Blood and Lymph (The Carriers)
Uses of the Blood
Mephistopheles, in Goethe’s Faust, is biologically quite right when he exclaims: “Blut ist ein ganz besonderer Saft!” (Blood is a very peculiar fluid!)
In the first place it is not a lifeless fluid incapable of metabolic changes, but a circulating tissue, made up of detached living cells floating in a liquid plasma. The fact that it moves about marks it off distinctly from all other tissues. It is conspicuously kaleidoscopic in character, changing constantly in its intimate composition as it passes through the different parts of the body, for it is not only the common carrier to the various tissues of everything needful for their maintenance, but also the collector from the tissues of the products of metabolism, such as carbon dioxide and soluble nitrogen compounds.
In the last analysis cells of every kind within the animal body sooner or later contribute something to the blood and receive something in return, so that the blood reflects the entire metabolism of the body. In spite of this fact its component parts are normally kept at nearly a constant level. When serious deviations occur, as in the excessive loss of water from the blood during cholera, or the diminution of the number of blood cells in anaemia or hemorrhage, pathological consequences are sure to follow.
In general the following functions may be performed by the blood.
Equilibration of Water Content
Water is the fluid universal that facilitates the internal transport of materials, making good losses by evaporation and otherwise, as well as preventing the drying up of tissues. It is also the great solvent of all sorts of substances in the food and throughout the tissues. The degree of activity exhibited by any tissue is directly dependent upon the fluidity of the cytoplasm within its cellular units, which in turn is ultimately a matter of the amount of water supplied by the blood.
Liberation of Energy
Tissues “burn” in the presence of oxygen, thus releasing energy, which is what constitutes “living.” Certain softer tissues, like the muscles for example, lend themselves particularly to this oxidative process, while others, such as skeletal tissues, resemble more the iron girders of a “fire-proof” building, and do not burn as readily. The oxygen necessary for the release of stored energy is delivered to the tissues of vertebrates by the haemoglobin in the red corpuscles of the blood.
Distribution of Food
From one point of view blood is a solution or an emulsion of food substances carried in the plasma. To some extent also it transports food as solid undissolved particles engulfed in the white blood cells. It is thus the grocery delivery boy for the cellular community.
Regulation of Temperature
Body temperature, which results from the oxidation of the tissues, is equalized by means of the circulation of the blood, much as is the temperature of a building by the hot-water pipes of its heating plant. Such equalization is necessary because of the unequal production of heat-energy by different tissues of the body.
In so-called “warm-blooded” animals the body temperature is maintained at a practically constant level, regardless of the temperature of the environment, thus enhancing the animal’s independence. “Cold-blooded” animals, on the other hand, owing partly to the low oxygen-carrying capacity of their blood, have a body temperature which fluctuates in response to that of the surroundings. A cold-blooded animal is consequently a thermal slave to the environment in which it finds itself.
It has been demonstrated, however, that even cold-blooded fishes when ill may show fever-like fluctuations in temperature.
Transmission of Chemical Substances
Hormones, the chemical messengers from endocrinal glands, frequently perform metabolic feats at some distance from their point of origin, after traveling along the blood highways. Drugs and poisons introduced into the organism likewise gain ready disposal over the body by means of the circulating blood. This is why a person with malaria, for example, feels “sick all over,” since the blood carrying the organisms producing malarial poison literally goes over the whole body.
Defense against Parasitic Invasion
Troublesome foreign invaders, such as infective bacteria and protozoans, are regularly combatted by white blood cells which capture and devour them. The cures of most “catching” diseases depend upon the successful outcome of this function of the blood.
Disposal of Cell Wreckage
The blood is a continual funeral cortege, in which are being borne away the “ashes” of dead cells, foreign bodies, bacterial products, and wastes of metabolism generally.
Furthermore, blood may be regarded as a peripatetic laboratory in which chemical transformations of wide variety are constantly going forward, as for example, the formation of “antibodies” of various sorts, oxidation and reduction of haemoglobin, elaboration of fibrin, and changes of fats and sugars to and from soluble states.
All of the functions of the blood thus far indicated have to do with personal biological benefits to the animal itself. Blood may also be useful, outside of the individual who elaborates it, to the physician in identifying disease. No other tissue gives to the diagnostician so true a flashlight picture of the present state of the varying metabolism of the body as does the blood. The ease with which a sample of blood may be obtained for examination without injury to the patient, and the readiness with which deviations from the normal are revealed therein, have resulted in an increasing dependence upon it as a means of clinical diagnosis. For example, in a suspected case of either typhoid fever or appendicitis, the examination of the blood furnishes an immediate differential diagnosis, since in typhoid fever the number of white blood cells is below, while in appendicitis it is above normal. There is no doubt that dependence upon blood examination in future medical practice will increase as technic is further perfected and new approaches to the study of blood are developed.
Amount of Blood
In adult man the amount of blood is estimated to vary from about one twentieth to one fifteenth of the total body weight, that is from seven and a half to ten pounds for a person weighing one hundred and fifty pounds. This is approximately six quarts. In a new-born child the percentage of blood to body weight is less than in the adult, while in lower vertebrates the relative amount of blood is less than in mammals. Haempel gives the quantity of blood in fishes as less than two per cent of the total body weight.
The blood supply is temporarily increased in those regions that are active, as for example, in the wall of the stomach immediately after eating, or in that of the small intestine during digestion.
As to specific gravity, which is dependent mainly upon the amount of haemoglobin present, “blood is thicker than water.” For man the figures have been given as 1.035 to 1.067 (with distilled water at 1.000).
Our sanguinary forebears, as well as our contemporaries, were well acquainted with the general appearance of blood, for the pages of history are copiously stained with it. Not until 1696, however, about two centuries after Columbus had discovered America and his adventurous bones had turned to dust, did the Hollander, Anthony van Leeuwenhoek, find, with his primitive lenses, that blood is “composed of exceeding small particles.” These he named globules which he said “in most animals are of a red color, swimming in a liquor, called by physicians the serum,” and further, that “by means of these globules the motion of the blood becomes visible, which otherwise would not be discoverable by sight.”
Red corpuscles are for the most part peculiar to vertebrates, although a few invertebrates, including the worms Glycera and Phoronis, the “blood clam” Area, and the holothurian Thyone, also possess red blood cells. Ordinarily whenever invertebrates show red blood, as for example the pond snail Planorbis, the earthworm Lumbricus, or the larvae of the midge Chironomus, the haemoglobin producing the color is not located in red corpuscles but is dissolved in the plasma.
Red corpuscles, or erythrocytes as they are technically known, are directly concerned with respiration, the exchange of gases involved being facilitated by means of the respiratory pigment haemoglobin, which is present inside of the corpuscles. This pigment, which has a very complex molecule 68,000 times as heavy as the molecule of hydrogen, is a compound of iron and globulin, and possesses the ability to take on and give off oxygen readily. It is thus a sort of a shuttle device between outside oxygen and cells in the body that are in need of oxygen. Haemoglobin in the red blood cells is said to have the power of taking on seventy times as much oxygen as an equal volume of blood plasma, which can carry oxygen only in solution. The haemoglobin molecule thus loaded with oxygen assumes a brighter red color and becomes a very unstable substance, called oxyhaemoglobin. The peculiar ability of this molecular structure to transport the amount of oxygen necessary in breathing, may be destroyed by the action of certain “poison gases,” such as carbon monoxide, for which haemoglobin has 250 times the affinity that it has for oxygen. When this gas, escaping from the exhaust of a running automobile engine in a closed garage, is inhaled, the oxygen of the oxyhaemoglobin molecule may be supplanted by carbon monoxide with the result that survival and recovery" from suffocation will follow only if the person is hastily removed to fresh air where the oxygen will slowly replace the carbon monoxide. Haste is important to minimize the destruction of cells, particularly irreplaceable neurons. (See U. S. Pub. Health Bull. Vol. 195; 1930, No. 211.)
Erythrocytes of most vertebrates are oval discs that appear to bulge in the center on account of the presence of a nucleus. Among mammals (and lampreys!) erythrocytes are more circular in outline, with a single exception in the case of camels and llamas which have oval erythrocytes resembling non-mammalian red blood cells in form. The nucleus in mammalian red blood cells disappears by extrusion, leaving the cell a degenerate sac, or stroma capsule, having an internal structure imperfectly understood but containing a concentrated solution of haemoglobin. The original name “corpuscle” (small body) fits the erythrocyte with more accuracy than “red blood cell,” since nuclei are always associated with cells. Diagrams of the method of nuclear loss are shown in Fig. 273.
In size erythrocytes, measured from dried smears of blood, range from 75 micra (a micron is one one-thousandth of a millimeter) in the caudate Amphiuma to 2.5 micra in the musk deer Tragulus. Other measurements in micra for the longest diameter of blood corpuscles from dried smears have been reported as follows: Proteus, 58; frog, 22; turtle, 20; carp, 17; pigeon, 14; lamprey, 13; chick, 12; conger eel, 11; elephant, 9.4; man, 7.5; dog, 7.3; rabbit, 6.9; cat, 6.5; horse, 4.6; goat, 4.1.
In man the measurement is from 7.1 to 8.3, with an average of 7.5. In all these cases fresh corpuscles are slightly larger than dried smear specimens.
In general the smaller the corpuscles the more surface they expose for oxygen transfer in a given volume of blood, just as there is more “skin” in a bushel of small crab apples than in a bushel of big apples. One of the factors determining the “cold-bloodedness” of lower vertebrates as contrasted with mammals is the larger size of their erythrocytes with correspondingly smaller total surface of exposure for oxygen intake.
The number of erythrocytes in the blood is of considerable clinical importance. In man it is normally about 5,500,000 per cubic millimeter in the male and 5,000,000 for the somewhat less metabolic female, while in the highly metabolic infant the count is greater than in adults of either sex. The total number of red corpuscles in the average human being has been estimated at 30 trillions representing a respiratory surface 1500 times as large as the surface of the body itself. The number of erythrocytes varies with regard to the time when taken and other factors. According to Vierrodt the number of red blood cells of hibernating animals drops to as little as one third of the normal count during their "winter sleep,” The red blood cells are more numerous during the day than at night and directly after e a tiny or violent exercise, as well as in high altitudes when mountain climbing or in airplane flights. Patients who are combating tuberculosis sometimes resort to high altitudes where the lessened pressure of rarified air is supposed to demand a greater surface exposure to haemoglobin to accomplish the normal amount of respiration, thus forcing the body to self-curative effort by producing more red blood corpuscles in compensation.
Haemolysis, that is the wearing out or destruction of erythrocytes, is the inevitable outcome of their strenuous travels through the blood channels. Physiologists have attempted to estimate the length of life of a single average erythrocyte by measuring the density of the pigments in the bile, since these are due principally to the haemoglobin released from the broken-down erythrocytes that are being eliminated. When capillaries of the skin are ruptured so that blood oozes out into the surrounding tissues, the liberated haemoglobin from the erythrocytes breaks down with a display of pigments, a good example of which is a “black eye” with all its rainbowlike variegations. The amount of haemoglobin necessary to produce a known degree of color in a measurable quantity of bile eliminated during a known interval of time, gives a rough idea of the rate at which new blood cells must be manufactured in order to maintain a comparatively constant level of erythrocytes throughout the entire body. Those who have ventured to speculate on this problem place the life span of a red blood corpuscle from ten to seventy days, which means that at the outside the erythrocyte population is completely renewed several times each year. Since the total number is estimated to be 30 trillion cells it means that the continuous production of red blood cells within the average human body, if reckoned on the most conservative basis, must go forward at the rate of several thousand every second.
The process of the formation of red blood cells, which is termed haemopoiesis, is accomplished before birth in the mesenchymatous tissues and also in the liver and spleen. In fishes and amphibians the spleen forms red cells even in the adult animal. In other adult vertebrates, particularly in mammals, haemopoietic tissue is mostly confined to the red marrow in the hollow bones, in which factory the major part of the astonishing output of erythrocytes takes place.
Intermingled with red corpuscles in the blood are “white blood cells,” or leucocytes, best described as wandering cells that are not always confined to the blood channels, and which are independent of the nervous system. Unlike the erythrocytes of mammals, these are detached cells that not only retain their nuclei throughout life, but also possess other characteristic features of true cells.
Within the same organism leucocytes show considerable differences with respect to the character of their nuclei, general size, shape, and function, differences that make possible their classification into three general categories, namely, lymphocytes, granulocytes, and monocytes. It should be noted that this classification is based on the leucocytes of human blood which have been most studied.
Lymphocytes (Fig. 274) constitute normally something like 22 to 25 per cent of all leucocytes. They are roughly spherical, with a single large nucleus, and are about the size of erythrocytes, being from 6 to 8 micra in diameter. No granules are present in their cytoplasm.
Monocytes are giant amoeboid mononuclear leucocytes, twelve or more micra in diameter, constituting normally from 2 to 10 per cent of all leucocytes. Their nuclei are relatively small while their abundant cytoplasm is without granules.
Granulocytes, which are somewhat larger than lymphocytes, being from 7 to 10 micra in diameter, are characteristically amoeboid in changing shape and are chemotactic in behavior. They are often referred to as “polymorphonuclear leucocytes” from the fact that their nuclei generally assume a variety of shapes. The granular cytoplasm, which gives the name “granulocyte” to these cells has differential staining properties that, according to Ehrlich, serve to classify them chemically still further into neutrophils, eosinophils, and basophils, depending upon whether the granules have an affinity for (philos, love) neutral, acid, or basic dyes, respectively. The two latter kinds are comparatively rare, forming only about 3 and 0.5 per cent respectively of the total number of leucocytes, while the neutrophils furnish in the neighborhood of 70 per cent. As these percentages vary within quite wide limits pathologically, they make an extremely valuable indicator of abnormal conditions for the clinician.
Dana and Carlson have pointed out that the number of new leucocytes contributed to the blood stream daily may be greater than the total average number present at any one time in the blood. In man the number of leucocytes of all kinds varies from 2000 to 13,000 per cubic millimeter with a normal average of around 7000. The numerical variation is proportionately much greater than that of erythrocytes. There is a normal increase in the total number of leucocytes for instance after vigorous exercise or eating, upon exposure to cold, in infections, and during pregnancy. When the number rises over 10,000, a pathological condition is indicated.
With regard to their origin different kinds of leucocytes, like erythrocytes, may be produced, in different parts of the body. In mammals certain embryonic cells in the marrow, haemoblasts, that do not circulate within the blood stream, are no doubt the busiest agencies for the manufacture of granulocytes as well as of red blood cells. Lymphocytes and monocytes are formed in lymphoid tissue throughout the body, in the lymph nodes and lymph “glands” of which the spleen is the largest representative.
The three different kinds of leucocytes accomplish a variety of functions. For example, the wandering granulocytic neutrophils, as well as monocytes, remove worn-out tissue cells and invading bacteria by engulfing and digesting them in true amoeboid fashion, when they are known as phagocytes (phag, eat).
Owing to their amoeboid facility in assuming a variety of shapes they are able to squeeze between even the irregular edge-to-edge margins of the flat endothelial cells forming the thin walls of the capillaries (Fig. 275), thus escaping entirely from the closed blood system into the interstices between the cells of tissues everywhere in their phagocytic forays. This escape of the phagocytes through the capillary walls is termed diapedesis. There is indeed hardly a nook or cranny within the body that cannot be sought out and penetrated by these nomadic benefactors in the course of their sanitary and curative peregrinations.
The mobilizing of phagocytes is particularly well demonstrated when a wound becomes infected by bacteria. The “inflammation” that results in swelling and pain is due to the crowded ranks of phagocytes assembled for a battle royal with the invading army of bacteria. If the bacteria win, “blood poisoning” with its gruesome consequences results. If the phagocytes win, health is restored. “Pus” is largely made up of dead phagocytes that have fallen in battle. Inflammation of the mucous membranes, or “catarrh,” does not result in pus formation ordinarily, but in the production of a local excess of lymphatic fluid.
The holes in the capillary walls through which the phagocytes escape are immediately closed, like a puncture in an automobile tire, so that the red blood cells are kept within the blood vessels. Vagrant phagocytes, however, like the prodigal son, return to the blood stream. They do not reenter the capillaries from which they have escaped but are picked up by the lymphatic vessels that permeate everywhere between the cells of the tissues. By means of a system of valves these lymph-containing vessels forward their cargo by one-way traffic towards veins that enter the heart, and thus restore the runaway phagocytes to the general circulation.
Lymphocytes are neither amoeboid nor phagocytic, but monocytes and granulocytic neutrophils are both. Moreover, the non-phagocytic lymphocytes retain their spherical contour, never by diapedesis joining the phagocytes as “free lances of our corporeal militia” (Slosson). Instead they collect in the villi of the small intestine to engage in the transfer of fat globules, enmeshed in their cytoplasm, by way of the lacteals to the blood stream.
In addition to erythrocytes and leucocytes there are present in the vertebrate blood less well-known bodies, generally called thrombocytes.
In the frog these have been described as “spindle cells,” intermediate in character between red and white blood cells, and able possibly upon occasion to be transformed into either.
Although true spindle cells with nuclei have been found in the blood of certain fishes, amphibians, reptiles and birds, they are not present in mammalian blood, their place being taken apparently by small bodies which Bizzozero has named blood platelets (Fig. 274).
The unstable character of the thrombocytes is shown by the fact that they tend to mass together and disintegrate as soon as the blood is shed and exposed to air, which makes careful detailed observation of them difficult.
The term “thrombocyte” (thrombus, clot; cyte, cell) is not a very happy one to apply to blood platelets since it is doubtful if they are true cells but more likely small enucleated fragments of cells, with slight amoeboid motility. They have to do, however, with forming the “thrombus,” or clot, that prevents excessive hemorrhage in case of wounds.
The different kinds of thrombocytes in human blood vary in size from 0.5 to 4 micra in diameter, thus being considerably smaller than erythrocytes. They have been estimated to number from 200,000 to 778,000 per cubic millimeter, with 500,000 given by Howell as an average for human blood. According to Wright blood platelets have their origin as fragments of the giant cells of bone marrow from which they are constricted off.
Two thirds of the blood is fluid plasma in which the different kinds of cellular elements are borne along through blood vessels.
Plasma is about 90 per cent water, 9 per cent organic substances such as fibrinogen, paraglobulin, and serum albumin, and about one per cent organic salts, which brings it up to approximately the same density as sea water. Animals with blood of balanced density living submerged in sea water do not suffer from upsetting osmotic exchange, which can be dangerous or even fatal when it occurs suddenly as in the case of salt-water fishes that are transferred to fresh water or vice versa. The salts dissolved in human blood plasma are reminiscent of osmotic conditions long ago when our remote ancestors had not yet emerged from an aquatic habitat.
The plasma is a non-living fluid of much more chemical complexity than appears in the test tube. It contains a constantly changing variety of substances in solution, chief among which are dissolved food materials on the way to cellular delivery, and waste products that are being collected for elimination. There are also present enzymes of divers sorts which activate chemical changes: opsonins, that prepare trespassing bacteria for phagocytosis; hormones, the chemical messengers from endocrine glands on their way to the performance of tasks of internal regulation; antibodies and other problematical substances engaged in constant warfare against harmful invasion; and finally, fibrinogen, which although ordinarily free-flowing like other dissolved substances, can be turned when necessary into insoluble fibrin, that forms an entangling mesh like a barbed wire barrier through which cells do not easily pass. This is the clot which acts as an emergency plug to prevent the escape of blood from wounds while organic repairs are being made.
According to Howell, a substance in the plasma known as prothrombin, together with calcium salts, may form thrombin upon exposure to a rough or ragged surface, such as the edges of a wound that are unlike the smooth inner walls of blood vessels. Thrombin has the power of transforming soluble fibrinogen into insoluble fibrin which in turn entangles the blood cells and forms a clot.
Sometimes a blood clot forms around a solid body or breaks free from a wound, when it becomes an embolus. Such a clot circulating within blood vessels may obstruct a capillary or a larger vessel and cause trouble. For example, if it blocks the first branching of the lung artery, it holds up the entire circulation and may cause sudden death. An embolus may arise from other causes than an outside wound, as in the case of “hardening of the arteries,” when the wall of the blood vessel may become ruptured. If a traveling embolus is caught in the capillaries of the brain, it may give rise through pressure to a “shock,” or apoplexy, recovery from which is dependent upon the removal or absorption of the embolus within a reasonable time.
If it were not for the mechanism of the blood clot, loss of blood from even slight wounds, or breaks in the walls of the blood vessels allowing leakage, would prove to be much more serious than it is.
Haemophilia is a hereditary condition in which some link in the chain that normally results in clot formation is missing so that the inability to stop blood leakage from even a small wound may result fatally. Persons thus afflicted are known as “bleeders.” Males are more susceptible to haemophilia than females, since it requires inheritance of the trait from both sides of the house to make a female haemophilic, while inheritance through one parent is enough to cause a male bleeder.