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HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



for example, becomes less efficient in the kidnevs of 

 anesthetized animals, thus leading to correspondingly 

 lower extraction ratios. With lowered hematocrit, 

 more plasma passes through the hypothetical shunt 

 circulation, bypassing the tubular elements. A reduc- 

 tion in extraction ratio to 60 per cent of control value 

 was noted under this circumstance (160). 



The peculiarities of oxygen supply to the kidney, 

 resulting from the implications of this hypothesis, have 

 been discussed earlier. In brief, the peritubular circu- 

 lation is supplied with a cell-poor component of blood, 

 and the oxygen saturation in blood leaving the 

 actively metabolizing tissue of the kidney may be far 

 lower than in the renal vein. This was proposed as the 

 basis for the flow-limited nature of the organ despite 

 high venous oxygen content, a proposal challenged by 

 Levy (178, 179). 



The provocative cell-separation theory has served a 

 useful purpose in stimulating a sizable amount of re- 

 search. From this has grown a considerable body of 

 data which has challenged several of the fundamental 

 precepts of Pappenheimer and Kinter. These facts 

 are summarized : 



/) In the first instance, the hypothetical short 

 shunt from the efferent arterioles to interlobular vein, 

 bypassing the peritubular capillaries, has never been 

 anatomically demonstrated. While the vasa recta 

 circuit might conceivably function in this role, it is a 

 long circuit with a slow circulation and is low in 

 erythrocytes, not cell-rich as the hypothesis demands. 

 In all probability, less than 10 per cent of the total 

 renal blood flow passes through this circuit, based 

 upon the extraction ratio of PAH (256), and the flow 

 estimates of Kramer el al. (166); hence its role in 

 autoregulation is dubious. 



2) Studies of cell-plasma transit time show no 

 great differences in speed of red cell transit compared 

 to labeled albumin, hence do not favor the idea of 

 preferential shunting. 



3) Studies of distribution of erythrocytes through 

 the zones of the kidney reveal no increase in concen- 

 tration from outer medulla to cortex. 



./) Autoregulation can persist with anemia (305, 

 330) or with perfusion of kidneys with cell-poor fluids, 

 e.g., dextran (143, 306, 308, 330, 331, 333). But in 

 support of Pappenheimer & Kinter (240), Haddy el 

 al. ( 1 24) saw no autoregulation in kidneys perfused 

 with dextran. Autoregulation, when initially present, 

 has been shown by Waugh and Shanks to disappear 

 after perfusion of the kidney with dextran for variable 

 periods of time. Of considerable interest is the finding 

 that a plasma factor is needed in order to maintain 



satisfactory autoregulation (330) and may explain 

 some of the differences in results. 



5) The cell-separation hypothesis must necessarily 

 advocate differential filtration in glomeruli at different 

 levels, highest in the juxtamedullary, lowest in the 

 peripheral. From this a "splay" in the Tm G titration 

 curve could be expected, whereby nephrons attached 

 to glomeruli with high filtering capacity would be 

 saturated first, those with low filtration last. No such 

 splay was observed in anemic dogs ( 1 58) and humans 

 (256), indicating that all nephrons are saturated ap- 

 proximately simultaneously. 



6") When few or no red cells are present in arterial 

 blood the proportion of plasma flowing through the 

 preferential channels should increase with increasing 

 pressure, and hence E PAiI and E D should decrease in 

 anemic animals at the higher flow of elevated pressure 

 (159). This was found to be the case in cats. According 

 to Kinter and Pappenheimer, this would not occur 

 when red cells are present because the tendency for 

 plasma flow through the shunts to increase, owing to 

 the distensibility factor, would be counteracted by 

 more efficient plasma skimming. On the other hand, 

 Thompson el al. (305) found no significant effect on 

 £ PAH of variations in blood pressure in either normal 

 or anemic dogs. 



7) The appearance curves of PAH in the urine of 

 normal and anemic subjects are superimposable, 

 suggesting no difference in traversal pathway (256). 



In summary, the numerous weighty arguments 

 which have ben raised in opposition to the cell- 

 separation hypothesis appear to necessitate abandon- 

 ment of this theory as being important in explaining 

 renal autonomy, although Winton (344) has taken 

 the view that it may be a participating mechanism in 

 the over all phenomenon. 



tissue pressure theory. Advocates of this theory 

 must of necessity demonstrate an increase in IRP as 

 arterial perfusion pressure is elevated. Such evidence 

 has been offered by Hinshaw et al. (141 -144) for the 

 isolated kidney-lung-pump preparation. Representa- 

 tive experiments are shown in figure 25 (143). It is 

 seen that stabilization of flow coincides with an abrupt 

 rise in IRP at ca. 80 mm Hg. Although flow with 

 dextran is higher, because of lower viscosity, the 

 same relationship prevails. In another study (142), 

 it was shown that kidney weight increased with pres- 

 sure, 0.6 g per 10 mm Hg rise before onset of auto- 

 regulation (range 40 to 80 mm) and only 0.3 g per 

 100 mm Hg after. Thurau & Kramer (307), as well 

 as Scher (265), observed a weight increase with sudden 



