Mineral deposits and pathological pigmentation
Pathological calcification
Pathologic calcification is the deposition of calcium salts in tissues other than bone and teeth. The calcium deposited 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
Dystrophic calcification-1
It is the deposition of calcium salts in the necrotic or • degenerated tissues. Dystrophic calcification has no .relation with calcium content of blood :Pathogenesis •
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
Calcification in arteriosclerotic blood vessel
Calcium stain black by Von-Kossa stain
Psammoma Bodies
Calcified bodies in meningial and ovarian tumors
Metastatic calcification-2 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 Pathogenesis and causes • Increase plasma calcium level results from hyperparathyroidism, • which lead to resorption of calcium from bone is one of the . most important causes of metastatic calcification Excess vitamin D in diet leads to hypercalcemia and calcification • . of the wall of arteries and other tissues Retention of phosphate as in case of renal failure leads to • secondary renal hyperparathyroidism and hypercalcemia. Moreover, metastatic calcification can be observed associated with osteoporosis, osteomalacia and tumor of bone and .multiple myeloma
Renal calcification
:Macroscopic appearance 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. Microscopic appearance: 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. Significance Calcification is usually permanent but it harmless depending in its location.
Gout
It is diseases of purine metabolism where the • characteristic lesions are 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
Causes
Uric acid and urates is 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, and nephrogenic viral strain of infectious bronchitis, increase dietary .protein and calcium besides vitamin A deficiency
Pathogenesis
:
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.
Microscopic appearance 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. 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.
Tophacious gout
Gout needle –like crystals in renal tubules surrounded by granulomatous reaction
Needle crystals in renal tubules accombanied by granulomatos reaction
Gouty material deposite in joint capsule
Macroscopic appearance 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. Significance: Visceral gout is serious disease in birds causing deaths. The articular gout is recurrent in human and rare in animals.
Skin ulceration due to presnce of subcutaneous tophi
Deformed hand joints
Pigmentation
______________________________________________________________________ : Endogenous pigmentation Lipofucine and ceroid pigments ( Melanin (melanosis : Hemoglobin derivatives include Hemoglobin Hematoidin ( Hemosiderin (hemosiderosis ( Hemobilirubin (jaundice
(
Cholebilirubin (jaundice : Exogenous pigmentation They are not that important in veterinary pathology,as they are not me- tabolic disturbances.They cause foreign body inflammatory reaction. The foreign bodies which are relatively insoluble may enter the body through the respiratory tract,digestive tract or skin.Only exogenous pigmentat- ion which enter through inhalation is of some interest to us.They may be found free inside the bronchioles,and alveoli,or inside macrophages in al-veoli or inside the endothelial cells of the peribronchial and interlobular lymph vessels,or in the peribronchial lymph nodes.The inhalation of dust for a long time irritates the pulmonary tissue which responds by a lesion
Anthracosis
______________________________________________________________________ generally called pneumoconiosis (lung + dust), when there is some fibrosis besides pigmentation.Several names are used to identify the various types of pigmentation according to the cause eg.silicon dioxide causes si- licosis, iron oxide causes siderosis and coal dust causes . anthracosis.The exogenous pigmentation is usually harmless except silicosis and asbesto- osis : Anthracosis This is the deposition of coal-dust in the pulmonary tissue by inhalation,as seen in animals and people working in the mines,and in most city-dogs and people.It is caused by inhalation of coal-dust or smoke for long periods.The inhaled coal-particles(carbon particules)are partially trapp- ed by the mucus which covers the epithelium of the bronchioles,or come in contact with the epithelial lining of air-sacs. Macrophages carry these pigments through the epithelial lining of the bronchioles and the air sacs; to accumulate around the respiratory bronchioles,or travel through the ly- mphatics to the draining lymph nodes.The pigments may be carried through the epithelial lining by the tissue-fluids,without macrophages.Micro-scopically, minute black carbon granules are seen free or in macrophages on the epithelial lining of the bronchioles and air-sacs, or in the wall of
Pneumoconioses Disorders caused by inhalation of • inorganic elements, primarily .metals :Injury is determined by • Length of exposure Physicochemical characteristics Host factors
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Carbon dust - Coal worker’s • :pneumoconiosis
Anthracosis Simple coal worker’s pneumoconiosis Progressive massive fibrosis
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Silicosis •
Silicotic nodules
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Asbestos •
(Asbestosis (pulmonary fibrosis Pleural disease (fibrous plaques, (.mesothelioma
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Smoking-related diseases
Lung Type I pneumocyte
Type I pneumocyte Alveolar space
Capillary lumen Type II pneumocyte Endothelium
Anthracosis evidenced by the presence of coal-dust in the medulla of the mediastinal . lymph node, H & E
_______________________________________________________ bronchioles and the interstitial tissue, particularly peribronchial.Pigments may be seen in the draining lymph nodes (bronchial and mediastinal) (Fig. 31).Contamination of the coal-dust with silica causes local fibrosis which may lead to bronchiolectasis and often emphysema.Macroscopically,the affected pulmonary tissue has grayish-black spots according to the concentration of the coal-dust in the tissue.The ventral portions of the lobes are affected more than the dorsal.The draining lymph nodes are dark.This should not be confused with the dark medulla of bovine lymph nodes draining an area of hemorrhage. The pigments in the latter are not seen microscopically;as they dessolve during tissue processing. Anthracosis is permanent The coal-dust is harmless,but when it is contaminat- ed with other particles (e.g.silica or iron), it . stimulates focal fibrosis which causes bronchiolstenosis and emphysema : Silicosis This is the deposition of fine silicon dioxide (silica) particles in the pulmonary tissue by inhalation of dusty air for periods as long as 10 years.It is characterized by formation of fibrotic . nodules (silicotic nodules) around the terminal respiratory bronchioles
Silicosis
_______________________________________________________ Silicosis is caused by inhalation of silicon dioxide, particularly the fine particles over 10 years or more. A lot of dust is trapped by the nasal filter and mucus, but the fine particles escape to be phagocytized by the alveolar macrophages to travel through the lymph vessels to the local lymph nodes to be discharged from the body. Some macrophages,containing silica, settle in the pulmonary tissue and die. They release soluble products (which accumulate inside their cytoplasm) in the interstitial pulmonary tissue which stimulate a foreign body reaction.Microscopically, macrophages, giant cells and fibroblasts form nodules with silica particles in the center (seen with the polarized light). Nodules may coallesce together and compress blood vessels, lymphatics and bronchioles. Emphysema may be seen.Macrophages may coallesce together to form giant cells.Inf- lammatory nodules are usually seen adjacent to the terminal bronchioles. These nodules undergo necrosis and fibrosis which become widely spread in the advanced cases.The pulmonary tissue becomes less resistant to infections, particularly tuberculosis.Emphysema is a common complication. Adhesion between the visceral and parietal pleura is due to fibrosis. The latter distorts pulmonary tissue, which interfers with -the normal ex . Polarized = Able to show the poles of objects
.Asbestosis& Siderosis
______________________________________________________________________ __ pansion and contraction of the lungs; resulting in difficult breathing and hypoxemia. Hypertrophy of the right ventricle (cor-pulmonal), is due to resistance in the pulmonary . circulation. Death occurs due to right heart-failure and asphyxia : Asbestosis Asbestosis is induced by Inhalation of mineral fibers (asbestos fibers) for a period of 3-4 years. These occur mainly during manufacturing, fabrication or installation of products containing .asbestos 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 obliterate 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
Clinical signs of silicosis the following symptoms may be“ • present: shortness of breath following physical exertion, severe cough, fatigue, loss of appetite, chest pains and fever. Silica exposure may also impair the ability to fight infections, which makes one more susceptible to certain .illnesses, such as tuberculosis
Microscopic picture Asbestos appears as fine, white anisotropic or isotropic fibers. The asbestos bodies (bamboo Like), They are beaded or segmented with rounded ends, which are yellowish brown as a results of encrustation of iron that can be demonstrated with Prussian blue. Diffuse fibrosis resulting in scaring pleura and around bronchioles and alveolar ducts and within alveolar septa. Foreign body giant cells are seen adjacent to asbestosis particles. Macroscopic appearance The lungs are grayish and firm and the pleura are thickened. Significance and results: It causes difficult breathing and predisposing to pulmonary infection.It may lead to compansatory heart failure,decompansatory heart failure,pleural mesothelioma and lung cancer :Siderosis It is the deposition of inhaled iron particles, chiefly iron oxide in . the pulmonary tissue
?What is silica (Silicon Dioxide (SiO2 • A mineral found in quartz, • sand, rock, crystal, flint, .jasper, and opal High quality silica is a critical • component of silicon chips and is mostly found in .quartz Different from lower grade • silica used in glass bottles, lubricants for mechanical tools, concrete and bricks, and silicone implants
Silicosis
Health Effects Because it is so hard to destroy asbestos fibers, the body cannot break them down or remove them once they are lodged in lung or body tissues. They . remain in place where they can cause disease There are three primary diseases associated with : asbestos exposure Asbestosis • Lung Cancer • Mesothelioma • Oklahoma State University EHS
Relationship between smoking, asbestos, and lung cancer Most severe cases have been :experienced in
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Shipbuilding • Mining • Milling • Fabricating •
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Operations that could result in exposure Floor coverings • Ceiling tile •
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Operations that could result in exposure Pipe wrap •
Fireproofing • Acoustical/decorative • treatments
3c
Lung & Pleural involvement
Lung Cancer Lung cancer causes the largest number of deaths related to asbestos exposure. The incidence of lung cancer in people who are directly involved in the mining, milling, manufacturing and use of asbestos and its products is much higher than in the general . population The most common symptoms of lung cancer are coughing and a change in breathing. Other symptoms include shortness of breath, .persistent chest pains, hoarseness, and anemia Oklahoma State University EHS
Baritosis, Stannosis & Argyria
______________________________________________________________________ ___ :Baritosis .It is the deposition of inhaled barium oxide powder in the pulmona- ry tissue : Stannosis It is inhalation of tin oxide. Microscopically, the above three types of pneumoconiosis . produce several dense nodules of fibrous tissue with no clinical signs Other types of pneumoconiosis result from the inhalation of dry particles, derived from sugar. cane and cotton fibers The alimentary tract ,as a route for pigmentation, is not as important as the respiratory . tract. The ingested silver and lead salts cause pigmentation e.g. argyria and plumbism : Argyria The prolonged treatment with or consumption of silver salts causes argyria. It is characterized by the deposition of silver in the skin and conjunctiva as well as other internal organs. Microscopically, gray pigments
Plumbism,Tattooing & Exogenous hemochromatosis
______________________________________________________________________ ___ appear in the affected tissue. Macroscopically, the affected tissues and organs have ashen-gray . color.The silver pigments cause no disturbances. The skin-coloration is permanent :( Lead (Plumbism Prolonged ingestion of small amounts of lead compounds produces a blue-black line on gums of horse, dog and human due to reaction of soluble lead salts with H 2S which gives lead .sulfide : Tottooing Pigments may be introduced through skin as by tattooing.Fixed macrophages (histiocytes) phagocytize pigments and keep them permanently. Other macrophages may . carry these pigments to the local lymph nodes. The epithelium does not keep pigments : Exogenous hemochromatosis An exogenous pigmentation with hemosiderin in man is caused by re peated bloodtransfusion with more than 200 ml. blood.The lysed erythrocytes liberate hemosiderin which is phagocytized and carried to various tissues. Microscopically, the liver, spleen and pancreas have golden-yel-llow pigments.The dermis and the Brunner's glands of the duodenum show similar pigmentation in the severe cases.Hemosiderosis indicates hemolysis
Steatitis, Xanthomatosis
_________________________________________________________________ _______ .. : Steatitis of mink and pig This inflammation and pigmentation of fat is due to vitamin E deficiency.It is characterized by the formation of yellow acid-fast pigments (ceroid) in fat-cells and . macrophages : Xanthomatosis A tumor-like thickened yellow or orange-yellow pigmented areas in wattles, and skin of the white Leghorn pullets. It is also seen in human. It is not a real neoplasm, but a disturbance in the reticuloendothelial system. Its cause is unknown. Microscopically, the swelling consists of foam-cells, fibroblasts, lipoid droplets, and (lenticular spaces (cholesterol Orange-yellow or yellowish pigments are seen intracellular inside the epidermis, dermis and the subcutis of wattles, and areas of breast,abdomen and thigh. Macroscopically, tumor-like thickened yellow or orange-yellow pigmented areas are seen in wattles and skin
:Endogenous pigmentation
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Lipofucine pigments (lipochromatosis) and ceroid pigments (
Melanine pigments (Melanosis : Hemoglobin-derived pigments Hemoglobin Hematoidin
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Hemosiderin (hemosiderosis (Hemobilirubin (jaundice
Lipofuscin-1 Lipofuscin pigment is called wear and tear pigments, has in the past been described as accumulating with age and in certain pathologic condition. It accumulates in a time dependent manner in postmitotic cells (neuron, cardiac myocytes and skeletal muscle myocytes) or in slowly dividing cells such as hepatocytes and glial cells. It is resistant to fat solvents and stain with fat stain even after paraffin embedded procedures Lipofuscin is the end results of phagocytosis of cell constituents such as organelles and it is the final undegradable remnant. And can not be removed by further lysosomal degradation or exocytosis and stored in Lysosomes as a form of biological garbage. Macroscopic picture 1-It occurs most often in certain cells of aging organisms and seen in great quantity in organ suffering from atrophy. 2-The affected organs appeared brownish in color when present in sufficient amount. Microscopic appearance Lipofuscin pigments are minute yellow brown granules, which accumulate in cardiac myocytes near the poles of nuclei, but distributed in the cytoplasm of other cells. Significance It is usually indicates the presence of wasting disease.
Lipochromatosis in the kindney and liver below, compared with the : .normal above
Melanosis
______________________________________________________________________ ___ :Melanin Melanin is a sulfur-containing protein.It is normally found as minute intracellular brown granules in the basal layer of skin, mucous membrane of the oral cavity of particular breeds of dogs, in hair, iris,choroid coat of eye, and in the leptomeninges of sheep and cattle. Melanin gives a light- brown to black color according to its concentration.Melanin is formed from the amino-acid tyrosine by the action of tyrosinase (a copper-protein complex) inside the melanoblasts.The macrophages,which phagocytize melanin,are called melanophores. The absence of copper-ions inhibits tyrosinase. This absence of copper may be due to sulfydryl groups which bind the copper. The ultraviolet rays activate the formation of melanin by decreasing the concentration of sulfydryl group. Melanin may be pathologically increased .((hyperpigmentation),or decreased (hypopigmentation :Hyperpigmentation It is seen with melanosis, melanoma, acanthosis nigricans and freckles. Hyperpigmentation, or darkening of the skin, can occur in Addison’s disease but not in secondary adrenal insufficiency. This darkening is most visible on scars; skin folds; pressure points such as the elbows, knees, knuckles, and toes; lips; and mucous membranes such as the lining of the cheek Melanosis is the abnormal increase of melanin in the various organs,particularly the lungs and aorta. It is characterized by brown or black discoloration of tissue according to the concentration of melanin.It may be congenital as in congenital melanosis in calves and lambs, and seedy bellies in pigs.Melanoblasts produce melanin which is carried by the melanophores (macrophage carrying melanin inside its cytoplasm) to accumulate in some remote areas and produce melanosis. Microscopically,the affected area contains numerous macrophages filled with melanin (melanophores).The cellular details of these melanophores may be completely covered by melanin. No melanoblasts are found. Macroscopically, brown
33
34
35
36
Figs. 33-36 : MELANOSIS Lung (left) and esophagus (right) showing melanotic patches :33 Calf liver showing focal melanosis :34 . Normal melanosis of uterine caruncles in ewe :35 (. Albino steer showing defective pigmentation of the iris (lower eye :36
Melanosis
_______________________________________________________ or black coloration of the affected tissue which may be in the form of spots on lungs(Fig. 33), epicardium, endocardium, liver (Fig. 34) and kidneys. Fig. (35) shows melanosis in caruncles of ewe which is normal. It may be seen under the various mucous membranes, and in the covering of the central nervous system in congenital melanosis of calves and lambs. Ink-like pigments may diffuse from the cut-surface when immersed under water. The Fontana's silver solution stains melanin black. Melanin is harmless. It may disappear by age. Melanosis of cornea causes blindness in particular dogs. It allow the meat unfit for consumption NB.Dopa reaction is used to demonstrate the presence of melanoblasts. It is positive (give black precipitate) with melanoblasts,and negative with melanophores.It is based on the presence of oxidase enzyme (tyrosinase) in melanoblasts.Tyrosinase oxidizes dopa (dihydroxyphenylalanine) to melanin. Pseudomelanosis is a postmortem change which has nothing to do with melanin.It is due to the reaction between the liberated hemosiderin,from the hemolyzed erythrocytes, and the hydrogen sulfide, produced by the putrifactive bacteria. The result of the reaction may be iron- sulfide which stains the tissue black, or . sulfmethemoglobin, which stains the tissue green
(Normal skin: (white
Melanin stain specifically by masson fontana stain as black granules
DOPA reaction differintiate between melanosis and melanma
Hepatic melanosis.melanin carried by melanophore(macrophage) and transport to different parts
.Albinism, Leukoderma, Hemoglobin-Derived Pigments
______________________________________________________________________ __ : Hypopigmentation with melanin The melanin-pigments may be pathologically decreased, or absent from tissues where it is supposed to be normally . found e.g. albinism and leukoderma : Albinism It is a Albinism (from Latin albus, "white";, also called achromia, achromasia, or achromatosis) is a form of hypopigmentary congenital disorder, characterized by a partial (in hypomelanism, also known as hypomelanosis) or total (amelanism or amelanosis) lack of melanin pigment in the eyes, skin and hair, or more rarely in the eyes alone. Albinism results from inheritance of recessive alleles. The condition is known to affect mammals (including humans), fish, birds, reptiles and amphibians .Heriditary condition probably caused by the absence of the enzyme which converts dihydroxyphenyalanine to melanin.. It is frequent in mice, rats and rabbits, and encountered in horse, cattle and cat.It is characterized by the complete absence of melanin from tissue.Albinism is hereditary; it is not an infectious disease and cannot be transmitted through contact, blood transfusions, or other vectors. The principal gene which results in albinism prevents the body from making the usual amounts of the pigment melanin. Most forms of albinism are the result of the biological inheritance of genetically recessive alleles (genes) passed from both parents of an individual, though some rare forms are inherited from only one parent. There are other genetic mutations which are proven to be associated with (. albinism. All alterations, however, lead to changes in melanin production in the body. [1][ tissue (Fig. 36 Classification :There are two main categories of albinism in humans In oculocutaneous albinism (despite its Latin-derived name meaning "eye-and-skin" albinism), pigment is lacking in the eyes, skin and hair. (The equivalent mutation in non-humans also results in lack of melanin in the fur, scales or feathers.) . People with oculocutaneous albinism can have anywhere from no pigment at all to almost-normal levels In ocular albinism, only the eyes lack pigment. People who have ocular albinism have generally normal skin and hair color, . although it is typically lighter than either parent. Many even have a normal eye appearance
: Leukoderma
It is the local absence of melanin pigments from some areas of the skin due to injury as by saddle-sores, ionizing radiation and burns.It may be an auto-immune ( disorder(Vitilligo
Vitiligo Autoimmune Theory
It is known vitiligo appears in conjunction with several other autoimmune disorders, such as juvenile diabetes mellitus, Addison's disease, and pernicious anemia, and additionally organspecific antibodies can often be seen in patients with vitiligo. If the immune system raises antibodies or cytotoxic T cells to damage melanocytes
Hemoglobin-derived pigments
Hemoglobin is the oxygen-carrying pigment of the blood. It is in solution or in a colloid state inside the erythrocytes. Chlorophyl does the same job in plants. It contains magnesium instead of the loose iron of hemoglobin. Normally,a particular number of old erythrocytes die daily and liberate hemoglobin.The latter is broken down into globin (protein goes to the protein pool),and heme.The heme gives hemosiderin (iron- containing pigment which travels inside siderocytes to form new blood inside the bone-marrow),and hematoidin (needle-shaped,iron-free crystals which are converted to bilirubin by the reticuloendothelial cells of the bone-
.)marrow and spleen
.Hemoglobin-derived pigments ____________________________________________________ __ The liver normally congugates the bilirubin with glucoronic acid to form soluble brownish glucoronide (cholebilir- ubin)which is excreted with bile to the intestine to be reduced by the int- estinal bacteria to fecal urobilinogen (colorless). It is oxidised to brown urobilin which is mostly excreted with feces, and colors it brownish-yel- low.Both cholebilirubin and urobilinogen can pass through the renal filt- er, but the hemobilirubin cannot pass. Pathologically, hemoglobin-pigments may be seen in the vicinity of a large hemorrhage in avascular tissue as cartilage. Such tissue, when fixed in non-buffered formalin,shows precipitate of hemoglobin in the form of brown,black or greenish-black angular granules (acid hematin) of variable shapes and sizes among cells or dying erythrocytes. Hemosiderin is an amorphous golden yellow iron-containing pigment.It is usually found inside the macrophages (siderocytes), or inside the hepatic and renal epithelium.It is normally found in the red pulp of the spleen which is the greatest in horse and the least in dogs. It is more in the old than in the young animals.
.Hemosiderosis
_______________________________________________________ : Hemosiderosis It is an endogenous pigmentation caused by increased amount of hemosiderin in the tissues. It may be local as in hemorrhage or general as in the systemic hemolysis.The local is seen around old hemorrhage.Excessive hemolysis as by bloodparasites, septicemic diseases and toxins, is another cause besides the chronic congestion of lungs and liver.Hemosiderin is excessively liberated from the hemolysed erythrocytes, phagocy-tized by macrophages, and parenchymatous cells of the liver and kidneys Microscopically, golden-brown amorphous granules, usually within the macrophages, as in the spleen, liver and lungs (heart-failure cells). The cellular details may be blurred by the hemosiderin.The increased blood-pressure,in chronic congestion of the lungs,stimulates fibrosis in addition to hemosiderosis (brown induration of the lungs). Hemosiderin may be seen in cytoplasm of renal and the hepatic-cells.The hemosiderin is stained bright blue with prussian-blue stain,where potassium ferrocyanide takes the iron in place of potassium to form ferricferrocyanide (blue ). Fresh tissue is stained blue if excess hemosiderin is present. Hemosiderin is harmless but may interfer with the renal excretory function.It may disappear within few days. .Its presence indicates hemolysis
Bile pigments (Hemobilirubin and (:cholebilirubin
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 absorbs hemobilirubin 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
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Jaundice or Icterus :Definition • It is not a disease but it is a clinical signs or postmortem • condition of increase level of hemobilirubin and cholebilirubin in the blood. It is characterized by yellow coloration of many tissue particularly skin and mucous . membranes The jaundice is classified into three types according to the • cause: (1) Hemolytic or prehepatic jaundice, (2) toxic or intrahepatic jaundice and (3) obstructive or posthepatic .jaundice
Jaundice
Common Causes of Jaundice Pre Hepatic (Acholuric) - Hemolytic • Unconjugated/Indirect Bil, pale urine •
Hepatic – Viral, alcohol, toxins, drugs • Liver damage - unconjugated • Swelling, canalicular obstruction - Conjugated •
Post Hepatic (Obstructive) – Stone, tumor • , Conjugated/Direct Bil, High colored urine •
Hemolytic or pre-hepatic jaundice-1 It is the yellowish coloration of most body tissue due to in crease level of hemobilirubin in blood. It occurs due to excessive . hemolysis of blood instead normal liver Cause
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I. Excessive hemolysis of blood due to (1) blood parasites such as piroplasmosis, anaplasmosis and leptospirosis. (2)bacteria such as Clostridium hemolyticus bovis, and Hemolytic streptococci (3) viral diseases as in infectious equine anemia and (4) poisoning such as plant poisons( ricin and saponin) chemical poisons (potassium or sodium chlorate and chronic lead poisoning) and animal (.poisons (snake venoms .Massive internal hemorrhage with absorption of hemobilirubin from hemolysed blood . 2 :Pathogenesis
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• It occurs due to increased hemolysi of RBCs with production of excessive amounts of hemobilirubin .The normal liver cannot convert all hemobilirubin into cholebilirubin, leading to increase level of hemobilirubin in the blood and stains tissues yellow. The feces stained darker due to more cholebilirubin and the urine becomes more yellow due to the excessive urobilinogen and . urobilin Lesions
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The yellowish coloration of most body tissue is outstanding and pathognomonic. The bile pigments can not see microscopically. .Moreover hemosiderin is seen in macrophages in spleen, liver and in hepatic cells Significance
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.The bile pigments are harmless. Moreover, it indicates presence of severe blood hemolysis besides normal hepatic function
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Blood Conjugated & Conjugated Urine – Urobilinogen Stool – Stercobilin
Bilirubin Metabolism
Toxic or intra-hepatic jaundice
• It is occurs subsequent to direct damage of liver cells and characterized by more intense yellowish coloration of most tissues of the body, due to increase level of both hemobilirubin and cholebilirubin in .the blood Cause
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The causative agents caused damage to the hepatic tissue such as salmonellosis, infectious canine hepatitis and leptospirosis. Moreover non infectious as inorganic (phosphorus, arsenic, and lead), plant poisons ((senicio and lupines) and organic compounds (clay pigeons :Pathogenesis
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If liver cells are injured or necrotic, they are not able to conjugate normal hemobilirubin into cholebilirubin result in increase hemobilirubin in blood. Moreover, damage hepatic tissue and breaks in bile canaliculi . permit the escape of cholebilirubin into the blood sinusoids Lesions
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.The body tissue showed intense yellowish coloration besides the damaged liver can be detected Microscopically, the liver cells showed various degenerative and necrosis Significance
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.It indicates damaged liver
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clay pigeons
Cresols and creosote produce contact irritation and nonspecific liver and kidney lesions. In pitch poisoning, the liver is markedly swollen with a diffuse, mottled appearance. The lobules are clearly outlined by a lightcolored zone, and their centers contain deep-red dots the size of a pinhead. There is centrilobular liver necrosis, with blood replacing the lost cells and filling the center of the lobule. Renal tubular degeneration and necrosis also can be present. The blood clots slowly or not at all. The carcass is ictericDifferential diagnoses include toxic plant poisonings ( Crotalaria , Senecio , cocklebur), aflatoxicosis, fumonisin toxicosis, gossypol toxicosis, yellow phosphorus poisoning, and vitamin E or selenium deficiency. Fragments of clay pigeons, tar paper, or other sources of coal tars found in the GI tract, or chemical detection of coal-tar products in liver, kidney, serum, or urine, aid in confirming the diagnosis. A rapid presumptive test is to mix 1 mL of urine with 0.1 mL of 20% ferric chloride; purple color is indicative of phenol, but results should be confirmed by a laboratory.. Excessive fluid is found in the peritoneal . cavity
:Acute viral Hepatitis
:Acute viral Hepatitis C
:Acute viral Hepatitis
Obstructive or post-hepatic jaundice
It is type of jaundice that occurs due to obstruction to the normal flow of bile characterized by the accumulation of bile pigments mainly .cholebilirubin in the blood Cause
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It associated with obstruction of bile canaliculi by the swollen hepatic cells in degenerative changes. Obstruction of bile ducts by parasites (Ascaris lumbricoides in swine and Fasciola hepatica in cattle and sheep) and gall stones (common in man but uncommon in animals) is a .common cause
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Moreover, pressure from outside as periductal tumors, abscesses or granuloma in the walls of bile ducts or structures adjacent to it as pancreas and portal lymph nodes may cause obstruction of bile duct. Inflammatory changes as cholangitis and cholecystitis, in addition to duodenitis that .obstructs papilla duodeni :Pathogenesis
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• There are increase level of cholebilirubin in blood due to that the cholebilirubin and bile produced by the hepatic cells cannot pass to the intestine. Moreover, the bile diffuses to the surrounding tissue and hepatic tissue adjacent to the duct system, where it enters the blood and .lymphatic systems. The animal become yellow in color. Urine, sweat, saliva and even milk become colored Lesions
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The body tissue is stained yellowish. The feces is clay colored as no bile reach the intestine and is greasy because fat digestion is incomplete. The obstruction can be detected. Microscopically, distended bile canaliculi with bile are detected and the bile pigments may be deposited .among cells :Significance and results
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.The bile outflow is obstructed and hepatic function is normal
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N.B. The type of jaundice can be determine using Van Den Bergh test
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PSC: cholangiogram & pathology
Endoscopic retrograde cholangiogram: beaded bile ducts with strictures
Bile duct with “onion-skin� periductal fibrosis and mononuclear inflammation
Bile Duct Carcinoma: pathology
Primary mass (yellow central superior) with innumerable intrahepatic satellite tumors ((smaller yellow lesions
Moderately differentiated adenocarcinoma forming distorted ducts within prominent sclerotic stroma
Fig. 18-45, Pathologic Basis of Disease, 7th ed, Elsevier 2004