Carbon tetrachloride cirrhosis in relation to liver regeneration
01 Jan 1936-The Journal of Pathology and Bacteriology (John Wiley & Sons, Ltd)-Vol. 42, Iss: 1, pp 1-21
About: This article is published in The Journal of Pathology and Bacteriology.The article was published on 1936-01-01. It has received 350 citations till now. The article focuses on the topics: Liver regeneration & Cirrhosis.
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TL;DR: Necrogenic Action of Carbon Tetrachloride in the Rat: A Speculative Mechanism Based on Activation
Abstract: Necrogenic Action of Carbon Tetrachloride in the Rat: A Speculative Mechanism Based on Activation
419 citations
TL;DR: Regression parameters were found in all livers and were prominent in the majority and a continuum of regressive changes was seen within individual livers, allowing one to understand visually how fibrous regions of hepatic parenchyma can be returned toward a normal appearance.
Abstract: ○ Context.-Cirrhosis is widely regarded as being irreversible. Recent studies have demonstrated that fibrosis may decrease with time in humans and experimental animals if the disease activity becomes quiescent. The histologic appearance of regressing cirrhosis in the human has not been described in detail. Objectives.-To define histologic parameters that indicate regression of cirrhosis and to provide an interpretation of how regression occurs from a histologic point of view. Design.-A patient who underwent a series of biopsies that showed apparent regression of hepatitis B cirrhosis is presented. In addition, 52 livers removed at transplantation having cirrhosis or incomplete septal cirrhosis were graded for histologic parameters that suggest progression or regression of fibrosis. Progression parameters were steato-hepatitis, inflammation, bridging necrosis, and piecemeal necrosis. The regression parameters (collectively called the hepatic repair complex) were delicate perforated septa, isolated thick collagen fibers, delicate periportal fibrous spikes, portal tract remnants, hepatic vein remnants with prolapsed hepatocytes, hepatocytes within portal tracts or splitting septa, minute regenerative nodules, and aberrant parenchymal veins. Results and Conclusions.-Regression parameters were found in all livers and were prominent in the majority. Livers with micronodular cirrhosis, macronodular cirrhosis, and incomplete septal cirrhosis demonstrate a histologic continuum. A continuum of regressive changes was also seen within individual livers. These appearances allow one to understand visually how fibrous regions of hepatic parenchyma can be returned toward a normal appearance. Many examples of incomplete septal cirrhosis could be the product of regressed cirrhosis.
308 citations
306 citations
TL;DR: A new approach to this old problem of severe decompensated micronodular cirrhosis is described in which both variation and level of critical damage are monitored by the daily weight change of the rat in response to intragastric carbon tetrachloride given during light halothane/oxygen anesthesia.
278 citations
TL;DR: These models have provided unparalleled insights into the mechanisms underlying hepatic fibrosis and are the best characterized with respect to histological, biochemical, cell, and molecular changes associated with the development of fibrosis.
Abstract: Animal models of hepatic fibrosis provide a means to study the cell and molecular mediators of fibrosis in a serial manner during both progression and recovery. Several approaches to induction of fibrosis have been described. Of these, CCl(4) intoxication in rats and mice is probably the most widely studied. In addition, the CCl(4) model is the best characterized with respect to histological, biochemical, cell, and molecular changes associated with the development of fibrosis. CCl(4) can be given intraperitoneally or by oral gavage; it induces zone III necrosis and hepatocyte apoptosis with associated hepatic stellate cell activation and tissue fibrosis. With repetitive dosing CCl(4) can be used to induce bridging hepatic fibrosis (4 wk of twice-weekly dosing), cirrhosis (8 wk of twice-weekly dosing) and advanced micronodular cirrhosis (12 wk of twice-weekly dosing). In addition, for each of these models spontaneous recovery from fibrosis can be studied after cessation of dosing. Mechanistic studies using gene knockout and transgenic animals can also be established using CCl(4). Together these models have provided unparalleled insights into the mechanisms underlying hepatic fibrosis.
234 citations
References
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TL;DR: The association of ascites with lesions of the liver seems to have been known since the earliest times and was apparently recognized by Vesalius, Harvey, and Morgagni.
Abstract: CLINICAL FEATURES OF THE ASCITIC STAGE OF CIRRHOSIS OF THE LIVER By Dr. Snell The association of ascites with lesions of the liver seems to have been known since the earliest times and was apparently recognized by Vesalius, Harvey, and Morgagni. 1 One of the first known descriptive drawings of cirrhosis was by John Brown 2 who, in 1685, described a case under the title "A Human Liver Appearing Glandulous to the Eye" (fig. 1). Matthew Baillie 3 gave a good gross description in "Morbid Anatomy," and also noted the frequency of dilated superficial venous channels in the presence of dropsy. Legg 4 called attention to a description of cirrhosis published by John Andree, 5 in 1788, who wrote as follows: "Another kind of indurated and diminished liver which I have also met with, is that in which its surface is raised in half-rounded eminences, appearing like granulations, covered with
66 citations
TL;DR: Pain, hyperaesthesia, and contraction of muscle in a definite area, but vomiting, cardiac, vasomotor, and other reflexes, including visceral pain, are of common occurrence in ill health.
Abstract: and can be more or less influenced by nerve impulses from higher levels, especially by those wlhich are concerned in emotional states. Other centr es, or pathways, are formed by education, and this is particularly the case in those reflexes which take place through the cerebral cortex. Such reflexes are conditioned,\" and are therefore liable to various alterations and especially to inhibition. Functional centres or pathways may be formiied in abnormal states. Fixed ideas probably result from the establishmiient of certain pathways in the cortex of the cerebrum. In asthma afferent nerve impulses resulting frlom certain stimuli produce a reflex contraction of the bronchial muscle anid a narrowing of the bronchioles. The reflex may become a \" conditioned \" one, and be induced by any afferent impulse resulting from a stimulus which has been associated with its occurrence. The pathways in time are so \" grooved \" that the reflex takes place very readily, and is excited by any afferent nerve impulse which has previously been associated with the asthmiia. The phenomenon of pain, anid especially of visceral pain, imiay be influenced in the same way. The frequent carriage of nerve impulses from the heart along the pain paths results in a lessened resistance of the synapses along the pathways taken. The occurrence of pain is facilitated, and a conidition of status anginosus may be set up in which afferent impulses from other sources may spread into the same paths and produce pain. An attack of angina may be induced in this condition by a carious tooth or other source of pain. In the production of visceral pain the afferent impulses from the organ affected spread into the pain paths in the lower level of the central nervous system, but the sensation of pain is located in some part of the body wall which is supplied with afferent nerves the impulses in which are capable of exciting a nmore or less localized sensation. In the areas supplied by these nerves various phenomena occur. Hyperaesthesia is sometimes miet with, and the margins of the hyperaesthetic area are constantly varying in position. The hyperaesthesia is probably due to a decreased resistance of the synapses leading to the pain pathways, so that nerve impulses which would not ordinarily cause pain now do so because they pass more readily into the pain pathways. The fluctuation in the extent of the area affected may be due to variations in resistance of the synapses in the .pathways of the afferent neurones coming from the bordersof the area, and be ascribable to the phenomenon of fluctuation or variation in the actual units employed in carrying the nerve impulses. But other changes than sensory are usually found. Increased tone, or the actual contraction of muscle, often occurs in the body wall. The rigidity of muscle, especially well seei in the abdominal wall as the result of irritation of an abdominal viscus, is a reflex phenomenon, and is subject to the same variations as that affecting the sensory' changes. A tenmporary centr e is created in the central nervous system, and afferent impulses from the irritated viscus m11ake use of certain pathuways with the production of a number of end-results. If the afferent impulses are sufficiently numerous, or if there is any condition presenit -which decreases the resistance of the synapses, the impulses may spread and occasion not onlv pain, hyperaesthesia, and contraction of muscle in a definite area, but vomiting, cardiac, vasomotor, and other reflexes. Sensation and reflex action are closely bound up together. Even visceral reflexes may be productive of sensation. Alterations in the heart beat, palpitation, respiratory disturbances, vaso-constriction, and vaso-dilatation give rise to subjective phenomena. Irritability, exhaustion, and depression are of common occurrence in ill health. The fatigue of a synapse renders that synapse more resistant to the passage of a nerve impulse, and fatigue of the afferent pathways should be a negation. But fatigue and the sensations met with inl ill health are positive sensations amidl not mere negations. They are, as a r-ule, general and miot localized to any particular part. Their cause is unsknown.l but must be sought for in some alteration in tIme afferenlt nerve impulses affecting the conscious state. REPORT OF THREE AUTOPSIES FOLLOWING CARBON TETRACHLORIDE TREATMENT-
65 citations
TL;DR: In this article, the authors reported that dogs on a lean meat diet can be made either highly resistant or susceptible to carbon tetrachloride intoxication by adding or withholding calcium salts for a few days previous to the administration of the poison, and that calcium therapy was found highly effective in the treatment of cases of poisoning.
Abstract: An earlier note1 reported the rather empirical observation that dogs on a lean meat diet can be made either highly resistant or susceptible to carbon tetrachloride intoxication by adding or withholding calcium salts for a few days previous to the administration of carbon tetrachloride. Furthermore calcium therapy was found highly effective in the treatment of cases of poisoning.The intoxication produced in susceptible dogs was described in the earlier note and is characterized by gastro-intestinal irritation, nervous disturbances and convulsions, followed by weakness, depression, and death. There is a retention of bile pigments in the blood and a hypoglycemia which usually becomes extreme before death and which seems in most cases to be the immediate cause of death. The level of total calcium in the blood is usually within normal limits, nevertheless either a lack of or excessive demand for calcium ions seems to be indicated by the relief afforded by the furnishing of extra available calcium. It was at fi...
53 citations
TL;DR: In medicine it is used as a vermifuge in the treatment of ankylostomiasis and in industry as a solvent for gums, resins and fats and as a fire extinguisher.
Abstract: Carbon tetrachloride is used in industry as a solvent for gums, resins and fats; it is used as a dry cleanser and is a constituent of some of the rubber elements; it is used also to clean oil from machinery and, under the name of pyrene, as a fire extinguisher. 1 In medicine it is used as a vermifuge in the treatment of ankylostomiasis. Cases of poisoning have been reported from time to time. I have recently observed seven men who were affected by it, simultaneously, in a small plant where it was used as a solvent for cleaning. Carbon tetrachloride (CCl 4 ) is a colorless, transparent liquid, like chloroform. It is insoluble in water and glycerin and is miscible with chloroform, alcohol and benzene. It is soluble in all fixed and volatile oils. It is volatile at ordinary temperatures but noninflammable. Investigations as to the toxicity of carbon tetrachloride
43 citations
TL;DR: The discovery in 1921 of the anthelmintic properties of carbon tetrachloride, which is relatively so harmless and so effective that it can be given to whole communities in which hookworm is prevalent, with the assurance that it will remove from 95 to 100 per cent of the hookworms harbored by infested individuals, made it unnecessary to reexamine the patients for hookworm after treatment, as had been the case previously.
Abstract: In the last ten years great advances have been made in the treatment of hookworm disease. These have been due largely to two factors: the campaign carried out by the International Health Board of the Rockefeller Foundation, making it possible to treat very large numbers of cases and to study the best methods of treatment, and the discovery in 1921 by Dr. Maurice C. Hall1of the anthelmintic properties of carbon tetrachloride, which is relatively so harmless and so effective that it can be given to whole communities in which hookworm is prevalent, with the assurance that it will remove from 95 to 100 per cent of the hookworms harbored by infested individuals. On account of this certainty of action, it became unnecessary to reexamine the patients for hookworm after treatment, as had been the case previously. The increase in the number of persons treated by this new method
35 citations