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HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



mechanism for the removal of water and concentra- 

 tion of albumin in the vasa recta loops. 



METABOLIC ASPECTS 



Oxygen Utilization 



The renal venous blood contains considerably more 

 oxygen than does venous blood from other tissues. 

 The resulting small A-Y oxygen difference [1.7 vol % 

 in man (287), and ca. 3.0 vol % in the dog and cat] 

 remains constant over a wide range of renal blood 

 flows (66, 74, 102, 164, 180, 181, 317), although it 

 may change at very low rates of flow. Thus, oxygen 

 consumption (normally .08 to o. 10 ml/g/min in the 

 dog) is related to flow, so that when flow is reduced 

 as in shock (74) the organ ordinarily does not increase 

 its extraction but apparently suffers curtailment of 

 oxidative metabolism. As Pappenheimer & Kinter 

 (240) have pointed out, the kidney behaves in a sense 

 as a " flow-limited" tissue. The "cell-separation" 

 theory proposed by them has attempted to reconcile 

 the paradox of high renal venous oxygen saturation 

 and flow limitation. If the majority of the red cells 

 coursed through hypothetical shunts, then blood of 

 low erythrocyte count, low in oxygen, would supply 

 the tubular cells with a barely adequate supply of 

 oxygen. If flow were impaired, oxygen supply would 

 become insufficient, unless the blood flow could be- 

 come redistributed to supply the tubular cells. 



Levy (178) has brought evidence to bear against 

 this hypothesis by showing that when additional 

 oxygen was made available, the extraction of oxygen 

 still remained constant over a wide range of blood 

 flows, unattended by alteration of intrarenal hemato- 

 crit. In addition, 2 ,4-dinitrophenol was found to 

 increase the renal oxygen extraction very signifi- 

 cantly without altering the intrarenal hematocrit 

 ratio. This implied that the capillarv blood perfusing 

 the renal tubules must not be virtually desaturated 

 at normal or even at moderately reduced flows. 



An alternative ingenious explanation was offered 

 by Levy for the apparent flow limitation (179), based 

 upon the earlier observation of Longley et al. (190). 

 The latter showed that krypton 85 attained equilibrium 

 very slowly between the circulatory system and the 

 renal medulla. If these findings implied that krypton 

 diffused from arterial to venous limbs of the medullary 

 capillary circuits, it might be that oxygen would 

 also diffuse across this path. Experimental verification 

 appeared to be offered by the simultaneous injection 



of highly oxygenated blood and blood containing 

 methemoglobin-labeled red cells into the renal artery. 

 Analysis of renal vein blood showed that the peak of 

 elevated oxygen tension arrived slightly ahead of the 

 labeled cells (1.25 ± 0.97 sec). Since the erythrocytes 

 represent the portion of the blood that passes through 

 the kidney most rapidly, it was concluded that some 

 of the oxygen must diffuse from the vascular system 

 and re-enter at some point downstream. The likely 

 site for this operation is between the upper arterial 

 and venous limbs of the vasa recta. In support of this 

 is the fact that oxygen pressure of the renal venous 

 blood is always higher than that of the urine (253). 

 This could be explained by supposing that urine in 

 the collecting tubules tends to equilibrate with blood 

 of low oxygen tension in the vasa recta before enter- 

 ing the pelvis. 



The implication of this is that the medullary zone 

 of the kidney and particularly the region of the papilla 

 would be a zone of decreased oxygen tension com- 

 pared to the cortex. The low hematocrit here would 

 further compromise the oxygen supply (84, 166, 184). 

 Lastly, volume flow in the medulla has been measured 

 by an ingenious intrarenal photoelectric technique 

 and found to be small, 21.8 ml per min per 100 g 

 compared to 400 ml per min per 100 g in the cortex 

 (166). 



But the operation of the countercurrent system 

 does not demand increased oxygen utilization by the 

 cells of the medulla. Ullrich (314) has summarized 

 the result of a number of Warburg tissue-slice studies 

 made in the guinea pig, dog, and cat. The average 

 values are as follows in cubic millimeter per milli- 

 gram of dry tissue per hour: cortex, 21.3; outer 

 medulla, 15.1; inner medulla, 6.2. A representative 

 experiment made on guinea pig kidney tissue by 

 Grupp & Hierholzer (115) appears in figure 20. 



These findings would support the conclusion that 

 the important structures of the inner medulla (loops 

 of Henle and collecting ducts) do not have important 

 energy requiring functions. Ullrich & Pehling (313) 

 have shown that tissue slices of the outer medulla of 

 the dog kidney increased their oxygen uptake as a 

 linear function of NaCl concentration in the bath. 

 While oxygen uptake of the outer medulla was 

 stimulated by addition of 200 /jm NaCl per ml, this 

 produced only a slight depression of oxygen uptake by 

 slices from the cortex and inner medulla. It is the 

 outer medullary zone that contains the portion of the 

 ascending thick limb of the loop of Henle where the 

 active sodium pump appears to be located, based on 

 the puncture studies. However, evidence of active 



