Studies on the photosensitisation of animals in South Africa. IX. The bile flow of the Merino sheep under various conditions

Abstract

In the various experiments outlined above, attempts have been made to elucidate some of the important factors influencing the normal bile excretion in Merino sheep. This work was undertaken primarily with the view of explaining the severe generalised icterus seen in the disease geeldikkop caused by excessive ingestion of wilted Tribulus plants. In this disease the icterus is of an exceptionally intense paralytic nature in which the liver appears to lose all power of bile excretion, with the result that the bile is regurgitated into the blood and lymph stream. Except for the bile pigmentation there is, however, little morphological change of the liver parenchyme to indicate the type of damage caused. The effect, therefore, seems to consist very largely of a functional derangement of the liver. In previous articles of this series, it was pointed out that administration of the plant Lippia although in no way related to Tribulus, provoked a closely similar or identical symptom complex in experimental sheep. Moreover the symptoms following surgical obstruction to the bile flow appeared to be the same. The only difference between the latter condition and that caused either by Lippia or Tribulus is the marked cavernous like dilatations of the extra and intrahepatic bile tracts above the point of obstruction following ligation of the common bile duct. In Lippia and Tribulus poisoning it would appear that the liver makes no such attempt at accommodating the bile in its own channels. In the sheep there is no physiological bilirubinaemia comparable to that found in some other species of domesticated animals. Judging from the clear appearance of the serum and the absence of pigments from it one can conclude that bile elimination is very efficient and that the liver treats the bile pigments as non-threshold bodies. In spite of this efficiency, however, the bile flow can be very severely depressed or totally inhibited in cases of Tribulosis or Lippia poisoning thus leading to a pronounced degree of icterus. From the results obtained from sheep with a biliary fistula it is seen that the daily bile flow amounts to volumes of over 200 c.c. When, therefore, elimination is interfered with, the severity of the jaundice can be well understood. The kidneys under these conditions compensate to some degree for the loss of the liver function as shown by the intensely yellow brown urine voided. The compensation however is not complete since the jaundice persists as long as liver action remains distended. Investigations carried out on the effect of cholagogues on the bile flow of these experimental animals show that the dosing of bile definitely causes an increase in the bile flow from the liver. Bile elimination may however proceed at a steady rate in the absence of any bile constituents returning to the liver, i.e. the entero-hepatic bile salt circulation is not essential for the continued excretion of bile in the sheep. Moreover the appetite and digestion of such fistula annuals are fairly well maintained although a slow and progressive decrease in the body weight is frequently noticeable, this being more evident in some animals than in others. Under the influence of Lippia poisoning, the bile flow of experimental sheep can be very promptly depressed and ultimately even completely inhibited. The main effect of the Lippia toxin on the liver is as yet not clearly understood. It appears to have a paralysing effect on the normal bile excretion for although the liver cells themselves are still capable of allowing the bile to pass through as indicated by the direct van den Bergh reaction, the bile tracts including the smallest bile capillaries seem to be incapable of moving the bile in the normal manner and at the normal rate towards the large bile tracts. This sluggishness in the bile flow results in some of the biliary constituents, e.g. the pigments to escape into the small blood and lymph vessels and so carried back into the general circulation where an extensive and severe jaundice may be caused. The difficulty in explaining the genesis of the icterus arises from the fact that morphological changes in the liver may be slight even in very severe cases of jaundice. This point has also been stressed by other workers. Thus Cantarow and Stewart, studying the morphological changes in the liver and bile passages of cats with total biliary obstruction, state that "these observations seem to indicate that there is no demonstrable correlation in individual instances, between the changes in the liver and bile ducts and the serum bilirubin concentration at any given time during the period of total bile stasis''. The various experiments undertaken with the object of re-establishing the normal bile flow after the onset of Lippia jaundice, have been disappointing in that none of the cholagogues or purgatives used had any definite beneficial effect on the icterus and on the bile flow. Improvement, when it did come about, appeared as a slow process and governed by the powers of the body itself. Other liver poisons, such as chloroform and phosphorus which were also studied, caused acute and severe fatty changes of the liver and frequently accompanied by bilirubinaemia. In no case however was the same intense and persistent jaundice of "geeldikkop" or Lippia poisoning observed.