Fatty infiltration of liver

Phosphoenolpyruvate carboxykinase (PEPCK) deficiency is distinctly rare and even more devastating clinically than deficiencies of glucose-6-phosphatase or fructose-1,6-bisphosphatase. PEPCK activity is almost equally distributed between a cytosolic form and a mitochondrial form. These two forms have similar molecular weights but differ by their kinetic and immunochemical properties. The cytosolic activity is responsive to fasting and various hormonal stimuli. Hypoglycemia is severe and intractable in the absence of PEPCK [12]. A young child with cytosolic PEPCK deficiency had severe cerebral atrophy, optic atrophy and fatty infiltration of liver and kidney. 

Deo, M. G. and Ramalingaswami, V., Production of periportal fatty infiltration of liver in rhesus monkey by protein-deficient diet, Lab. Invest., 9, 319, 1960. 

Fatty infiltration of the liver. In this pathology, the triglyceride concentration in the liver is 10-fold superior to the norm. The accumulation of fat in the cyto-plasm of hepatic cells leads to an impaired liver function. The causes of this pathol-ogy are numerous one of these may be a deficiency in lipotropic factors and the associated therewith synthesis of excess triglycerides. 

Rabbits died from exposure to 5000 ppm for 3 hours, but 10,000 ppm for 1 hour was not lethal. Effects were conjunctival irritation, lacrimation, slow respiration with some rales, incoordination, ataxia, and weakness. Autopsy of animals exposed to lethal concentrations revealed severe fatty infiltration of the liver and moderate kidney damage. ... 

Adverse gastrointestinal symptoms (nausea, vomiting, anorexia, metallic taste, abdominal discomfort, and diarrhea) occur in up to 20% of individuals taking metformin this can be minimized by starting at a low dose and slowly titrating the dose upward with food. Like phenformin, metformin can cause lactic acidosis, but its occurrence is rare except when renal failure, hypoxemia, or severe congestive heart failure is present or when coadministered with alcohol. Metformin is also contraindicated in persons with hepatic dysfunction, but it appears to be safe for use in the hepatic steatosis that often occurs with fatty infiltration of the liver in poorly controlled type II diabetics. 

The transsulfuration pathway involves conversion of homocysteine to cysteine by the sequential action of two pyridoxal phosphate (vitamin B6)-dependent enzymes, cystathionine- 5-synthase (CBS) and cystathionine y-lyase (Fig. 21-2). Transsulfuration of homocysteine occurs predominantly in the liver, kidney, and gastrointestinal tract. Deficiency of CBS, first described by Carson and Neill in 1962, is inherited in an autosomal recessive pattern. It causes homocystinuria accompanied by severe elevations in blood homocysteine (>100 (iM) and methionine (>60 (iM). Homocystinuria due to deficiency of CBS occurs at a frequency of about 1 in 300,000 worldwide but is more common in some populations such as Ireland, where the frequency is 1 in 65,000. Clinical features include blood clots, heart disease, skeletal deformities, mental retardation, abnormalities of the ocular lens, and fatty infiltration of the fiver. Several different genetic defects in the CBS gene have been found to account for loss of CBS activity. 

There are three main histological stages of alcoholic liver disease, as highlighted in Figure 3.3 stage 1, steatosis (fatty infiltration of the hepatocyte) stage 2, alcoholic hepatitis and stage 3, fibrosis and cirrhosis. 

Liver is the target organ for aflatoxins, and aflatoxicosis leads to proliferation of the bile duct, centrilobular necrosis and fatty infiltration of the liver, hepatomas and hepatic lesions. The susceptibility of animals to AFB] varies with species [reviewed in Eaton and Groopman, 72]. In addition to the liver, AFB] also affects other organs and tissues, such as the lungs and the entire respiratory system [73-75]. 

Giorgio, A., Francica, G., Aloisio, T., Tarantino, L., Pierri, R, Pellicano, M., Buscarini, L., Livraghi, T. Multifocal fatty infiltration of the liver mimicking metastatic disease. Gastroenterol. Internal. 1991 4 169 — 172... 

Scott, W.W. jr., Sanders, R.C., Siegelman, S.S. Irregular fatty infiltration of the liver diagnostic dilemmas. Amer. J. Radiol. 1980 135 ... 

Surprisingly, alcoholic fatty infiltration of the liver and alcoholic hepatitis often display ascites as well, mostly only discernible when applying ultrasonic methods of examination. This might suggest that certain pathogenic mechanisms in the formation of ascites (such as increase in portal pressure, structural sinus changes, and stimulation of biochemical or sympathoadrenergic factors) are favoured or become more intense as a result of alcohol (and possibly also its chemical additives). Ascites can also occur in severe acute viral hepatitis, in which case the course of disease deteriorates considerably. (28,46,64)... 

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