Gastrointestinal Pathology II Case Studies


CASE 6: Alcoholic Liver Disease


Clinical History:

A 63-year-old man sought medical help because of increasing abdominal girth over many months along with a recent episode of vomiting blood. Serum chemistries showed sodium 120 mmol/L, potassium 4.2 mmol/L, chloride 99 mmol/L, CO2 20 mmol/L, glucose 75 mg/dL, total protein 6.2 g/dL, albumin 1.9 g/dL, total bilirubin 5.0 mg/dL, AST 190 U/L, ALT 123 U/L, and protime 18 seconds (control 12). A gross photograph (image 6.1) shows how his liver and spleen would appear. The microscopic section is also representative of his liver. It shows a diffusely disorganized architecture with nodules of hepatocytes with focal cholestasis and surrounded by fibrous bands with bile duct proliferation (images 6.2 and 6.3). At high magnification, globular eosinophilic material is seen in some hepatocytes (image 6.4).
  1. What is the diagnosis? What do the clear vacuoles in the hepatocytes represent? What is the clumped eosinophilic material seen in some of the swollen hepatocytes?

    2. This is cirrhosis. It can be further classified as a micronodular cirrhosis on the basis of the size of the nodules (<5 mm). The vacuoles are composed of lipid accumulation (fatty change). The clumped eosinophilic material is Mallory's hyaline (aggregates of cytoskeletal elements).

  2. What is the probable etiology?

    3. Given the above findings, the most probable etiology is chronic alcoholism.

  3. Correlate the clinical and laboratory findings in this patient.

    4. Patients with cirrhosis can develop portal hypertension with esophageal varices, which may explain the hematemesis. Liver failure from cirrhosis can lead to hypoalbuminemia, hypoprothrombinemia, and ascites.

  4. What are potential complications of this disease?

    5. Complications leading to morbidity and mortality include gastrointestinal hemorrhage, hepatic coma, infection (pneumonia, peritonitis), renal failure with hepatorenal syndrome, and hepatocellular carcinoma.

  5. What does an elevated blood ammonia signify?

    6. Metabolism of amino acids leads to disposal of amino groups via the urea cycle in hepatocytes. Free ammonia is complexed with CO2 to form carbamoyl phosphate which is linked to ornithine by the enzyme ornithine transcarbamylase within mitochcondria to form citrulline. The citrulline passes into the cytoplasma and has an additional amino group from aspartate added, eventually forming arginine which is cleaved by arginase to form urea and citrulline. The urea enters the bloodstream and is excreted by the kidneys. Severe liver disease results in a diminished ability of the hepatocyte to metabolize ammonia to urea, leading to a rise in the blood ammonia.

  6. Is a transplant indicated?

    7. A diagnosis of cirrhosis can lead professional staff to feel no empathy at all, and even say (away from the patient) that he did this to himself, as if it were intentional, or--worse--deserved. Reinforce empathic reactions and discourage judgmental reactions.

    One method: ask if anyone they know ever went through a period of drinking too much, or taking recreational drugs. It is not that far from there to not knowing when to stop, and ending up drinking too much quietly for years, or taking IV drugs.

    Should these patients be allowed to go on transplant lists? The answer is yes! Alcoholic liver disease (ALD) is the second leading indication for transplantation in the United States. Most transplant programs in the U.S. require a minimum abstinence period of 6 month's prior to transplantation, but how strenuously that is tested varies from center to center, and maybe even from surgeon to surgeon. Most studies demonstrate a recidivism rate from 20 to 30% by 2 years after transplantation.

    But won't the patient go and waste another liver? Equal post-transplant survival for ALD patients and non-ALD patients has been demonstrated. Look up survival rates. Liver transplant is nothing like kidney: the surgery is more involved and much harder to recover from, and transplants last a shorter time.