrects for incomplete extraction and 

 yields total blood flow. Schwalb et al. (268) made a 

 similar comparison and found a ratio ot 1.06 ± 

 0.17. But after the kidney was poisoned with Na 

 fluoride, the agreement did not hold. Then flow 

 measured by the bubble flowmeter was often much 

 higher than that measured by PAH clearance. Since 

 the use of the Fick method should correct for incom- 

 plete extraction due to impairment of the PAH secre- 

 tory mechanism, the authors believed that PAH was 

 stored in the kidney (possibly in the tubular cells) 

 so that excretion (I'V) was low, relative to the ap- 

 parent removal. 



Reubi et al. (255) compared simultaneous Fick 

 plasma flows for PAH, mannitol, endogenous creati- 

 nine, and thiosulfate. For example, the ratio between 

 Cpah ;'£pAH and C M /E M varied between 1 .54 and 

 0.645. Disparities were further exaggerated by in- 

 jection of epinephrine and histamine causing rapid 

 transients in blood pressure and urine flow. Suggested 

 causes for the discrepancies were: differences in the 

 extraction and blood flow in separate kidneys; intra- 

 renal extraction; conjugation or breakdown of PAH, 

 mannitol, creatinine, and thiosulfate; removal of part 

 of the substances from the kidney through lymphatic 

 vessels, thus bypassing the renal vein; changes in 

 the permeability of the red cells to the test substances; 

 or, finally analytical difficulties. Balint & Fekete (8) 

 found great disparities between direct blood flow and 

 the Fick method (C'pah, £pah) in hemorrhagic hypo- 

 tension, hemorrhagic shock, and shock from pyloric 

 obstruction in dogs. The indirect method was always 

 lower by varying degrees than the direct method. 



Since errors are compounded by the analysis of 

 Reubi et al., it would be more desirable to compare the 

 indirect methods against a direct method in tests for 

 fidelity under experimental conditions. Under cir- 

 cumstances of rapidly changing blood flow resulting 

 from nerve stimulation or action of vasoactive drugs, 

 as has been suggested, the clearance method may not 

 accurately follow direct flow. Study & Shipley (298) 

 found excellent agreement between the Fick method 

 (Diodrast) and direct flow (rotameter in renal vein) 

 during control conditions. During stimulation of the 



