H°4 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



venous difference when radioactive tracers are used 

 (234). For the splanchnic bed the actual ratio is 

 much lower, approximating unity under most cir- 

 cumstances. A more serious problem is loss of tracer 

 en route either into the interstitial fluid or into col- 

 lateral channels that bypass the liver. The first 

 possibility is usually not very important. The second 

 does not affect the measurement in normal subjects, 

 but with cirrhosis and other conditions leading to the 

 development of a collateral circulation measurement 

 may be impossible. This consideration applies with 

 equal force to evaluation of the "mean" circulation 

 time. 



An accurate analysis of the time required for blood 

 to move through the splanchnic bed requires de- 

 termination of tracer levels in artery and hepatic 

 vein at i-sec or 2-sec intervals owing to the rapidity 

 of the change which must be followed (303). The 

 development of satisfactory means of doing this by- 

 Wheeler (303), Tornvall (290), and their associates 

 has made it possible to apply and to extend analyses 

 of transit times worked out in the course of a study 

 of urine formation (51). Since blood must be drawn 

 through a catheter there is distortion of the concentra- 

 tion curve by the velocity differential produced by 

 laminar flow (215, 274). This factor may be allowed 

 for by sampling arterial and hepatic venous blood 

 at the same rate through catheters having the same 

 dimensions. Wheeler's collection technique involves 

 the use of a 30-foot length of polyethylene tubing 

 into which the blood is drawn together with droplets 

 of mercury to break up the column of blood and to 

 prevent streamlining. Since the tubing has a uniform 

 calibre and since withdrawal is carefully timed, seg- 

 ments of tubing containing blood collected during 

 successive i-sec intervals can be heat sealed and cut 

 off as separate "timed" segments for determination 

 of I 131 activity, after removal of the mercury droplets 

 by centrifugation. Tornvall's device consists of a 

 magazine of 50 U-shaped channels, each with a 

 capacity of 3 ml, arranged in a carrier that auto- 

 matically fills each channel in succession, at i-sec to 

 2-sec intervals, as blood is withdrawn at a constant 

 rate. It is possible to apply values so obtained in the 

 construction of a frequency distribution of arterial- 

 hepatic venous transit times. The effluent from a 

 system of tubes draining a reservoir describes a 

 frequency distribution of transit times from reservoir 

 to sampling site when the reservoir tracer concentra- 

 tion is suddenly set at some arbitrary level (taken as 

 1 00 7c) at zero time. Changes in reservoir (or arterial) 

 concentration are reflected in distortions in the effluent 



(or venous) concentration curve which may be taken 

 into account by sequential comparison and graphic 

 integration. Although hepatic arterial and mesen- 

 teric vasculatures are undoubtedly characterized by 

 markedly different mean circulation times, there is 

 so much dispersion and overlap between these and 

 other splanchnic beds that separation of specific 

 populations has proved impossible. Nevertheless, the 

 method affords a more precise indirect approach to 

 an understanding of the intrasplanchnic distribution 

 of flow and volume than any other now available. 



NORMAL PARAMETERS OF THE HEPATIC CIRCULATION 



Although methodology is now far-advanced, a 

 reliable quantitative description of the hepatic and 

 splanchnic circulation at rest in man and experi- 

 mental animals is still a major desideratum. Un- 

 certainty results from all the technical difficulties 

 already noted. In addition, the control or "resting 

 state" is extremely difficult to define and is perhaps, 

 like the "normal," a relatively meaningless concept. 

 The splanchnic circulation (hence, the hepatic out- 

 flow) serves at one and the same time the demands of 

 viscera engaged in a diversity of metabolic activities 

 and the needs of the cardiovascular system as a 

 whole. The establishment of a steady state referable 

 to each of these factors would be almost impossible 

 and, in any case, of limited applicability. For this 

 reason it has seemed preferable to abstract suitable 

 "control" approximations from the literature and to 

 consider these as the basis for a reasonable appraisal 

 of what may be characterized as the "reference 

 state." 



Hepatic Blood Flow 



Of necessity, data obtained in studies of man and 

 dog must dominate the picture. Although the hepatic 

 circulation has been investigated extensively in the 

 cat, rat, mouse, rabbit, and other species, the in- 

 formation obtained has been largely qualitative; of 

 considerable importance in elucidating physiologic 

 and pathologic adjustments, of but inferential value 

 quantitatively. Systematic exploration of the field of 

 comparative physiology with the methods at hand 

 would be most rewarding. In both man and dog, 

 the figures for hepatic blood flow, portal venous and 

 sinusoidal pressures, and splanchnic blood volume 

 range widely. In 91 apparently normal fasting human 

 subjects, studied resting in recumbency, the BSP 



