Freshly shed blood contains minute particles, termed “platelets,” in diameter measuring about a quarter that of a red blood-corpuscle. When the inner coat of a vessel is injured, platelets accumulate at the injured spot. They form a little white heap, from which coagulation starts. Evidently they supply the ferment, or a precursor of the ferment. As yet their origin has not been traced. They are too large to be the unchanged granules of granular leucocytes, but that they are in some way derived from leucocytes seems probable.
The further study of coagulation has shown that the conditions under which it occurs are more complicated than the simple explanation just given would seem to imply. This explanation holds good, so far as it goes, but facts connected with the details of the process have recently been brought to light which warn the physiologist that as yet his theory of coagulation is incomplete.
The presence of salts of lime has an important relation to coagulation. If blood is received into a vessel in which has been placed some powdered oxalate of potash, or soap, or any other chemical which fixes lime, the blood does not coagulate. All other conditions are as usual, but lime is withdrawn from the plasma. The non-coagulation of oxalated plasma was interpreted as indicating that lime, under the influence of fibrin-ferment, combines with fibrinogen to form fibrin; that fibrinogen altered by fibrin-ferment combines with lime. This hypothesis was based upon the analogy of the curdling of milk. Milk cannot curdle if lime be absent. If rennin (milk-ferment), prepared from milk from which lime has been removed, be added to a solution of caseinogen (the coagulable protein of milk), also prepared from lime-free milk, no curd is produced. The addition of a few drops of a solution of chloride of lime results in the immediate curdling of the mixture. Evidently rennin so alters caseinogen as to bring it into a condition to combine with lime. But the analogy does not hold good for blood. In the case of plasma, lime acts, not upon fibrinogen, but upon the fibrin-ferment—or rather upon a precursor of fibrin-ferment—in such a way as to render it effective. Leucocytes produce a prothrombin, which in contact with lime salts is converted into thrombin, which coagulates fibrinogen.
Fibrinogen is the substance which fibrin-ferment combined with salts of lime changes into fibrin. Yet even now the story is not complete, if the theory of coagulation is to be brought up to date. A perfectly clean cannula is passed into an artery of a bird. If it be thrust well beyond the place where the vessel has been cut, if the vessel be tied so gently as to avoid injury to its inner coat, and if the blood which first passes through the cannula be allowed to escape, the blood subsequently collected will not clot. It contains fibrinogen, lime salts, and fibrin-ferment, ordinarily so called; but the ferment is ineffective. The addition to the blood of a fragment of injured tissue, or of a watery extract of almost any tissue, immediately sets up coagulation. This observation brings fibrin-ferment into line with other ferments. Digestive ferments are secreted as zymogens, which require to be influenced by a kinase before they acquire fermentative activity. So, too, must thrombogen be changed into thrombin, under the influence of thrombokinase, before it can act upon fibrinogen. Almost all tissues yield the kinase which actuates fibrin-ferment. The utility of this provision is manifest. A bird’s blood contains everything necessary to form a clot with the exception of thrombokinase. The injury which brings the blood into contact with a broken surface supplies this ferment of the ferment. Fibrin-ferment, rendered active, at once changes fibrinogen into fibrin. The same interaction is necessary before the blood of a mammal is susceptible of clotting. But a mammal’s blood is even readier to clot than is the blood of a bird; for not only will a broken surface provide it with thrombokinase, but the leucocytes contained within the blood, when injured, also yield it. And the leucocytes are exceedingly sensitive of any change of circumstance; on the slightest indication that conditions are not normal they set free, perhaps owing to their own disintegration, the kinase which turns thrombogen into thrombin.
There is a constitutional condition, fortunately rare, in which blood does not coagulate. A person subject to this abnormality is said to suffer from hæmophilia. It is alleged that this condition is due to deficiency of lime in the blood; and the deficiency of lime is said to be due to excess of phosphates. The subject suffers from phosphaturia. His kidneys get rid of the superabundance of phosphates by excreting them in combination with lime. If this explanation be correct, there is a chronic insufficiency of lime in the blood, because it is being constantly withdrawn in the process of removing phosphates.
The difficulty in the way of establishing a complete theory of the coagulation of blood increases when the phenomena of incoagulability are considered. Blood may be rendered incapable of clotting in a variety of ways. Leeches and other animals which suck blood have the capacity of rendering it incoagulable. If the heads are removed from a score of leeches, thrown into absolute alcohol, dried, ground in a pepper mill, extracted with normal saline solution, a dark turbid liquor is obtained. This liquor, after filtration and sterilization at a temperature of 120° C., injected into the veins of an animal, renders its blood incoagulable.
The preparation sold by druggists under the name “peptone,” when injected into the veins of a dog, renders its blood incoagulable. Commercial “peptone” is a mixture of many substances. Its anticoagulation-effect is not due to the peptone which it contains. It has been supposed to be due to imperfectly digested albumin and gelatin (proteoses), but products of bacteric fermentation (toxins and ptomaines) are more probably the active bodies. Not only is the peptonized blood of a dog incoagulable, but if this blood be injected into the veins of a rabbit (an animal upon which the direct injection of peptone has no effect), it diminishes the coagulability of the rabbit’s blood. If peptonized blood be mixed in a beaker with non-peptonized blood, it prevents the coagulation of the latter. There is little doubt but that the poison, whatever it may be, acts upon the leucocytes; and there are some reasons for thinking that the poison is not contained in the “peptone,” but is secreted by the liver of the animal into which the “peptone” has been injected.
A still more remarkable property in relation to coagulation must be assigned to leucocytes. The blood of a dog which has been rendered incoagulable by injection of peptone recovers its coagulability after a time. If a further injection of “peptone” be made, the animal is found to be immune. Injection of “peptone” no longer renders its blood incoagulable. In a similar manner the blood develops a power of resisting the action of agents which induce its coagulation whilst circulating in the vascular system. Nucleo-proteins contained in extracts of lymphatic glands and other organs when injected into the veins of living animals cause their blood to clot, provided they are injected in sufficient quantity. If they are injected in quantity less than sufficient to induce coagulation, they render the animal immune to their influence. A larger quantity given to an animal thus prepared fails to take effect. This brings the phenomena of coagulation and resistance to coagulation to the verge of chemistry. They extend into the domain in which pathology reigns. Tempting though it be to record other facts with regard to these phenomena which recent investigation has brought to light, it is probably judicious to leave the problem at the frontier. Across the frontier lies a fascinating land, rich with unimaginable possibilities for the human race. Settlement is rapidly proceeding in this country, which is charted, like other border-lands, with barbarous names: “antibodies,” “haptors,” “amboceptors,” “toxins,” “antitoxins,” and the like—finger-posts to hypotheses which show every sign of hasty and provisional construction. But certain facts stand out, in whatever way theory may, in the future, link them up. The virus of hydrophobia, modified by passing through a rabbit, develops in human beings, even when injected after they have been infected, the power of resisting hydrophobia. The serum of a horse which has acquired immunity to diphtheria aids the blood of a child, which has not had time to become immune, in destroying the germs of this disease. It is a contest between the blood and offensive bodies of all kinds which find entrance to it, whether living germs or poisons in solution; with victory always, in the long-run, on the side of the blood, provided its owner does not die in the meantime. And not only is the blood victorious in the struggle with any given invader, but having repulsed him, it retains for a long while a property which neutralizes all further attempts at aggression on his part. In the past, physicians have fought disease with such clumsy weapons as mercury, arsenic, and quinine. Now they anticipate disease. In mimic warfare with an attenuated virus the blood is trained to combat. Smallpox which has been passed through the body of a cow is suppressed by the blood’s native strength. The exercise develops skill to deal with the most virulent germs of the same kind. In cases in which physicians cannot anticipate disease in human beings, they train the blood of animals to meet it; and, keeping their serum in stock, they can, when the critical moment arrives, reinforce the fighting strength of the patient with this mercenary aid.
The Spleen.—The spleen is placed on the left side of the body, and rather towards the back. It rests between the stomach and the inner surface of the eighth, ninth, tenth, and eleventh ribs. It is quickly distinguished from other organs by its brown-purple colour, a sombre hue to which it owed its evil reputation with the humoralists. The liver’s yellow bile tinged man’s mental outlook, preventing him from seeing objects in their natural brightness; but the spleen made black bile, which, mounting to the brain, displayed its malign influence upon the action of that organ, as, or in, the worst of humours.
The spleen is invested with a capsule of no great toughness. Inside the capsule is “spleen-pulp.” When the fresh organ is cut across, it is seen that, although most of the pulp is of the colour of dark venous blood, it is mottled with light patches. In some animals—the cat, for example—these whitish patches are small round spots, regularly arranged at a certain distance from the capsule. The distinction into “red pulp” and “white pulp” marks a division into two kinds of tissue with entirely different functions. The white pulp is lymphoid tissue, lymph-follicles developed in the outer or connective-tissue coat of the branches of the splenic artery. Its function is to make lymphocytes, of which, for reasons which will shortly appear, the spleen needs an abundant supply. The constitution of the red pulp is entirely different, and peculiar to the spleen. The branches of the splenic artery divide in the usual way into smaller and still smaller twigs until the finest arterioles are reached; but these arterioles do not give rise to capillary vessels. At the point at which in any other organ their branches would attain the calibre of capillaries, the connective-tissue cells which make their walls scatter into a reticulum. They are no longer tiles with closely fitting, sinuous, dovetailed borders, but stellate cells with long delicate processes uniting to constitute a network. The blood which the arterioles bring to the pulp is not conducted by closed capillary vessels across the pulp to the commencing splenic veins. It falls into the general sponge-work. The venules commence exactly in the same way as the arterioles end. Stellate connective-tissue cells become flat tiles placed edge to edge. The endothelium of an arteriole might be likened to a column of men marching shoulder to shoulder, three or four abreast; the connective tissue of the pulp, to a crowd in an open place. The column breaks up into a crowd. On the other side the crowd falls into rank as the endothelium of veins. The capsule and the red pulp are largely composed of muscle-fibres. These relax and contract about once a minute. By their contraction the blood is squeezed out of the sponge.