Physiological forms of iron storage
Normally, iron not used for hemoglobin synthesis is stored in the body in the form of two main protein complexes.
- Ferritin. This is a water-soluble metalloprotein. Its protein shell (apoferritin) conceals a core capable of holding up to 4,500 iron atoms. Normally, inactive oxidized SS-ferritin circulates in the blood. When oxygen is deficient, active reduced SH-ferritin is formed, which has pronounced vasoparalytic and hypotensive effects.
- Hemosiderin. This is a water-insoluble aggregated form of ferritin. It is formed during iron overload in macrophages. The molecules crystallize inside special membrane-bound particles called siderosomes. Cells synthesizing this pigment are called sideroblasts, and macrophages engulfing it after the death of neighboring cells are called siderophages. Iron from hemosiderin is difficult to mobilize and is practically not used by the body.
Hemosiderosis and hemochromatosis
Excessive accumulation of hemosiderin is called hemosiderosis. It can be local (in extravascular hemolysis within hemorrhage sites or venous diapedesis, e.g., "brown induration of the lungs") and general (in intravascular erythrocyte breakdown). The pigment itself rarely damages cells.
If iron overload is accompanied by parenchymal cell death, atrophy, and organ sclerosis, it is referred to as hemochromatosis.
- Primary hemochromatosis is a genetic disease with an autosomal recessive inheritance pattern. Due to increased iron absorption from food, a classic triad develops: liver cirrhosis, diabetes mellitus, and bronze skin pigmentation. Notably, the skin color changes not only due to iron, but also due to excess melanin resulting from bilateral adrenal involvement.
- Secondary hemochromatosis occurs due to exogenous or endogenous oversaturation: frequent blood transfusions, parenteral iron therapy, vitamin C overdose, or anemias with erythroid hyperplasia.
Non-iron-containing pigments and artifacts
Not all hemoglobin derivatives retain iron or are formed through physiological pathways:
- Hematoidin. Bright orange rhombic crystals chemically identical to bilirubin. The pigment does not contain iron. It forms after 5–10 days in the center of old hematomas and scarring infarcts where oxygen does not penetrate. Unlike hemosiderin, hematoidin lies freely among dead tissues.
- Hydrochloric acid hematin (hemin). Formed in the stomach when hemoglobin contacts enzymes and hydrochloric acid. It gives coffee-ground emesis its characteristic appearance during gastrointestinal bleeding.
- Hematoporphyrin. A purple pigment excreted in large quantities in the urine during lead poisoning, anemias, and liver diseases.
- Formalin pigment. Dark brown needles that represent an artifact. They form if tissue is fixed in acidic formalin (pH below 6.0).
Bilirubin metabolism and types of jaundice
Bilirubin is the main bile pigment produced by macrophages during hemoglobin breakdown. Initially, indirect (unconjugated) bilirubin is released. It is toxic and soluble only in lipids. Upon reaching the liver, it enzymatically binds to glucuronic acid and is converted into direct (conjugated) water-soluble bilirubin, which is excreted into bile.
In the intestine, bacterial action converts it into urobilinogen. Part is excreted in feces (stercobilin), part is reabsorbed into the portal vein (enterohepatic circulation), and a small amount is excreted in urine (urobilin).
Impairment of this metabolism leads to jaundice, which is divided into three types:
- Suprahepatic (hemolytic) — due to massive intravascular hemolysis.
- Hepatic (parenchymal) — due to damage to the hepatocytes themselves.
- Subhepatic (obstructive) — due to biliary tract obstruction.
Briefly: answers to topical questions
Which pigments belong to the hemoglobinogenic group?
Hemoglobinogenic pigments include hemoglobin derivatives classified by the presence of iron in their composition.
- Iron-containing — hemoglobin, ferritin, hemosiderin, hematins.
- Non-iron-containing — bilirubin, hematoidin, porphyrins.
According to their occurrence, they are divided into those formed normally (hemoglobin, ferritin, hemosiderin, bilirubin) and those formed only in pathology (hematoidin, hematins, porphyrins).
What types of hematins exist in pathological anatomy?
In pathological anatomy, there are three types of hematins, which are iron-containing pigments formed during the hydrolysis of oxyhemoglobin.
- Hemomelanin — malarial pigment.
- Hydrochloric acid hematin — hemin.
- Formalin pigment — tissue fixation artifact.
Morphologically, they appear as dark brown or black rhombic crystals or granules that are birefringent under polarized light and contain bound iron.
What do the lungs look like macroscopically and microscopically in brown induration?
In brown induration of the lungs (induratio fusca pulmonum), the organ acquires a characteristic color and density, and specific macrophages are detected at the cellular level.
- Macroscopic appearance — the lungs acquire a brown color and dense consistency.
- Microscopic appearance — hemosiderophages (macrophages loaded with hemosiderin), called "heart failure cells," are found in the tissue and sputum.
Tissue compaction is caused by diffuse proliferation of connective tissue in the interalveolar septa, around bronchi and blood vessels.
What are porphyrias and how are they classified?
Porphyrias are a group of disorders caused by impaired porphyrin biosynthesis, in which their precursors are found in blood, feces, and urine. The classification of porphyrias includes the following types:
- Acquired — occur under the influence of toxins (hexachlorobenzene, heavy metal salts, drugs) or vitamin deficiencies.
- Hereditary — include acute intermittent porphyria, congenital erythropoietic porphyria, and hereditary coproporphyria.
By causes of occurrence, they are also divided into primary (hereditary gene defects) and secondary (associated with impaired regulation of heme synthesis).
The triad of primary hemochromatosis: "Bronze diabetes + Cirrhosis." It is important to remember that the bronze skin color is caused not only by iron deposits, but also by melanin accumulation due to adrenal damage.
Class and exam questions
What is the principal difference between hemosiderosis and hemochromatosis?
In hemosiderosis, the pigment simply accumulates within cells, typically without disrupting their function. Hemochromatosis, by contrast, is always accompanied by tissue damage, parenchymal cell death, decreased organ function, and the development of sclerosis.
How to distinguish hemosiderin from hematoidin under a microscope?
Hemosiderin lies inside cells (macrophages) and stains greenish-blue in the Prussian blue reaction. Hematoidin contains no iron, appears as orange rhombic plates, and is located freely among necrotic masses.
Does free hemoglobin have a toxic effect on tissues?
Free hemoglobin is not toxic in itself. Severe tissue hypoxia is caused by its pathological forms—methemoglobin and myoglobin (e.g., in crush syndrome)—since they dissociate poorly and do not release oxygen.
What else to study on this topic
- Mechanisms of SH-ferritin formation during hypoxia and its effect on vascular tone
- Morphological picture and pathogenesis of "brown induration of the lungs"
- Enterohepatic circulation of urobilinogen in health and disease
- Toxic effects of myoglobin in crush syndrome
- Differences between direct and indirect bilirubin: biochemistry and clinical significance
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