156 THE BLOOD 



Heidenhain was the first to question the adequacy of the blood-pres- 

 sure and filtration hypothesis. He showed that many of the conditions 

 under which lymph formation takes place are not sufficient to produce filtra- 

 tions of the material found. He advanced the hypothesis that the living 

 endothelial lining of the blood vessels exerted a secretory activity in lymph 

 production. He discovered that various substances known as lymphagogues 

 when introduced into the circulatory system produce a remarkable increase 

 in the flow of lymph from the thoracic duct. Further, he noticed that the 

 concentration of the lymph was changed; i.e., increased. Heidenhain 

 thought that the lymphagogues acted directly on the capillary and endothelial 

 lining stimulating these cells to produce a greater quantity of lymph. He 

 divided such substances into two classes. The best known representatives 

 of the " first class" are such as proteoses and peptones, leech extract, ex- 

 tract of crustacean tissue, etc. The lymphagogues of the second class are 

 the neutral inorganic salts, sugars, and other crystalline substances. These 

 all cause a marked flow of lymph. The lymphagogues as a class cause fall 

 of blood-pressure; for example, proteose-peptone injections. This fact 

 argues against their purely physical action. Many drugs act to increase 

 the flow of lymph in a way which cannot be presumed to be other than nor- 

 mal; i.e., they stimulate the physiological processes going on in the endo- 

 thelial cells. Such observations contribute strongly to the view advanced 

 by Heidenhain. Many investigations have been brought to the support of 

 the hypothesis that lymph formation is largely a process of secretion, yet 

 it seems at the present time that we cannot wholly deny that filtration and 

 osmosis play a part in the processes. 



In following the action of peptones and proteoses, Pick and Spiro came 

 to the conclusion that it was not peptone, but some contaminating substance 

 which produced the characteristic action. This hypothetical substance 

 they called peptozyme. Underhill re-examined the influence of peptones, 

 using preparations made from plant proteins by hydration with enzymes, 

 heat, and acid, carrying the hydrolysis to a greater extent than did Pick and 

 Spiro. Underhill still obtained the great increase in the flow of lymph 

 together with the usual fall of blood-pressure. Mendel published the 

 result of a demonstration of post-mortem lymph flow in which he showed 

 that ' ' the lymph continued to flow for four hours without any extraordinary 

 mechanical assistance" after the death of the animal. This observation 

 would seem to give complete refutation of the filtration hypothesis. A 

 similar post-mortem salivary secretion has been observed, and in each case 

 the processes involved must be assumed to be physiological rather than 

 purely physical phenomena. Certainly the permeability or activity of the 

 endothelial lining of the blood vessels varies greatly at different times in 

 the life of an individual, and this variation in function is associated with the 

 marked change in the character and quantity of lymph produced. 



