D. R. Drury

The Source of Fibrinogen.

The formation of fibrinogen has been ascribed to many tissues and organs of the body. Whipple, 1 Goodpasture 2 and others suggested that this substance takes its origin from the liver and intestinal tract; and recently Foster and Whipple 3 have presented excellent evidence that the liver is the main if not the sole source of fibrinogen. Schultz, Nicholes and Schaefer 4 have produced corroboratory data. Final proof in the matter has waited, however, upon the findings in liverless animals. In 4 hepatectomized rabbits 5 we have determined the concentration of blood fibrinogen before operation and at various periods thereafter. A postoperative decrease in the substance was always found. In 6 others a partial depletion of fibrinogen was accomplished after hepatectomy and its concentration in the blood was followed until death. Controls subjected only to defibrination were also studied. The initial defibrination was accomplished under ether anesthesia by slowly injecting into the jugular vein 100-150 cc. of compatible defibrinated blood while removing an identical quantity from the carotid artery. The procedure was repeated 4 or 5 times. This reduced the blood fibrin concentration to one third to one fifth its original amount. By continuing the blood exchange a still greater reduction was sometimes brought about in the controls. Fibrinogen was estimated in the form of fibrin by the method of Foster and Whipple 6 as modified by Schultz, Nicholes and Schaefer. 4 In the controls fibrinogen regeneration was exceedingly rapid. Within 5 or 6 hours after a 90% reduction, a complete return to the previous amount was observed, regeneration far more rapid than has been reported for the dog. 7 Twenty-four hours later the concentration had reached a level 50% above the normal figure and in two instances it had doubled within 48 hours. The findings were wholly different in the liverless rabbit. In 6 animals blood fibrin determinations were made immediately after the hepatectomy and then the partial defibrination was carried out, reducing the circulating amount by 65 to 80%.

Relation of Liver to Fat Metabolism. I. Respiratory Quotient in Conditions of Liver Insufficiency.

It has long been known that animals fail to survive extirpation of the liver. The recognized changes in the blood resulting from this procedure show clearly that the liver is essentially concerned with both carbohydrate and protein metabolisms. Does the organ possess a vital function in relation to fat metabolism as well? For the purpose of solving this and other problems, a successful method of inducing liver insufficiency in rabbits has been devised, whereby slightly more than 90% of the liver is removed without demonstrable interference with the return of blood to the heart. Unless treated, the animals survive but 6 to 18 hours, dying with low blood sugar and convulsions. If given glucose, they live for varying periods up to 5 days, dying eventually in a state resembling that developing in dogs deprived of the entire liver. 1 A study of the respiratory quotient of rabbits deprived of 90% of the liver has brought out the fact that fat metabolism is carried on as readily and as rapidly after the operation as before. The respiratory quotient of intact rabbits, fasted 3 days, was found to be low, indicating that the body metabolism was largely that of fat. Fasting rabbits were, therefore, employed for the work and, after the preliminary determination of the respiratory quotient, 90% of the liver was ablated. Six to 8 hours thereafter, when the immediate effects of operation and anesthesia had worn off, the respiratory quotient was again determined. No glucose had been given and at this time the blood sugar concentration was found to be 0.60 to 0.70 mg. per cc. In several instances another respiratory quotient was determined on the following day, 24 hours after operation. The animals in which this was done received just enough glucose by mouth to maintain the blood sugar level above the minimum compatible with life.

Irreversible Character of the Late Changes after Hepatectomy

We have endeavored to learn whether rabbits manifesting the symptoms characteristic of the advanced stage of liver insufficiency 1 , 2 can be clinically improved by the circulation of their blood through the livers of healthy animals or by cross transfusion with normal rabbits. “Liver transfusion.” In an initial series of 14 experiments, rabbits, hepatectomized under ether and with cannulae placed in the left carotid artery and left jugular vein, were given sufficient glucose to maintain the blood sugar level well above normal. Fourteen to 24 hours later, when the characteristic signs of advanced hepatic insufficiency in the rabbit 1 , 2 had appeared, the portal vein and vena cava connecting with the liver of a healthy animal were rapidly cannulated, the hepatic artery was tied and the organ was removed. It was submerged at once in a bath of paraffin oil at 40° C., and connected with the circulation of the liverless animal by means of the cannulae already present in the carotid artery and jugular vein of the latter. In this way the circulating blood of the liverless animal was passed for as long as an hour through the freshly removed liver of the healthy rabbit. Of 14 experiments 4 were carried to completion without lapses of technique which might render the findings questionable. In none of the 14 did clinical improvement of the liverless animals take place though the “transfused” liver was actively functioning as shown by a copious formation of bile.

The genesis of gall stones in the dog

In dogs permanently intubated for the collection of bile, gall stones not infrequently develop despite the absence of infection, stasis and gall bladder activity. The character of the stones has already been discussed. 1 They are always discrete to begin with, scattered upon the glass and rubber wall of the collecting tube. What determines this punctate localization? In certain instances, of almost pure calcium carbonate concretions, the answer is plain. These form in the midst of organic debris, not infrequently around bits of talc from the tube surface. In other cases minute, rounded, pigmented particles from the bile lodge upon the tube wall, and stone formation takes place upon these as nuclei. To trace the source of such particles and their significance we have made day to day studies of the sediment from sterile 24 hour specimens of bile centrifuged on removal from collecting balloons devoid of air. Also we have followed the early stages of calculus formation in the collecting tubes of the same animals. The bile was found to yield formed elements identical with those later recovered from the tube system and from the interior of stones forming upon the walls of the latter. The nature and the amount of the sediment vary with the condition of the animal. For a day after the operation whereby intubation is effected it may consist merely of mucus, which later is seldom met with. Usually one obtains from the specimen of the second 24 hours after operation and perhaps more abundantly from that of the third, a slight brown deposit, made up, as the microscope shows, of minute, highly ref ractile, translucent, yellow-brown granules. The shape of these tends to be spherical, but is rendered various by the partial merging of the spheres.