1911 Encyclopædia Britannica/Lymph and Lymph Formation
LYMPH and LYMPH FORMATION. Lying close to the blood-vessels of a limb or organ a further set of vessels may be observed. They are very pale in colour, often almost transparent and very thin-walled. Hence they are frequently difficult to find and dissect. These are the lymphatic vessels, and they are found to be returning a fluid from the tissues to the bloodstream. When traced back to the tissues they are seen to divide and ultimately to form minute anastomosing tubules, the lymph capillaries. The capillaries finally terminate in the spaces between the structures of the tissue, but whether their free ends are closed or are in open communication with the tissue spaces is still undecided. The study of their development shows that they grow into the tissue as a closed system of minute tubes, which indicates that in all probability they remain permanently closed. If we trace the lymphatic vessels towards the thorax we find that in some part of their course they terminate in structures known as lymphatic glands. From these again fresh lymphatic vessels arise which carry the fluid towards the main lymph-vessel, the thoracic duct. This runs up the posterior wall of the thorax close to the aorta, and finally opens into the junction of the internal jugular and left subclavian veins. The lymph-vessels from the right side of the head and neck and from the right arm open, however, into the right subclavian vein (see Lymphatic System below).
Chemical Constitution of Lymph.—The lymph collected from the thoracic duct during hunger is almost water clear and yellowish in colour. Its specific gravity varies from 1015 to 1025. It tastes salt and has a faint odour. It is alkaline in reaction, but is much less alkaline than blood-serum. Like blood it clots, but clots badly, only forming a soft clot which quickly contracts. The lymph collected from a lymphatic before it has passed through a lymph gland contains a few leucocytes, and though the number of lymphocytes is greater in the lymph after it has flowed through a gland it is never very great. In normal states there are no red blood corpuscles.
The total solids amount to 3.6 to 5.7%, the variations depending upon the amount of protein present. The lymph during hunger contains only a minute quantity of fat. Sugar (dextrose) is present in the same concentration as in the blood. The inorganic constituents are the same as in blood, but apparently the amounts of Ca, Mg and P2O5 are rather less than in serum. Urea is present to the same amount as in blood. If the lymph be collected after a meal, one important alteration is to be found. It now contains an abundance of fat in a very fine state of subdivision, if fat be present in the food. The concentrations of protein and dextrose are not altered during the absorption of these substances.
The Significance of Lymph.—In considering the significance and use of lymph we must note in the first place that it forms an alternative medium for the removal of water, dissolved materials, formed elements or particles away from the tissues. All materials supplied to a tissue are brought to it by the blood, and are discharged from the blood through the capillary wall. They thus come to lie in the tissue spaces between the cells, and from this supply of material in a dissolved state the cells take up the food they require. In the opposite direction the cell discharges its waste products into this same tissue fluid. The removal of material from the tissue fluid may be effected either by its being absorbed through the capillary wall into the bloodstream, or by sending it into the lymphatic vessels and thus away from the tissue. From this point of view the lymphatics may be looked upon in a sense as a drainage system of the tissues. Again, besides discharging fluid and dissolved material into the tissue spaces, the blood may also discharge leucocytes, and under many conditions this emigration of leucocytes may be very extensive. These also may leave the tissue space by the path of the lymph channels. Moreover, the tissues are at any time liable to be injured, and the injury as well as damaging many cells may cause rupture of capillaries (as in bruising) with escape of red blood-cells into the tissue spaces. If this occurs we know that the damaged cells are destroyed and their débris removed either by digestion by leucocytes or by disintegration and solution. The damage of a tissue also commonly involves an infection of the damaged area with living micro-organisms, and these are at once admitted to the tissue spaces. Hence we see that the lymphatics may be provided as channels by which a variety of substances can be removed from the tissue spaces. The question at once arises, is the lymph channel at all times open to receive the materials present in the tissue space? If such be the case, lymph is simply tissue fluid, and anything that modifies the constitution or amount of the tissue fluid should in like proportion lead to a variation in the amount and constitution of the lymph. But if the lymph capillary is a closed tubule at its commencement this does not follow.
From these considerations we see that in the first instance the whole problem of lymph formation is intimately bound up with the study of the interchanges of material between the blood and the various tissue cells. The exchange of material between blood and tissue cell may possibly be determined in one or both of two ways. Either it may result from changes taking place within the tissue cell, or the tissue cell remaining passive material may be sent to or withdrawn from it owing to a change occurring either in the composition of the blood or to a change in the circulation through the tissue. Let us take first the results following increased activity of a tissue. We know that increased activity of a tissue means increased chemical change within the tissue and the production of new chemical bodies of small molecular size (e.g. water, carbonic acid, &c.). The production of these metabolites means the destruction of some of the tissue substance, and to make good this loss the tissue must take a further amount of material from the blood. We know that this takes place, and moreover that the waste products resulting from activity are ultimately removed. The question then becomes: When does this restoration take place, and what is the intermediate state of the tissue? We know that increased activity is always accompanied by an increase in the blood-supply, indicating a greater supply of nutritive material, though it may be that the increased supply required at the actual time of activity is oxygen only. Simultaneously the opportunity for a more rapid removal of the waste products is provided. We have to inquire then: Does this increased vascularity necessarily mean an increased outpouring of water and dissolved material into the tissues, for this might follow directly from the greater filling of the capillaries, or from the increased attracting power of the tissues to water (osmotic effect) due to the sudden production of substances of small molecular size within the tissue? The other possibility is that the increased volume of blood sent to the tissue is for the sole purpose of giving it a more rapid supply of oxygen, and that the ordinary normal blood-supply would amply suffice for renewing the chemical material used up during activity. Tissues undoubtedly vary among themselves in the amount of water and other materials they take from the blood when thrown into activity, and their behaviour in this respect depends upon the work they are called upon to perform. We must discriminate between the substance required by and consumed by the tissue, the chemical food which on combustion yields the energy by which the tissue performs work, and, on the other hand, the substance taken from the blood and either with or without further elaboration discharged from the tissue (as, for instance, in the process of secretion). The tissue contains in itself a store of food amply sufficient to enable it to continue working for a long time after its blood-supply has been stopped, and everything indicates that the supply of chemical energy to the tissue may be slow or even withheld for a considerable time. Hence we are led to conclude that the increased flow of blood sent to a tissue when it is thrown into activity is first and foremost to give that tissue an increased oxygen supply; secondly, to remove waste carbonic acid; thirdly, and only in the case of some tissues, to provide water salts and other materials for the outpouring of a secretion, as an instance of which we may take the kidney as a type. Hence there is no need to suppose that an extensive accumulation of fluid and dissolved substances takes place within a tissue when it becomes active. This must be an accumulation which would lead to an engorgement of the tissue spaces and then to a discharge of fluid along the lymph channels. To enable us to determine the various points just raised we must know whether an increased blood-supply to a tissue necessarily means an increased exudation of fluid into the tissue spaces, and moreover we must study the exchange of fluid between a tissue and the blood under as varied a series of conditions as possible, subsequently examining whether exchange of fluid and other substances between the tissue and the blood necessarily determines quantitatively the amount of lymph flowing from the tissue. Hence we will first study the exchanges between the blood and a tissue, and then turn our attention to the lymph-flow from the tissues.
The Exchanges of Fluids and dissolved Substances between the Blood and the Tissues.—Numerous experiments have been performed in studying the conditions under which fluid passes into the tissues and tissue spaces—or in the reverse direction into the blood. We may group them into (1) conditions during which the total volume of circulating fluid is increased or decreased; (2) conditions in which the character of the blood is altered, e.g. it is made more watery or its saline concentration is altered; (3) conditions in which the blood-supply to the part is altered; (4) conditions in which the physical character of the capillary wall is altered.
1. The total volume of blood in an animal has been increased among other ways by the transfusion of the blood of one animal directly into the veins of a second of the same species. It is found that within a very short time a large percentage of the plasma has been discharged from the blood-vessels. It has been sent into the tissues, notably the muscles, and it may be noted in passing without producing any increase in the lymph-flow from these vessels. An analogous experiment, but one which avoids the fallacy introduced by injecting a second animal’s blood, has been performed by driving all the blood out of one hind limb by applying a rubber bandage tightly round it from the foot upwards. This increases the volume of blood circulating in the rest of the body, and again a rapid disappearance of the fluid part of the blood from the vessels was observed—the fluid being mainly sent into the muscles, as was indicated by showing that the specific gravity of the muscles fell during the experiment. The experiments converse to these have also been studied. Bleeding is very rapidly followed by a large inflow of fluid into the circulating blood—this fluid being derived from all the tissues, and especially again from the muscles. Or again, when the bandage from the limb in the above-cited experiment was removed, the total capacity of the circulatory system was thereby suddenly increased, and it was found that the total volume of blood increased correspondingly, the increased volume of fluid being drawn from the tissues and especially again from the muscles. The rapidity with which this movement of fluid into or out of the blood takes place is very striking. The explanation usually offered is that the movement is effected by changes in the capillary pressure due to the alteration in the volume of blood circulating. While this seems feasible when the volume of blood is increased, it does not offer a satisfactory explanation of the rapid movement of fluid from the tissues when the volume of the blood is decreased. One must therefore look for yet further factors in this instance.
2. Let us next turn attention to the second of our three main variations, viz. that in which the composition of the blood is altered. It has long been known that the injection of water, or of solutions of soluble bodies such as salts, urea, sugar, &c., leads to a very rapid exchange of water and salts between the blood and the tissues. Thus if a solution less concentrated than the blood be injected, the blood is thereby diluted, but with very great rapidity water leaves the blood and is taken up by the tissues. Again, if a strong sugar or salt solution be injected, the first effect is a big discharge of water from the tissues into the blood and the movement of fluid is effected with great rapidity. In these instances a new physical factor is brought into play, viz. that of osmosis. When a solution of lower osmotic pressure than the blood is injected the osmotic pressure of the blood falls temporarily below that of the tissues, and water is therefore attracted to the tissues. The converse is the case when a solution of osmotic pressure higher than the blood is injected. This at first sight seems to be an all-sufficient explanation of the results recorded, but difficulties arise when we find that the tissues are not equally active in producing the effects. Thus it is found that the muscles and skin act as the chief water depot, while such tissues as the liver, intestines or pancreas take a relatively small share in the exchange. Again, when a strong sodium chloride solution is injected a considerable part of the sodium chloride is soon found to have left the blood, and it has been shown that the chloride depot is not identical with the water depot. The lung, for instance, is found to take up relatively far more of the salt than other tissues. Simultaneously with the passage of the salt into the tissue an exchange of water from the tissue into the blood can be observed, both processes being carried out very rapidly. The result is that the blood very quickly returns to a state in which its osmotic pressure is only slightly raised; the tissue, on the other hand, loses water and gains salt, and its osmotic pressure and specific gravity therefore rises. Again, the tissues do not participate equally in producing the final result, nor is the tissue which gives up the largest amount of water necessarily that which gains the largest amount of salt. The results following the injection of solutions of other bodies of small molecular size, e.g. urea or sugar, are quite analogous to those above described in the case of the non-toxic salt solutions. Hence we see that the rate of exchange of fluid and dissolved substance between a tissue and the blood can be extremely rapid and that the exchange can take place in either direction. We may also conclude that the main cause of the exchange, and possibly the only one, is the osmotic action set up by the solution injected, and that muscle tissue is particularly active in the process.
Seeing that a very considerable amount of water or of dissolved substance can be taken up from the blood into a tissue, the question next arises: Where is this material held, in the tissue cell or in the tissue space? Immediately the water or salt leaves the blood it reaches the tissue space, but unless the process be extreme in amount it probably passes at once into the tissue cell itself and is stored there. If the process is excessive oedema is set up and fluid accumulates in the tissue space.
These, taken quite briefly, are some of the more important conditions under which fluid exchanges take place. They are selected here because of the extent and rapidity of the changes effected.
3. The third factor which may bring about a change in the amount of fluid sent to a tissue is a variation in the capillary pressure. A rise in capillary pressure will, if filtration can occur through the capillary wall, cause an increased exudation of fluid from the blood. Thus the rise in general blood-pressure following the injection of a salt solution could cause an increased filtration into the tissues. Or again, the hydraemia following a salt injection would favour an increased exudation because the blood would be more readily filtrable. We, however, know very little of the effect of changes in capillary pressure upon movement of fluid into the tissue spaces and tissues, most of such observations being confined to a study of their effect upon lymph-flow. We will therefore return to them in this connexion.
4. The remaining factor to be mentioned is a change in the character of the capillary wall. It is well known that many poisons can excite an increased exudation from the blood and the tissue may become oedematous. Of such bodies we may mention cantharidin and the lymphogogues of Class I (see later). A like change is also probably the cause of the oedema of nephritis and of heart disease. It has also been suggested that the capillaries of different organs show varying degrees of permeability, a suggestion to which we will return later.
Lymph Formation.—There are two theories current at the present day offering explanations of the manner in which lymph is formed. The first, which owes its inception to Ludwig, explains lymph formation upon physical grounds. Thus according to this theory the lymphatics are open capillary vessels at their origin in the tissues along which the tissue fluid is driven. The tissue fluid is discharged from the blood by filtration, and therefore its amount varies directly with the capillary pressure. The amount of fluid movement also is further determined by osmotic actions and by the permeability of the capillary wall.
The second theory first actively enunciated by Heidenhain regards lymph formation as a secretory process of the capillary wall, i.e. one in the discharge of which these cells perform work and are not merely passive as in the former theory. As we shall see, it is now probable that neither theory is completely correct.
In considering lymph formation we have to examine both the total amount of lymph formed in the body and the variations in amount leaving each separate organ under different conditions. In most investigations the lymph was collected from the thoracic duct, i.e. it was the lymph returned from all parts of the body with the exception of the right arm and right side of the head and neck. The collection of the lymph from organs is much more difficult to effect, and hence has not, to the present, been so extensively studied. We will consider first variations in the amount of the thoracic duct lymph. Lymph is always flowing along the thoracic duct, and if the body is at rest, it has been shown that this lymph is coming practically entirely from the intestines and liver, chiefly, moreover, from the liver. The variations in the amount flowing under various conditions has been extensively studied. We will discuss them under the following headings: Changes brought about (a) by altered circulatory conditions, (b) by the injection of various substances, and (c) as a result of throwing an organ into activity.
Ligature of the portal vein leads to an increased flow of duct lymph. Ligature of the inferior vena cava above the diaphragm also leads to a large increase in the flow of duct lymph. Ligature of the aorta may result in either an increased or decreased flow of direct lymph. One explanation of these results has been offered from a study of the changes in capillary pressure set up in the main organs involved. Thus, after ligature of the portal vein the capillary pressure in the intestines rises, and it was proved that the increase in thoracic duct lymph came from the intestines. Ligaturing the inferior vena cava causes a big rise in the pressure in the liver capillaries, the intestinal capillary pressure remaining practically unaltered. Here it was proved that the increase in lymph-flow came from the liver and was more copious in amount than in the former instance. A further difference is that this lymph is more concentrated, a feature which always characterizes liver lymph. Ligature of the aorta may or may not cause a rise in the liver capillary pressure, and it has been shown that if the pressure rises there is an increased lymph-flow from the liver and conversely. The increase of lymph comes entirely in this instance also from the liver. It is in fact but a special instance of the former experiment. From these results it has been argued that lymph formation is simply a filtration fundamentally, and the lymph-flow is determined mainly by the capillary pressure. Variations in the quantity of lymph issuing from different organs have been on this theory ascribed to differences in the permeability of the capillaries of the organs. Thus as liver lymph is richest in protein content and is produced in greatest amount, it has been concluded that the liver capillaries possess the highest permeability. The intestines stand next in producing a concentrated lymph, and their capillaries are therefore assumed to stand second as regards permeability. Lastly, the lymph coming from limbs and other organs is much poorer in solids and much less copious in amount. Hence it is argued that their capillaries show the least permeability. It is, however, very unsafe to compare the liver capillaries with those of other organs, since they are not in reality capillaries but rather venous sinuses, and their relation to the liver cells is characteristically different from that of ordinary capillaries. If an animal is at rest, no lymph flows from the hind limbs. To obtain a sample of limb lymph it is necessary to massage the limb. If, however, the veins to the limb be ligatured, we obtain a flow of lymph. The ligature of course causes a rise of the capillary pressure, and it has been argued that this rise of pressure starts a filtration through the capillary wall and hence a flow of lymph. But the stoppage of the blood-flow also damages the capillary wall and tissue cells by asphyxiation, and the resulting lymph-flow is in all probability the resultant of many complex processes. This case is analogous to the production of oedema in cases of heart disease where the circulation is feeble and the oxygen supply to the parts deficient. The results of these experiments form the main evidence in support of the filtration theory of lymph formation. They were first systematically studied by Heidenhain, to whom we owe so much of our knowledge of lymph formation. He did not, however, conclude that they established the filtration theory.
In continuing his observations Heidenhain next studied the results following the injection of a number of substances into the blood. He found many which on injection gave rise to an increased lymph-flow from the thoracic duct, and arranged them in two classes. As instances of lymphogogues of the first class we may mention extract of mussels, leech extract, peptone, extract of crayfish muscle, extract of strawberries, of raspberries and many other like substances. Lymphogogues of the second class comprise neutral salt solutions, urea, sugar, &c. Considering the latter class first we may take as a type a solution of sodium chloride. Injection of such a solution causes a large increase in the lymph-flow, and it has been proved that the lymph comes from the liver and intestines only—chiefly from the former. It is especially to be noted that there is no lymph-flow from the limbs, and the same is true for all lymphogogues of this class. As indicated above, the injection of a saline solution leads to a large and rapidly effected transport of fluid from the blood into muscle tissue, but though there is this large increase in tissue fluid, no lymph flows from the tissue. This result very powerfully disfavours the filtration theory of lymph formation. It practically refutes the idea that lymph formation is solely dependent upon such processes as filtration, osmosis and capillary permeability only. It brings out quite clearly that the exchange of fluid and dissolved salts, &c., between the blood and a tissue, and the flow of lymph from that tissue, are two separate and distinct processes, and especially that the first does not determine the second. Also it is to be noted that the injection of a strong salt solution also excites a flow of duct lymph, again arising from the liver and intestines, but none from the limbs. In this instance, as previously stated, the muscles of the limbs are losing water, and so presumably are the liver and intestinal cells. This independence of tissue-blood exchange and lymph-flow is distinctly in favour of the view, which is rapidly gaining ground from histological observations, that in all instances the lymphatics commence in a tissue as closed capillary vessels.
Turning, in the next place, to the lymphogogues of the first class, it has been proved that the origin of this increase of flow is again from the liver. Very many of the substances of this class are bodies which may when taken cause urticarial (nettle-rash) eruptions, a state which is generally regarded as being due to an action upon the capillary endothelium. Their action as lymphogogues is also generally ascribed to an effect upon the capillary wall rendering it according to some more permeable, according to others leading to a direct secretory action on the part of the endothelium. We also know that many of the bodies of this class act upon the liver in other directions than in exciting an increased lymph production. Thus they may cause an increase in bile secretion, or, as in the case of peptone, the liver cells may be excited to produce a new chemical material, in this instance an antithrombin.
We have now to consider the effect of throwing an organ into activity upon the lymph-flow from the organ. In all cases in which it has been examined it is found that increased activity is accompanied by increased lymph-flow. Thus, to take the instance of the submaxillary gland, which at rest does not discharge any lymph, stimulation of the chorda tympani is followed by a flow of lymph accompanying the flow of saliva simultaneously excited. The stimulation of the nerve also produces dilatation of the blood-vessels and therefore a rise in capillary pressure. But that this vascular change is not the factor determining the lymph-flow is proved by the administration of a small dose of atropine, which arrests the secretion without influencing the vascular reaction following chorda stimulation. After the atropine no lymph-flow occurs on stimulating the nerve. Many other instances of a similar kind might be adduced. Thus, we have seen that peptone specifically excites the liver cells and also causes an increased lymph-flow from the liver; or, as a last instance, the injection of bile salt excites a flow of bile and also excites a flow of lymph from the liver. The supporters of the filtration theory have argued that as activity of a tissue is necessarily accompanied by the discharge of metabolites from the active tissue cells, and as these are of small molecular size, they must set up an osmotic effect. Water is therefore drawn into the tissue spaces, and this rise in fluid content results mechanically in a flow of lymph from the organ. The lymph simply drains away along the open lymphatics. This argument, however, loses all its force when we recall the fact that we may set up an enormous flow of fluid and salt into a tissue and its tissue spaces without causing the least flow of lymph. Further, there is no reason to suppose that the metabolites discharged from a tissue during activity are produced in large quantities. The chief metabolite is undoubtedly carbonic acid, and this diffuses very rapidly and is quickly carried away by the blood. If, moreover, as is probably the case, the lymphatics commence as closed capillaries, we have a further difficulty in explaining how the fluid is driven through the lymphatic wall. Either we must imagine the wall to be porous or there must be a greater pressure outside than inside, and it is very difficult to conceive how this is possible. As a general conclusion, then, it seems much more probable that we are here dealing with a secretory process, and that the active tissue produces some substance or substances—it may be carbonic acid—which throws the lymphatic capillary cells into activity.
To sum up in a few words the present state of our knowledge as to lymph formation we may say that the exchange of water and salts between the blood and the tissues is probably entirely determined by processes of filtration and osmosis. Further, that the physical condition of the capillary cells is frequently altered by many chemical substances, and that in consequence it may permit exudation into the tissue spaces much more freely. In the next place, the flow of lymph from a tissue is not solely determined by the amount of the tissue fluids. The lymph capillaries start as closed tubules, and the endothelial walls of these tubules play an active part (secretory) in determining when water and other substances shall be admitted into the capillary and further determine the quantity of such discharge. Apparently, too, these cells are specifically excited when the tissue is thrown into activity, the exciting substance being a metabolite from the active tissue. Leucocytes also are capable of passing through or between the endothelial cells of the lymph capillary. (T. G. Br.)