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HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



in his laboratory in 1850. According to Ludwig: 



". . . the blood which is contained in the vessel 

 tends to equalize, through the porous vessel walls, its 

 pressure and its chemical composition with those of 

 the fluids which lie outside the vessels. If, for example, 

 the contents of the vessels increases, the pressure in 

 the vessels also increases, and immediately a portion 

 of blood passes out into the tissues, driven by a fil- 

 tration pressure." 



But this "filtration pressure" proved unable, by 

 itself, to explain either the control of the volume of 

 lymph flow or the regulation of the constancy of 

 blood volume. Many of Ludwig's earlier experiments 

 supported his belief that this was accomplished by a 

 direct relationship between blood pressure, filtration, 

 and lymph formation, followed by return of this 

 lymph to the blood stream. Elevating venous pressure 

 in portions of the circulation of a whole animal in- 

 creased lymph flow, as did also elevating arterial 

 pressure in perfused tissues. However, others showed 

 very soon that elevations of blood pressure produced 

 by vasomotor changes did not always produce the 

 predicted increase of filtration. Moreover, little 

 lymph could be obtained from the resting limb; 

 whereas Ludwig's filtration hypothesis required that 

 even resting blood pressure should have produced 

 both filtration and lymph flow. 



The problem became temporarily still more obscure 

 after 1880 when Heidenhain began studying the 

 abundant flow of lymph from the thoracic duct which 

 continued even during rest. The actions of his two 

 classes of lymphagogues, coupled with slight but 

 definite inequalities of solute concentrations in plasma 

 and lymph (explained now, in large part, by the 

 Gibbs-Donnan equilibrium) led him to postulate 

 active secretion by the cells of the capillary walls and 

 possibly by the lymphatics (145a). Heidenhain found 

 Ludwig's simple filtration theory adequate for some 

 conditions and quite unable to explain others. On 

 the other hand, Heidenhain's secretion theory was 

 supported by no direct proof. At this point Starling 

 measured the osmotic pressure of the plasma proteins 

 and added absorption to Ludwig's filtration. In 1896, 

 under the title "On the absorption of fluids from the 

 connective tissue spaces," Starling wrote: 



". . . although the osmotic pressure of the proteids 

 of the plasma is so insignificant, it is of an order of 

 magnitude comparable to that of the capillary pres- 

 sures; and whereas capillary pressure determines 

 transudation, the osmotic pressure of the proteids 

 of the serum determines absorption." (345) 

 This hypothesis, despite its attractiveness, did not 



find general acceptance for several decades until 

 improved methods were developed for measuring the 

 osmotic pressure of the plasma proteins and also 

 capillary blood pressure. Apparent exceptions to the 

 hypothesis became explicable as investigators learned 

 more about the nature of the capillary wall itself, 

 the hydrostatic pressure of the interstitial fluid, and 

 the osmotic pressure of the proteins in that fluid. 

 For purposes of summary, and of consecutive, more 

 detailed discussions of each factor, a general relation- 

 ship can be formulated. It must be emphasized, how- 

 ever, that this formulation is a composite which is 

 based on many overlapping experiments, each of 

 which dealt simultaneously with several of the varia- 

 bles, but not with all. 



em. -- k(p - n. -p. +n.) (1.1) 



+ - filtration 

 - - absorption 



F.M. represents fluid movement through the 

 capillary wall, with a plus sign to indicate filtration, 

 and a minus sign to indicate absorption. P r is capil- 

 lary blood pressure (hydrostatic); LT P ;, the osmotic 

 pressure of the plasma proteins; P,<, the pressure in 

 the interstitial fluid compartment (hydrostatic); 

 and Hi/, the osmotic pressure of the proteins in the 

 interstitial fluid immediately outside the capillary 

 walls. The proportionality factor, k, has been called a 

 filtration constant or, more appropriately, a filtration 

 coefficient and is a measure of the permeability of 

 the capillary wall to isotonic fluid. Each of these 

 factors will be considered in succession. 



2. CAPILLARY BLOOD PRESSURE, P c 



A. Methods of Measuremt ni 



The pressure under which blood flows through the 

 capillary vessels was very much in the minds of the 

 earliest investigators even when pressure measure- 

 ments were limited to large blood vessels and to lower 

 animals. Thus Hales, in 1773, having determined 

 the first arterial and venous pressures, went on at 

 once to make certain assumptions and then calculated 

 the "force of the blood in the capillary vessels" to be 

 1.838 gr. with the qualification that to this "must 

 be added the velocity which the blood has acquired 

 at its first entrance in the capillary vessel, which can 

 be but small as appeared by the great resistance it 

 meets within the capillary vessels. . ." (140). In 

 1828 Poiseuille (286) devised the U-tube mercury 

 manometer and measured the gradient of pressure 



