Hemosiderin: Characteristics, Diseases And Diagnosis

The hemosiderin is a pigment in the form of prills or granules where stored iron in animal tissues. These granules are poorly assimilated by the body, they are stored inside the cells and usually appear after severe bleeding events.

Despite their iron nature, hemosiderin corpuscles have a poorly defined molecular nature. However, they are known to be made up of ferritin, denatured ferritin, and other materials. In addition, hemosiderin granules are always opposite or contrary to blood flow.

Hemosiderin is most commonly found in macrophages called “siderophages.” These are macrophages responsible for phagocytosis to red blood cells (erythrocytes) and due to this phagocytosis, iron is released inside them and is stored in an organelle called “siderosome”.

Siderophages are cells produced by the bone marrow, responsible for storing iron to supply it to the erythrocyte stem cells during the formation of red blood cells (erythropoiesis).

The appearance of siderophages is indicative of bleeding due to some pathological agent or some mechanical stress. Siderophages generally appear 48 hours after bleeding and can persist for 2 to 8 weeks after bleeding.

Haemosiderin is detected through blood smears, tissue samples or substances from different regions of the body. These blood samples are treated with staining methods, where the siderophages are easy to identify due to their size and intense blue coloration.


Hemosiderin represents a set of structures that serve as intracellular iron stores, which are insoluble in water and are stored in phagocytes of the reticulum endothelial system of the spleen, liver and bone marrow. Each hemosiderin granule can have up to 4500 iron atoms inside it.

The iron stored in hemosiderin granules is thought to be ferric phosphate. This compound is the main component of cellular iron stores in the form of ferritin.

However, iron deposits in the form of ferritin are much smaller and assimilable by cells than hemosiderin granules. It has been observed that cells with the presence of ferritin also share the presence of hemosiderin granules.

50% of the constitution of hemosiderin deposits consists exclusively of iron atoms.

Scientists who have observed hemosiderin grains through electron microscopy have determined that they are complexes of ferritin, denatured ferritin, proteins, carbohydrates, lipids, and other materials.

Hemosiderin granules can range in size from 1 nanometer to more than 20 nanometers, which are large crystals or granules. They are only thought to be assimilable by the cell through iron-induced lipid peroxidation.

It has been proposed that hemosiderin represents a “protective” biological mechanism, since it reduces the availability of iron that promotes the reactions that originate free radicals inside cells.


The full functioning of the iron regulation mechanisms in the body of animals is essential for health, since insufficient iron causes anemia; while the iron overload in the system promotes the accumulation of hemosiderin in the tissues.

This accumulation of hemosiderin can cause tissue damage and leads to a condition called “hemosiderosis.” This disease is characterized by causing liver cirrhosis, most likely accompanied by liver carcinomas.

Hemochromatosis, which consists of a defect in the HLA-A locus on the short arm of chromosome 6, can present deficiencies in the mucosal regulatory system, behaving as if there were a permanent iron deficiency, even with abundant intake of this mineral .

This disease can present in two forms, by primary or secondary hemochromatosis. Primary hemochromatosis is an autosomal recessive disease. In this case, people tend to store iron in the tissues in the form of hemosiderins in an uncontrolled way.

However, primary hemochromatosis can be controlled with transfusions and blood draws. This in case it is diagnosed early, before there is an excessive accumulation of hemosiderins in the person’s tissues.

Secondary hemochromatosis occurs when the iron regulatory system is overwhelmed by excessive amounts of iron due to death and destruction of red blood cells, liver disease, or a chronic increase in iron intake.


Haemosiderins are diagnosed from many different points of view. For pathologists they are lumps that contain iron inside, while for biochemists they are heterogeneous compounds of iron, carbohydrates, proteins and lipids.

For electron microscopists, hemosiderin clumps are electron-dense assemblages found inside siderosomes (bodies that carry pigments).

However, despite different positions about hemosiderin granules, all agree that they are insoluble granules rich in iron and that their excess content is harmful to the health of the body.

Haemosiderin granules form especially large clumps in cells and can easily be stained within tissues to be seen clearly under the light microscope.

The hemosiderin granules are stained with the Prussian blue reaction through a technique called Perl stain. Using this technique, differences have been described between isolated hemosiderin iron nuclei with different conditions, for example:

– The hemosiderin nuclei of patients with secondary hemochromatosis have a crystalline structure similar to goethite, with the chemical formula α-FeOOH

– Patients with primary hemochromatosis (of genetic origin) have the iron nuclei of hemosiderin granules in an amorphous form, composed of iron III oxide.

In normal human spleen cells that store iron in some hemosiderin granules, the nuclei are seen to be crystalline ferrihydrite, very similar to the nuclei of ferritin molecules.

Using electron microscopy, more detailed diagnoses can be made to discriminate between patients with primary hemochromatosis and secondary hemochromatosis.

Generally, hemosiderin particles in humans with primary hemochromatosis are between 5.3 and 5.8 nanometers; meanwhile, in patients with secondary hemochromatosis they measure between 4.33 and 5 nanometers in diameter.

This information is relevant to determine the type of disease that patients have. Furthermore, genetic analysis confirms what is the genetic composition of the cells of the organisms in these diseased tissues.


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