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 in intracellular antioxidants, which triggers lipid peroxidation of membrane lipids. However, the pigment does not impair basic cell function.
Excessive accumulation of this pigment is called lipofuscinosis:
- Primary (inherited): Selective accumulation in a specific organ. Examples include hepatocytes in inherited hepatosis (Dubin–Johnson syndrome) or nerve cells in neuronal ceroid lipofuscinosis (Spielmeyer–Vogt–Sjögren syndrome, manifested by intellectual decline, seizures, and visual impairment).
- Secondary (brown atrophy): Occurs during slow regressive changes, in advanced age, or in wasting diseases (cachexia, cancer cachexia). Organs (liver, myocardium, striated muscles) decrease in size, become firm, and acquire a brown color. Microscopically, the liver shows shrunken hepatocytes with cytoplasmic pigment and dilated sinusoids.
Ceroid is a lipopigment formed in macrophages via heterophagy (during lipid resorption). The process occurs in stages: lipophagosomes form first, then transform into secondary lysosomes (lipophagolysosomes) where enzymes partially digest lipids. Eventually, tertiary phagolysosomes (telolysosomes) containing ceroid are formed. It most commonly appears in areas of tissue necrosis and hemorrhage.
Lipochromes consist predominantly of lipids containing carotenoids (a source of vitamin A). Their excessive accumulation is characteristic of diabetes mellitus (due to a profound 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 Disorders of Its Metabolism
Melanin (from Greek melas — black) is a brownish-black pigment of neuroectodermal origin. It is synthesized by melanoblasts within specialized organelles — premelanosomes and melanosomes. As they mature, these cells develop into melanocytes.
Hyperpigmentation (excess melanin):
- Primary Addison's disease: A rare autoimmune destruction of the adrenal glands.
- 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 small spotted hyperpigmentation, areas of depigmentation, telangiectasias, and skin fissures.
- Focal hyperpigmentation: Found in pituitary adenomas, hyperthyroidism, and diabetes mellitus. Acquired focal hypermelanosis (melanosis coli) is characteristic of patients with chronic constipation. Local forms include freckles, melasma, lentigines, melanocytic nevi (moles), and malignant melanoma (a tumor derived from melanocytes).
Hypopigmentation (decreased melanin synthesis):
- Albinism: A widespread autosomal recessive disorder caused by the absence or reduced activity of the enzyme tyrosinase. Histologically, melanocytes are present in the body but fail to produce pigment.
- Vitiligo: Localized hypopigmentation appearing as sharply demarcated, often symmetrical macules. Histologically, melanocytes are absent from the affected areas. Causes include genetic predisposition, trauma, endocrine and autoimmune diseases, as well as the aftermath of inflammatory or necrotic processes (burns, syphilis, bullous dermatoses).
Other Tyrosine-Derived Pigments
This group includes adrenochrome and the pigment found in enterochromaffin cell granules.
Adrenochrome is a dark brown pigment appearing as fine granules, localized in cells of the adrenal medulla and tumors arising from them (pheochromocytomas). It exhibits argentaffin and chromaffin properties (it stains with chromic acid and reduces bichromates). Biochemically, it is a product of the quinoid oxidation of adrenaline by free radicals during oxidative stress. Historical note: In 1952, J. Smythies and H. Osmond hypothesized that the pathogenesis of schizophrenia was linked to abnormal adrenaline metabolism. Modern data indicate that the cause lies not in excessive adrenochrome synthesis, but in a genetically determined deficiency of the enzyme glutathione S-transferase, which participates in its metabolism.
Enterochromaffin cell granule pigment is closely related to the synthesis of biogenic amines and is part of the APUD system (Amine Precursor Uptake and Decarboxylation). Cells of this diffuse neuroendocrine system are numerous and located in many organs (predominantly in the gastrointestinal tract and bronchi). They contain biologically active substances (serotonin, gastrin, histamine) that regulate organ function.