IPLab:Lab 12:Alcoholic Cirrhosis
This 56-year-old white male came to the emergency room because of weakness, lack of appetite, shortness of breathShortness of breath is a common clinical manifestation of heart failure., abdominal distention, and an altered mental status. He was a known alcoholic who drank approximately one pint of whiskey per day. Physical examination revealed a wasted appearance, icterusHyperbilirubinemia making the patient appear yellow. Also called jaundice.Jaundice (or icterus) is a state of hyperbilirubinemia (increased bilirubin in the blood) in which bile pigment is deposited in the skin, mucous membranes, and scleras. This deposition of bile pigment results in a yellow appearance., a protuberant abdomen, bilateral gynecomastia, sparse axillary hair, and spider angiomataA focal network of small arteries and arterioles arranged in a radial pattern with a central red spot. on his chest. Liver and spleen were not palpable, the testes were atrophic, and the legs showed petechial hemorrhages and 3+ edema. Admission laboratory values revealed a hemoglobin of 9.5 g/dLNormal hemoglobin for a male is 14 to 17.2 gm/dL., an MCV of 106 fLThe normal mean corpuscular volume (MCV) is 83 to 99 fL., a platelet count of 97,000/mL, and a prothrombin time of 19.2 secondsA normal prothrombin time is 12.6 to 14.6 seconds.. In addition, his albumin was 2.3 g/dLThe normal albumin level 3.9 to 4.8 gram/dL., bilirubin, total 6.5 mg/dLA normal total bilirubin level is 0 to 1.0 mg/dL., AST 21.0 U/LA normal aspartate aminotransferase (AST) for a male is <37 U/L., ALT 56 U/LA normal alanine aminotransferase (ALT) is 7 to 56 U/L., alkaline phosphatase 180 U/LA normal alkaline phosphatase is 39 to 117 U/L., and GGT 320 U/LA normal gamma-glutamyl transpeptidase (GGT) is 0 to 65 U/L.. The patient was treated with thiamine, folate, multivitamins, and vitamin K and an intravenous line was placed to infuse 5% dextrose. An esophagogastroduodenoscopy (EGD) was performed which demonstrated large esophageal varices with evidence of previous bleeding sites. Two days after admission the patient developed a massive hematemesisHematemesis is the vomiting of blood. and his hematocrit dropped to 17%A normal hematocrit for a male is 39 to 49%.. Emergency EGD showed ruptured esophageal varices. Despite successful sclerotherapy and supportive transfusions, the patient lapsed into coma and died the next day.
In this is medium-power photomicrograph of trichrome stained liver the bands of fibrous tissue are seen to form "bridges" between triad areas (arrows); this is called "bridging fibrosis." Also note the fibrous tissue (arrows) and how the hepatocytes are separated into nodules by this fibrous tissue.
In this high-power photomicrograph of trichrome-stained liver, the bands of fibrous tissue surround the hepatocyte nodules. There is some degeneration and dropout of hepatocytes in this nodule. Also note the increased numbers of bile ducts in the triad area (arrows). Bile duct proliferation is a common feature in many hepatitides.
This photograph taken from still another patient at autopsy demonstrates the esophageal varices in the distal esophagus (arrows). The esophagus was clamped before removing the esophagus from the body in order to trap the blood in these distended varices. It is obvious how easily these thin-walled superficial varices could rupture and bleed.
Initial changes include hepatocellular steatosis. This is caused by altered metabolism with high levels of NADH from lactate dehydrogenase resulting in increased lipid biosynthesis. Mobilization of lipids from peripheral fat stores and decreased lipid acceptor protein synthesis leads to insufficient lipoprotein production.
Alcohol induces free radical production as it is broken down by the microsomal ethanol oxidizing system. Alcohol also impairs microtubular and mitochondrial function and membrane fluidity.
Acetaldehyde, the major ethanol metabolite, can cause lipid peroxidation and acetaldehyde-protein complexes that further inhibit the microtubular system.
Finally, alcohol also induces an immunologic reaction in the liver. This immune-mediated liver damage is thought to result from the expression of neoantigens on hepatocytes possibly due to alcohol-induced alterations in membranes or acetaldehyde binding to proteins leading to neoantigen formation.
Since most of the clotting factors are produced by the liver, chronic liver damage with loss of liver parenchyma will lead to a reduction in clotting factors. In addition, this patient had bleeding esophageal varices and ascites which could both use up or sequester clotting factors, respectively.
Hepatic cirrhosisCirrhosis is a liver disease characterized by necrosis, fibrosis, loss of normal liver architecture, and hyperplastic nodules. with extensive parenchymal damage and fibrosis results in an increased resistance to portal blood flow. The increased portal pressure leads to increased pressure in the coronary veins of the stomach. This results in increased pressure in the esophageal plexus in the terminal portion of the esophagus as the blood travels through this plexus to empty into the azygous vein. The increased pressure and increased flow of blood through this plexus of thin-walled veins leads to dilation and formation of varices. These varices can then rupture and lead to life-threatening hemorrhage as was seen in this case.
Increased portal pressure also leads to increased pressure in the inferior hemorrhoidal veins and can lead to the formation of anorectal varices.
Wernicke's encephalopathy is caused by thiamine (Vitamin B1) deficiency. Chronic alcoholics often have poor diets and alcohol inhibits intestinal absorption of thiamine. Thus, some chronic alcoholics can develop Wernicke's encephalopathy which consists of foci of symmetric discoloration, softening, and punctate hemorrhages in the paraventricular regions of the thalamus and hypothalamus, in the mamillary bodies, around the aqueduct in the midbrain, in the floor of the fourth ventricle and in the anterior cerebellum. There is demyelinization and loss of neuropil. Even after treatment with thiamine, there is significant memory deficit.
- eMedicine Medical Library: Cirrhosis
- eMedicine Medical Library: Cirrhosis Imaging
- Merck Manual: Alcoholic Liver Disease
- Fujimoto J. Gene therapy for liver cirrhosis. J Gastroenterol Hepatol 2000 Mar;15 Suppl:D33-6.
- Ge PS and Runyon BA Treatment of Patients with Cirrhosis. NEJM 2016 Aug 25 375(8):767.
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