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Vol. XXXVII.

Incorporating

The Kansas City Medical Index-Lancet

Original Contributions

An Independent Monthly Magazine

JANUARY, 1918

[EXCLUSIVELy for the medical herald.] PATHOLOGY OF TRAUMATIC WOUNDS* O. C. MORRISON, M. D., Carroll, Iowa A traumatic wound is the destruction of the epithelial covering of the body by external violence, with or without the destruction of underlying tissue. The pathological classification of this class of wounds will be limited in this paper to:

1. Grave infected wounds.

2. Grave uninfected wounds.

We are not concerned whether the wound be lacerated, clean cut, or punctured, but we are concerned with the type of bacteria infecting it. The reaction of the wound locally is not always the guide in our judgment to the severity of the remote reaction. The invasion of other tissues proximal to the wound is usually by Phlegmonous Cellulitis.

The remote effects are by metastasis or toxemia. Phlegmonous Cellulitis is the result of any of the pyoginic bacteria. We were taught to believe that the amount of gangrenous tissues found in a wound was due to the so-called direct gangrene which was the result of the traumatism. The examples cited us were those with which many of you have contended. Time and again the beautiful work in the resected stump was made to look like a field that had been devastated by a German army, and the flap which you so carefully tried to preserve was found to be in a state of necrosis. This slough was in many instances hastened by the rapid action of bacteria. Koch has declared that: "Bacteria secrete a soluble substance which comes in contact with the surrounding tissue by diffusion, which substance produces a deleterious action on the tissue cells, and they perish as a result."

Should the reaction of the tissue be slow and the virulence of the infective agent great, we can readily imagine that a maximum slough will be the ultimate result. Some patients will react quickly aided by proper treatment which is based upon an influx of lymph supply to the

*Read before the Medical Society of the Missouri Valley at Keokuk, Ia., March 21, 1917.

No. 1

wound area as this will give us the best result and the minimum damage to tissue. On the contrary, with the poor reaction of tissue, coupled with bad treatment, gives us the maximum damage to the tissue with ugly scars, or with the sacrifice of the tissue or limbs of the patient.

I have never felt that I should be so greatly concerned about a possible infection by gas bacillus, pyocyaneus, or kindred infections but I should have a thorough understanding of the action of bacteria and their toxins upon the cellular tissues of the body and the resulting pathology. We have spent much time in learning the characteristics of the many bacteria and in juggling their development to suit our fancy. The life of any uni-cellular organism will serve as a unit of comparison. We know that it gathers its food from the fluid in which it lives. It excretes its own toxins or waste products. It attracts another uni-cellular organism with which it fuses for reproduction. The questions are: "By what method does it get its nourishment, and how does it expel the waste products from its body?" In answering these questions logically we are forced to revert to a comparison of similar actions in the inorganic world. There is a force which causes the sodium ion to unite with an atom of chlorine or with two atoms of hydrate. They unite in definite quantities and only to form a certain substance or specific compound. A further study of this ion teaches us that it is the ultimate division of matter which represents both a physical and chemical substance. We have learned that this socalled ion can be driven by an electrical current and deposited at the respective positive and negative pole, hence, the chlorine will be found at one pole, the sodium at the other.

We have not learned the relationship existing between the socalled ion and its cargo of electricity but many chemists testify that the size of the ion bears relationship to the quantity of electricity it carries. Mann says: "The socalled pure ash-free proteins are chemically inert and in the true sense of the word are dead bodies. That which puts life into them is the presence of electrolytes."

Some men have defined the ion as the smallest division of matter capable of carrying an electrical charge. It is not visible; it cannot be

brought to the vision nor the senses of a person excepting in one splendid illustration, that of radium. We can see in a dark tube the ions of radium dissemination into the surrounding atmosphere. The ultimate division of that substance carrying with it the electrical spark is perhaps the smallest division of that strange substance.

Through this we reason that if radium represents the smallest electrical ion and we think of electricity as being the basic principle of all matter we remember that electricity plays through the blue ether expanse of the universe at ease, as per wireless. We gather the conception that electricity is the true challenger of creation since it is everywhere.

The Atheist reasons, "I have my God and Creator. It is everywhere, permeates all things, is the essential to life;" and so brings his challenge to the very door of creation. But we readily observe that in work where we are not definite, where we are not able to demonstrate the actual happenings, that in this field there is liable to originate the wildest theories and superstitions. I bring this to your attention to emphasize one fact; that cells have certain chemicals within their bodies which attracts certain other chemical substances, both organic and inorganic, and by this means they obtain their food and give exodus to their waste products. Ehrlich has plainly demonstrated the fact that they attract certain organic substances, when he worked out his theory for staining the various substances. comprising the cell body.

It is through the staining property of cells that we have been able to study them. The various salts, potassium, sodium, etc., which the cell contains are not merely dissolved in the fluid of the cell but are combined in the organic constituents of the cell protoplasm. They are not merely salts to the proteins but are ions, both anions and kations, and are a chemical combination of the large proteid molecule.

The affinity of a nucleus for a basic stain depends upon the nucleic acid found within the cell. Ex. The head of the spermatozoa contains much nuleic acid bound to simple protein and readily forms a saltlike combination with the basic dyes, hence the intensely stained nucleus. The chromaffin fibres, which are a part of the nucleus, stain lighter at all times excepting in karyokinesis when they stain identical with the nucleus. Marallum claims that the nucleus contains no chloride since it will not admit of a silver nitrate stain. He further states that the nucleolus has a special affinity for an acid stain and attracts it quickly as compared with the basic stain of the nucleus and many of the granules found within the cell which differentiates it, especially the phagocyte, is a striking example of the chemical attraction a cell pos

sesses for other chemical substances, namely: the analine dyes. Again, the proteids are placed in the body in stock solution of serum albumin and serum globulin. These are organic compounds which are broken up by the ferments within the cell body into the various purin ring compounds which formulate an important part of the cell, especially in muscle tissue. They are most certainly attracted to the tissues by a chemical attraction. We note another very striking truth when we observe that a dead cell within a paraffin mount has the same chemical attraction for analine dyes as does the living cell in the frozen specimen which proves the chemical attraction or chemotaxis which the cel! possesses is chemical and not biological.

There are many other illustrations in medicine; for instance, the specific action of quinine upon the plasmodium malaria, the action of emetine upon the entamoeba buchalis or the action of salvarsan upon the spirochaeta pallida are other striking examples. We note in this that bacteria do not have the selective action to protect their own bodies but are subject to the behavior of the organic substances contained within them. The by-products of bacteria certainly have a chemical composition and are attracted to the cells of one's body by the power of chemotaxis. Ehrlich was unable to explain this chemical phenomenon and did the best he could by offering his "Side Chain Theory." Another step further in showing the attraction that cells possess for each other is found in Metchinkoff's theory of phagocytosis. It is again found in the attraction the ova has for the spermatozoa. It is again found in the attraction that many of the uni-cellular organisms have for each other which causes them to unite for the purpose of reproducing their own type. It is certainly beautifully illustrated in the attraction that the cells of the body possess for certain bacteria and their toxins. The streptococcus has been found by Rosenow to possess a special affinity for the mucosa. On taking the streptococcus from an appendix or gall bladder of an animal, culturing it in artificial media and injecting it into another animal of the same species will produce the same disease in the animal injected. We must make allowance for environment however, as the streptococcus under one environment will produce localized abscesses, under another phlegmon, another scarlet fever, another erysipelas, another septicemia, another osteomyelitis, another endocarditis, another pernicious anemia (Smithies), another neuritis, another herpes zoster, etc. All of these depend upon the environment of the bacteria but the basic principle is the same for the bacteria and its toxin.

Every tissue of the body possesses its special affinity for certain bacteria. The nervous tissue

attracts streptococcus, tetanus, rabies, poliomyelitis anterior, etc. Bone tissue attracts streptococcus and staphylococcus, pneumococcus spirochaeta pallida, etc. Muscle tissue attracts all pus producing organisms, as does connective tissue.

The blood carries all bacteria and their toxins. The red cells attract the plasmodia malaria especially. The lymphatics are no exception to the blood stream in general. I could indulge indefinitely but time does not permit. The important point in the application of this argument lies in maturing our judgment in how to handle septic wounds. Locally the wound may look ever so encouraging but remotely we find the chronic disintegration of liver 'cells, of kidney cells or of heart cells and other tissue. We ask ourselves as young practitioners when should we amputate a compound infected arm or leg? When should we resort to heroic measures in trying to eradicate the foci of infection?

Now our study will apply with a great deal of satisfaction and we answer, before these secondary changes, of which I have just spoken, occur. We have studied the destruction of cells from chemicals and toxins from without, now I wish to discuss the pathology produced in the body by the death and the liberation of chemicals and toxins produced by ferments from within the cells. Wells says: "The intracellular ferment is the most important part of the cell's metabolism."

Proteids are continuously being broken down into urea, C02 and water. Crile has observed that after unusual stimulation of the cells the exhaustion produces a marked acidity of the cell content. Wiener says: "The reason cells do not digest themselves is from the fact that they are alkaline in reaction. Autolysis does not begin until acids replace the normal alkalinity and the cell begins dying. If alkalies are added the death of the cell does not occur." Jacoby says: "Heterolysis (foreign body digestion) is accomplished by the phagocytic enzyme which is capable of digesting any proteid from serum albumin to cat-gut." The autolytic action of any cell body is accomplished only when the cell media is acid. The endotoxic bacteria, as typhoid and cholera, are examples of the autolytic properties of intercellular enzymes and their action. Some scientists claim that they act only when liberated after having digested the cell capsule.

The very interesting phase of this topic to me is that of grave un-infected wounds. I refer to wounds and tissues deprived of their ability to assimilate food, no matter from what origin, whether it be traumatic, thrombosis of blood supply or injury to the trophic nerve supply. When a cell is destroyed the nuclus disappears and liquefaction necrosis supervenes. Should

we lay a liver out separate from an animal's body in aseptic media we find autolytic ferments present in the cells of the liver which causes self- digestion of these cells or autoliquefaction necrosis. The cells of muscles especially break down by these ferments and free a very great amount of by-products composed of purin ring compounds carrying the nitrogen radical. We note in gluttonous persons and high livers that the urea output is very great. In gout and diseases of metabolism the urea compounds are especially increased in the urine. V. Norden has talked this for years. Chittenden did a number of diatetic experiments showing us that the proteid in-take was excessive in many cases and that we can get along better with a reduction in the calory in-take from V. Norden's standard.

There are two ways that we may get an excessive output of nitrogenous compound: 1. Excessive in-take.

2.

Excessive destruction of tissue.

In grave sepsis we have the maximum destruction of cells of every kind and the nitrogen output in the urine, is always increased. In some diseases of metabolism we get an increase in the non-nitrogenous purin ring compounds within the body. In conditions where great destruction of tissue is present, as per thrombosis or the destruction of trophic nerve supply, we get an excessive amount of nitrogenous purin ring compounds within the body. I have analyzed fourteen cases where thrombosis, traumatism or trophic nerve supply destroyed the tissues, causing the following symptoms in the patients:

They showed a queer illness. Pulse rapid; delirious; appetite gone; no fever; they were very yellow and looked quite ill. The color of the wound was perfectly normal; no redness nor swelling.

Blood: reds gradually fell to two million cells. Whites climbed to 23,000. Hemoglobin 35 per cent (Tal). Remainder of physical examination was negative except the urine. Sp. g. 1035; a trace of albumin and urates were plus. I was at a loss to know what had happened to my patients. They did not improve with time, either, and I was very much alarmed. The normal look of the wound, the lack of an increased temperature, the specific gravity of the urine led me to study the pathology of these cases closely. In fact, they looked like a diabetic in coma, but there was no sugar. I well remember the words of Prof. Chittenden: "Proteid decomposition products are a constant menace to the well being of the body. Any quantity of proteid beyond the real requirements of the body may prove injurious. We see the evil effects of uric acid in gout, but there are many more nitrogenous waste-products of proteid.

catabolism which with excess of proteid food, are liable to be unduly conspicuous in the fluids of the body, and many do great harm before they are eliminated from the body through the kidneys. Further, we must concede the terrific strain upon the liver and kidneys before and during the transit of their elimination. They also cause very marked disturbance in the central and peripheral nervous system and must be eliminated as speedily as possible to prevent this occurance."

From this statement we see that proteids may cause pathology, if the system is saturated with their end-products over a long period of time. Stress has been laid on faulty elimination of proteid decomposition or their catabolism products. But few essayists have devoted time to the increased production. Diabetes is a disease due to acid bodies which do not carry the nitrogen radical but are purin ring compounds derivative of fat catabolism. The gouty diathesis is due to purin ring compounds carrying the N radical. The urate crystals deposited as tophi illustrate their accumulation within the system as a chronic deposit, and seem to be due to faulty elimination. The acute type of acidosis is illustrated in gangrenous tissue deprived of its nutrition from any cause, and which must be absorbed thus throwing an avalanche of amin acids, due to the sudden destruction of the proteid tissues of the body into the circulation. (We are here dealing with the catabolism of proteid cells.)

We ask if the body proteid can be broken down within the system and thrown into the circulation as cleavage products or amin acids. A beautiful example is found in postmortum autolysis of the liver, which is accomplished by the intercellular ferments, causing a liquefaction necrosis and the liberation of amin acid. When the blood supply or trophic nerve supply is cut off to a certain group of muscles we all know that the system reacts very gravely. There is something about it that has not been explained. These patients are gravely ill. There may not be a single external symptom. You do not get this phenomenon if you amputate a normal limb. If you amputate before gangrene sets in, he may suffer from something that savors of seriousness. Now and then a thrombus is overcome and the patient will slowly get well but the question is: "What happens to make this man or patient so ill?"

Taylor, of Pennsylvania, says that the destruction of body proteids is always amin acid carrying the N radical. No matter with what reagents, steam, ferments, alkalies or acids, the end-result is amin acid. Then by the destruction of large masses of proteids we must have an enormous increase of these acid bodies in the circulation. We know that they unite with the CO2 of the blood for elimination as ammonia

carbonate or urea. If they are set free in avalanches the blood C02 cannot care for them and they float free and must react as Chittenden states, or are similar in pathology to that of diabetic crises.

There is a great deal that might here be used in support of this idea but time does not permit a long scientific discussion of this subject. If we know that these bodies carry a nitrogen radical, we can estimate the damage done as the N radical will be an index in amount correspondingly larger or smaller as the amount of proteid destroyed within the body. I used Kjeldahl's method of determining the amount of nitrogen, and followed the plan of Otto Folin for proteid destruction.

One gram of proteid will produce 1-3 gram of urea. The urea nitrogen equals 87.5 per cent of the entire nitrogen output. An orderly record of his diet was kept and the nitrogen balance estimated. Of the cases studied their average output was three times the nitrogen intake for four weeks, when they gradually returned to their normal balance. Their loss of weight was very marked. The necessity of having CO2 suggested the soda treatment. They had soda by mouth, proctoclysis, hypodermoclysis and intra-venus infusions of normal solutions of soda until the urine reacted alkaline. Under this alkaline treatment they made a rapid and sure recovery. I offer these cases and their history to illustrate the fact that the essayist has treated many of these cases as low grade infection. I give the chromaffin system of accumulation and retardation and glandular secretions, their enzyme place, and grant their influence in metabolism. But the pathology of tomorrow will be based upon the cell and its biochemistry. Tomorrow will unfold the simple, intricate, chemical reaction and the administration of Salvarsan will no longer be done empirically.

We note that cellular catabolism products are the same whether produced by an invading bacteria or by death due to some other cause. I grant that there are other bacterial by-products with which we must deal. We recognize the influence chemistry plays in these matters. We all recognize and accept the fact that therapy will always follow the analysis pathology makes.

I am intensely interested in the truths underlying the composition and structure of all matter. The one great law of simplicity given us by no less chemists and scientists than Curies, Rutherford, Sir Wm. Ramsey and Prof. J. J. Thompson, who all concur in the positive and negative balance of corpuscles necessary to formulate the atom of any substance of matter. They show that acids are pregnant with negative, and alkalies with positive electrical ions. They do not limit this great law of simplicity

to the inorganic world but prove that it holds equally true in the more complex molecule of organic matter comprising both plants and animals. They go further and prove that the spectrum brings this great truth from the ends of the universe.

Resume

There is a very broad application of the

truths set forth in this paper. Every specialty has its phases. We observe that the new books on pediatrics are discussing intestinal acidosis from an absorption of stasis products and bacterial by-products. They outline etiology, symptomotology and treatment. The new books on Obstetrics apply these principles to involution of normal uterii as well as to toxic pregnancy which shows a nitrogen imbalance. The bacteriologist and serologist will study its phases carefully in the future.

Proteid is builded in the fields from the soil and the action of the sun's rays is stored in the wheat kernel. This same proteid is transferred to the beef and stored in the cells. Man gets this proteid and transforms it to his cells. It is modified and held as stock solution of serum albumin and serum globulin within the body.

The mother's breast or mammary gland changes this type to that found in the mother's milk. How necessary it is to have a babe born of its mother. The proteid of its body is very similar in type to hers. Those of you who do blood transfusions know that you select some blood relative. Why? Because the recipient is less liable to be poisoned by the foreign proteid. The child will build this proteid of its mother into its own more easily than it will the proteid of a cow or goat or the proteid of some manufactured milk. In this same mother, if her gland cannot build the proteid perfectly the child cannot handle it. If the mother has a sick attack or becomes angry, the proteid is disturbed or changed and poisons the child. The introduction of proteid serums will kill for the same reason. Von Bergman has shown that the pancreas will make a very great effort to change the enzyme of proteid to accommodate. the system, that it may handle a new and strange proteid to which the body is not accustomed.

Now our problem of intestinal obstruction. Von Furth shows that an inflamed bowel will absorb faster than one that is not inflamed. We have the picture of inflamation, passive congestion, moist gangrene death of millions of cells, and over this area the pancreatic trypsin pouring constantly. We add bacteria to this and our picture is auto-digestion, autolysis, acidosis, and the splitting of proteid by bacteria. Why does the sight of obstruction have

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have a great application of these principals. In the field of bacteriology and serology we We note that all bacteria pathogenic to man are proteid splitters, they grow on proteid culture media best, they require proteid for their food and as shown, select the tissues of the body that serve them best; that they may split that proteid best, to acquire their food and for no other reason. This bacterium has 15 times more weight in proteid in its body than all other substances which lends support to the fact that they are proteid feeders, and that their intra and extra cellular enzyme are proteid splitters, for the purpose of splitting off the proteid for its food. All bacteria seem to be alike in this particular, that they are unable to utilize proteid cleavage which they have split off the proteid cell and are unable to again bind it into a usable food. It poisons them as it does man and they die after they have used the food of the media. There may yet remain much. cleavage proteid in this media but he cannot get it for his food. His own waste products from his own metabolism is also in the media. This is not a serious thing. Man's most serious menaces are proteolitic enzymes and the cleavage by-products from any .origin.

In establishing an immunity it is not logical to establish an immunity against this cleavage proteid. This is a fact that we have lost sight of in our serums and leaves our immunity lacking in efficiency. We saw that the body builded the autolitic proteid cleavage into urea and excreted it as such and that if the production was out of balance with this synthesis the body was poisoned by the cleavage product. In infection we have the same problem of building these bacterial cleavage products into elimination forms that are not irritating to the body. But is not the urea also increased in infection? Then wherein do they differ? In the cleavage only. There is a difference in the various cleavage proteids of digestion. It requires a different synthesis of each one in accordance to the enzyme splitting it. Von Bergman saw this and found that the pancreas would adjust itself to liberate an enzyme which would differ just a little that the various proteids in nature would be split and the proper cleavage proteid provided for the body synthisis. This is the function of the pancreas. Physiologists were satisfied to not trace proteids beyond the bowel

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