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Hemoglobinogenic Dystrophies

Q: 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 identified at the cellular level. Macroscopic appearance — the lungs acquire a brownish hue and dense consistency.Microscopic appearance — hemosiderophages (macrophages laden with hemosiderin), termed "heart failure cells," are found in the tissue and sputum. The tissue induration is caused by diffuse proliferation of connective tissue in the interalveolar septa, around bronchi, and blood vessels.

Haemoglobinopathiae

For medical students2 min readUpdated 2026-10-10

Hemoglobinogenic dystrophies are a group of dysproteinemias associated with impaired metabolism of endogenous pigments. They are based on the excessive production or retention of red blood cell breakdown products in tissues, which in some cases leads to severe organ damage.

HemolysisThe primary process triggering the formation of hemoglobinogenic pigments

Perls' reactionStains hemosiderin granules a greenish-blue color (Prussian blue)

Pigment synthesisA macrophage becomes fully saturated with iron and forms hemosiderin in just 4 hours

Iron storeExcess iron accumulates predominantly in the liver, spleen, muscles, and bone marrow

Physiological Forms of Iron Storage

Normally, iron not utilized for hemoglobin synthesis is stored in the body as two main protein complexes.

Ferritin. 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. Under oxygen deprivation, active reduced SH-ferritin forms, exhibiting pronounced vasoparalytic and hypotensive effects.
Hemosiderin. An insoluble aggregated form of ferritin. It forms during iron overload in macrophages. The molecules crystallize inside special membrane-bound particles called siderosomes. Cells synthesizing this pigment are termed sideroblasts, while macrophages engulfing it after the death of neighboring cells are termed siderophages. Iron from hemosiderin is mobilized with difficulty and practically unused by the body.

Hemosiderosis and Hemochromatosis

Excessive accumulation of hemosiderin is called hemosiderosis. It can be localized (in extravascular hemolysis within hemorrhage foci or venous diapedesis, e.g., "brown induration of the lungs") or generalized (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 termed hemochromatosis.

Primary hemochromatosis is a genetic disorder with an autosomal recessive inheritance pattern. Due to enhanced dietary iron absorption, the classical triad develops: liver cirrhosis, diabetes mellitus, and bronze skin pigmentation. Notably, skin color changes not only due to iron but also due to melanin excess secondary to bilateral adrenal involvement.
Secondary hemochromatosis occurs due to exogenous or endogenous overloads: frequent blood transfusions, parenteral iron therapy, vitamin C overdose, or anemias with erythroid hyperplasia.

Iron-Free Pigments and Artifacts

Not all hemoglobin derivatives retain iron or form via physiological pathways:

Hematoidin. Bright orange rhombic crystals chemically identical to bilirubin. The pigment contains no iron. It forms 5–10 days later in the center of old hematomas and healing infarcts where oxygen does not penetrate. Unlike hemosiderin, hematoidin lies freely among dead tissues.
Hydrochloric acid hematin (hemin). Forms in the stomach when hemoglobin contacts enzymes and hydrochloric acid. It gives vomitus a characteristic "coffeeground" appearance during gastrointestinal bleeding.
Hematoporphyrin. A purple pigment excreted in large amounts in urine during lead poisoning, anemias, and liver diseases.
Formalin pigment. Dark brown needles acting as an artifact. They form when tissue is fixed in acidic formalin (pH below 6.0).

Bilirubin Metabolism and Types of Jaundice

Bilirubin is the primary bile pigment formed by macrophages during hemoglobin breakdown. Initially, indirect (unconjugated) bilirubin is released. It is toxic and lipid-soluble. Reaching the liver, it is enzymatically conjugated with glucuronic acid to form 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).

Disruptions in this metabolism lead to jaundice, classified into three types:

Prehepatic (hemolytic) — due to massive intravascular hemolysis.
Hepatic (parenchymal) — due to hepatocyte injury.
Posthepatic (obstructive) — due to biliary tract obstruction.

Mnemonic

Primary hemochromatosis triad: "Bronze diabetes + Cirrhosis." Remember that the bronze skin color is caused not only by iron deposits but also by melanin accumulation due to adrenal involvement.

Frequently asked questions

Which pigments belong to the hemoglobinogenic group?

Hemoglobinogenic pigments are hemoglobin derivatives classified by the presence of iron in their composition.

Iron-containing — hemoglobin, ferritin, hemosiderin, hematins.
Iron-free — bilirubin, hematoidin, porphyrins.

By occurrence, they are divided into those forming normally (hemoglobin, ferritin, hemosiderin, bilirubin) and those forming only in pathology (hematoidin, hematins, porphyrins).

What types of hematins exist in pathologic anatomy?

Pathologic anatomy distinguishes three types of hematins, which are iron-containing pigments formed during oxyhemoglobin hydrolysis.

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 identified at the cellular level.

Macroscopic appearance — the lungs acquire a brownish hue and dense consistency.
Microscopic appearance — hemosiderophages (macrophages laden with hemosiderin), termed "heart failure cells," are found in the tissue and sputum.

The tissue induration 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, with precursors detectable in blood, feces, and urine. Porphyria classification includes:

Acquired — occurring due to toxins (hexachlorobenzene, heavy metal salts, drugs) or vitamin deficiencies.
Hereditary — including acute intermittent porphyria, congenital erythropoietic porphyria, and hereditary coproporphyria.

By etiology, they are also divided into primary (hereditary gene defects) and secondary (associated with disrupted heme synthesis regulation).

What is the fundamental difference between hemosiderosis and hemochromatosis?

In hemosiderosis, the pigment merely accumulates in cells without typically disrupting their function. Hemochromatosis, by contrast, is always accompanied by tissue damage, parenchymal cell death, decreased organ function, and sclerosis.

How can hemosiderin be distinguished from hematoidin under a microscope?

Hemosiderin resides intracellularly (within macrophages) and stains greenish-blue with Perls' reaction. Hematoidin contains no iron, appears as orange rhombic plates, and is located freely among necrotic masses.

Does free hemoglobin exert toxic effects on tissues?

Free hemoglobin by itself is not toxic. Severe tissue hypoxia is caused by its pathological forms—methemoglobin and myoglobin (e.g., in crush syndrome)—because they dissociate poorly and fail to release oxygen.

Go deeper

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