io 3 6 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



300 B.C.; Erasistratus, 310-250 B.C.) the documented 

 study of lymphatics dates from 1622, when Asellius 

 (3) demonstrated "lacteals"' in the mesentery of a 

 well-fed dog and at a later date had the opportunity 

 of observing these channels in a criminal who had 

 been executed following a large meal. Jean Pecquet 

 (169) in 1651 described the cisterna chyli and the 

 thoracic duct. The term "lymphatics" was first used 

 by Thomas Bartholin (12, 13) and he and Rudbeck 

 (186) are usually considered to be the co-discoverers 

 of the lymphatic system.' 2 In 1692 Nuck (160) intro- 

 duced the use of mercury for injection of lymphatic 

 vessels, a method which was used extensively by 

 many investigators during the eighteenth century to 

 describe the location and distribution of the main 

 lymphatic vessels. Of particular importance was the 

 work of Hewson (99), a pupil of William Hunter, 

 who made extensive dissections of the lymphatic 

 system and noted that lymph glands were absent in 

 fishes (also in the turtle), few in number in birds, 

 and well developed only in mammals. He also noted 

 the presence of lymphocytes in lymph and thought 

 they came from lymph glands to enter blood via the 

 lymph channels. Hunter himself speculated that "the 

 lymphatic vessels are the absorbing vessels, all over 

 the body" (101). 



Anatomical studies during the nineteenth century 

 further delineated the distribution and characteristics 

 of the lymphatic supply of various organs (194), but 

 it remained for Ludwig (129) and Heidenhain (96) 

 to provide the stimulus for studies of function. Ludwig 

 developed techniques for the collection of lymph by 

 cannulating lymph vessels in different parts of the 

 body. He contended that lymph was a filtrate derived 

 from blood, a point of view contested by Heidenhain 

 who maintained that it was actively secreted by the 

 lymphatic epithelium. This classic controversy was 

 finally settled by the extensive work of Starling during 

 the first part of this century (203), who demonstrated 

 the relationships between hydrostatic and osmotic 

 pressures in the exchange of substances between 

 plasma and lymph, concepts still fundamental and 

 generally applicable. These relationships have been 

 discussed in Chapter 29. 



The study of lymph and lymphatics has lagged 

 behind that of other parts of the circulation because 

 of inherent difficulties in identification and dissec- 

 tion of the lymphatics and their cannulation. Since 



2 There is an interesting biographical note by G. Liljestrand 

 and a translation of Rudbeck's "Nova exercitatio anatomica" 

 by A. E. Nielsen in the Bulletin of the History of Medicine 1 1 : 

 3 4-339. I942- 



lymph is virtually colorless, it does not help in the 

 visualization of these small vessels. Even the identi- 

 fication and dissection of the largest trunk, the thoracic 

 duct, is a formidable challenge to the uninitiated 

 investigator unless its visualization is aided by previous 

 injection of dyes or feeding of fats. Once identified 

 and dissected, cannulation of a lymphatic still 

 presents a problem because of the ease with which 

 the thin vessel can be torn. This may explain the 

 temptation for investigators to forsake the actual 

 collection of lymph for the much less frustrating 

 study of the effects of ligation of the vessels. Rudbeck 

 expressed these difficulties very well in 1653 when he 

 said: 



"Of the many structures difficult to find in ana- 

 tomical dissections, these vessels, I must confess, are 

 by no means the least. For usually they will not 

 tolerate the finest blunt probe, a sharp knife, a suction 

 tube, or any other instrument whatever. And even 

 though abundantly present, they are often obscured 

 by fat, or are overlooked if not at the moment filled 

 with fluid. When seen they may disappear if not 

 ligated. Thus in elusiveness they rival the lacteals 

 and must be handled with utmost care." 



Several recent developments have, however, made 

 the lives of the lymphatic investigators less trying 

 and their labors more rewarding. Availability of 

 nontoxic and radiopaque dyes has facilitated tracing 

 of lymphatic pathways and stimulated a new interest 

 in this aspect, particularly in surgery (20, 52, 112). 

 To the physiologist, the greatest boons have been 

 the availability of polyethylene tubing and isotopes. 

 The range of sizes and flexibility of polyethylene 

 tubing and relative freedom from clotting in this 

 tubing have made cannulation easier and have 

 made chronic experiments possible not only in un- 

 anesthetized experimental animals but in man (16, 

 31, 54, 125, 177, 201, 208). Small vessels entered 

 with glass cannulae only with the greatest difficulty 

 can now be studied (198, 199). The use of isotopes 

 has facilitated the study of lymphatic uptake from 

 subcutaneous tissues (100, 209). It has also made 

 possible more quantitative studies on the exchange 

 of substances between plasma and lymph. These 

 gains will be apparent in the discussions to follow. 



DEVELOPMENT AND STRUCTURE OF 

 LYMPHATIC VESSELS 



It is now generally agreed that lymphatic vessels 

 are derived from veins. To quote Sabin (190) "Lym- 



