Veterinary Pathology

The normal cells are in steady state where anabolic and catabolic processes are in equilibrium. Regressive or retrogressive changes are seen when catabolism exceeds anabolism. Non lethal injury of the cells may produce degeneration or infiltration.

Degeneration is derived from the Latin word degeneration, which means deterioration. Degeneration is a reversible biochemical, functional and morphological abnormalities in the cells resulting from any injury not severe enough to cause cell death. The nucleus not affected, but the changes observed in cytoplasm. Degeneration is reversible but may be progress to necrosis if the injury persist (Figure 1) .

Fig. 1: Heart showing either normal heart (middle), or non lethal cell Metabolism (adaptation lead to hypertrophy, Top) or lethal Metabolism lead to necrosis (lower one).

Infiltration means intracellular or extracellular deposition of substances natural to the cell but in excess (fat and glycogen) or foreign to the body (amyloid and urates).

The degeneration or infiltration may be reversible or irreversible depending on the degree of injury.

Acute cell swelling is the first manifestation of almost all forms of injury to cells due to the inability of cells to maintain ionic and fluid homeostasis. It is the mildest, reversible retrogressive change of parenchymatous organs. It reversible and characterize by water accumulation inside the cytoplasm which causes the cell to swell.

All injuries cause firstly acute cell swelling. The cell swelling are usually seen with mild irritants as toxin and hypoxia.

Toxins: The toxin may be exogenous (bacterial toxins (chemical poisons and snake venom) or endogenous toxins acetone, urea and uric acid).

Hypoxia: It occurs associate with respiratory diseases, anemia, cardiac disease and incase of inability of the hemoglobin to carry oxygen as in carbon monoxide and hydrocyanic acid poisoning.

To cause cell swelling the injurious substances must cause damage to the plasma membrane barrier that control water and electrolytes transports through cell surface. Normally the intracellular water regulated by energy dependent ionic pump. Any damage in the sodium potassium pump lead to leaky plasma membrane, which permit entrance of sodium, calcium and lost potassium. Accumulation of sodium is followed by entry of water. The cells become markedly swollen.

The affected organ is increased in size and weight if generalized swelling of cells occurs. The organ color is pale or parboiled beside the consistency is soft and the border is rounded. The cut section is bulges and appears convex.

Firstly, the cells are swollen and the cytoplasm appears opaque and granular. The granules are eosinophilic and can be melted in alkaline and weak acetic acid. Then some cells burst. The cytoplasm appears crowded, with dilute, dispersed or indistinct appearance (Hydropic degeneration or may be contains large vacuole or small tiny vacuoles especially around the nucleus (vacuolar degeneration). The vacuoles have indefinite borders. Such vacuoles are negative for fat and glycogen. The nucleus is normal. The swollen cells compress the blood vessels. The nucleus is not affected.

Figure 2: Fig. 2: Gross picture of kidney suffering from cloudy swelling showing pale color, round border and enlarged.

Fig. 3: Kidney showing microscopic picture of cloudy swelling. The renal epithelium are swelling with granular cytoplasm leading to narrowing of tubular lumen, star shape or completely obliterated. H&E

Fig. 4: Liver showing hydropic degeneration represented by swollen hepatocytes which contain granular cytoplasm. The hepatic sinusoids are obliterated. H&E

Figure 5: Liver showing vacuolar degeneration represented by small vacuoles in the cytoplasm containing pale eosinophilic fluid. H&E.

Connective tissue mucin is one of the intercellular components of connective tissue matrix, which is abundant in embryo connective tissue. Pathological mucoid degeneration is reversible retrogressive changes characterized by abnormal accumulation of bluish translucent material (mucin), which is secreted by modified fibroblasts. In serous atrophy of fat the background is pinkish due to the presence of potassium soap.

The principal causative agent is lack of proper nutrition. Moreover, it is accompanied of cachectic diseases as parasitism and chronic wasting diseases besides starvation. Mucoid degeneration is observed in myxoma, myxosarcoma and myxoedema (a disease associated with thyroid deficiency). It is usually observed around the coronary grove of the heart, in inter muscular fat and in omentum and mesentery.

The affected organs are those organs contain at least small amount of fibrous or adipose connective tissue. The affected organ translucent, flabby, shrunken besides watery slimy, stringy material exudes from cut surfaces.

The connective tissue cells show the embryonic characters. The cells are round, oval, spindle and stellate with interlacing thin branches. The intercellular matrix has a bluish ting. The nucleus is oval or stellate and hyperchromatic.

Mucoid degeneration is very important indicators for general health and nutrition of animals. Mucoid degeneration is reversible.

Fig. 6: Connective tissue showing mucoid degeneration represented by round, oval or satellate cells with interlacing branches. H&E

Amyloid infiltration is one of the serious condition results from extracellular deposition of a homogenous translucent eosinophilic proteinaceous substance (amyloid) that resemble starch in its chemical reaction. Formerly, the amyloid was thought to be starch like, so it called amyloid; however, it is now known to be composed of protein. Once amyloidosis begins, it really cannot be stopped.

Originally it was called amyloid because when iodine was added to it, it turned brown. If you put on it diluted HCl, it would become blue and scientists thought that meant it was starchy. Therefore, if expressed in English, amyloid means "starch-like" material. It has fibrinous structure on EM with pentagonal bodies (P-bodies).

If amyloid amount is large enough, it causes atrophy of the normal cells in the area - pressure atrophy. Amyloid may also accumulates in the blood vessel and compromise circulation to the organ causing atrophy. If there is enough accumulation in organ, the organ will be enlarged, waxy, firm and rubbery.

1. Primary amyloidosis is not really primary but is secondary to plasma cell dysplasia. The primary amyloidosis is rare and usually of unknown causes. It has two types. The first one is systemic or generalized, which seen in heart, tongue, intestine, skin and skeletal muscles. The second is localized type and is seen in larynx, urinary bladder and the heart.

2. The most common type of amyloidosis is the secondary amyloidosis or reactive systemic amyloidosis. It is secondary to certain chronic destructive diseases as tuberculosis, chronic bronchopneumonia, chronic suppurative arthritis, chronic suppurative oesteomyelitis, lung abscess, chronic pyelonephritis, and chronic empyema. Moreover it is seen with malignant tumors as multiple myeloma and renal carcinoma.

Amyloid was detected by adding aqueous iodine solution to the surface of affected organ, which stain brown. Moreover, he Congo red is used for the detection of amyloidosis clinically. In paraffin sections, the amyloid stain pink by H & E, rose red by methyl violet, gentian violet and crystal violet stains and orange red by Congo red.

The affected organ is increased in size and weight beside sharp border. The color is pale and firm in consistency. Cut section shows flat waxy translucent surface. The kidney may be appear unchanged, or pale, firm and enlarged or atrophied in late stage. Two types of amyloidosis are present in spleen. The spleen is moderately enlarged rubbery and firm. In cut surface of focal type, It shows waxy light brown bodies against red background (sago grain). The diffuse type shows diffuse amyloid deposit in the form of waxy translucent streaks. The amyloidosis in liver represented by waxy light brown streaks (amyloid) deposit among yellowish brown hepatic tissue.

Amyloid is most prominent in spleen, liver and kidneys and deposited mainly in the loose connective tissue between the endothelial lining and the adjacent cells of capillaries and around the sinusoids leading to narrowing in of the capillaries, sinusoids or arterioles or venules. The narrowing leading to ischemia of the affected organ and the cells suffer from pressure atrophy and necrosis. The amyloid appear as pale eosinophilic homogenous translucent in section stain by H and E. In liver the amyloid is deposit in tunica media of the arterioles and venules, between the sinusoids and the hepatic cells. The liver cells degenerate from anoxia and show pressure atrophy and necrosis. In the kidneys, the amyloid is deposit in the tunica media of the arteriole and venules.

basement membrane of glomerular capillaries and basement membrane of the collecting tubules. Moreover, the renal epithelium shows fatty changes. In focal amyloidosis in spleen, The amyloid is deposit in the walls of the central arterioles of the lymph follicles and in the stroma of the lymph follicles causing narrowing of the arterioles and replacement of the follicles by eosinophilic homogenous translucent material. In diffuse type (bacon spleen) the amyloid is deposited in the sinusoids of red pulp.

Amyloidosis is producing its serious effects through destruction of the parenchymal cells and overloading of reticuloendothelial system by amyloid precursors. Although, the amyloid deposit interfere with normal function of any organs, the fatal effects occurs in kidneys and animal usually die from uremia. Amyloidosis may be reversible in the liver and not in the kidneys.

Fig. 7: Pericardium showing serous atrophy of fat. The adipose tissue replaced by embryonic cells showing round, oval or satellate cells with interlacing branches. H&E

Fig. 8: Liver showing microscopic picture of amyloidosis represented by pale eosinophilic homogenous substances under the endothelial lining of hepatic sinusoids. The hepatocytes compressed and showed pressure atrophy. Moreover, the hepatic cords are disorganized. H&E

Fig. 9: Liver showing pale eosinophilic substance amyloid under the endothelial lining of hepatic cells. H&E

Fig. 10: Liver amyloidosis appear violet by crystal violet stain. The amyloid stained violet against deep basophilic hepatic cells.

Fig. 11: Kidney, Micro, amyloidosis represented by pale eosinophilic homogenous material under the endothelial lining of glomeruli. Moreover, the glomerular tufts are compressed. H&E

Fig. 12: Kidney showing microscopic picture of amyloidosis represented by pale eosinophilic homogenous material under the endothelial lining of glomeruli. H&E.

Fig. 13: Kidney showing peritubular amyloidosis represented by pale eosinophilic homogenous materials under the basement membrane of renal tubules. H&E

Fig. 14: Spleen showing focal amyloidosis (sago spleen) represented by focal replacement of splenic parenchyma with pale eosinophilic homogenous material. H&E.

Hyaline used to describe substance with white, glossy, solid, dense, and smooth homogenous in texture. So, hyaline degeneration is retrogressive change characterized by the transformation of the tissue into homogenous structureless translucent smooth material and stains pink with eosin. The hyaline is seen physiologically in the superficial layer of the skin, cornea of the eye and in ovulation scars of the ovary.

It occurs in old scars, mesodermal tumors, in the walls of diseased blood vessels as in arteriosclerosis, afferent arterioles of kidneys as a result of hypertension, glomeruli in diffuse glomerulonephritis. Moreover, the central arterioles of the lymph follicles of spleen in old besides the blood vessels of atrophic organs ovary in old age.

In muscle Zenker’s degeneration or hyaline degeneration of the skeletal muscles, which occurs in case of vitamin E deficiency and bacterial toxins

The hyaline material may be too small to be seen. Hyaline degeneration is observed in case of large area affected. The affected tissue is translucent, firm, glassy, shiny and inelastic. In muscle, the affected muscle appear grayish-white resemble fish-flesh and friable and flabby.

The collagen fiber fuses together, become thick loose their striation and converted into a homogenous translucent structureless eosinophilic material. The nucleus not affected. In muscle, The muscle fibers are swollen, more eosinophilic and lose the cross striation.

The main cause is a lack of nutrients. Moreover, it occurs in old age and in injured tissues besides toxin substances carried through circulation.

It observed in corpora amylecea which seen in acini of the mammary gland, lung alveoli and the acini of the prostate gland in senile prostatic hyperplasia. It appears as round, homogenous, or concentrically laminated pink bodies tinged zonally with blue.

Moreover, it observed in old thrombi, islets of Langerhan’s in diabetes mellitus, hyaline and cellular casts inside renal tubules, hyaline globule in the degenerated hepatocytes in heavy alcohol drinker, which called Mallory’s bodies.

Russell’s bodies are seen in plasma cell in old chronic inflammation undergoes hyalinosis and changed to red oval a nuclear body.

Hyaline droplet degeneration: It seen in animals suffered from chronic nephritis. Microscopically, Large hyaline droplet appear in the proximal convoluted tubules resulted from excessive protein filtration from the diseased glomeruli and the tubular reabsorption is overloaded.

Hyaline degeneration is irreversible condition. The affected tissue has less strength than normal. Hyaline degeneration may lead to rupture of the affected vessel walls and hemorrhage due to loss of elasticity and flexibility. Hyaline degeneration may be followed by calcification.

Fig. 17: Skeletal muscle showing hyaline degeneration. The muscle fibers become homogenous more eosinophilic structure less. The nucleus not affected. H&E

Fig. 18: Corpora amylecea in the acini of mammary gland which appears as round, homogenous, or concentrically laminated pink bodies. H&E

Glycogen infiltration is the excessive intracellular accumulation of glycogen in tissues. Glycogen is normally stored in liver and muscles.

1. Glycogen infiltration is seen in prolonged hyperglycemia, which occurs in poorly controlled diabetes mellitus. The glycogen accumulates in renal tubular epithelium, cardiac muscles and beta cell of islets of Langerhan.

2. Glycogen storage diseases resulted from congenital absence of enzymes as glucose 6- phosphatase deficiency, which is necessary for the breakdown of glycogen into glucose. The lake of this enzyme lead to accumulation of glycogen in the liver and myocardial muscles.

The affected organ is enlarged and whitish in color in case of very large amount were present Microscopically, the cells are containing irregular shaped vacuoles in the cytoplasm. The glycogen stained crimson red by Best’s carmine and red by PAS stains.

Fig. 19: Kidney showing hyaline casts (eosinophilic structureless materials) inside lumen of renal tubules. H&E

Fatty change means accumulation of discrete droplets of neutral fat (triglycerides) in the cytoplasm of tissue other than adipose tissue especially in parenchymatous organs.

A mild irritant of prolonged action or a severe irritant of short action causes fatty change. Bacterial toxins of acute infections as diphtheria or chronic infections as tuberculosis or chemical toxins as chloroform, carbon tetrachloride may cause fatty change. Moreover, anoxia or hypoxia as in severe anemia or chronic venous congestion beside deficiency of lipotropic factor and diseases of the liver cells as viral hepatitis lead to fatty change. Dietary causes as: Excess intake of fats and carbohydrates Starvation with excess mobilization of fats from fat droplets.

Before we explain the pathogenesis of fatty change we have to know the normal metabolism of fat.

Normally, fatty acids arrive to the liver via plasma from two sources. The first one is from the intestine and the second from fat depot. Triglycerides absorbed from the intestine in the form of chylomicron. Which enter the general circulation through lacteal and thoracic duct. They are converted into fatty acids in the capillaries of skeletal and cardiac muscles and adipose tissue. The free fatty acids are used as a source of energy. In the liver, the fatty acids are used for energy production or esterofied into triglycerides, which converted into cholesterol or phospholipids. Moreover, the liver couples the triglycerides to specific protein called apoprotein-forming lipoprotein used by other tissue.

So any defect in the metabolism will lead to fatty changes. Here we are going to discuss some basic mechanisms involved in pathogenesis fatty change.

Absorption or release of high amount of fatty acids than normal. It occurs in excess absorption from intestine or release from adipose tissue as in case of ketosis.

Decrease utilization or oxidation of fatty acids due to interference with cofactors as carnitine as in case of diphtheria toxin.

Decrease phospholipids synthesis results from deficiency of lipotrope factors as methonine and choline.

Inability of liver to synthesis apoprotein. It occurs in case of liver diseases and some intoxication with methonine, carbon tetrachloride and phosphorus. The lipoprotein can not formed and lead to accumulation of triglycerides.

The color is yellow with the degree of yellow is depend on the severity of fatty change. In sever case the organ is enlarged with rounded borders. The consistency is soft with tense capsule. The cut surface is bulged and greasy. In the heart, the fatty change appear as yellow tan streaking (thrush breast). In the kidney, it appears as radial yellow tan streaking in the cortex and medulla.

The cytoplasm of affected cells contains many tiny vacuoles in early stage or large clear vacuoles pushing the nucleus to periphery giving the cell the signet ring appearance. The fat appear as rounded vacuoles with H & E., orange yellow with Sudan III, red with Oil Red O, black with osmic acid and blue with Nile blue sulfate stain fat blue. Fatty change is reversible. But necrosis, cirrhosis of the liver, acute heart failure, cysts formation from the affected cell, open into capillaries forming emboli may occurs if the cause persist.

When fat are excessively deposit in the fat depot it called obesity or lipomatosis. It associate with excessive ingestion of fat or carbohydrates and lowered metabolic rate.

Fig. 22: Liver showing fatty changes represented by large clear vacuoles in the cytoplasm of hepatic cells (Signet ring appearance). H&E

Fig. 23: High power of the previous Fig. to show Liver fatty change. The hepatocytes are filled with clear vacuoles pushing nucleus to one side. H&E

Fig. 24: Liver showing microscopic picture of fatty change. The fat stained red with Oil red O.

It is the presence of normally appearing lipocytes into the interstitial connective tissue of organs that normally don’t contain lipocytes as in heart. It is usually associates with obesity.

It is the deposition of calcium salts in tissues other than bone and teeth bone or in soft tissues. The calcium deposit in the form of calcium carbonate or phosphate.

The calcium ions are critical for many cell activities. It is present in plasma in ionic form and pound to plasma protein. It is required for skeletal and cardiac contractility. The plasma level of calcium is controlled under the effect of two hormones. The first is the parathyroid hormone, which cause hypercalcemia through bone resorption. The second one is calcitonin, which cause hypocalcemia. Others hormones as estrogen play a role in calcium metabolism. Moreover, the plasma calcium is 10mg/100ml blood. Normally, the calcium of normal bone occurs as calcium phosphate and calcium carbonate in the proportion of 9:1 respectively. The same is present in pathologic calcification.

Calcification is differing from ossification where the later in the deposition of calcium and phosphorus in bone. The pathologic calcification is divided into dystrophic calcification and metastatic calcification.

It is the deposition of calcium salts in the necrotic or degenerated tissues. Dystrophic calcification has no relation with calcium content of blood.

In dystrophic calcification, the calcium needs an alkaline media to deposit in it. This media is present in necrotic and degenerated tissues, where the circulation is deficient and the carbon dioxide tension is low (alkaline media. The phosphate and carbonate deposited in the same proportion as is found in bone.

Metastatic calcification is the precipitation of calcium salts as a result of high level of plasma calcium without necrosis or degeneration of tissues. It observed in organs secreting acid as stomach, kidneys and lungs.

Increase plasma calcium level results from hyperparathyrodism, which lead to resorption of calcium from bone is one of the most important causes of metastatic calcification. Excess vitamin D in diet lead to hypercalcemia and calcification of the wall of arteries and other tissues.

Decrease excretion of calcium as in case of renal failure lead to hypercalcemia and calcification. Moreover, dystrophic calcification can be observed associated with osteoperosis, osteomalacia and tumor of bone and multiple myeloma.

If the deposition is enough to observe grossly, the deposit is white or gray granular in appearance. Grating sound and gritty feeling are recorded in cut section.

The calcium carbonate and phosphate are observed as irregular fine granular deposits. The calcium stained purplish to bluish in color with hematoxylin and eosin, depending on the thickness of the particles. Von Kossa stains calcium black.

Fig. 25: Liver showing microscopic picture of fatty change. Sudan black stained fat black.

Fig. 26: Kidney showing microscopic picture of fatty change The fat stained black with Sudan black.

Fig. 28: Lymph node of sheep showing dystrophic calcification in area of caseous necrosis The calcium stained blue with H&E.

Fig. 29: Kidney showing metastatic calcification. The calcium deposit in the renal medulla and stained blue with H&E.

It is diseases of purine metabolism where the characteristic lesions are the deposition uric acid and urates, sodium and calcium urates, in the joints, and serous membranes of the internal organs. It is most common in birds, snakes and human.

Uric acid and urates are the end product of purine metabolism. The cause is due to incomplete metabolism of purine derivatives. The defect in metabolism is due to decrease or increase activity of specific enzymes involved in purine metabolism. Moreover, active excretion of uric acid may interfere by chronic nephritis and genetic factors.

In birds the causes are due to impaired renal function and excretion of urates, nephrotoxic drugs, nephrogenic viral strain of infectious bronchitis, increase dietary protein and calcium besides vitamin A deficiency.

Gout is not seen in domesticated animals due to presence of uricase enzymes in their livers, which convert uric acid to allantoin, which excreted in urine. In birds and human, the uric acid and urates start to deposit in the kidneys and on the serous membrane of internal organs when the level of them are elevated. In birds and reptiles two forms are observed, a rare articular form and visceral form.

In renal gout, the urates and uric acid are seen in the renal tubules and ureters, which show necrosis and degenerative changes in its epithelium besides, inflammatory reaction and fibrosis of the interstitial tissue.

In visceral gout, the gouty unstained crystals are deposits on its serosal surface.

In articular gout the pathognomonic lesions is the presence of sharp acicular crystals or cavities (after they dissolve) surrounded by neutrophils, macrophages and giant cells on the articular surface, adjacent tissue and joint capsule.

Grossly visible white chalky material called tophi are present on the joint surface, adjacent tissue and subcutaneous tissue causing inflammation and ulceration. These tophi associate with joint swelling, deformity and loss its function.

In visceral gout, a thin layer of grayish white material covers the serous surface of pericardium, liver and peritoneum.

Visceral gout is serious disease in birds causing deaths. The articular gout is recurrent in human and rare in animals.

Fig. 30: Lymph node of cattle infected with tuberculosis showing focal calcification. The calcium stained blue with H&E.

Fig. 31: Lymph node, Micro, focal calcification, Von Kossa stain. The calcium stained black.

Fig. 32: Kidney showing renal gout represented by urates and uric acid in the renal tubules and ureters, which show necrosis and degenerative changes in its epithelium besides, inflammatory reaction and fibrosis of the interstitial tissue. H&E

Pigment is coloring substances that normally present, either extracellular or intracellular, in some tissues such as corpus luteum, iris of the eye and others. In some pathological condition deposition of pigments either intracellular or extracellular in the tissues of an animal are important components of diseases.

Pigments may be exogenous that derived from outside the body through skin or natural orifice or endogenous produced within the body.

Exogenous pigments are coloring substances derived from the surrounding environment, which enter the body through respiratory and digestive opening and through skin. The environmental pollution of the air through these years plays an important role in spread of pathological exogenous pigmentation. Most of exogenous pigments are usually caused by inhalation of dusts that are observed in lung and draining lymph nodes. In the pulmonary tissue, presence of pigment and the body reaction against it is called pneumoconiosis. If the pigment produce irreversible reaction, which characterized by destroying alveolar architecture, significant stromal cell proliferation and collagen deposition, it called fibrogenic pigment. This group of pigments includes silicon dioxide, magnesium silicate and asbestosis.

The non-fibrogenic dust is characterized by intact alveolar architecture, minimal stromal proliferation and the reaction is reversible. This group includes kaolin, barium sulfate, and coal.

It is the presence of carbon particles as dark black pigments in the pulmonary tissue and associate lymph nodes.

It occurs in animals and human due to inhalation of coal dust. Most of inhaled dusts are trapped by the mucus blanket and rapidly, removed from the lungs by ciliary movement. However, some of the particles come in contact with the alveolar epithelial lining which phagocytize by macrophages to accumulate around the respiratory bronchioles or travel through the lymphatic to the draining lymph nodes.

The coal particles appear as minute black granules in macrophages or free around the bronchioles, in interalveolar connective tissue or in the lymph nodes between the lymphoid cells. Macrophages can carry carbon particles to other tissues. Carbon can be distinguished from other pigments by its black color and by its resistance to all solvents and bleaching agents.

The lungs have may be gray to black in color according to the amount of pigment present. Moreover, the ventral lobe more affected.

Presence of little amount does little harm and cause no pathologic alteration. Excessive amount may cause pulmonary fibrosis.

Fig. 33: Kidney showing visceral gout resulted in destruction of epithelial lining of renal tubules with gouty material surrounded with macrophages and giant cells. H&E

Fig. 34: Joint showing microscopic picture of articular gout represented by the presence of sharp acicular crystals. H&E

Fig. 35: Lung showing microscopic picture of anthracosis. The carbon particles appears as black granules free or inside macrophages. H&E

It is the deposition of fine silica particles in the lung tissue leading to formation of silicotic nodules.

Causes and pathogenesis

Inhalation of very fine silica dust for long periods. It occurs in animals live in desert atmosphere, which is rich in silica particles.

The phagocytize silica particles (especially less than 0.5 µm that pass the nasal filter and mucus barrier) causes necrosis of macrophage due to damage of lysosomal membrane. Moreover, hydrolytic enzymes leak from necrotic macrophage besides chemotactic factors secreted by macrophages cause necrosis and inflammation of the pulmonary tissue. Re-phagocytosis of silica particles, which cannot break down, lead to more destruction of tissue which finally walled of by granulomatous reaction forming silicotic nodules.

Microscopic appearance

Silicotic nodules focally replace the affected pulmonary tissue. The silicotic nodules is consists of concentrically arranged hyalinized collagen fibers surrounding amorphous center. Fine anisotropic silica particles (seen only by polarized light) are seen in the center. In early stage the silicotic nodule is consisted of silica particles surrounded by macrophages, giant cells and fibroblasts are found, forming nodules in the lungs. Later on the nodules may coalesce and compress or occludes blood vessels or lymphatics.

Macroscopically

The lungs are nodular and firm and may be pigmented as a result of concomitant anthracosis

Significance

Silicosis is permanent and lead to decrease resistant to infection especially tuberculosis. Moreover, it causes emphysema and hyalinized nodules lead to difficult breathing besides right sided heart hypertrophy.

Fig. 36: Lung showing microscopic picture of anthracosis. The carbon particles appears as black granules free or inside macrophages. H&E

3. Asbestosis

It is one of exogenous pigmentation of the lungs due to inhalation of asbestos (magnesium silicate) which lead to diffuse fibrosis with the presence of bamboo-like asbestos fibers.

Causes and Pathogenesis

Asbestosis is induced by Inhalation of mineral fibers (asbestos fibers) for a period of 3-4 years.

The asbestos particles pass the respiratory filter trapped in the respiratory bronchioles and their evaginating alveoli, where reticulin is formed upon the alveolar surfaces that obliterates these alveoli. Then the reticulin is converted to collagen. Due to more mineral deposition, fibrosis becomes diffuse around alveoli and blood vessels. Some alveoli remain patent but their walls and the walls of respiratory bronchioles are thickened by fibrous tissue proliferation. The asbestos particles may be present in inflammatory area or free in alveoli and become coated by an iron containing protein, which are segmented and clubbed, red-brown or golden in colors.

Microscopic picture

Asbestos appears as fine, white anisotropic or isotropic fibers. The asbestos bodies, which are similar to bamboo, are long, beaded or segmented with rounded ends. Diffuse fibrosis with foreign body giant cells is seen.

Macroscopic appearance

The lungs are grayish and firm and the pleura is thickened.

Significance and results

It causes difficult breathing and predisposing to pulmonary infection.

Fig. 37: Lymph node, Gross, Anthracosis. The lymph nodes appears black in color.

Fig. 38: Lung showing silicosis. The silicotic nodules consists of concentrically arranged hyalinized collagen fibers surrounding amorphous center. H&E

4. Argyrosis

The ingestion of silver compounds over a long period lead to ashen-gray pigmentation of the skin conjunctiva and internal organs

Macroscopic and microscopic picture

The affected areas appear ashen gray in color. The silver is seen principally in the connective tissue fibers in the upper corium as brown to black insoluble pigment.

5. Plumbism

It is the pigmentation of tissues with black color results from presence of lead and hydrogen sulphide in the tissues.

Causes and pathogenesis

Plumbism occurs when ingestion of lead in the form of paint or when water or food containing lead is consumed. Pigmentation of tissues occurs in these areas of the body where hydrogen sulphide comes in contact with lead results in formation of lead sulphide, which is a black pigment.

Macroscopic appearance

Lead line is seen on the gum due to combination of lead with H₂S liberated by putrefactive bacteria. Moreover, Lead stain the intestinal contents a gray or-black appearance.

Microscopically

Lead in the tissue can not stained with H&E but special staining techniques or chemical analyses must be used to demonstrate

6. Lipochromatosis

These are insoluble, greenish yellow pigments. The name is derived from the Latin fuscus, which meaning brown. The pigment present normally in epithelial cells of adrenal gland, lutein cells, testes, Kupffer cells of liver and ganglion cells. Two types of pigments present. b and a carotine.

Causes

It is seen in cells suffering from slow regressive changes particularly in liver and heart of aging animals, severe malnutrition and cancer cachexia (wear and tear pigment). Moreover, it is usually accompanied organ shrinkage (brown atrophy).

Lesions

The pigment is seen microscopically as yellow or brown granules in the cytoplasm near to the poles of the nuclei. The fat solvent not dissolve the pigment, but the granules stained with fat stain as Sudan IV.

Fig. 39: Lung showing the microscopic picture of asbestosis represented by fine, fibers ( asbestos bodies) which are similar to bamboo, H&E

Fig. 40: Lung showing gross picture of asbestosis.

7. Tattoos

Several pigments are including India and China ink, Bismark brown and kurkuma. The pigment is introduced through skin into the dermis and subcutis of animals to identify them. The pigments do not produce no tissue reaction and seen extracellular between connective fibrous tissue.

II. Endogenous pigmentation

Endogenous pigments are pigments present and produced in body under normal conditions. In mammals, four groups of endogenous pigments are present. These groups are melanin, lipofuscin, hemosiderin and bilirubin. Under certain pathological conditions, these pigments are accumulating in large amount or present in tissue that normally not present.

It is the brown pigment of skin, hair, leptomeninges and iris. Melanin is high molecular weight bichrome bound to protein (sulphur containing protein). It is produced in melanocytes from tyrosine by the action of tyrosinase enzyme (a copper-containing enzyme). In skin the melanin pigment transformed from melanocytes and stored in melanophores. a&b melanocyte stimulating hormones are produced by pituitary and act on melanocytes to initiate melanin synthesis. Moreover, adrenocorticotrophic hormone has a melanocyte stimulating effect.

Melanosis

It is the deposition of melanin in various organizes especially in lung and aorta forming black or brown spots of irregular shape and often a cm. or more in diameter. The melanosis is seen during necropsy or during inspection of carcasses in slaughterhouses.

Lesions

The affected organ show brown to black irregular shaped spots. Ink like pigment diffuse from cut section immersed in water. Microscopically, numerous macrophages filled with melanin are seen in the affected area. Melanin appears as minute, rounded granules of light or dark brown color ,which may be over-shadow the details of the cells, in the cytoplasm of melanophore. Moreover, melanin is stained black by Fontana’s silver stain.

Significance

Melanin is harmless, but excessive amount of melanin indicates pathologic condition as adrenal disease, hormonal imbalance and neoplasia.

N.B. Albinism is characterized by absence of melanin within an individual. It is resulted from inability of melanocytes to synthesis a sufficient active tyrosinase. It is commonly observed in laboratory animals as rat, mice, rabbits and guinea pigs. It is occasionally seen in human beings, horses, dogs and cats.

Fig. 41: Liver showing lipochrome pigment in the cytoplasm of hepatocytes, H&E stain.

Fig. 42: Esophagus showing black spots, melanosis.

Fig. 43: Uterus of sheep showing dark black spots.

Fig. 44: Brain meninges of calf showing dark black melanin pigments inside melanophore. H&E

Hemoglobin derived pigments

Hemoglobin is oxygen carrying pigment of the blood.. Normally, certain number of erythrocytes dies daily and liberates hemoglobin. The later is broken down into globin and heme. Globin goes to protein pool. Heme is further divides into hemosiderin and hematoidin. Hematoidin is converted to bilirubin reticuloendothelial of bone marrow and spleen. Hemosiderin is used to re synthesis of new erythrocytes.

Hemosiderosis

Hemosiderin is a shiny golden yellow pigment derived from hemoglobin break down. It is usually found inside macrophages, hepatic cells and renal epithelium.

Hemosiderosis is accumulation of hemosiderin in tissue. It may be local as with hemorrhage or systemic as in case of blood hemolysis.

Lesions

The color of the affected tissue is brownish. Moreover, the lungs are brownish in color and firm and indurated (brown induration of the lungs). Microscopically, the hemosiderin appears as golden-brown amorphous granules in the macrophages of the spleen, liver, and lungs (sidrocytes). Moreover, the hemosiderin is present in the parenchymatous cells of the liver and kidneys. For accurate diagnosis the hemosiderin is stained bright blue with Prussian blue.

Significance

The presence of hemosiderin is indicates that there is excessive destruction of erythrocytes due to hemorrhage or hemolysis

Fig. 45: Spleen showing dark brown to black multifocal melanosis. H&E

Fig. 46: Spleen, Micro, hemosiderosis. The hemosiderin pigments appear as golden yellow pigment in side macrophage (Sidrocytes). H&E

Fig. 47: Spleen, Micro, hemosiderosis. The hemosiderin is seen inside sidrocytes or free and stained yellow with H&E

Bile pigments (Hemobilirubin and cholebilirubin)

As mentioned before hemoglobin liberated by the hemolysed erythrocytes is phagocytized by the reticuloendothelial system, and metabolized into globin that passes to the protein pool of the body, hemosiderin and hematoidin. Hemosiderin travels inside siderocytes to from new blood inside the bone marrow.

Hematoidin combines with a large protein molecule to form hemobilirubin which cannot pass through the renal filter and is used for the production of bile. The hepatic cell absorb haemobilirubin from the blood, and the pigment is separated from the large protein molecule and is conjugated with glucouronic acid to form the brownish cholebilirubin.

It is excreted with bile to the intestine to be reduced by the intestinal bacteria to fecal urobilinogen which is colorless. Urobilinogen is oxidized to brown urobilin which is mostly excreted with feces and colors it brownish yellow.

Both cholebilirubin and urobilinogen can pas through the renal filter. The normal level of hemobilirubin is 0.1-0.8 mg/100 ml. of serum. When this level increases to 3 mg/100 ml serum, the pigment is deposited among cells or in the tissue spaces and stains them yellow.

The sclera and conjunctive of the eyes, mucous membranes, skin, intema of aorta, adipose tissue are stained yellow and in severe cases the liver and kidney are also stained. This condition is called jaundice or icterus.

Microscopically

The bile pigments cannot be seen because they dissolve in body fluids.

Fig. 48: Liver, Micro, hemosedirosis, Prussian blue. The hemosiderin stained blue.