HEPATIC NECROSIS FOLLOWING PARACETAMOL OVERDOSE

Paracetamol is a main metabolite of phenacetin, and since its introduction it has become increasingly popular as a mild analgesic which is available without prescription. When taken in the recommended therapeutic dose of l g 6-hourly, paracetamol is relatively free from unwanted effects, and in particular, unlike phenacetin, there is little to associate it with renal damage. However, when taken as a single overdose, paracetamol can cause hepatic necrosis, the severity of which seems to be proportional to the dose of drug absorbed. All patients ingesting over 10 g (20 × 500 mg tablets) are at risk from liver damage, which may be potentiated by previous consumption of substances that induce microsomal enzymes, such as barbiturates or alcohol. Since the first reported cases of fulminant hepatitis due to paracetamol overdose in 1966 the number of cases of such self-poisoning has risen annually, with a concomitant increase in the number of deaths.

Download Full-text

Fine Structural Alterations in Thyroid Follicular Cells (FC) and Changes in Serum Thyroxine Produced by Feeding Polychlorinated Biphenyl (PCB) to Rats

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100079929 ◽

1977 ◽

Vol 35 ◽

pp. 498-499

Author(s):

W.T. Collins ◽

Charles C. Capen ◽

Louis Kasza

Keyword(s):

Feed Efficiency ◽

Polychlorinated Biphenyl ◽

Serum Proteins ◽

Skin Lesions ◽

Hepatic Necrosis ◽

Ultrastructural Changes ◽

Lymphoid Tissues ◽

Heat Transfer Fluids ◽

Thyroid Follicular Cells ◽

Peripheral Metabolism

The widespread contamination of the environment with PCB, a compound used extensively by industry in hydraulic and heat transfer fluids as well as plasticizers and solvents in adhesives and sealants, has resulted in detectable tissue levels in a large portion of the human population, domestic animals, and wildlife. Intoxication with PCB produces severe hepatic necrosis, degeneration of lymphoid tissues and kidney, skin lesions, decreased reproductive performance, reduced feed efficiency, and decreased weight gain. PCB also has been reported to reduce the binding of thyroid hormone to serum proteins and enhance the peripheral metabolism of thyroxine with increased excretion of thyroxine-glucuronide in the bile (Bastomsky, Endocrinology 95: 1150-1155, 1974).The objectives of this investigation were (1) to investigate the histopathologic, histochemical, and ultrastructural changes in thyroid FC produced by the acute (4 week) and chronic (12 week) administration of low (50 ppm) and high (500 ppm) doses of PCB to rats, (2) to correlate these alterations to changes in serum immunoreactive thyroxine concentration, and (3) to investigate the persistence of the effects of PCB on the thyroid gland.

Download Full-text

Early Development of Drug-Induced Hepatic Necrosis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100066942 ◽

1971 ◽

Vol 29 ◽

pp. 576-577

Author(s):

F. G. Zaki ◽

E. Detzi ◽

C. H. Keysser

Keyword(s):

Early Development ◽

Hepatic Necrosis ◽

Screening Tests ◽

Dense Matrix ◽

Sprague Dawley ◽

Electron Microscopic ◽

Drug Induced ◽

Hepatocellular Damage ◽

Sprague Dawley Rats ◽

Microscopic Studies

This study represents the first in a series of investigations carried out to elucidate the mechanism(s) of early hepatocellular damage induced by drugs and other related compounds. During screening tests of CNS-active compounds in rats, it has been found that daily oral administration of one of these compounds at a dose level of 40 mg. per kg. of body weight induced diffuse massive hepatic necrosis within 7 weeks in Charles River Sprague Dawley rats of both sexes. Partial hepatectomy enhanced the development of this peculiar type of necrosis (3 weeks instead of 7) while treatment with phenobarbital prior to the administration of the drug delayed the appearance of necrosis but did not reduce its severity.Electron microscopic studies revealed that early development of this liver injury (2 days after the administration of the drug) appeared in the form of small dark osmiophilic vesicles located around the bile canaliculi of all hepatocytes (Fig. 1). These structures differed from the regular microbodies or the pericanalicular multivesicular bodies. They first appeared regularly rounded with electron dense matrix bound with a single membrane. After one week on the drug, these vesicles appeared vacuolated and resembled autophagosomes which soon developed whorls of concentric lamellae or cisterns characteristic of lysosomes (Fig. 2). These lysosomes were found, later on, scattered all over the hepatocytes.

Download Full-text

A Comparison of the Ultrastructural Morphology of Hepatic Necrosis in BDF1 Mice

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100099350 ◽

1981 ◽

Vol 39 ◽

pp. 586-587

Author(s):

Becky Jackson

Keyword(s):

Endoplasmic Reticulum ◽

Smooth Endoplasmic Reticulum ◽

Preliminary Investigation ◽

Hepatic Necrosis ◽

Hepatic Tissue ◽

Pronounced Increase ◽

Glycogen Store ◽

Ultrastructural Morphology ◽

Mitochondrial Integrity ◽

Glycogen Stores

Preliminary investigation has indicated similarity in hepatic ultrastructural morphology in nutritional deprivation, and cyanide induced hepatic necrosis. Analysis of hepatic tissue has indicated disruption of intracellular membranes, specifically, reduction in rough endoplasmic reticulum (RER) mitochondrial integrity, and glycogen stores. An increase in smooth endoplasmic reticulum (SER) portion was observed.To further investigate the apparent equivalence of necrotic morphology, ultrastructura1ly, BDF1 mice were subjected to senescence, nutritional deprevation, potassium cyanide (KCN) induced toxemia, and acetaminophen induced toxemia. Controls were utilized to ellucidate non-necrotic hepatocellular normals. U1trastructura1 investigation of controls (Fig. 1) shows densely granular RER, abundant glycogen stores, and morphologically normal mitochondria. Subjects with acetaminophen induced necrosis exhibit reduced normal RER with increased levels of dialated, vesicular RER in apparent conversion to SER (Fig. 2), loss of mitochondrial integrity, and glycogen store reduction. Senescent subjects exhibit a pronounced increase in SER and loss of glycogen store. (Fig. 3). Investigation of the senescent SER at high magnification (Fig. 5) indicates that the SER is arising from degranulating and vesiculating RER.

Download Full-text