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HANDBOOK OP II I YSIOI.OGY 



CIRCULATION II 



renal nerves, resulting in a 53 per cent reduction in 

 direct flow, the calculated RBF was from 1 to 70 

 per cent of the true values because of reduction in 

 mine How and incomplete excretion (UV). All calcu- 

 lated flows exceeded the direct flows on cessation of 

 stimulation as stored urine was washed out. They 

 emphasized the need to correct for possible shifts of 

 Diodrast (or PAH) from erythrocytes to plasma during 

 the venous sampling. To the extent that this occurs, 

 the E u or £ PAH will be vitiated, and the Fick applica- 

 tion inaccurate. Phillips et al. (247) have given meth- 

 ods for correction of PAH shift. Whole blood extrac- 

 tion eliminates errors incurred by the shift from cells 

 to plasma, and Bergstrom et al. (16) have found 

 the use of radioactive Diodrast (containing I 131 ) 

 particularly helpful in this respect. The possibility has 

 been examined that opening of vascular shunts not 

 perfusing excretory tissue might occur following nerve 

 stimulation or drug action and invalidate the clear- 

 ances. Epinephrine (0.1 /xg) in rabbits caused the 

 £ PAH to fall to negative values in seven of nine cases 

 [average for the seven, — 26.6 c 1 (214)]. This was 

 restored in 10 to 40 min. The negative values have 

 been explained by a return to the venous outflow 

 of stored PAH (interstitial fluid of papillary zone?). 

 Injections of Thorotrast in these pictured the possi- 

 bility of juxtamedullary shunting of blood. Ephedrine 

 produced a similar picture in cats [India ink injection 

 (189)], but Lofgren points out that the picture of 

 cortical ischemia and medullary filling could result 

 from congestion of the vasa recta following contrac- 

 tion of venous effluent constrictors, rather than from 

 opening of a bypass and increased flow. Mover et al. 

 (222) employed sciatic stimulation and epinephrine 

 in dogs and rabbits. With sciatic stimulation, blood 

 flow decreased ca. 36 per cent, but renal venous blood 

 never became arterialized, as the original Trueta 

 shunt operation would demand. In fact, the A-V oxy- 

 gen difference actually increased. India ink distributed 

 fairly equally throughout cortex and medulla after 

 nerve stimulation. The rabbit kidney after epineph- 

 rine, however, appeared to confirm the appearance 

 of cortical ischemia and subcortical injection. But the 

 latter does not necessarily mean increased medullary 

 flow. Epinephrine and histamine caused a maximum 

 decrease of E,, XH of only 1 1 .4 per cent in the human 

 kidney (254). 



In an interesting experiment Cargill (48) infused 

 human serum albumin into patients. E PAH invariably 

 decreased significantly, even as C PAH increased. 

 C\ n rose proportionally to (.',. ul , so that the filtered 



fraction remained constant. These results could readily 

 be explained by increased shunting of blood through 

 the medullary vasa recta system. 



EXTRACTION RATIO AS A TEST OF VALIDITY OF THE 



clearance method. The extraction ratio has been 

 one of the measurements which yields insight into 

 the efficacy of the tubular transfer process or the 

 adequacy of tubular vascular perfusion. It is reduced 

 during shunting of blood away from the tubular 

 secretory sites, or as the result of actual impairment 

 of the transport mechanism. Some of the physiological 

 and pathological conditions in which renal extraction 

 has been evaluated follow. 



£p AH is not reduced by abdominal compression 

 which elevates control venous pressure from ca. 6 mm 

 Hg to 18 mm Hg (32). This lack of effect on £ PAH 

 may be due to the probability that transmural renal 

 venous pressure would not be changed by this maneu- 

 ver (329). Werko et al. (334) found no change in 

 £ PAH during the renal ischemia induced by tilting. 

 £ PAH may be normal or only slightly impaired in 

 essential hypertension. A series examined by Reubi 

 & Schroeder (254) averaged 0.84, including one of 

 69.8. CargilPs (49) series of hypertensive patients 

 including those with nephrosclerosis averaged 0.79 

 (0.58-0.91). The lowered values are associated with 

 reduction of C HAH below 300 ml per min. In anemia, 

 there is only a slight decrease of the ratio (256, 305). 

 In nine observations on subjects with no renal pathol- 

 ogy but in congestive heart failure, Merrill (202) 

 found only two below 0.85 (0.64, 0.63); Edelman 

 et al. (78) reported an average of 0.90 (0.88-0.91) 

 in ten congestive heart failure subjects. 



In nephritis there may be considerable reduction 

 in the extraction ratio. Bradley et al. (33) obtained 

 values for £ PAH ranging from 0.58 to 0.76 in six sub- 

 jects with chronic glomerulonephritis. It may be 

 supposed that in the course of disorganization of the 

 renal vascular pattern, channels are established in 

 which blood flows from the artery to vein without 

 exposure to functional tubular tissue (abnormal shunts 

 or destroyed excretory tissue). Marked reduction in 

 £ PAH (as low as 0.034 and 0.106) was noted with 

 tubular damage resulting from carbon tetrachloride 

 poisoning (284). £ PAH decreased during acidemia 

 which developed during the apnea of diffusion respira- 

 tion in dogs (27). The control E PAH of 0.86 at pH 

 7.4 decreased to 0.53 at 7.05. 



Renal ischemia and anoxic damage resulting from 

 hemorrhagic shock will impair extraction. Twenty 



