Protein Turnover and Amino Acid Catabolism: Hemochromatosis

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Protein Turnover and Amino Acid
CatabolismHemochromatosis

• By Megan Brewster
• Megan Strand
• Christina Stanalker

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Case History

• 54-year-old woman was admitted to the hospital
  due to dypsnea and an altered mental status.
• Had history of arthritis and gallstones which
  resulted in her getting a cholecystectomy.
• Has no personal or family history of liver
  disease or anemia.
• She did not use alcohol, illicit drugs, or
  tobacco.

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Case History continued

• Only Significant finding mild abnormality of
  liver function tests. Normal
• ALT - (alanine aminotransferase) 42 IU/l 31
• AST- (aspartate aminotransferase) 35 IU/l 31
• AP - (alkaline phosphatase) 140 IU/l 120
• TB- (Total Bilirubin) 1.9 mg/dl 1.2
• She was lost in the follow and admitted later
  when she presented increasing dyspnea, peripheral
  edema, and lethargy.

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Physical Examination

• Core temperature Optimum Temp
• Blood Pressure 170/80 mmHg (Systolic
  Hypertension)
• Moderate obesity
• Yellow discoloration of eye
• No spider Angioma
• 3 peripheral Edema
• Liver normal size, but spleen was not palpable.
• No ascites (fluid in abdomen)

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Updated Lab Results

• ALT - (alanine aminotransferase) 126 IU/l
• AST- (aspartate aminotransferase) 298 IU/l
• AP - (alkaline phosphatase) 175 IU/l
• TB- (Total Bilirubin) 6.8 mg/dl
• Serum ferritin level 1200 Mg/l (ULN 300)
• Serum Iron 169 Mg/dl (ULN 150)
• Total Iron binding capacity 295 mg/dl
• Urine positive for urobilinogen
• Radiographs show pulmonary congestion
• Echocardiogram left-atrial enlargement but
  normal left-ventricular function.

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Treatments

• First she was treated for complications
• Then she was prescribed a restricted protein diet
  of 60 grams/day
• Avoidance of iron supplements, vitamin C, and was
  referred for periodic phlebotomy.

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Diagnosis

• After a liver biopsy
• Examination revealed micronodular cirrhosis
• Staining for iron showed fine granules within
  many hepatocytes.
• 226mmol of iron per gram
• Hepatic iron index of 4.2
• ? consistant with hemochromatosis.
• Genetic test revealed homozygosity of C282Y in
  the HFE gene (confirming the diagnosis).

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Metabolic Process Involved
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Q A

• What is cryptogenic cirrhosis and approximately
  what fraction of cases can be attributed to this
  type?
• Approximately 18 of cirrhosis cases can be
  attributed to cryptogenic cirrhosis.

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Continued

• Patients with cirrhosis are often very sensitive
  to the affects of medications. Why might this
  be?
• This may be to due to the fact that the liver has
  a decreased ability of detoxification making it
  hard for the liver to detoxify the medications.

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Continued

• Why are cystic fibrosis patients at increased
  risk for cirrhosis?
• Cystic fibrosis patients are at increased risk
  for cirrhosis because cystic fibrosis is a
  disease that affects mainly the lungs, liver,
  pancreas and intestines. If a cystic fibrosis
  patients the bile secreted by the liver block the
  bile ducts, leading to liver damage which
  overtime can lead to cirrhosis.

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Continued

• Hemochromatosis is more often manifested in men
  than in woman. What might be the reason?
• Hemochromatosis is caused be a defect in the gene
  that regulates amount of iron absorbed from food.
  Men typically maintain higher iron levels then
  women so hemochromatosis is more often manifested
  in men.

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Continued

• The transferring saturation (TS) is a common
  screening test for hemochromatosis, with levels
  greater than 45 suggesting disease. From the
  laboratory results provided in the case,
  calculate the TS in this patent.
• 169 mg/dl(serum iron) 295 mg/dl (total iron
  binding capacity) x 100 57.28. 45 is
  considered abnormal, and her levels exceed this.

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Continued

• Hepatic encephalopathy is often triggered by an
  event that causes liver damage, such as an
  alcoholic binge or an infection, or by
  consumption of a large amount of protein. Why
  might a large amount of protein cause hepatic
  encephalopathy?
• Through the urea cycle, ammonia is produced from
  protein going through the liver, but normally
  gets filtered out of the body. If a large amount
  of protein is being processed, an influx of toxic
  NH3 will occur and could cause hepatic
  encephalopathy since it is not properly being
  filtered out and could result to poisoning the
  brain and other parts of the body as these toxins
  are put back into the bloodstream.

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Continued

• How does administration of lactulose in the
  treatment of hepatic encephalopathy inhibit
  protein absorption by the intestine?
• The conversion of Lactulose to lactic acid
  results in acidification of the gut lumen. This
  favors conversion of NH4 to NH3 and the passage
  of NH3 from tissues into the lumen. Gut
  acidification inhibits ammoniagenic coliform
  bacteria, leading to increased levels of
  nonammoniagenic lactobacilli. Lactulose also
  works as a cathartic, reducing colonic bacterial
  load.

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Continued

• What causes edema in patients with cirrhosis?
• With cirrhosis, congestion in the liver leads to
  an increase in pressure within the blood vessels
  in the liver and subsequently, in the blood
  vessels leading into the liver, causing ascites.

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• Questions??

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Works Cited

• Brissot, Pierre. October 2003. Hemochromatosis.
  Orphanet Encyclopedia. http//www.orpha.net/data/p
  atho/GB/uk-hfe.pdf
• http//www.emedicine.com/med/topic3185.htm
• http//www.uptodate.com/patients/content/topic.do?
  topicKeykidn_dis/4639
• http//www.liverdoctor.com/index.php?pageliver-te
  sts