Part 3

Two problems now present themselves for solution. In the first place we have to account for the fact of the snake-poison leaving the lower forms of animal life intact and being fatal to the higher ones. The symptoms we have observed in the frog point unmistakably to an affection of the nervous system as their cause. Now we know that the lower forms which the poison does not affect have no such system, and we are justified to infer that to the absence of this system they owe their immunity. This inference leads us on to a second one equally justifiable, namely, that there is a certain unaccountable attraction between the delicate nerve tissue and the subtle ophidian poison, which renders the latter a specific nerve poison.

Our second problem is to ascertain the nature of the change in the nerves, to find out, if possible, whether it is merely functional or an actual interference with the structure of either cells or fibres. With this end in view we once more consult the microscope. We make two preparations, one of nerve fibres and of nerve cells of the poisoned frog, and, under the microscope, compare them carefully with an analogous one from the killed healthy frog. The result is purely negative as regards structural change. Both present identical and perfectly normal pictures of apparently healthy cells and fibres. There being no visible structural change we are driven to the conclusion that only a functional one has been effected by the poison, and with the symptoms observed all pointing in that direction, that it is of central origin.

The writer's theory as to the action of snake-poison, formed, in the first instance from observations made at the bedside of his patients only, is thus confirmed by experiments specially instituted by him for that purpose. Further proof of its correctness we have in the brilliant results of the strychnine treatment of snakebite in Australia, which is the outcome and practical application of this theory. In those desperate cases more especially, reported from all parts of the colonies, in which death was imminent, and pulse at wrists as well as respiration had already ceased, the strychnine injections could not possibly have effected complete recovery within a few hours if the structure of the nerve centres had been impaired or blood changes brought about incompatible with life.

Feoktistow's experiments, made with viper poison, fully bear out the correctness of the writer's theory, besides proving that there is no essential difference between the action of the viperine and colubrine poisons. He proved conclusively that snake-poison does not destroy protoplasm or interfere with infusorial life, that injected into the heart of a mollusc it causes an almost immediate cessation of its action, that hypodermic injections of it in fish produce contraction of the pigment cells and bleaching of the integuments, followed by asphyxial respiration, general paralysis and death. Similar results were observed on frogs. In mammals the symptoms were: dyspnoea, asphyxia, paresis and paralysis of the lower extremities with succeeding general paralysis, sometimes tonic and clonic convulsions, hæmorrhages from bowels, lungs, nose and bladder, and finally complete paralysis of respiration and of heart.

Action of Snake-Poison on Special Nerve Centres.

It must be borne in mind that the symptoms as about to be detailed are successive only to some extent in the order presented. They commence generally at the lower part of the spinal cord, but immediately afterwards, if not simultaneously, are ushered in with great rapidity from other centres, masking each other and rendering it extremely difficult to observe and analyse them separately. They are also very variable through the poison concentrating its action on special centres, leaving others comparatively intact, and this not only when from different varieties of snakes, but also from snakes of the same variety. Another element increasing the difficulties of correct analysis are the depressing effects of fear, inseparable in all but the strongest minds from the consciousness of having been bitten, and so similar in appearance to those of snake-poison, that sometimes it is by no means easy to decide which of the two is in operation, and that only those cases are of real value to the observer from which this element of fear is completely excluded.

A.--Action on the Anterior Cornua of the Spinal Cord.

The anterior cornua are almost invariably the first of the motor-centres attacked by the snake-poison, the affection (commencing with paresis and in serious cases generally culminating in paralysis) beginning in the lumbar ganglia and taking an upward course. The lower extremities feel unnaturally heavy and a paretic condition of the muscles supervenes simultaneously on both sides. The walk becomes unsteady and staggering, very similar to that of persons under the influence of large doses of alcohol. By a powerful effort of the will, however, persons in this condition are often able to walk and even run for some distance, especially if by prompt ligature the absorption of the poison has been checked. As the affection proceeds, though still able to move the legs in a sitting posture, they are unable to rise again. Ere long even sitting up becomes impossible and they collapse helplessly. At this stage sensation is still intact, and reflex action, by pricking the skin, &c., still takes place. The upper extremities generally retain the power of voluntary motion, even after the muscles of the neck have become paretic and the head is held up with difficulty or sinks to one side.

With birds, according to Feoktistow, the reverse is the case. The wings are usually first attacked, or paresis comes on in wings and legs at the same time.

B.--Action on the Medulla Oblongata.

a.--The Vaso-Motor Centre.

Whilst the voluntary muscles are thus brought under the influence of the poison, symptoms denoting the invasion of the oblongata are rapidly developing. The first of these is the deadly pallor and ashy hue of the cold skin, evidently due to the blood receding from the surface, a condition not unlike that obtaining in extreme anæmia. As persons in this state complain of an agonising feeling about the heart and of deadly faintness, a paretic condition of the heart suggests itself as the most obvious cause, more especially when taken in conjunction with the small, frequent, and compressible pulse. But though the heart muscle is no doubt participating in the general paresis, the condition of the surface of the body is in reality one of anæmia. The blood, even at this early stage, begins to accumulate in the large veins of the abdomen, which expand gradually in consequence of the diminishing motor force supplied by the splanchnicus, keeping them in the normal state of contraction when intact and having its centre in the medulla oblongata. When this large vaso-motor nerve is cut in animals anywhere in its course, the veins of the abdomen become distended enormously. The animal is, so to say, bled into its own belly.

By a series of most interesting experiments Feoktistow has shown conclusively that snake-poison has the same effect on the abdominal circulation as section of the splanchnicus. Even slight intravenous injections of the poison produced quickly a high degree of paresis of the nerve and a corresponding engorgement of the veins of the abdomen, whilst after lethal doses, the paresis culminated in a few minutes in complete paralysis, followed by rapid collapse, excessive weakness of the bloodless heart, and death from paralysis of the latter and anæmia of the nerve-centres. One experiment deserves special record, as it also shows the untenability of the blood-poison theory.

The whole vascular system of an animal poisoned by intravenous injection was thoroughly washed out with the warm defibrinised blood of four animals of the same species, the blood being infused into an external jugular vein and allowed to flow out of a crural artery. Although blood exceeding its normal quantity was left in the animal, when the vessels named were closed, the nerve affection remained unchanged. The blood pressure raised during the infusion sank at once again to zero, when it ceased, and the paralysed veins of the abdomen became engorged once more with the whole, or nearly the whole, of the blood-mass, leaving the rest of the body anæmic as before. This interesting experiment also shows how strong a hold the snake-poison has on the nerve-cells when they are thoroughly under its influence, and how independent this paralysing action is of the blood, persisting, as it was in this case, after all the poison had been washed out of the animal.

The heart in vaso-motor paresis and paralysis is weakened in the first instance by the direct action of the poison on the medulla oblongata and the intracardiac ganglia. Its pulsations, at first retarded in frequency, become accelerated soon after the introduction of the poison, the pulse rate increasing rapidly and the waves becoming smaller and more easily compressible in proportion to the frequency of the pulse, which generally counts from 100 to 120 and more per minute at a comparatively early stage of the poisoning process. But an equally potent cause of heart failure is its depletion by the simultaneous stagnation of the blood mass in the veins of the abdomen. Finally, to complete the mischief, we have not only anæmia of the semi-paralytic oblongata, but the scanty blood supply this important centre receives becomes also surcharged with carbonic acid. Oxyhæmaglobin disappears almost entirely from the blood under the circumstances detailed, as both pulmonary and internal respiration are greatly interfered with, the blood tending more and more towards that thin dark condition which it presents after death, and which has been taken as prima facie evidence of the direct blood-poisoning action of snake virus by one and all of previous investigators.

That under the powerful combination of causes, each of which is in itself sufficient to endanger life, and greatly intensified as paresis gradually deepens into paralysis, the heart, even of large animals, succumbs in a comparatively short time, may be readily understood.

The blood-pressure, under the circumstances just detailed, must necessarily be nil. Observations by means of the sphygmograph at the bedside of a person suffering from snake-poison are scarcely feasible, except, perhaps, in a hospital, and thus far are not on record. We must, therefore, once more fall back on Feoktistow's experiments, which show that even the smallest doses (0.02 to 0.04 mllgr.) of the dried poison per kilo injected into the vein of a cat caused a fall in the blood-pressure almost immediately, without influencing either pulse or respiration, but that two to four mgr. were sufficient to reduce the blood-pressure to zero and bring on collapse, infusions of blood only raising it temporarily. Of drugs raising the blood-pressure he found ammonia the most effective, but only after slight doses of the poison; after lethal ones it had no effect whatever on the blood pressure but greatly increased the hæmorrhagic process in all internal organs. This important observation should be kept in mind by those who inject ammonia in serious snakebite cases, and it probably applies likewise to the excessive use of alcohol.

This leads the writer on to the discussion of this singular hæmorrhagic process principally characteristic of viperine poisoning, and only very exceptionally produced by the poison of colubrines. It is among the symptoms of snakebite poisoning one of the most interesting ones, but also one most difficult of explanation. There can be no doubt that it is produced by vaso-motor paresis and paralysis. We further know that it is preceded by dilatation of the capillaries and small veins, and that it is effected principally through the process known as diapedesis, or the passage of both red and white corpuscles with plasma through the unruptured capillary membrane, and even the thin one of small veins, which is nearly of the same structure, being composed of endothelial cells united by cement. This membrane possesses a certain degree of porosity, which is probably increased by dilatation. In the absence of plain muscular fibres contraction and dilatation of the capillaries can only be effected by a corresponding contraction and expansion of the nuclei of the endothelial cells. As fibrils derived from non-medullated nerves terminate in small end-butts in connection with the capillary membrane, we may assume that the nuclei of the endothelial cells are under the sway of vaso-motor nerve currents, that weak ones will expand, strong ones contract them. We may further assume that the red and white corpuscles force their way out of the vessels through pores in the cement substance, since a passage of cell through cell is not thinkable. Thus far we see our way fairly clear. But the question now arises: what causes the solid constituents of the blood to force their way through the capillary membranes all over the mucous surfaces, even the conjunctiva, and not these alone, but also through serous membranes such as the pericardium, and strangest of all, through old scars in the skin? If the most modern ideas as to the cause of diapedesis being blood pressure are correct, it is quite incomprehensible how it can take place in the absence of blood pressure, and take place so extensively. The theory of blood pressure may apply to diapedesis accompanying the inflammatory process. In snakebite poisoning it is more likely to be due to passive engorgement of the capillary system and probably also to blockage of corpuscles in the finest capillary tubes. In vaso-motor paresis, and still more paralysis, the arterioles supplying the capillaries are widely dilated, and at the lowest blood pressure probably send more blood into the latter than in the normal state. This circumstance in itself is apt to cause capillary engorgement. In the finest capillaries permitting only a string of corpuscles, one behind the other but none abreast, to pass through in the normal state, dilatation may cause blockage by two or three becoming wedged in abreast and closing the lumen of the vessel by a sort of embolism. On the arterial side of this obstruction the crowded corpuscles force their way through the porous cement substance by what little "vis a tergo" there may be left yet, whilst in the venous side, in the small veins corresponding with the closed capillaries, engorgement must necessarily take place through this "vis a tergo" being entirely absent, and diapedesis, which here also has been observed, follow in due course. The writer has always been inclined to take this view, the correctness of which appears to be borne out by an experiment recorded by Feoktistow. He found on sprinkling a two per cent. solution of snake-poison over the mesentery of an healthy animal, that wherever a drop of the solution fell, almost immediately the capillaries and small veins became dilated and small point-like effusions of blood appeared, gradually enlarging and ultimately becoming confluent with adjoining ones. Large hæmorrhagic surfaces were thus formed in a comparatively short time. Here paralysis of the nerve-cells interspersed in the vaso-motor nerve-ends was evidently the first effect, followed by dilatation of the capillaries and immediately afterwards by effusion. Without some obstruction within the capillaries, like that above described, effusion in this purely local poisoning process appears unexplainable.

The special preference which the viper-poison has for the vaso-motor sphere will hereafter be referred to. Hæmorrhages from Australian snake-poison are comparatively rare. Even at the bitten place there is as a rule very little swelling and effusion and frequently none at all. When it occurs it quickly disappears after strychnine injections. Only a few cases have been reported as yet of blood-vomiting. In one of these the hæmorrhage took place soon after the bite and was so considerable that it must have arisen from actual rupture of vessels consequent on abdominal engorgement and not from mere diapedesis. It is very doubtful whether the latter ever takes place here as it does after viper-bite in India and elsewhere. Even the death-adder, although half a viper, and producing more swelling and effusion locally than any other one of our snakes, is not known to have ever produced the extensive effusions from mucous surfaces in pericardium, lungs, &c., described above. More research however is necessary, especially more carefully conducted autopsies. Since Australia has taken the lead in this hitherto so obscure department, every practitioner should make it his object and special ambition to contribute his quota towards the elucidation of the subject, not only by reporting successful cases, but also the post-mortem appearances in unsuccessful ones, wherever it is practicable. It is not by experiments on animals but by a hearty co-operation of Australian practitioners that we can ever hope to supplement our knowledge on this subject.

b.--The Respiratory Centre.

Paresis of this centre does not play as important a part here as it does in India, more especially after cobra-bite. The peculiar, and as yet unexplained, tendency of snake-poison to act with special virulence on some centres, passing others by comparatively little disturbed, is markedly shown by the cobra poison of India as compared with that of our Australian cobra (hoplocephalus curtus.) The unfortunate victims of the former are tortured by an ever-increasing dyspnoca, and finally die from asphyxia, under what are supposed to be carbonic acid convulsions. They retain their consciousness more or less unclouded to the last, the poison spending all its force on the respiratory centre, and leaving the brain intact. Here we hardly ever see actual dyspnoca after the bite of hoplocephalus or any other Australian snake. Respiration becomes quicker at an early stage, and then, from hour to hour, shallower; but our patients soon pass from sleep into coma, and suffer no respiratory distress even when, in consequence of general paralysis, the respiratory muscles cease to act, which usually takes place a few minutes before the heart stands still.

Feoktistow records the following observations on cats with reference to the respiratory centre:--Small intravenous injections of the fresh poison (0.07-0.13 mllgr.) produced a great increase in frequency of respirations (280-360 per minute). Section of both vagi at once reduced this frequency, from which he infers that small doses act as an irritant to the respiratory centre. When small doses were repeated several times, the respiratory movements were gradually retarded, and asphyxia set in through paralysis of the centre. Large doses produced this effect at once, without any previous acceleration. Very large ones paralysed respiration, heart, and vaso-motors almost simultaneously, and caused the blood pressure to fall to 0. By the kymograph respirations were found to become shallower in proportion to their frequency. As the latter was reduced, they became at first deeper, but ere long shallower again, and were occasionally interrupted by spasmodic inspirations. Artificial respiration prolonged life for a short time only.

C.--Action on Centres of Cranial Nerves.

Among the symptoms denoting paresis of motor-centres of cranial nerves, together with sympathetic ganglia, the first and most noteworthy is the early dilatation of the pupil. This truly pathognomic condition is never absent, and becomes intense when paresis becomes intensified into paralysis. The most glaring light, in immediate proximity to the eyeball, has then no effect whatever on the pupil. If it remains dilated after strychnine injections have restored consciousness and the power to walk, it is a sure sign that the snake-poison is not completely counteracted, and will in all probability re-assert itself, necessitating another injection, whilst a pupil restored to its normal condition justifies the conclusion that the patient is safe.

Another symptom denoting paresis of the cranial nerve-centres is a marked change in the expression of the face. The features become relaxed, and lose their mimetic play. The cornea is dull, and, together with the anterior surface of the eyeball, becomes dry, as the eyelids are moved imperfectly, if at all, and the tears in consequence are not properly distributed over the conjunctiva. The nostrils become more or less immovable, and the naso-labial fold is obliterated, whilst the lower lip hangs down. The lips are apart, as the lower jaw is not held up by the muscles. When paralysis supervenes it drops entirely, and the tongue protrudes.

Deglutition, somewhat difficult in paresis, is completely suspended in the paralytic stage, through paralysis of the soft palate, the pharynx, and oesophagus. Liquids forced on the patient in this extremity may partly flow down the oesophagus, but will also enter the larynx, and their administration should be carefully avoided.

D. Action on motor-centres of Cerebellum and Basal Ganglia.

Of this action little if anything is patent to observation. A certain want of co-ordination in the movements has been noticed in the early stage of paresis, and the peculiar staggering walk of persons in this stage is probably owing to an affection of the motor-centres of the cerebellum. That they do not escape the action of the subtle poison, when symptoms denoting the invasion of all the other motor-centres throughout the body are in evidence, we have every reason to assume. The co-ordination and automatic regulation of the lower motor-centres must necessarily escape observation when the function of these centres is partially suspended, and when, moreover, the powerful currents of nerve force the cerebellum and basal ganglia receive from the motor cortical centres of the cerebrum are partially if not wholly withdrawn.