Porphyrias

Biochemical nature of porphyrins and types of pigments

From a chemical standpoint, porphyrins are complex cyclic compounds. Their spatial structure is formed by exactly four pyrrole rings. The main biological role of these substances is that they are direct precursors of heme—the essential non-protein moiety of hemoglobin.

In medical practice and biochemistry, several types of pigments associated with porphyrin metabolism are distinguished:

• Natural metabolism pigments. During normal physiological breakdown and metabolism of hemoglobin in the human body, compounds such as uroporphyrin (specifically, uroporphyrin I) and coproporphyrin (for example, coproporphyrin III) naturally form. Protoporphyrin IX is also involved in the biosynthetic chain.
• Artificial pigments. A striking example is hematoporphyrin. It does not form under natural conditions and is obtained exclusively in the laboratory. To achieve this, hemin is treated with a mixture of hydrobromic acid (HBr) and acetic acid. Hematoporphyrin obtained in this manner possesses unique properties that allow its successful use in modern medicine for photodynamic therapy.

Etiological classification of porphyrias

All diseases in this group are generally divided into two main categories based on their causes:

1. Acquired porphyrias. This form of the disease is not associated with genetic defects. It arises as a consequence of severe exogenous impact on the body. The main triggers are various toxins. These include industrial poisons (e.g., hexachlorobenzene), heavy metal salts, and adverse effects of certain aggressive medications. In addition, the acquired form can manifest against the background of pronounced avitaminoses, when the normal course of enzymatic reactions is disrupted.
2. Hereditary porphyrias. Caused by genetic mutations transmitted from generation to generation. This group includes a number of distinct nosologies, among which the most significant are acute intermittent porphyria, congenital erythropoietic porphyria, and hereditary coproporphyria.

Pathogenesis and detailed clinical presentation

The pathogenesis of porphyrias is based on a profound disturbance of pigment metabolism both in circulating blood and directly in tissues. The accumulation of porphyrins leads to the development of a severe symptom complex.

The most specific and destructive manifestation of the disease is photosensitization—abnormal sensitivity to sunlight. Under the direct action of ultraviolet rays, pathological breakdown of hemoglobin is triggered. As a result of this process, its non-protein part (heme) transforms into an extremely toxic substance. This metabolite exhibits necrotizing effects and literally corrodes living tissues.

Clinical manifestations of porphyria are diverse and affect various systems:

• Skin lesions. Patients' skin becomes severely thinned and acquires an unhealthy brown tint. Upon the slightest exposure to sunlight, the skin ruptures, and deep, painful ulcers rapidly form on it, which subsequently heal with the formation of rough, deforming scars.
• Dental changes. Excess porphyrin is actively deposited in dental tissue. This causes the teeth to be stained a frightening red or saturated reddish-brown color.
• Changes in urine. Due to massive pigment excretion, the patients' urine acquires a characteristic reddish color.
• Systemic disorders. Toxic heme precursors circulate throughout the body, causing severe lesions of the central and peripheral nervous system, gastrointestinal tract, liver, kidneys, and suppressing bone marrow function.

Class and exam questions

What else to study on this topic

• Biochemical stages of heme synthesis from porphyrins.
• Mechanism of the toxic action of hexachlorobenzene and heavy metal salts.
• Features of the clinical course of acute intermittent porphyria.
• Congenital erythropoietic porphyria: pathogenesis of bone marrow damage.
• Principles of photodynamic therapy using hematoporphyrin.

Other topics in the section "Morphology of Metabolic Disorders — Dystrophies"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.