This 61-year-old female was first admitted to the hospital because of ascites and pedal edema. A liver biopsy revealed a marked intracellular accumulation of iron. The serum iron concentration was reported as 220 mcg/dLNormal serum iron levels are 35 to 160 micrograms/dL.. On the basis of these studies, the diagnosis of hemochromatosis was made. It should be noted that the patient also exhibited an abnormal glucose tolerance testThe glucose tolerance test (GTT) is a measure of active insulin and also reflects the power of normal liver to absorb and store large amounts of glucose. Following the administration of a 75-gram dose of glucose, blood glucose levels should return to normal in less than 3 hours. at this time (following the ingestion of a test dose of glucose, the blood glucose level rose to 290 mg/dLAfter glucose challenge, the blood glucose level should be back to 110 to 180 mg/dL by 2 hours. at one hour and remained at this level for the next three hours). Subsequent to the first admission, the patient was admitted on several occasions for ascites. The patient's last admission was necessitated by the development of symptoms and signs of hepatic failure (hepatic coma) characterized by jaundiceJaundice (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. and coma.
The liver weighed 820 gramsA normal liver weighs 1650 grams (range: 1500 to 1800 grams).. The cut surface was described as golden-brown in color, having a fine, diffuse nodularity, and being extremely firm in consistency.
Diabetes mellitus, skin pigmentation, and hepatic fibrosis.
Primary or idiopathic hemochromatosis (also called hereditary hemochromatosis - HHC) is an autosomal recessive heritable disorder. The hemochromatosis gene is located on the short arm of chromosome 6, and the associated HLA haplotypes include A3 in 70% of hemochromatosis patients with fewer numbers of patients expressing B7, B14, or Bw35. Males are affected more than females (5 to 7:1) but this earlier and more severe clinical presentation in males is partly due to physiologic iron loss (menstruation, pregnancy) in females which delays iron accumulation. Even though the gene has been isolated and many aspects of the disease are known; the exact mechanism responsible for iron overload in primary hemochromatosis is not known.
The second type of hemochromatosis where the source of iron overload can be explained is called secondary hemochromatosis. Severe anemias due to ineffective erythropoiesis are the most common causes of secondary hemochromatosis. In these anemias the excess iron accumulation results from transfusions and also from compensatory increases in iron absorption. Alcoholic liver disease is also associated with increased iron accumulation in liver cells. Other more obtuse causes of iron overload leading to secondary hemochromatosis include: transfusions of packed RBCs, iron-dextran injections, and long term hemodialysis.
- Compare and contrast the pathogenesis and clinical features of hemochromatosis and Wilson’s disease.
Hereditary hemochromatosis is an autosomal recessive disorder which results in increased iron absorption and iron induced parenchymal tissue damage. The exact mechanism of this functional defect is unknown. The iron overload leads to ferritin and hemosiderin in the parenchymal tissues of the body; primarily the liver, pancreas, myocardium, endocrine glands, and joints. Iron is a direct hepatotoxin and results in micronodular cirrhosisCirrhosis is a liver disease characterized by necrosis, fibrosis, loss of normal liver architecture, and hyperplastic nodules.. Tissue damage and fibrosis is also evident in the pancreas, heart, and endocrine organs. The "bronze diabetes" of hemochromatosis is produced by excess melanin in the skin and by accumulation of hemosiderin in the dermal appendages. The diabetes is caused by destruction of pancreatic islets. Hemosiderin in the joint synovial lining leads to acute synovitis.
Wilson's Disease is also an autosomal recessive disorder that results in the accumulation of toxic levels of copper. Like hemochromatosis, the gene defect has been localized but the exact nature of the genetic defect is unknown. In this disorder, copper absorption and transport to the liver are normal; however, the copper does not get back into the circulation as ceruloplasmin and copper excretion into bile is severely impaired. The accumulation of copper leads primarily to liver, brain and eye damage. The liver develops fatty change and nuclear vacuolization in the setting of acute or chronic hepatitis which later progresses to cirrhosisCirrhosis is a liver disease characterized by necrosis, fibrosis, loss of normal liver architecture, and hyperplastic nodules.. Neurologic manifestations include toxic neuronal injury primarily in the basal ganglia. Accumulation of copper in the cornea results in the formation of Kayser-Fleischer rings.
- eMedicine Medical Library: Hemochromatosis
- Merck Manual: Iron Overload: Hemosiderosis and Hemochromatosis
- Powell LW, Seckington RC, Deugnier Y. Haemochromatosis. Lancet 2016.
- Ayonrinde OT, Milward EA, Chua AC, Trinder D, Olynyk JK. Clinical perspectives on hereditary hemochromatosis. Crit Rev Clin Lab Sci 2008;45(5):451-84.
- Bassett ML. Haemochromatosis: iron still matters. Intern Med J 2001 May-Jun;31(4):237-42.
- PEIR Digital Library: Hemochromatosis Images
- WebPath: Hepatic Pigmentary Disorders
- WebPath: Cellular Accumulations
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