12. Hemoglobinogenic pigments II. Pathological forms of iron storage

Haemosiderin

The other haemoglobin-derived pigment is haemosiderin. It has a golden yellow-brownish colour and accumulates in tissues when there is a local or system excess of iron.

Iron is usually stored in cells being bound to the protein apoferritin, together forming ferritin. Haemosiderin is comprised of denatured ferritin. While the iron inside ferritin can be used when the body needs it, the iron inside haemosiderin is lost, and cannot be used by the body anymore.

Haemosiderin stains blue with the Prussian blue stain. The pigment is only physiologically found within mononuclear phagocytes in the bone marrow or spleen.

The body has no way to excrete excess iron. Therefore, is the absorption of iron from the gastrointestinal tract very tightly regulated. The only way the body can lose iron is by bleeding.

When haemosiderin is present in other tissues as well the condition is called haemosiderosis if there is no damage to the tissue, or haemochromatosis if there is damage to the tissue.

Patients most often receive blood transfusion to replace blood they’re losing because they’re bleeding, in which case there is no accumulation of iron. However, if the patient cannot produce healthy, working RBCs by themselves (due to e.g. thalassaemia or myelodysplasia) will the patient need blood transfusion anyway. This causes a continuous accumulation of iron since the body cannot get rid of it. This accumulation of iron causes generalized haemosiderosis.

Local haemosiderosis

Local haemosiderosis is caused by local excess of iron and therefore haemosiderin. It is commonly seen in large bruises, where there is a bleeding under the skin. Bruising has four steps:

1. Bleeding into the area of the bruise causes haemoglobin to accumulate, which gives the red and blue colour
2. The porphyrin rings of haemoglobin (but not the iron!) is degraded into biliverdin, giving the green colour
3. Biliverdin is degraded into bilirubin, giving the yellow colour
4. The leftover iron from the haemoglobin forms haemosiderin, giving the golden-brown colour.

Small internal accumulations of blood are usually caused by congestion inside the vessels, often caused by heart problems. Examples are brown induration of the lung, nutmeg liver (hepar moschatum) or fibrosiderotic plaques in the spleen.

Haemochromatosis

In haemochromatosis the haemosiderin level is so high that cells are damaged by it. You can read about its causes and morphology here.

Haemochromatosis is usually seen when 20 grams of extra iron has accumulated. The excessive iron is toxic to cells. The iron creates free radicals that oxidize lipids and proteins and causes damage to DNA. Excess iron also stimulates formation of collagen, which can result in fibrosis.

Clinical consequences

The liver is most affected by haemochromatosis. Hepatocytes are very susceptible to the damage caused by the iron excess. The liver becomes enlarged and brownish, and eventually cirrhotic as well. The risk for hepatocellular carcinoma is 200 times higher in haemochromatosis patients than in healthy people.

The pancreas also becomes pigmented and fibrotic. The pancreatic parenchyme undergoes atrophy. All other endocrine organs become atrophic as well. The damage to the pancreatic parenchyme eventually leads to diabetes, together called bronze diabetes because of the skin coloration.

The heart becomes enlarged with haemosiderin granules inside the muscle fibres.

The skin becomes brownish, although this isn’t just caused by the haemosiderin deposition in the skin, but also by an increased melanin production.

Deposition of haemosiderin in the synovial linings of the joint causes arthritis and joint pain.

Treatment

It’s important to catch haemochromatosis early, before organ damage develops. Serum iron and ferritin screening is important. If it is caught early enough the life expectancy is normal.

The main treatment is phlebotomy (voluntary bleeding) and use of iron chelators, which remove iron from the body.