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Pigments are colored substances, some of which are normal constituents of cells (melanin), while others are abnormal and collect in cells under special circumstances. The various pigments (intracellular accumulations) discussed in this section differ greatly in origin, chemical composition and biological significance. Traditionally, pigments are classified as exogenous (coming from outside the body) and endogenous (synthesized within the body itself).
Once this section is completed, the student should be able to perform the following tasks.
Carbon or coal dust pigment is the most common exogenous pigment encountered in animals and man. It is virtually a ubiquitous air pollutant of urban life and occurs primarily in the lungs and related lymph nodes. When inhaled, carbon is picked up by alveolar macrophages and transported through lymphatic channels to the regional lymph nodes. Accumulations of this pigment blacken lung tissues and the related lymph nodes. Anthracosis is the condition that occurs when carbon particles are found as a black pigment in the lungs. (Pneumoconiosis is a general term which refers to the condition that develops in the lungs subsequent to inhaling any of the exogenous pigments.)
Microscopically, lesions in the lungs are centered around small bronchioles as collection of black granules which may be found in macrophages or free in the tissue. In sections, carbon can be distinguished from other pigment by its black color and by its resistance to all solvents and bleaching agents. Grossly, the lungs may be gray or mottled in color. The regional lymph nodes may be black, particularly in the medullary region where the particles are held in sinusoidal macrophages.
In general, anthracosis does not interfere with normal respiratory function, nor does it predispose to infection. However, slight lung fibrosis may occur if excessive amounts are inhaled over long periods. Regardless, carbon is the only exogenous pigment of concern in animals.
There are several mineral dusts (including carbon) that may cause visible discolorations in the lungs and related lymph nodes. These pigments are of considerable concern in human occupational health safety, but they are not of concern in animals.
The student should read and understand the material in the textbook (Jones and Hunt, page 76) relative to:
These are a closely related group of exogenous pigments which are yellow or brown and soluble in fat solvents. They include carotene and xanthophyll which collect in various body tissues. The amount absorbed and retained in the body varies with the breed and species. (The student should be able to distinguish hepatic carotenosis from a liver filled with retained bile.)
6.4.1 LIPOFUSCIN
Lipofuscin is an insoluble pigment which represents the indigestible residue of autophagic vacuoles within cells formed during aging or atrophy. The pigment appears to be composed of polymers of lipids and phospholipids complexed with protein. The following is the manner in which lipofuscin is formed:
"During atrophy and aging, degenerating cellular organelles are enclosed in autophagic vacuoles. Subsequently, lysosomes discharge their hydrolytic enzymes into these membrane bounded vacuoles and the cellular organelles are digested by autophagy. However, some of the organelle components may resist digestion or be incompletely digested. (Lipoproteins and other lipids make up most of the indigestible debris and their accumulation reflect the lack of sufficient quantities of lipase in most lysosomes.) When organelles are not digested completely, the debris persists as membrane-bounded residual bodies. Some of these residual bodies may be extruded from the cytoplasm, or may be eventually digested. However, in some instances, the residual bodies persist in the cytoplasm of atrophic or aging cells. Microscopically, lipofuscin pigment appears as minute yellow-brown granules. In cardiac muscle cells, the granules are located chiefly near the "poles" of the nuclei. In other organs and tissues, they are distributed throughout the cytoplasm. Grossly, the lipofuscin pigment may impart a brownish discoloration to tissues when present in sufficient amounts (brown atrophy). Lipofuscin itself is not injurious to the cell or to its function."
Lipofuscin occurs in a variety of organs and tissues, but it is especially prominent in the brain neurons, myocardial cells and in the adrenal and thyroid glands. Vitamin E deficiency may accentuate lipofuscin formation. In vitamin E deficient dogs, for example, large amounts of lipofuscin is found in the smooth muscle of the intestine. The involved gut becomes brown in color and the condition is oftentimes referred to as "brown dog gut.
6.4.2 CEROID
is an acid-fact variant of lipofuscin which is commonly associated with disturbances in vitamin E and fatty acid metabolism. Sometimes, for obscure reasons, lipofuscin (or a pigment indistinguishable from lipofuscin) undergoes physical or chemical transformation so that it becomes autofluorescent and stains positively with acid-fast stains.
6.4.3 MELANIN
Melanin is a normal endogenous brown-black pigment which gives color to the skin, hair, leptomeninges and choroid of the eyes. The pigment is pathological when it occurs in places or amounts that are not considered normal for the species concerned.
Melanin is a high molecular weight biochrome bound to protein. It is synthesized by melanocytes where it resides in characteristic granules called melanosomes. Melanocytes stem from melanoblasts which are non-pigmented precursor cells of neural crest origin. Melanophages are phagocytic cells in the dermis which accept and store melanin, but do not synthesize it. Melanophores, or contractile cells, are melanocytes of some lower vertebrate that participate in the rapid color changes by intracellular aggregation and dispersion of melanosomes. The formation of melanin begins with the enzyme tyrosinase, a copper-protein substance that facilitates the oxidation of tyrosine to dihydroxyphenylalanine (DOPA) and DOPA to dopaquinone in the initial stages of synthesis.
Remember, the biosynthesis of melanin occurs in melanocytes. In the process of normal pigmentation in the skin, for example, the basal epithelial cell of the epidermis acquires melanin from the melanocytes. The dendrites of the melanocytes form "bridges" between the epithelial cells and the melanocytes and actually inject the pigment-containing melanosomes into the epidermal cells. In domestic mammals, the only known function of melanin is protection against solar ultraviolet radiation.
Under normal or physiologic conditions, melanin may be observed under the conditions listed in the textbook (Chapter 2, page 79).
6.4.4 MELANOSIS
Refers to the presence of melanin in an abnormal location and represents a congenital mislocation of melanocytes. It is usually found incidentally during necropsy or at the time of slaughter. Grossly, lesions are irregular in size and shape and they appear black in color. There is no change in texture or consistency of the involved organ or tissue. Microscopically, there are scattered melanocytes mixed with fibroblasts (lesions are usually on the surface of organs).
6.4.5 MELANOMAS
Are neoplasms derived from melanoblasts and melanocytes. These neoplasms may be benign or malignant. Melanomas can occur in many tissues, but they usually originate where precursor cells are numerous (skin, etc.).
6.4.6 ALBINISM
Is a congenital defect characterized by an absence of melanin (hereditary inability to synthesize melanin). Apparently, melanocytes are unable to synthesize sufficient tyrosinase.
The dihydroxyphenylalanine (DOPA) test is used to identify cells that have the capability to make melanin. Melanin is made from tyrosine (DOPA is a closely related chemical). When a suitable solution of DOPA is placed on tissue containing cells capable of producing melanin, a black granular precipitate forms. Fontana's silver solution may be employed to detect melanin granules.
Hemoglobin, the oxygen-carrying pigment of erythrocytes, is a combination of globin and the pigment complex heme. During normal and pathologic breakdown of hemoglobin, different types of pigment complexes are formed. Most of these are heterogeneous and are not chemically defined. Ferratin and hemosiderin are the principal iron storage compounds in the body. Hemoglobin itself is usually not visible in tissues. However, it may become visible in renal tubules as a reddish-orange color if released from erythrocytes in large quantities. Free hemoglobin in the blood is referred to as hemoglobinemia. Hemoglobinuria refers to free hemoglobin in the urine.
Hemosiderin is a brown, granular iron-containing pigment which forms when erythrocytes are lysed. It develops within macrophages anywhere in the body, but is particularly common in the spleen, liver and in foci of hemorrhage.
In the body, iron is absorbed in the ferrous form and changed to the ferric form in the bloodstream where it is normally carried by transferrins (transport protein). In cells, iron is normally stored in association with a protein, apoferratin, to form ferritin micelles. Ferritin is diffuse in cells and is not visible. However, when there is a local or systemic excess of iron, ferratin forms hemosiderin granules which are easily observed with the light microscope. Thus, hemosiderin pigment represents aggregates of ferritin micelles. Under normal conditions, small amounts of hemosiderin can be seen in reticuloendothelial cells of the bone marrow, liver and spleen (all actively engaged in erythrocyte breakdown).
In general, hemosiderin is seen in tissues whenever there is excess breakdown of erythrocytes (these situations are outlined in your textbook).
Microscopically, hemosiderin is usually found within macrophages in the form of yellow to brown, sharply circumscribed masses. The Prussian blue reaction can be employed to confirm its presence in both gross and microscopic sections. Grossly, large accumulations of hemosiderin impart a brownish color to the organs or tissues.
Hemosiderin itself is not harmful; however, its presence indicates previous hemorrhage or a hemolytic disease (destruction of red blood cells).
(Fibrosiderotic plaques) are organized focal hemorrhages found along the edges of the spleen which contain a heavy concentration of hemosiderin. In addition to hemosiderin laden macrophages, these foci contain calcium salts encrusted over fibrotic connective tissue and elastic fibers.
Are hemosiderin laden alveolar macrophages that occur subsequent to chronic left heart failure and passive congestion of the lungs.
Refers to a group of disorders, primarily occurring in man, which are characterized by cirrhosis and fibrosis of the liver and widespread hemosiderosis. Occasionally, similar conditions occur in animals.
is a pigment formed from the action of acid or alkali on hemoglobin after death (it is not a metabolite or precursor of hemoglobin). Brownish crystals (similar to hemosiderin) are formed but they are extracellular whereas hemosiderin is intracellular. Hematin is most commonly encountered when unbuffered formalin is used during the fixation of tissues. It does not stain blue with Prussian blue stain because the iron is too tightly bound to react.
Is an orange-yellow pigment derived primarily from the breakdown of hemoglobin (hemoglobin is derived from the breakdown of erythrocytes after their normal life span of approximately 120 days). After the breakdown of hemoglobin into globin and heme, the heme (iron-porphyrin compound) is separated into iron and porphyrin components. The porphyrin ring is split by heme oxygenase to form biliverdin. The biliverdin is then reduced by a reductase to bilirubin. Bilirubin is formed by reticulo-endothelial cells any place in the body, but especially in the spleen. following its formation, bilirubin goes through the following steps leading to the formation of bile pigments:
Initially, bilirubin is transported from reticuloendothelial cells (spleen, etc.) to the liver as a complex with plasma albumin. This bilirubin-albumin complex is known as non-conjugated bilirubin (indirect reacting bilirubin, hemo-bilirubin). At the liver cell plasma membrane, bilirubin dissociates from albumin and is subsequently conjugated within liver cells with glucuronic acid. This bilirubin-glucuronic complex is known as conjugated bilirubin (direct reacting bilirubin, cholebilirubin). The conjugated bilirubin is secreted by liver cells into the bile canaliculi. It is subsequently transported to the duodenum via the biliary tree. In the colon, conjugated bilirubin is reduced by bacterial enzymes to urobilinogen. Eighty to ninety percent of the urobilinogen is oxidized to urobilin and excreted in the feces. The remaining urobilinogen is reabsorbed into the portal circulation and returned to the liver (constituting the so-called enterohepatic circulation), while some reaches the general circulation and is excreted by the kidney (this urobilinogen imparts a sight yellow color to urine as it is oxidized to urobilin on standing).
Icterus is the condition in which tissues are stained (yellowish) with either non-conjugated or conjugated bilirubin. It implies hyperbilirubinemia. Grossly, the yellowish discoloration is best observed in the sclera or other tissues which are pale normally. Microscopically, bilirubin is not observed under ordinary conditions since it is soluble. However, in some situations, the pigment may collect in large enough quantities to be seen in the bile capillaries of the liver as yellowish-brown to slightly green material.
Traditionally, icterus is classified according to the causative mechanism into:
Is the result of excessive breakdown of erythrocytes and subsequent catabolism of increased amounts of heme pigment by the reticuloendothelial cells. Thus, large quantities of unconjugated bilirubin (bilirubin + albumin) are released into the bloodstream. Since the liver cannot process all of the excess unconjugated bilirubin, it builds up in the bloodstream and stains body tissues (it is not filtered across glomeruli into the urine). In addition, the liver cells are required to handle more unconjugated bilirubin than normal, resulting in the formation of excessive conjugated bilirubin. Thus, large amounts of urobilinogen are found in the feces and urine.
Occurs subsequent to direct damage to liver cells and subsequent release of conjugated and unconjugated bilirubin into the bloodstream. If liver cells are injured or necrotic, they are unable to convert even normal amounts of unconjugated bilirubin to conjugated bilirubin. Therefore, unconjugated bilirubin remains in the bloodstream to stain tissues (just as in hemolytic icterus). At the same time, swelling of hepatic cells (cellular swelling, fatty change, etc.) may be sufficient to block the bile canaliculi. Thus, the conjugated bilirubin formed in liver cells cannot pursue its normal course to the gallbladder and intestine. It accumulates in the liver and is reabsorbed into the bloodstream to stain tissues and pass through the glomerular filter to appear in the urine. In summary, toxic icterus is characterized by the presence of both unconjugated and conjugated bilirubin in the bloodstream.
Occurs subsequent to obstruction to the normal flow of bile anywhere in the biliary system. This results in the accumulation of conjugated bilirubin in the bloodstream and in the urine. The obstruction may be complete or it may be partial. If it is complete, conjugated bilirubin is unable to reach the intestine and urobilinogen is absent (feces are pale and no urobilinogen is in the urine). If the obstruction is partial, the amount of urobilinogen in the urine and feces is diminished. Regardless, conjugated bilirubin is reabsorbed into the bloodstream and stains body tissues.
Is adequately discussed in your textbook. Some of the methods and procedures employed in the diagnosis of icterus include:
6.5.9.1 ICTERUS INDEX TEST:
This test is used to determine the presence or absence of icterus by comparing in a colorimeter the color of the blood serum with the yellow tint of a solution of potassium dichromate of standard strength. A high icterus index indicates the presence of icterus.
6.5.9.2 THE VAN DEN BERGH REACTION:
A positive direct Van den Bergh reaction indicates the presence of conjugated bilirubin (obstructive icterus), whereas a positive indirect Van den Bergh reaction indicates the presence of non-conjugated bilirubin (hemolytic icterus). If a positive direct and indirect Van den Bergh reaction is attained, this indicates the presence of both conjugated and non-conjugated bilirubin which is characteristic of toxic icterus.
6.5.9.3 URINE UROBILINOGEN:
A small amount of urobilinogen in the urine is normal. Its absence indicates obstructive icterus. Large amounts of urobilinogen in the urine indicate hemolytic icterus or it may indicate the presence of toxic icterus.
6.5.9.4 COLOR OF FECES:
In obstructive icterus (complete), the feces are pale. In hemolytic icterus, the feces are darker than normal.
Remember, icterus is not a disease, but an important clue to any one of several different disorders.
Photosensitizing pigments are fluorescent pigments which accept light rays of one wavelength and transform them into rays of a longer wavelength. Photosensitization is the condition that results when light acts on a fluorescent pigment in tissues.
The three sets of circumstances which give rise to the presence of photosensitizing pigments in tissues are:
In this condition of man and some animals, there is a defect in hemoglobin synthesis. The substance porphyrin is formed in the nucleus of the developing normoblast. The porphyrin skeleton consists of four pyrrole rings united by carbon bridges and there are four possible arrangements of the porphyrin molecules. Of the four, only two (designated I and III) have been isolated in nature. The Type I porphyrin cannot be used in hemoglobin formation and, in the normal animal, this form is changed to Type III by an isomerase. In the animal affected with congenital porphyria, this isomerase is thought to be absent and porphyrin I accumulates in the tissues. When the porphyrins are exposed to ultraviolet light, an intense red fluorescence results.
Congenital porphyria in cattle is transmitted as a simple, recessive characteristic. The animals are normal except for brownish pigmentation of the bones, teeth and urine. If these animals are exposed to sunlight, marked photosensitization occurs and the skin (especially in unpigmented areas) may be damaged.
In the porcine and feline, congenital porphyria is inherited as a dominant characteristic. A photosensitizing dermatitis has not been reported in these species.
occurs when certain toxins damage the liver directly and prevent it from eliminating in the bile some of the end products of chlorophyll metabolism. One of these end-products, phylloerythrin, is a fluorescent pigment. Therefore, phylloerythrin enters the general circulation, reaches the skin and causes photosensitization when the animal is exposed to sunlight.
(photosensitization without liver damage) occurs when certain plants which contain fluorescent pigments are ingested. Plants of the Fagopyrum (buckwheat) and hypericum (goatweed) species are examples.
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