Excessive accumulation of iron and liver damage

Fibrosis and damage to liver cells are directly related to the content of iron in them. The nature of the damage does not depend on the cause of the accumulation of iron, whether hereditary hemochromatosis or frequent blood transfusions. Fibrosis is most pronounced in the periportal zones - places of predominant iron deposition. Feeding of iron carbonyl rats results in chronic damage and liver fibrosis.

With a small amount of iron, it is stored in the form of ferritin. With excess intake into the cell, iron is deposited in the form of hemosiderin.

Removal of iron by bleeding or the introduction of chelators leads to an improvement in the status of patients and biochemical indicators of liver function, a reduction or prevention of its fibrosis.

Several mechanisms of the damaging effect of iron on the liver are possible. Under the influence of iron, lipid peroxidation of membranes of organelles is intensified, which leads to a disruption of the function of lysosomes, mitochondria and microsomes, and a decrease in the activity of mitochondrial cytochrome-C oxidase. The stability of the lysosomal membranes is violated, with the release of hydrolytic enzymes into the cytosol. In animal experiments it has been shown that iron overload leads to activation of stellate liver cells (lipocytes) and to enhanced synthesis of type I collagen. Currently, the mechanisms of activation of stellate cells are being studied. Animal administration of antioxidants prevents liver fibrosis, despite iron overload.

Other diseases accompanied by increased accumulation of iron

Insufficient transferrin

A case is described when a child with an excessive accumulation of iron lacked this iron-binding protein. Hematologic changes corresponded to severe iron deficiency, while the tissues contained an excessive amount of iron. Parents were heterozygous, and the child was homozygous.

Iron overload caused by a cancerous tumor

It is believed that the primary cancer of the bronchi, in which abnormal ferritin is produced, may be the cause of excess iron deposition in the liver and spleen.

Late skin porphyria

The reason for the elevated iron content in the liver with late skin porphyria is considered to be its combination with heterozygous for the hemochromatosis gene.

Erythropoietic siderosis

Siderosis is combined with an extremely high level of erythropoiesis. Bone marrow hyperplasia can somehow lead to absorption of excess amounts of iron by the intestinal mucosa, which continues even with significant iron stores. Initially, iron is deposited in the macrophages of the reticuloendothelial system, then in the parenchymal cells of the liver, pancreas and other organs.

Thus, siderosis can develop in diseases accompanied by chronic hemolysis, especially with beta-thalassemia, sickle cell anemia, hereditary spherocytosis and hereditary dyseritropoietic anemia. The risk group also includes patients with chronic aplastic anemia. The development of siderosis is possible even in patients suffering from a mild form of sideroblastic anemia and not receiving blood transfusion.

Siderosis increases with blood transfusions, because the iron injected with blood can not be excreted from the body. Clinical signs of siderosis appear after transfusion of more than 100 doses of blood. Misadministration of iron therapy improves siderosis.

Clinically, siderosis is manifested by increasing pigmentation of the skin and hepatomegaly. In children, the growth and development of secondary sexual characteristics slows down. Rarely, hepatic insufficiency and obvious portal hypertension are observed. The fasting glucose level rises, but the clinical signs of diabetes develop extremely rarely.

Although a relatively small amount of iron is deposited in the heart, myocardial damage is the main factor determining the prognosis, especially in young children. In children, the symptoms of the disease appear with the accumulation in the body of 20 g of iron (transfusion 100 doses of blood); with the accumulation of 60 g, death from heart failure is likely.

Treatment of siderosis presents difficulties. The need for blood transfusions decreases after splenectomy. A well-balanced diet with a low iron content is almost impossible to pick. Effectively subcutaneous injection into the anterior abdominal wall of 2-4 g deferoxamine for 12 hours using a portable syringe pump. However, this treatment because of the high cost is available only for a few children with hemoglobinopathies. The possibility of treatment with oral iron chelators has been studied in an experiment.

Sideroz of Bantu

This disease is observed in African blacks who eat porridge, fermented in an acidic environment in iron utensils. Sour food and malnutrition contribute to increased absorption of iron. In rural areas of sub-Saharan Africa, there are still cases of siderosis, caused by the tradition of drinking beer made in steel containers. Studies have shown that the degree of iron overload in these patients is influenced by both genetic factors (not related to HLA) and environmental factors.

Alcohol cirrhosis

The increase in iron deposition in the liver depends on many factors. One of the most common factors is protein deficiency. Increased absorption of iron in the intestine is found in patients with cirrhosis of the liver, regardless of its etiology. With cirrhosis with pronounced portosystemic collaterals, iron absorption increases somewhat.

Alcoholic beverages, especially wine, contain a large amount of iron. Chronic pancreatitis, which develops during alcoholism, apparently contributes to increased absorption of iron. Iron can also be overloaded with iron-containing drugs and hemolysis, while gastrointestinal bleeding reduces it.

Accumulation of iron rarely reaches the extent inherent in hereditary hemochromatosis. With alcoholic cirrhosis, shortly after multiple bleeding, iron deficiency develops, which indicates only a moderate increase in its accumulation in the body. Histologically, in the liver, along with the deposition of iron, signs of alcoholism are revealed. The determination of the hepatic index of iron makes it possible to distinguish the early stage of hemochromatosis from alcoholic siderosis. The emergence of diagnostic methods based on genetic analysis will help to establish that some patients with alcoholic liver siderosis may be heterozygous for hereditary hemochromatosis.

Siderosis caused by portocaval shunting

After the imposition of the portosystemic shunt, as well as the spontaneous development of portosystemic anastomoses, rapid accumulation of iron in the liver is possible. Probably, shunting is the reason for an increase in the severity of siderosis, often observed with cirrhosis.

Hemodialysis

Significant overload of the liver and spleen with iron in the treatment of hemodialysis can be caused by blood transfusions and haemolysis.

Influence of the pancreas on iron metabolism

With experimental damage to the pancreas, as well as in patients with cystic fibrosis and chronic calcific pancreatitis, increased absorption and accumulation of iron; while in patients with cystic fibrosis, absorption of inorganic iron, but not iron, associated with hemoglobin was enhanced. This suggests the presence of a pancreas secret factor that can reduce iron absorption.

Hemochromatosis of newborns

Hemochromatosis of newborns is a very rare disease with a fatal outcome, which is characterized by the development of hepatic insufficiency in the prenatal period, iron overload of the liver and other parenchymal organs. The question of whether this is due to a primary impairment of iron accumulation or the result of some other liver disease physiologically already saturated with iron remains unclear. The hemochromatosis of newborns is not related to hereditary hemochromatosis.

Chronic viral hepatitis

Almost half of patients with chronic hepatitis B and C show an increase in the degree of saturation of iron transferrin and / or serum ferritin levels. At present, the only reliable method of diagnosis of hereditary hemochromatosis is a liver biopsy, which allows to identify the deposition of iron and determine the hepatic index of iron. With a high iron content in the liver, the effectiveness of treatment with alpha-interferon of chronic hepatitis C is reduced. Determining the appropriateness of bleeding to improve the effectiveness of treatment requires prospective studies.

Non-alcoholic steatohepatitis

The parameters of iron exchange in plasma were changed in 53% of alcoholic steatohepatitis, but none of them, according to the night index of iron, did not suffer from hemochromatosis.

Excessive accumulation of iron associated with acetuloplasminemia

Aceruloplasminemia is a very rare syndrome caused by a mutation of the ceruloplasmin gene and accompanied by excessive deposition of iron, mainly in the brain, liver and pancreas. Patients develop extrapyramidal disorders, cerebellar ataxia and diabetes mellitus.

[1], [2], [3], [4]