Proteinogenic dystrophies: pigments

Lipopigments: lipofuscin, ceroid, and lipochromes

Lipofuscin is an insoluble yellow-brown pigment composed of lipid and phospholipid polymers bound to protein. It accumulates in the cytoplasm due to organelle damage. The primary cause is a deficiency of intracellular antioxidants, which triggers membrane lipid peroxidation. Notably, the pigment does not impair the cell's function itself.

Excessive pigment accumulation is termed lipofuscinosis:

• Primary (hereditary): selective accumulation in a specific organ. For example, in hepatocytes in hereditary hepatosis (Dubin–Johnson syndrome) or in nerve cells in neuronal lipofuscinosis (Spielmeyer–Sjögren syndrome, manifested by intellectual decline, seizures, and visual impairment).
• Secondary (brown atrophy): occurs during slow regressive changes, in old age, or in debilitating diseases (cachexia, cancer cachexia). Organs (liver, myocardium, striated muscles) decrease in size, become firm, and acquire a brown color. Microscopically, the liver shows diminished hepatocytes with cytoplasmic pigment and widened sinusoids.

Ceroid is a lipopigment formed in macrophages via heterophagy (during lipid resorption). The process proceeds in stages: lipophagosomes form first, then transform into secondary lysosomes (lipophagolysosomes) where enzymes partially digest lipids. Ultimately, tertiary phagolysosomes (telolysosomes) containing ceroid are formed. It most commonly appears during tissue necrosis and in areas of hemorrhage.

Lipochromes consist predominantly of lipids containing carotenoids (a source of vitamin A). Their excessive accumulation is characteristic of diabetes mellitus (due to severe disruption of lipid-vitamin metabolism, the pigment accumulates in adipose tissue, skin, and bones) and cachexia (condensation of lipochromes imparts an ochre-yellow color to adipose tissue).

Melanin and metabolic disorders thereof

Melanin (from Greek melas — black) is a brownish-black pigment of neuroectodermal origin. It is synthesized by melanoblasts in specialized organelles — premelanosomes and melanosomes. As they mature, the cells turn into melanocytes.

Hyperpigmentation (excess melanin):

• Primary Addison's disease: a rare autoimmune adrenal disorder.
• Xeroderma pigmentosum: a congenital generalized melanosis (autosomal recessive inheritance). The pathogenesis is based on the inability of skin cell DNA to undergo repair following ultraviolet exposure. Following sun exposure, patients develop fine spotted hyperpigmentation, areas of depigmentation, telangiectasias, and skin fissures.
• Focal hyperpigmentation: occurs in pituitary adenomas, hyperthyroidism, and diabetes mellitus. Acquired focal hypermelanosis (melanosis coli) is characteristic of patients with chronic constipation. Local forms include freckles, melasma, lentigo, melanocytic nevus (mole), and malignant melanoma (a tumor of melanocytes).

Hypopigmentation (decreased melanin synthesis):

1. Albinism: a widespread autosomal recessive disorder. It results from the absence or decreased activity of the enzyme tyrosinase. Histologically, melanocytes are present in the body but fail to produce pigment.
2. Vitiligo: local hypopigmentation appearing as well-demarcated, often symmetrical patches. Histologically, melanocytes are absent in the affected areas. Causes include familial predisposition, trauma, endocrine and autoimmune diseases, as well as the aftermath of inflammatory or necrotic processes (burns, syphilis, bullous dermatoses).

Other tyrosinogenic pigments

This group includes adrenochrome and the pigment of enterochromaffin cell granules.

Adrenochrome is a dark brown pigment in the form of fine granules, localized in the cells of the adrenal medulla and tumors arising from them (pheochromocytomas). It exhibits argentaffin and chromaffin properties (stains with chromic acid, reduces dichromate). Biochemically, it is a product of quinoid oxidation of adrenaline by free radicals during oxidative stress. Interesting fact: In 1952, J. Smythies and H. Osmond hypothesized that the pathogenesis of schizophrenia is linked to abnormal adrenaline metabolism. Modern data show that the cause lies not in the excessive synthesis of adrenochrome, but in a genetically determined deficiency of the enzyme glutathione S-transferase, which is involved in its metabolism.

Enterochromaffin cell granule pigment is closely linked to biogenic amine synthesis and is part of the APUD system (Amine Precursor Uptake and Decarboxylation system). Cells of this diffuse neuroendocrine system are numerous and located in many organs (predominantly the gastrointestinal tract and bronchi). They contain biologically active substances (serotonin, gastrin, histamine) that participate in the regulation of organ activity.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Mechanisms of lipid peroxidation in antioxidant deficiency
• Pathogenesis of neuronal lipofuscinosis (Spielmeyer–Sjögren syndrome)
• Histological picture of brown atrophy of the liver and myocardium
• Differential diagnosis of focal hypermelanoses (nevi, lentigo, melanoma)
• Functions of biogenic amines (serotonin, gastrin, histamine) in the APUD system

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

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