case study 1

A 63 years old man with a long history of alcohol use presents to his new primary care physician with a 6 months history of increasing abdominal girth. He has also noted easy bruisability and worsening fatique. He denies any history of GI bleeding. He continues to drink three to four coktails a night but says he is trying to cut down. Physical examination reveals a cachectic man who appears older than his stated age. Blood pressure is 108/70 mm Hg. His scleras are anicteric . his neck vein are flat, and chest examination demonstrates gynecomastia and multiple spider angiomas. Abdominal examination is significant for protuberant abdomen with a detectable fluid wave, shifting dullness, and an enlarged spleen. The liver edge is difficult to appreciate. He has trace pitting pedal edema. Laboratory evaluation shows anemia, mild thrombocytopenia, and elevated prothrombin time. Abdominal ultrasounogram confirms a shrunken , heterogenous liver consistent with cirrhosis, significant ascites and spenomegaly.

Question:

1)       Describe possible mechanisms for alcohol induced cirrhosis.

2)       What is the proposed mechanism of portal hypertension, and how does it affect ascites formation?

3)       Significant hematologic abnormalities exist. How might they be explained?

Answer:

1)       The exact mechanism of alcohol induced injury to the liver is unknown; however , it is thought that the marked distortion of hepatic architecture , fibrous tissue deposition and scarring , and regenerative nodule formation result from multiple processes. Chronic alcohol use has been associated with impaired protein synthesis, lipid peroxidation , and the formation of acetaldehyde, which may interfere with membrane lipid integritiy and disrupt cellular functios. Local hypoxia, as well as cell mediated and antibody- mediated cytotoxicity, have also been implicated.

2)       Portal hypertension is in part responsible for many of the complication of cirrhosis, including clinically apparent ascites , a sign of liver disease associated eith poor long term survival. Although no single hypothesis can explain its pathogenesis, portal hypertension and inappropriate renal retention of sodium are important elements of any theory. Portal hypertension changes the hepatocellular architecture, resulting in increased intrahepatic vascular resistance. This elevates the sinusoidal pressure transmitted to the portal vein and other vascular bed. Spenomegaly and portal to systemic shunting result. Vasodilator such as nitic oxide are shuntrd away from liver and not cleared from thr circulation , resulting in peripheral arteriolar vasodilation. Decreased renal artery perfusion from this vasodilation is perceived as an intravascular volume deficit by the kidney, activated raas system causing sodium and water resorption. By overwhelming oncotic pressure , increased hydrostatic pressure from fluid retention in the portal vein result in ascitrs formation. Exceeding lymphatic drainage capacity, ascites accumulates in the peritoneum.

3)       Splenomegaly and hyperslenism are a direct consequence of elevated portal venous pressure. Thrombocytopenia and haemolytic occur as a result of both sequestration and these formed elements by the spleen and depressive effect of alcohol on the bone marrow. The frequent bruising and the elevated prothrombin time in this patient highlight the coagulopathy seen ic cirrhosis and chronic liver disease. As a result of inadequate bile excretion, there is impaired absorption of the fat soluble vitamin K, a vitamin necessary for the activation of specific clotting factors. In addition, inadequate hepatic synthesis of other  clotting factors causes a coagulopathy.