Disturbances in hemoglobinogenic pigments

Normally conditions, the following pigments are formed due to physiological decomposition of erythrocytes and hemoglobin: ferritin, hemosiderin, bilirubin. In pathological conditions, when erythrocyte decomposition increases, new pigments are synthesized except for the increase of the amount of the above pigments. They are hematoidin, hematins, porphyrin.

The most important disturbance is hemosiderosis, i.e. abundant production of hemosiderin.

Hemosiderosismay be general and local.

General (generalized) hemosiderosis is noted at intravascular hemolysis of erythrocytes (intravascular hemolysis). It occurs at 1) transfusion of rhesus- or group-incompatible blood, 2) poisoning with hemolytic poisons (mushrooms), 3) infections (malaria, relapsing fever), 4) diseases of blood (anemia, hemo-blastoses).

Hemosiderin is accumulated in monocyte-macrophage cells, histiocytes, endotheliocytes, epithelial cells of the liver, spleen, bone marrow, lymphatic nodes, lungs. The organs become enlarged, dense, brown-rusty.

Local hemosiderosis develops in extravascular hemolysis of erythrocytes (extravascular hemolysis), as a rule in the foci of hemorrhages, e.g., brown induration of the lungs which develops in the patients with rheumatic heart defects, cardiosclerosis in chronic

cardiac insufficiency. In all respects the knowledge in morphogenesis of brown induration of the lungs is important for physician.

Morphogenesis of brown induration of the lungs

Chronic venous congestion in the lungs causes hypoxia which results in increase of vascular permeability, development of diapedetic hemorrhages, erythrocytes occur in the interalveolar septa, alveoles, where they are destroyed and turn into hemosiderin. The erythrocytes are partially phagocytized by the alveolar macrophages. In this case, hemosiderin is formed in them. These cells are called sideroblasts. More often macrophages phagocytize ready hemosiderin, in this case they are called siderophages. Connective tissue begins to grow around the hemosiderin deposits. The lung becomes dense, enlarged and rusty-brown.

Hemochromatosismay be primary (hereditary) and secondary.

Primary hemochromatosis is associated with the defect of the enzymes of the small intestine, secondary — with the damage of these enzymes during the lifetime (after stomach resection, in alcoholism).

In hemochromatosis, iron absorption increases, the iron is deposited in the form of hemosiderin in the liver, pancreas, endocrine glands, heart, eye retina, the mucous membrane of the intestine. Ferritin and melanin amount increases simultaneously. Therefore,

the main features of the disease are bronze skin, bronzed diabetes (diabetes mellitus), pigment cirrhosis of the liver, pigment cardiopathy with cardiac insufficiency. When the level of ferritin in the blood decreases, ferritinemia develops (it may be observed in hemosiderosis). It is dangerous because SH-ferritin acts as adrenaline antagonist and may cause vascular collapse, resulting in irreversible shock.

Bilirubin.Hyperbilirubinemia refers to an increased serum bilirubin concentration (i.e., > 1.2 mg/dl). At serum bilirubin concentrations above 2 to 2.5 mg/dl, the skin, sclerae, mucous and serous membranes turn yellow — a condition known as jaundice.

Increase of its amount in the blood causes jaundice, i.e. yellow coloring of the skin, sclera.

According to the mechanism of its development, there are 3 types of jaundice:

Prehepatic (hemolytic, unconjugated hyperbilirubinemia) jaundice occurs as a result of the increased production of bilirubin at erythrocyte hemolysis. The liver produces increased amount of bilirubin. This disorder is characterized by elevated serum levels of unconjugated bilirubin; levels of conjugated bilirubin are within normal limits. This finding typifies conditions associated with increased red blood cell destruction (e.g., hemolytic anemia, ineffective erythropoiesis), reduced hepatic bilirubin uptake (e.g., as from such drugs as rifampin), and impaired bilirubin

conjugation (e.g., Crigler-Najjar and Gilbert's syndromes). This condition is observed in intoxications, infections, autoimmune processes, etc. It results from failure of hepatocytes to conjugate bilirubin and inability of bilirubin to pass from the liver to the intestine.

Hepatocellular (parenchymatous) jaundice occurs in hepatocyte damage (acute and chronic hepatitis, liver cirrhosis, autointoxications in gestosis).

Posthepatic (conjugated hyperbilirubinemia) or obstructive jaundice results from obstruction to the outflow of conjugated bilirubin (cholelithiasis, cancer of bile ducts, etc.). Levels of both conjugated and unconjugated bilirubin rise in this disorder. Intrinsic liver disease and extrahepatic biliary obstruction are the underlying causes of conjugated hyperbilirubinemia. Cholestasis is usually, but not always, present.

Hematins. Hemomelanin (malaria pigment) is produced from hemoglobin due to the Plasmodium vital activity. While circulating in the blood, it is phagocytizedby macrophages of the spleen, liver, bone marrow, lymphatic nodes, brain and causes hemomelanosis. The organs became bright grey, dense and enlarged.

Hydrochloride hematin is found in the erosions and ulcers of the stomach, its color is brown-black. It is formed from hemosiderin in the presence of HC1.

Formalin pigment looks like dark brown grains, it can be found in the tissues preserved with formalin.

Porphyriadevelops when porphyrin metabolism is disturbed. It is characterized by increase of porphyrin amount in the blood (porphyrinemia) and urine (porphyrinuria), sharp increase of sensitivity to ultraviolet radiation (photophobia, erythema, dermatitis). It may be congenital and developed. Developed porphyria is observed in intoxications (lead, sulfasol, barbiturates), avitaminosis (pellagra), pernicious anemia, diseases of the liver.

Disturbances in proteinogenic (tyrosinogenic) pigments.

Proteinogenic pigments are melanin, pigment of enterochromatous cell grains, adrenochrome.

Melanin is produced by melanocytes: epidermis, dermis, iris, retina, pia mater. Disturbance of melanin metabolism has different forms, either its increased production or disappearance. These disturbances may be congenital or developed, local or general (generalized).

Generalized developed hypermelanosis (melanoderma) characteristic for Addison's disease. It is caused by bilateral destruction of adrenal glands (tuberculosis, tumor). Hyperpigmentation of the skin is caused by melanin synthesis stimulation which, in turn, is due to the abundant production of ACTH by the pituitary body in response to the deficiency of adrenaline and other adrenal hormones (ACTH is responsible for melanin synthesis). Melanoderma also occurs in hypogonadism, pellagra, scurvy, cachexia.

Generalized congenital hypermelanosis (xeroderma pigmentosum) is associated with increased sensitivity of the skin to ultraviolet radiation and manifests by spot-like skin pigmentation with hyperkeratosis and edema.

Local acquired melanosis manifests by:

1) melanosis of the large intestine in elderly people suffering from chronic constipation;

2) black acanthosis (black acanthosis means skin areas with increased pigmentation) in hypophyseal adenoma, hyperthyroidism, diabetes mellitus;

3) pigmented nevi;

4) melanomas (malignant tumors). Generalized hypomelanosis (albinism) is due to

tyrosinase deficiency. Albinism is characterized by absence of melanin in the hair bulbs, epidermis, dermis, retina and iris. Focal hypomelanosis (vitiligo) occurs in the persons with disturbed endocrine regulation of melanogenesis (hyperparathyroidism, diabetes mellitus, Hasimoto's goiter, skin inflammation (syphilis).