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.
