Lymph

LYMPH, a fluid circulating in higher animals in formed (lymphatic) vessels that originate in the tissues. The fluid filling the tissue spaces and intercellular spaces is called tissue fluid. In a broader sense, L. can be called the entire fluid mass filling the space between blood vessels and tissue elements. The role of lymph follows from this definition: being an intermediary between tissue elements and blood, it represents the true direct nutritional medium for the cellular elements of tissues and organs. From L., cells draw substances that enter it from the blood, and in L. cells secrete products of their metabolism. It follows that the composition of L., on the one hand, should affect nutrition, and consequently the life and activity of a given organ, and on the other hand, the composition of L. should depend on the activity or condition of that organ from which it flows. It is therefore understandable that it is difficult to speak of the composition of L. in general. It is necessary at the same time to indicate that part of the body, that organ, where L. was formed. To a large extent, the inconsistency of data found in different authors is explained by the non-observance of this rule. Composition of L. Lymph from the extremities is poorest in organic substances, L. from the liver is richest in them, and L. of other visceral organs occupies an intermediate position in this respect. In view of the difficulty of obtaining L. from a specific part of the body, lymph obtained from the thoracic duct during fasting is used for studying its chemical composition, as practiced by Heidenhain and the school of Ludwig in the dog. Physical properties. L. in a fasting subject is transparent or very slightly opalescent, greenish-yellow or gray, of a cloying smell and salty taste. It clots fairly quickly, forming a soft, loose clot that captures the white blood cells present in L. The specific gravity of L. is significantly lower than that of blood: 1.026-1.023. The osmotic pressure of L. is significantly higher than that of blood. For human chyle, A 0.51-0.56 was found, and for L. of dog A 0.595-0.625°. The viscosity of L., determined by a viscometer (see Viscosimetry), is lower than that of blood serum: at 15° for L. 28'31.3" was found, while for water 18'41.3"; at 39° for L.-16'29.2", and for water-11'43.4". The reaction of lymph is alkaline, but pH is lower than in blood. The change in electrical conductivity does not go parallel to the change in osmotic pressure, as seen in the following table. Lymph from the thoracic duct after 18 hours of fasting. Viscosity Electrical conductivity Osmotic pressure A at 37° 153 0.60 at 39° 1.300 0.58 1.241 0.59 1.405 0.61 1.406 0.545 1.172 0.595 1.437 The number of formed elements in L. varies in humans from 2,000 to 20,000 in 1 mm³; in dogs-from 980 to 30,000 in the same volume. Under the influence of massage, this number increases significantly, reaching 65,000 and more, of which over 95% are lymphocytes. Along with lymphocytes, monocytes and a few eosinophils are found in L. Erythrocytes and blood plates are absent in normal lymph. Chemical composition. L. contains relatively few solid substances (3.6-5.7%). This amount changes in connection with the rate of lymph formation and depends mainly on the amount of protein substances (on average 3.4%). The proteins of L. are the same as in blood plasma. In humans, for 6 parts of globulin there are 2.4-4.0 parts of albumin. Approximately ^x/_в-₁/₁₀ of all N constitutes residual nitrogen, namely-urea and extractive substances, with urea constituting 0.01-0.66% of all solid substances, i.e. a very small part of the total residual N. L. from the liver is especially rich in proteins. Along with neutral fats, soaps are also found in L. The amount of reducing substances (mainly glucose) is about 0.1%. The remaining (after deducting protein substances) part of solid substances consists to a large extent of mineral salts, the amount of which on average is 0.8-0.9%, with NaCl constituting 67%, and Na₂CO₃-25% of the entire ash. In addition to Cl and alkalis, the ash of L. contains very significant amounts of H₃PO₄, Ca, Mg and Fe. The NaCl content is unusually constant. Of enzymes, diastase (which probably comes from blood), lipase, and in some authors also a glycolytic enzyme have been found in L. Toxic substances that are products of metabolism of various tissues and organs are also found in L. They differ from blood toxic substances by their thermolability; they are destroyed already at 55°. The introduction into the bloodstream of L. of this or that animal causes irritation, and then paralysis of the vasomotor centers. In addition, heat-stable bactericidal substances against paratyphoid A and B, against typhoid, against Shiga-Kruse bacteria, Flexner's, Bact. coli and against various cocci are found in L. The quantitative ratio of diffusing substances in L. is approximately the same as in blood, as seen in the following table. Lymph Animals Urea Sugar Blood Urea Sugar Cow Dog (in percent) 0.019 0.016 0.125 0.019 0.009 0.125 Data obtained from the study of L. during digestion differ significantly from those given above due to the significant admixture of L. from the gastrointestinal tract, the so-called chyle. Observations on this intestinal L., or chyle in humans, were made by Munk and Rosenstein, who used for this purpose a case with a lymph fistula through which intestinal L. was completely excreted. A characteristic feature of chyle is the rich fat content during digestion after a fatty meal, while the protein content does not change, and the carbohydrate content increases only very slightly. 2-3 hours after a fatty meal, L. taken from the thoracic duct takes on the character of chyle. The change in the composition of L. in connection with digestion is seen in the following table. Change in the composition of L. in humans after taking 103 g of protein, 300 g of carbohydrates and 41 g of fat. Reducing substances Ether extract (in percent) Time Protein 1 hour 0.095 0.216 Fasting..... 3.113 1 Through 1-2 hours . . 3.488 1 0.126 0.237 ! » 3-4 » . . 3.060 | 0.161 2.515 i » 5-6 » . . 3.133 | 0.164 3.863 j » 7-8 » . . 2.758 ! 0.205 2.180 1 An increase in the amount of neutral fat in L. is also noted after the administration of fatty acids or soaps. The ether extract of L. increases also after the administration of lecithin, but not after the administration of paraffin oil. A change in the chemical composition of L. is noted in connection with a change in the chemical composition of blood, on the one hand, and with a change in the activity and condition of individual organs and tissues-on the other. In the transition of substances from blood to L., the diffusibility of these substances plays a major role. The rate of introduction of substances into the bloodstream is also of great importance. With slow administration into the bloodstream, a substance does not pass into L., but with a sudden overload of the blood with this substance, its transition to L. is noted already after a few minutes. In general, it has been noted that different substances behave differently in this respect; poisons and toxins, especially bacterial ones, easily pass into L. (e.g. tetanus toxin and antitoxin). The reverse transition from L. to blood has been established for strychnine. A rapid change in blood composition does not always cause the same change in L. in the thoracic duct. Thus, for example, according to Cohnstein's data, the amount of water in L. does not change after the introduction of large amounts of hypertonic NaCl solution. Only after the amount of water in the blood returns to normal, an increase in the amount of water and salt is noted in L., but the NaCl content in lymph never exceeds its content in blood. Among other fluids in the lymphatic system, besides the fluids of serous cavities (peritoneal, pericardial, pleural, etc.), brain L., or cerebrospinal fluid, which differs by the constancy of its composition, is of particular interest. Amount of L. In humans, the amount of water constitutes approximately ²/₃ of the total weight; consequently in a human weighing 60 kg there are 40 liters of water and deducting 4.2 liters of blood, there remain approximately 36 liters of water in the tissues, partly in free form inside cells and in tissue spaces, partly in bound form as swelling water. In humans, according to Starling's data, about 100 cm³ pass from lymphatic vessels into the blood per hour, which constitutes ¹/₂₀ of all tissue fluid. It is interesting to note that the amount of flowing L. is not proportional to the amount of tissue fluid in different parts of the body. Thus, for example, the amount of fluid contained in skeletal muscles and skin constitutes about 70% of all tissue fluid, but under normal conditions, L. is almost not secreted from the lymphatic vessels of the extremities. On the other hand, visceral organs, such as the intestine, liver, spleen and kidneys, taken together, contain only ¹/₇ of all tissue fluid, but are the source of almost all L. flowing through the thoracic duct into the blood.

After the introduction of isotonic and hypotonic salt solutions into the organism, the outflow of L. from the thoracic duct is significantly increased, but not from the lymphatic vessels of the extremities, although 68% of all the fluid introduced into the organism accumulates in the muscles and only 14% in the visceral organs. Thus, on the basis of the magnitude of the outflow of L. from a given part of the body, one cannot judge either the amount of tissue fluid or the magnitude of the exchange between tissues and blood. The outflow depends not only on the intensity of the exchange between tissues and blood capillaries, but also on the ability of individual tissues to retain water. The amount of L. (in the narrow sense) varies considerably depending on the condition of the organism and of each organ individually. The total amount of L. is very difficult to determine. It is easier to determine the amount of L. flowing through the lymphatic duct (thoracic duct) during a certain period (24 hours). In a dog weighing 10 kg, an average of 500-600 cm³ of L. was found in 24 hours, while in a human weighing 60 kg in a state of rest and on an empty stomach - 1,200-1,500 cm³. The question of the transition of tissue L. into lymphatic capillaries is closely related to the resorption of water by tissues. A purely mechanical outflow of tissue L. is excluded, and there is no doubt that osmosis and diffusion play a significant role here. The cause of increased accumulation of L. in tissues may be changes in the walls of capillaries leading to a change in their permeability. Such changes are found, among other things, in areas adjacent to inflammatory (see Inflammation) foci, where tissues become saturated with fluid. With local irritation of the skin, the introduction of a physiological solution into the blood causes edema at this site. The same phenomenon is observed in certain poisonings (arsenic, chloroform, etc.). In all these cases, there is apparently an increased permeability of capillary walls. The importance of the condition of vascular walls, in particular capillary walls, for the formation of L. causes no doubt, and the role of permeability stands first. Theories of lymph formation can be reduced to three main ones: 1) the physical filtration theory of Ludwig, later modified by Starling, Cohnstein, and Fischer; 2) the secretory theory of Heidenhain; and 3) Ascher's theory, according to which the formation of lymph is a reflection of the cellular activity of organs. These three theories do not exclude, but rather complement each other. According to Ludwig and Starling, filtration plays the primary role. An increase in pressure in capillaries leads to filtration of fluid from vessels into tissues, and decreased pressure in capillaries causes a reverse flow of fluid from tissues into capillaries. Thus, after a blood transfusion, the liquid part of blood leaves the vessels, while blood corpuscles remain. By sequential determination of Hb, one can follow the transition of fluid from vessels into tissues. The reverse picture is obtained after bloodletting, as well as after the introduction of fluid under the skin. The transition of fluid from vessels into tissues and back is also observed with simple fluctuations in blood pressure. For example, an increase in pressure under the influence of adrenaline causes in a dog the transition of 24% of all blood fluid into tissues. Ligation of veins increases the amount of L., ligation of arteries decreases it. The amount of L. also increases in the case of plethora. L. was considered by followers of Ludwig as a product of filtration of blood plasma through vascular walls due to the pressure difference existing between blood inside capillaries and interstitial fluid. This theory was dominant until the end of the 19th century despite some observations that were difficult to reconcile with it. For example, it was noted that the flow of L. in the thoracic duct does not stop after complete clamping of the aorta at the place of transition into the abdominal aorta, despite the fact that in the area of the abdominal aorta pressure after this drops to zero. L. thus continues to form independently of blood pressure. This formation of L. occurs in the liver, because after ligation of the liver lymphatic vessels, the flow of L. stops immediately. These observations of Heidenhain were subsequently explained in the works of Bayliss and Starling and Ascher, who studied capillary pressure in various vascular areas when a particular vessel was clamped. For example, clamping of the portal vein increases the amount of L. 5-6 times due to an increase in capillary pressure in visceral organs (with the exception of the liver). Clamping of the inferior vena cava above the diaphragm, causing an increase in capillary pressure in the liver, increases the amount of L. 10-20 times with a simultaneous increase in the amount of proteins. After ligation of the liver lymphatic vessels, clamping of the inferior vena cava has no effect. Ligation of the aorta, lowering pressure in all visceral organs but not lowering, but even increasing, capillary pressure in the liver, does not therefore decrease the flow of L. In essence, it is not arterial but capillary pressure in visceral organs that regulates the formation and flow of lymph. Thus, by these experiments, Heidenhain does not refute the importance of filtration processes. Along with filtration, diffusion and osmosis phenomena play a significant role in the formation of L. The difference in the composition of L. and blood plasma indicates the participation of osmotic processes in the formation of lymph. In contrast to the school of Ludwig, which considered L. as a filtrate of blood plasma with subsequent diffusion, Heidenhain attributes a significant role in the formation of lymph to the secretory activity of the endothelium of capillaries. Although Heidenhain's observations on the effect of ligation of individual blood vessels on the flow of L., which he put forward against Ludwig's filtration theory, in essence do not refute the importance of filtration processes, nevertheless they showed that the flow of L. cannot be explained by these processes alone. The essential point in Heidenhain's work is that it demonstrates the action of chemical substances on the exchange between plasma, tissues, and L. Substances that promote the formation of L., lymphagogues, are divided by Heidenhain into substances of the first and second order. Lymphagogues of the first order, which increase the amount of L. at the expense of blood plasma, include various colloidal substances (for the most part chemically undefined): extracts of crab muscles, leeches, solutions of proteins and albumoses, bacterial toxins, peptones, histamine (so-called shocking poisons) and substances that cause anaphylaxis. The introduction of these substances into the circulation causes a significant and prolonged increase in the flow of L. in the thoracic duct. This L. comes almost exclusively from the liver, because preliminary ligation of the liver lymphatic vessels destroys the effect of these lymphagogues. L., obtained under the influence of lymphagogues of the first order, is richer in protein substances than ordinary L. It is interesting to note that lymphagogues of the first order, simultaneously with an increase in the amount of L., not only do not increase arterial pressure, but on the contrary, decrease it and often very significantly. The action of lymphagogues of the first order cannot also be explained by osmotic phenomena due to the small amount of substance introduced. This independence of the amount of L. from blood pressure on the one hand and the apparent at least partial independence of the composition of L. from the laws of diffusion on the other led Heidenhain to the conclusion that lymph formation must be attributed to the category of secretory processes. The endothelial cells of capillaries perform the role of secretory cells, and lymphagogues are excitants of these cells to the same extent as other substances are excitants of certain secretory cells. However, the effect of lymphagogues of the first order can be explained by their action on the permeability of capillaries; an increase in this permeability leads to enhanced filtration of lymph. Lymphagogue substances of the second order cause an increase in the amount of L. at the expense of tissue water. Such are crystalloids: concentrated solutions of neutral salts, sugar, and urea. The introduction into the bloodstream of such solutions greatly increases the flow of L. in the thoracic duct. This L. is more watery. Since at the same time the blood also becomes more watery, it must be recognized that the increase in the amount of L. in these cases occurred at the expense of tissue water. The process in this case is as follows: crystalloides introduced into the blood increase its osmotic pressure and consequently attract water from lymph into capillaries. On the other hand, due to the permeability of capillaries to crystalloides, the latter, passing into L., increase its osmotic pressure and consequently attract water from tissues into lymph spaces. The result of all this is an increase in the total amount of L., which flows per unit of time through the thoracic duct. Ascher's theory differs from Heidenhain's theory in that it attributes the main role in lymph formation not to the endothelium of capillaries, but to the cellular elements of tissues and organs. According to this theory, the increase in the amount of L. under the influence of lymphagogues is explained by their effect on metabolism. The introduction into the blood of so-called lymphagogues causes a series of changes in the chemistry of blood, indicating a change in the activity of individual organs.

Thus, for example, after the introduction of large amounts of peptone, along with an increase in the amount of L., there is noted an increased secretion of bile (leading to jaundice), an increase in residual nitrogen in the blood and non-coagulable nitrogen in the liver, an increase in globulins in L. and blood, a decrease in leukocytes and sugar, non-coagulability of the blood and immunity against subsequent introductions of peptone. The close connection between the formation of L. and the activity of organs is proven by the parallelism between protein breakdown, N secretion and the amount of L., an increase in the flow of L. from the corresponding part of the body with increased secretion of the thyroid gland, etc. This connection is especially clearly visible in the experiment with the salivary gland, under the influence of which irritation of the chorda tympani strengthens the flow of L. and the secretion of saliva, and under the influence of atropine the flow of L. and the secretion of saliva cease despite high capillary pressure. The action of certain hormones also speaks in favor of such a connection. Thus, according to Eppinger, the action of thyroxine on the water metabolism of the body consists in accelerating the lymph flow, which is a consequence of the intensified metabolism. If the participation of cellular elements in the formation of lymph is beyond any doubt, then on the other hand one cannot deny the importance of capillary permeability in this process. L., as already said, is a mixture of fluid passing from the blood through the walls of capillaries and of interstitial fluid. It is clear that the composition of L. will depend on the permeability of the vessel walls and on the condition of the tissues and organs. The permeability of the capillary walls or their resistance to the passage of certain substances from the blood into L. play an essential role for nutrition, and consequently for the life and activity of that organ for which this L. is the immediate nutritional medium. On the other hand, the composition of the interstitial fluid, depending on the activity of the cellular elements of a particular tissue, does not remain without influence on the condition of the corresponding capillary walls and changes their permeability in one direction or another. Speaking of the permeability of capillary walls, one must also keep in mind their barrier function, allowing them to regulate the composition of L. This barrier function of capillaries is very clearly expressed in the brain and is reflected in the process of lymph formation in the central nervous system. Lymph circulation. The movement of lymph is closely connected with its formation. One cannot speak of circulation in the true sense in this case, since lymph does not return to its place of origin. L. in general moves or flows from the interstitial spaces into lymph. capillaries and through larger lymph. vessels into the thoracic duct, which communicates with the venous system. The speed of lymph flow is usually determined by the amount of fluid flowing out in a unit of time from a fistula of the thoracic duct or another large lymph. vessel. In other words, the speed is identified with the amount of L. formed. This is of course correct only in the case if the capacity of the lymph. vessels remains unchanged. The speed of movement was also studied by determining the time required for the appearance in the thoracic duct of a substance introduced into a lymph. vessel of the leg. It was found that peptone passes this space in 20 minutes, and sodium indigotin in 10 minutes. The main factor promoting the movement of L. is the pressure of the forming lymph, so-called vis a tergo, as is evident from the fact that clamping or tying of a lymph. vessel causes strong swelling, sometimes leading to rupture of this vessel. Besides this main factor there is a whole series of additional factors: suction by the chest, abdominal pressure, pulsation of the aorta, movements of the gastro-intestinal tract, contractions of muscles and lymph. valves—in general the same factors that promote the movement of blood in the venous vessels (see Blood circulation).--The pressure of L., like the speed of its movement, fluctuates very much depending on all the above-mentioned factors. Therefore the average value is difficult to establish. In the lymph. vessels of the neck in a dog and a horse the pressure equals 10-20 mm of water column. The speed of flow of L. in a lymph. vessel is considerably less than in a venous vessel of the same diameter. Lymph circulation depends besides the above-mentioned factors also on the contraction of the lymph. vessels themselves, which is under the influence of the nervous system. It was noted that irritation of the mesenteric nerves causes constriction, and irritation of the nn. splanchnicorum causes dilation of the lacteal vessels and the cisterna chyli; irritation of the thoracic part of the n. sympathicus dilates the thoracic duct. There are no true lymph. vessels in the brain. L. fills besides the intercellular spaces (tissue fluid) of Virchow and Robin the periadventitial and perivascular spaces of His (His), the cerebral ventricles and the subarachnoid and subdural spaces. The fluid filling the ventricles, subarachnoid and subdural spaces is designated as cerebro-spinal FLUID.

L. Stern. Pathological lymph. Disorders of lymph circulation. Lymph under pathological conditions often undergoes significant changes of a quantitative and qualitative order. Increased lymph formation is observed in all cases of pathological transudation of fluid from the bloodstream, as well as with enhanced retention of fluid by the tissues themselves (see Edema). Any increase in metabolism entails an increase in the amount of outgoing L., which is especially vividly expressed in inflammation. Greater significance have deviations in the composition of L. itself. Thus, flowing from inflamed tissues, it is relatively richer in leukocytes, often contains desquamated endothelial cells; sometimes abundant admixture of cells and cellular detritus, for example in L. flowing from a resolving pneumonic focus, makes L. cloudy, milky, pus-like; increased content of fibrinogen in L. facilitates the process of thrombus formation in lymphatic. vessels, and indirectly in the circulatory system. In all cases of violation of the integrity of structural elements of an organ or part thereof, they can in the form of detritus get into L. and be transported by it. Thus, in softening of the brain and apoplexy the perivascular lymphatic. spaces often carry large amounts of blood pigment, tissue disintegration; in destruction of adipose tissue, bone marrow, fat droplets get into L. L. often contains various exogenous pigments, for example coal pigment in lymph. vessels of the lungs in anthracosis, etc. The growth of tissues by elements of neoplasms often leads to the appearance of the latter cells in L. with subsequent development of metastases. With L. bacteria can also be transported. Of the disorders of lymph circulation the greatest significance is attached to the so-called lymphostasis, when the outflow of L. is more or less completely delayed. In these cases, after the initial phenomena of lymphangiectasia (see) thickening of lymph can occur, sometimes its transformation into a whitish detritus. Difficulties in the outflow of L. in the usual direction can lead to various bypass movements of it, as well as retrograde outflow, and on this basis extensive and distant, going in the reverse direction, deposits of metastasizing with L. cancer elements, pigments, bacteria are possible, for example in lymphogenous generalization of tbc, in anthracosis of retroperitoneal glands, in lymphogenous metastases of stomach cancer in the ovaries, etc. Such a retrograde flow of L. becomes all the more possible that with dilation of the bed of lymphatic. vessels insufficiency of their valve apparatus arises, in consequence of which particles suspended in L. settle in the lower layers of an almost stationary column of lymphatic fluid. However, since even with dilation of lymphatic. vessels contractions of their walls occur, one must also admit the possibility of an active reverse flow of L. It is clear that the speed and practical significance of such a flow will depend on the number of lymph. glands in the path of L., on the degree of development of bypass paths bypassing the glands. In sharply expressed lymphangiectasias rupture of lymph. vessels and lymph effusion (lymphorrhea or lymphorrhagia) can occur. Such a rupture can be observed both in the largest lymph. vessels, for example in the thoracic duct (with the phenomenon of chylous hydrothorax, ascites), and in small ones, for example in the perivascular vessels of the brain, and as in hemorrhages (though to a much lesser degree), destructive changes from the side of the brain substance can be observed. Prolonged disorders in lymph circulation often lead to the so-called elephantiasis of tissues (see Elephantiasis).