EXCHANGE OF SUBSTANCES THROUGH CAPILLARY WALLS 



963 



in the arterial system. With smaller and smaller 

 cannulae he measured pressures in the aorta, carotid 

 artery, and even in a 2-mm branch of the crural 

 artery, and reported : "that a molecule of blood moved 

 with the same force throughout the course of the 

 arterial system, which a priori, with all physiologists, 

 we were far from thinking." It followed, therefore, 

 that the major fall of blood pressure must occur some- 

 where in the smaller vessels beyond the ones he can- 

 nulated. Poiseuille then turned his attention to 

 capillary tubes and studied the relation which volume 

 flow of liquids per unit time bears to pressure, viscosity, 

 tube radius, tube length, and wall surface (287-289). 

 Hence Poiseuille's equation, which underlies the 

 science of hydrodynamics, emerged from questions 

 concerning arterial and capillary blood pressure in 

 animals. 



In 1875 von Kries (182) tried to measure capillary 

 blood pressure in man by an indirect method. He 

 placed a glass plate, 2 to 5 mm 2 in area, on the skin 

 and hung from this plate a small scale pan on which 

 weights were placed until the skin blanched. Five 

 years later Roy & Brown (309) used a capsule fitted 

 with a distensible, transparent membrane to de- 

 termine, under the microscope, the pressures required 

 to modify or obstruct flows through single arterioles, 

 capillaries, and venules in the more or less trans- 

 parent tissues of experimental animals, e.g., the web 

 of the frog. From 1886 to the present, various modifica- 

 tions of these two basic methods were used for many 

 measurements but yielded discordant results, ranging 

 even in one species, man, and in one tissue, skin, from 

 1 to 71 mm Hg (207). Most of these studies were made 

 after 1900 because figures for capillary blood pressure 

 were necessary to prove or disprove Starling's filtra- 

 tion-absorption hypothesis. Even as late as 1925 no 

 conclusions could be reached because the lower values 

 were less than venous pressure and obviously ques- 

 tionable. 



The higher values were criticized because they were 

 based on blanching of the skin or on arrest of blood 

 flow by microscopic examination, and so indicated 

 arteriolar rather than capillary pressure. Moreover, 

 no indirect method could yield information concern- 

 ing the presence or absence of a gradient of pressure 

 in the capillary network itself. When reviewed in 

 1934 (207) indirect methods were found inadequate 

 a) because of variable transmission of pressure through 

 overlying tissues to the capillaries beneath, and b) 

 because of the arbitrary and unproved criteria 

 adopted by various investigators to indicate when 

 externally applied pressure equaled the pressure 



within the capillaries. Direct measurements of the 

 sort attempted by Poiseuille a century earlier were 

 still necessary. 



The requirements for direct measurements of 

 pressure in single capillaries are basically simple, 

 though technically somewhat difficult (198, 203). 

 Figure 2.1 shows (upper left) a micropipette, 5 n 

 in diameter at its tip, under the microscope and 

 ready for use. A somewhat smaller pipette (lower 

 left) is shown inserted into a capillary of the frog's 

 mesentery. The micropipettes are first carefully 

 filled with a saline solution containing heparin, 

 mounted in a micromanipulator and connected to a 

 manometer and syringe (right) so that the pressure 

 exerted on the saline at the tip of the micropipette 

 can be changed rapidly and accurately to balance 

 the changing pressure in the capillary. The micro- 

 manipulator is required not only to insert the pipette 

 into the capillary, but also to keep the lumen of the 

 pipette in free communication with the lumen of the 

 capillary. Minute rods (fig. 2.1, upper left), each 

 controlled by its own micromanipulator, are fre- 

 quently necessary in addition to hold steady thin 

 tissues such as mesentery. Pressure readings from the 

 manometer can be made only at true pressure equi- 

 librium without net flow of liquid through the tip 

 of the pipette because orifices of 5 to 10 n interpose 

 considerable resistance to flow and consequent 

 inaccuracies. Failure to observe this precaution has 

 yielded fallaciously low values for capillary pressure 



(3 6 > 2 °3)- 



With these requirements in mind, suitable criteria 

 were developed for measuring mean, systolic, and 

 diastolic pressures in single capillaries, arterioles, or 

 venules in mesentery (198), skin (205), and muscle 

 of lower animals as well as in the skin of man (203) 

 with an accuracy of a few millimeters of water. Tests 

 showed that changes of capillary pressure induced 

 by graded venous congestion could be detected 

 promptly and accurately by the direct method (203) 

 but not by an indirect method (88). 



B. Capillary Pressures in Various Tissues; Relation 

 to the Osmotic Pressure of the Plasma Proteins 



Direct measurements of pressures in single capil- 

 laries, arterioles, and venules provided answers to 

 Poiseuille's questions concerning the nature and the 

 location of the pressure gradient in the circulatory 

 system. Figure 2.2 shows that in the mesenteric blood 

 vessels of the frog, the major decrease of pressure 

 (70 to 80%) occurred in the arterioles, but there 



