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GENERAL PATHOLOGY......................................................................................................1 DEFINITIONS........................................................................................................................2 DISORDERS OF LIPID METABOLISM..............................................................................3 Hepatic LIPIDOSIS (liver STEATOSIS, fatty liver))............................................................3 Kidney STEATOSIS (in equine hyperlipemia)......................................................................5 DYSTROPHIES OF PROTEIC METABOLISM.................................................................6 Amyloid dystrophy (AMYLOIDOSIS, hepatic amyloidosis)................................................6 Kidney HYALINOSIS............................................................................................................7 DISORDERS OF HIDROELECTROLITIC METABOLISM............................................8 Kidney GRANULO-VACUOLAR DEGENERATION.........................................................8 DISORDERS OF MINERAL AND PIGMENTARY METABOLISM...............................8 Jaundice...................................................................................................................................8 Renal mineralization (Dystrophic calcification of kidney)...................................................10 PATHOLOGY OF CIRCULATORY CHANGES PART I.............................................11 Pulmonary congestion (hyperemia) and edema ...................................................................12 Muscle hemorrhage...............................................................................................................13 White kidney infarct..............................................................................................................13 PATHOLOGY OF CIRCULATORY CHANGES PART II...........................................14 Hepatic venous THROMBUS...............................................................................................14 Acute and passive liver congestion.......................................................................................16 INFLAMMATION.................................................................................................................17 ALTERATIVE INFLAMMATIONS....................................................................................19 Necrotic hepatitis (diffused and miliar)................................................................................19 Chronic gastric ulcer (Chronic ulcerative gastritis)..............................................................20 EXUDATIVE INFLAMMATIONS......................................................................................21 Fibrinous pneumonia (Lobar pneumonia).............................................................................21 Purulent (suppurative) leptomeningitis.................................................................................22 Pulmonary abscess................................................................................................................24 PROLIFERATIVE INFLAMMATIONS.............................................................................25 Echinococcus Hydatid Cyst..................................................................................................25 Actinobacillosis.....................................................................................................................27 Tuberculosis..........................................................................................................................28 REPARATORY PROCESSES (REGENERATION AND REPAIR) ..............................32 Granulation tissue (Young connective tissue).......................................................................34 Bone regeneration Bone callus...........................................................................................37 TUMORS PATHOLOGY......................................................................................................38 EPITHELIAL TUMORS.......................................................................................................40 Squamous cell carcinoma (SCC)..........................................................................................40 Trichoblastoma - Ribbon Type.............................................................................................41 Papillary carcinoma of the mammary gland.........................................................................41 MESENCHYMAL TISSUE TUMORS................................................................................44 Poorly melanotic MELANOMA............................................................................................44 Osteoblastic productive OSTEOSARCOMA ......................................................................45 Cavernous HEMANGIOMA................................................................................................47 FIBROSARCOMA...............................................................................................................48


Morfopatology. Morphe- shape, pathos- disease, logos-science. Anatomical pathology Ana (gr.)- through Toma (gr.)- cut - The study of disease (lesions but also cause) - Connects the study of normal form and function (histology, anatomy, physiology) to the study of clinical medicine - Makes sense how the various causes of disease interact with the host, resulting in clinically identifiable conditions The medical science and specialty practice, concerned with all aspects of disease, but with special reference to the essential nature, causes and development of abnormal conditions, as well as the structural and functional changes that result from the disease processes (Stedmans Medical Dictionary). The main methods of study (instruments) of anatomical pathology: 1. Necropsy: (necros-death, opsis-sight): opening and examination of the dead bodies for the establishment of the exact (nosologic) diagnose (nosos- disease, logosscience). 2. Histopatholoy and citopathology: continuation of the macroscopic studies in the laboratory with the help of the microscope. 3. Biopsy: tissue removed from lived animals, from organs with changes, to provide diagnose to help clinicians. 4.Experimental reproduction Pathology: -General pathology: -basic responses of cells and tissues to insults and injuries, irespective of the organs, systems or species involved Metabolism changes Blood and lymph changes Morphofunctional adaptation processes; Inflammations Regenerative processes Tumoral process -Special pathology (pathology of organ system, systemic pathology): -how each organ system reacts to injury associated with specific disease General plan of examination for organs and tissues 1. Inspection - development of organs (estrogenic micotoxicose) - color (carotenoids, bile pigments, blood circulation, fibrosis) - shape and dimensions - aspect of surface and margins 2. Palpation (consistency changes) - superficial 2

- profound (bony, flashy, hard, pasty, puffy, elastic, friable) - increased: coagulation necrosis, proliferative inflamations, mineralization, tumors with much connective tissue, compression atrophies - decreased: liquefaction necrosis, gangrenes, exsudative inflammations, autolysis, putrefaction, highly celularised tumors 3. Sectioning - standard (lung, liver, spleen, gut, stomach, kidney, brain) - whenever necessary 4. Collection of samples for laboratory exams - histopathology - hematology - cytology - bacteriology - parasitological - virusology - mycology - toxicological 5. Special exams - docimasy - choledoch exam


Cholesterol (ateromathosis) Complex lipids (cerebrosidosis) Triglycerides (obesity, steatosis, lipomatosis, cahexia)

Hepatic LIPIDOSIS (liver STEATOSIS, fatty liver))

Definition: Hepatic lipidosis is the term most often used to describe fatty livers of animals, whereas in humans, the term steatosis is more commonly used. Both refer to the visible accumulation of triglycerides (triacylglycerols) as round globules in the cytoplasm of hepatocytes. The threshold for application of these terms is vague because triglyceride storage and transport are normal hepatic functions, but they are appropriate when the amounts are greater than would normally be seen. Etyology: Hepatic lipidosis can be physiological or pathological. Increased mobilization of triglycerides during late pregnancy or heavy lactation in ruminants is associated with hepatic lipidosis. In some of these animals, severe energy deficiency can also lead to clinical ketosis with metabolic acidosis. In addition, severe lipidosis occurs in high-producing dairy cows fed diets where either the mix of available fatty acids is incorrect or lipids are oxidized and rancid. Hepatic lipidosis is common in injured hepatocytes. Physiologic fatty liver occurs in late pregnancy and heavy lactation, particularly in ruminants. Lipidosis is also seen in neonates, especially in those species whose milk is relatively rich in fat. Acute ketosis of lactating dairy cows with intake insufficiency or secondary to abomasal displacement is usually associated with fatty liver with a predominantly diffuse microvesicular pattern. Cows are more tolerant of ketosis associated with lactation than are 3

pregnant ewes that can die from starvation-induced pregnancy toxemia and ketoacidosis. In cows and ewes with increased mobilization oftriglycerides, there may be indistinct foci of white discoloration of abdominal fat that tend to be obscured when adipose tissue solidifies postmortem. Fatty liver of diabetes occurs when insulin is deficient or inactive due to lack of functioning receptors. Lipoprotein synthesis and transport are dependent on oxidative metabolism, so hypoxia of hepatocytes leads to triglyceride accumulation. The two most common causes of hepatocellular hypoxia are anemia and reduced sinusoidal perfusion in passive venous congestion. Local hypoxia is probably the basis for another example of fatty liver in bovine socalled "tension lipidosis". Fatty liver due to intoxication is common. Most toxins that cause fatty liver in naturally occurring situations, however, also produce a greater or lesser degree of hepatocellular necrosis. Tthere are some specific nutritional deficiencies that will produce fatty liver. Choline deficiency, in conjunction with deficiency of other lipotropic factors such as L-methionine and vitamin B12, rapidly produces fatty liver. Hepatic lipidosis is common in companion animals. Dogs eating diets deficient in vitamin E may develop severe hepatic lipidosis. The syndrome of feline hepatic lipidosis most commonly occurs in obese, nutritionally stressed female cats, presented with vomiting, anorexia, weakness and weight loss, jaundice, and hepatomegaly. Familial hyperlipoproteinemia has been described in cats, associated with congenital lipoprotein lipase deficiency. The microscopic appearance of triglyceride globules in hepatocytes ranges from small discrete microvesicles (acute) to large coalescing macrovesicles (chronic). o Small droplets of fat, usually in a periportal and juxtasinusoidal position, can normally be found in the liver. Increased mobilization and acute injury tend to produce microvesicular lipidosis in which numerous small and discrete micellar lipid globules are distributed around the central nucleus. Acute lipidosis with predominantly microvesicular accumulation tends to result grossly in a modestly enlarged pale liver without much change in texture. o In some more protracted toxic injuries, lipid globules tend to coalesce into large central macrovesicles that displace the nucleus (signet ring cell). Grossly, these fatty livers tend to be more yellow, enlarged, and the texture is more friable. Each hepatocyte usually contains one large globule (macrovesicle) that alters the contour of the cell and displaces the nucleus. The sinusoids are compressed and appear underperfused, and the tissue at low magnification resembles adipose tissue. The triglyceride globules themselves are not harmful to hepatocytes, so the amount of fat present is more an indicator of the duration of insult and triglyceride supply than of the severity of hepatic injury. Evolution: In severe degeneration, the liver is moderately or greatly enlarged, with a uniform light yellow color. The edges are rounded, and the surface is smooth. The cut surface has a diffuse greasy appearance, or a red and yellow lobular pattern if there is also hepatic congestion or zonal necrosis. The parenchyma is less dense and portions will float in water or fixative.

When lipid accumulates in large amounts, there is a tendency for groups of the fat-laden cells to rupture or fuse and eventually form a multinucleate rim about a foamy mass of lipid. This epithelial structure is known as a fatty cyst, as is the next stage, which occurs when released lipid is picked up by macrophages. Lipidosis is usually reversible, although a liver that has been fatty for some time is more likely to have concurrent damage, including fibrosis, pigment accumulation, and nodular hyperplasia.

Kidney STEATOSIS (in equine hyperlipemia)

Definition: kidney dystrophy due to TG accumulation in the nephrocytes. Etiology: - hyperlipemia in horses, - intoxications with Liliaceae in cats, - nutrition rich in lipids, - hipotyroidism, - chronic nephritis, - steroid hormones treatment. Equine hyperlipemia is almost exclusively a disease of ponies, and among these the Shetland breed predominates. The disease has also been reported in American miniature horses and donkeys. The disease is usually fatal after about a week. Pregnant or lactating mares are most likely to develop the disease, particularly if they are excessively fat and have recently suffered reduced feed intake due to onset of parturition, conditions such as laminitis or parasitism, or other causes of stress. At necropsy liver is severely fatty and may have ruptured; the lipidosis also extends to heart and skeletal muscle, kidney, and adrenal cortex. Evidence of disseminated intravascular coagulation is seen as serosal hemorrhages and microscopic thrombi in various organs, and even gross infarction of myocardium and kidney. The pathogenesis of this disease is obscure: 1. Since the excess lipid in liver and blood is in the form of triglyceride, the implication is that the liver is capable of esterifying fatty acid mobilized from depot fat. The triglyceride thus formed is presumably then exported to the plasma as VLDL until the plasma transport mechanisms are saturated , at which stage lipids begin to accumulate in the hepatocytes. 2. Another possibility is that there is an inability on the part of all tissues other than the liver to utilize fatty acids from VLDL at the normal rate, while triglyceride synthesis from fatty acids continues in the liver. 3. It has been proposed that an underlying cause of pony hyperlipemia is a comparative resistance to insulin in susceptible animals. Gross lesions: Friable kidneys, of yellowish color, greasy aspect on section, mainly in the cortical area. Microscopically findings: Foamy aspect of nephrocytes due to lipid accumulation (vacuoles) Increase in size of nephrocytes with reduced lumen of tubules Sometimes pyknotic nuclei (pushed to a side) - signed ring cell aspect Fatty cylinders are formed (fusion of affected cells) Evolution: renal insuficiency; renal failure.


Proteic dystrophies - Amyloidosis - Hialynosis and hyalinisation - Fibrinoid degeneration most frequently affecting arteries - Mucoid degeneration affecting mucus-secreting epithelium - Coloid degeneration (hipothyroidism) affecting thyroid follicles - Dyskeratosis - Premature keratinization in cells that are not in the keratinizing surface layer of the skin Hyaline substances: 1. Hyaline casts in the lumen of renal tubes (proteinuria). 2. Serum or plasma in blood vessels. 3. Plasma proteins in vessel wall (edema disease - swine). 4. Old scars. 5. Thickened basement membranes (glomerulonephritis and capillaries of choroid plexus aged animals). 6. Hyaline membranes of alveolar walls. 7. Hyaline microthrombi in DIC (disseminated intravascular coagulation). 8. Amyloid.

Amyloid dystrophy (AMYLOIDOSIS, hepatic amyloidosis)

Definition: Amyloidosis is a systemic disease in which the eosinophilic, homogenous material is deposited extracellular in multiple regions, particularly in the renal glomerulus. On hematoxylin and eosin staining, amyloid appears as homogeneous eosinophilic amorphous extracellular material. Staining with Congo red results in apple green birefringence when viewed with polarized light. Thioflavine T stain produces yellow-green fluorescent staining of amyloid viewed under ultraviolet light. Amyloidosis affects parenchymatous organs, especially the kidneys, liver and spleen. - At the hepatic level, amyloid is deposited first in the parenchyma about the portal tracts and appears gray and waxy. Amyloid is deposited in the perisinusoidal space between the sinusoidal lining and hepatocytes and is sometimes found in the walls of the afferent vessels. The surrounded hepatocellular cords atrophy. - In kidneys, amyloidosis is seen in the vascular glomerular ball form. - In the spleen, amyloidosis occurs around the lymphoid follicular arterioles. - Due to the predominant extracellular location of the amyloid (exceptions are BSEBovine Spongiform Encephalopathy where the amyloid is deposited intracellularly, in the affected neurons), amyloidosis is not a proper dystrophy since the hepatic dysfunction is produced after the compressive effect the amyloid plays on the hepatocytes. Etiology - Amyloidosis is seen in diseases with chronic, long lasting evolution as tuberculosis, leukosis, mink plasmocitosis, classical swine fever, chronic suppurative diseases, neoplasia and even in BSE. In cattle, amyloidosis is secondary to the chronic process of tissue distruction; in some cases it is associated with chronic suppurative and granulomatous lesions in other tissues. Horses used for the production of hyperimmune serum could also be affected by amyloidosis.

In horses, hepatic amyloidosis occurs chiefly as a result of chronic inflammation and has been well recognized in horses used for the production of hyperimmune serum. Horses may develop icterus and other signs of hepatic failure. Cattle die first of the primary disease or from uremia resulting from concurrent renal amyloidosis. Dogs and cats typically develop signs of renal dysfunction, although cats may be presented with spontaneous hepatic rupture. Familial AA amyloidosis is recognized in Chinese Shar-Pei dogs, in Abyssinian cats, and suspected in Siamese and Oriental cats. Depending on the mechanism of production, we can see: - Primary Amyloidosis (AL - amyloid light chain) occurs in plasma cell diseases and of B lymphocytes that have the capacity to form immunoglobulins following prolonged antigenic stimulation. It occurs in immune diseases and tumors eg. Multiple myeloma. - Secondary Amyloidosis or Reactive Amyloidosis (SAA - serum amyloidassociated) occurs when serum proteins are produced in excess by either hepatocytes or other cells, or following tissue destruction consecutive to a chronic disease. Gross lesions - The liver is: slightly enlarged in volume, with a pale gray-yellowish color reflection, friable, dense, and waxy to the touch, dry on cross-section and prone to fracture. Hepatic amyloidosis gives the organ the aspect of a wax block. In cattle, affected livers may be firm. Microscopically - at the level of the liver, the lesion starts inside the Space of Disse (between the Remak chords and the endothelial sinusoidal capillaries perisinusoidal space) which thus becomes obvious at this level due to the unstructured, homogeneous deposits that induces the narrowing of the sinusoid capillaries and the atrophy of the Remak chords. Hepatocytes appear atrophied, edgy, differ in shape and size, many of them undergoing necrosis (different stages) with barely distinguishable nuclei. Sinusoid capilaries ar also atrophied with histoarhitectural changes of liver. Evolution - The lesion is irreversible, leading to a chronic hepatic insufficiency and cirhosis. Affected livers are predisposed to rupture and bleed.

Definition: kidney dystrophy due to hyalin (homogenous granular protein aggregates) intracellular and extracellular accumulation (hyalinosation) in the nephrocytes of the epithelium tubes. Etiology: Hyalinosis (intracellular) -nephrocytes (cronic kidney disease, with massive proteine resorbtion albumin, myoglobin, hemoglobin -hepatocytes (chronic toxicity, viral diseases, chronic alcoholism in humans) -plasma cells (Russel body chronic diseases) Hyalinisation (extracellular) -vascular and epithelial (virosis) -muscle distrophy and necrosis -devitalized tissues (thrombosis, granulomas, scars)

Gross lesions: kidney enlargement, dry on section, pale aspect, (glassy aspect) Microscopically findings: - cell hipertrophy due to intracitoplasmatic accumulation of multiple granular oxifile Hyaline bodies (first stage) 7

cell membrane lysis, liberation of the bodies in the lumen and formation of Hyaline cylinders (second stage).


Cell edema Granular dystrophy Vacuolar dystrophy Hidropic degeneration (Balonisation)


Definition: kidney dystrophy due to excessive cell hidratation (disorders of Na-K ionic pumps) in the nephrocytes of the epithelium tubes. Other organs affected: liver, suprarenal glands, neurons, muscle a.o. Etiology: different toxically agents (As, P), tissue hypoxia (predominant cause), hipopatasemia, febrile syndrome, infectious diseases (Leptospirosis). Gross lesions: kidney enlargement, increased consistency, pale aspect, (boiled organ aspect). Microscopically findings: Granular dystrophy Vacuolar dystrophy

- nephrocytes enlarged -enlarged nephrocytes -granular, dirty aspect of cytoplasm due -vacuolar aspect of the cytoplasm due to cell to mitochondrial hypertrophy (water hiperhydratation (oedema of REN, mitochondria, accumulation) cytosol) foamy aspect Evolution Granular dystrophy 1. 2. Reversible Vacuolar dystrophy Vacuolar dystrophy Initially reversible, then cell necrosis


Definition: also known as icterus is a yellowish discoloration of the skin, the conjunctive membranes over the sclera and other mucous membranes caused by hyperbilirubinemia. Etiology and pathogenesis: Hemolytic jaundice - endoglobular parasites Hepatic jaundice - infectious hepatitis Posthepatic jaundice - Calculosis 8

(babesiosis, theileriosis); - Cu, As intoxication - sheep - Leptospirosis; EIAV - Hemolytic anemia - Resorbtion of blood from hemorrhage - Ineffective erythopiesis

(viral) - drug induced hepatitis (liver toxicity) - liver dystrophy - cirhosis

- tumors - parasites ( Ascaridosis, Dicroceliosis, Fasciolosis) - Chronic inflamation of the biliar ducts ( colangitis, colecistitis) - enteritis

Cholestasis is a general term for impedance of bile output from the liver. Jaundice (icterus) is the discoloration of tissues and body fluids by an excess of bile pigments. Jaundice can have prehepatic or cholestatic origins. Prehepatic jaundice is usually related to overproduction of bilirubin from heme catabolism in hemolytic disease. Cholestatic jaundice can be hepatic or posthepatic: - In hepatic jaundice, there may be impaired uptake, metabolism, secretion, and transport of bile pigments within the liver. - In posthepatic jaundice, cholestasis is related to obstruction of bile flow at the level of the major bile ducts or gallbladder. Hepatic causes of jaundice can be conveniently subdivided into: (1) failure of hepatocytes to take up or conjugate bilirubin; (2) impaired excretion and transport of conjugated bilirubin in canaliculi or ducts within the liver; (3) impaired function of hepatocellular adenosine triphosphate-binding cassette transporters and aquaporins that drive the osmotic flow of bile. The bile secretion pathway has multiple steps that can be a target of a particular cholestatic mechanism. These include impaired uptake of unconjugated bilirubin, reduced production of conjugated bilirubin, slow canalicular transport, leakage from the duct system, and physical obstructions at various levels within and beyond the liver. It is common for these prehepatic, hepatic, and posthepatic causes to be combined to various degrees in any case of jaundice. Extrahepatic biliary obstruction initially causes increased pressure in bile ducts with dilation and stasis of content in the smaller radicles in the portal triads. Shortly, however, the parenchymal changes are the same as in intrahepatic cholestasis. Brown bile pigment is present in canaliculi and hepatocyte cytoplasm. The canaliculi are distended and sometimes loculated. The bile plugs are homogeneous. In the hepatocyte cytoplasm, initially in periacinar zones and later in all zones, the pigment is present in large, irregular lysosomes. In longstanding cholestasis, such as may occur with extrahepatic biliary obstruction, cholangioles become hyperplastic and some hepatocytes become hydropic with a reticulated appearance to the cytoplasm and are coarsely impregnated with pigment. Foci of parenchymal necrosis release small lakes of bile that can become surrounded by macrophages and giant cells. Gross lesions: yellowish discoloration of the mucosal and serous membranes, connective tissue and internal organs. The recognition of jaundice at necropsy sometimes involves differentiation of bile staining of tissues from the yellow staining caused by accumulation of carotenoid pigments. These latter are limited to fat depots and are to be expected in certain species such as horses. Distinction of the fatty pigments from bile depends on the absence of the former from pale, nonfatty tissues such as periosteum and dermal collagen.

Microscopically findings: Hepatic jaundice - Accumulation of multiple fine granular bilirubin pigment (yellow- brown) in the hepatocytes, macrophages ( Kupffer cells) and endothelial cells; - dystrophy and/ or necrosis of hepatocytes due to excess of biliar pigment ( toxicity) in the cytoplasm Posthepatic jaundice - Bile accumulation in the biliary ducts distention of the ducts and epithelial atrophy - presence of bile in the intralobular hepatic ducts bile thrombi - macrophages ( Kupffer cells) laden with biliary pigments

Evolution: - dystrophy and/ or necrosis of tissue due to biliar toxicity - biliar cirrhosis, biliar nephrosis and neuronal injury. Disorders of mineral metabolism: - Calcinosis kidney, lung, arteries (calcification is a subtype) - Lithiasis or calculosis - Pseudocalculosis - Pathological osification ( in tumors, arteries, liver, lung ) - Decrease of calcium quantity (bone)

Renal mineralization (Dystrophic calcification of kidney)

Definition: kidney dystrophy due to excessive accumulation of calcium salts in the renal tubes (basal membrane and nephrocytes). Etiology: Metastatic calcification - involves a systemic calcium excess imbalance - pseudohyperparathyroidism chronic renal failure - primary hyperparathyroidism (benign tumors) - hypervitaminosis D - ingestion of plants with vitamin D like substances ( Trisetum flavescens) - high phosphorus diet - hypomagnesaemia Dystrophic calcification - in the devitalized tissue (necrosis, dystrophy) - Old animals: abdominal aorta in cows; aortic curve in horses, pulmonary aortic trunk and parenchyma in dogs; - TBC granulomas, thrombus, atherosclerosis - worms (Trichinella spp.)

Gross lesions: irregularly surface, grayish discoloration, white strips in the cortical (section), brittle aspect at palpation. Microscopically findings: - basal membrane of renal tubes is thickened and blue - calcium salts deposition - nephrocytes are enlarged, basophilic, necrotic - basophilic, calcium cast in the lumen of the renal tubes Evolution : isolation of the calcified foci with connective tissue or chronic renal failure death.



DEFINITIONS: General blood disorders: - Hypovolemia - a blood disorder consisting of a decrease in the volume of circulating blood - Anemia - a pathological deficiency in the oxygen-carrying component of the blood (of hemoglobin, red blood cell volume, or red blood cell number) - Hypervolemia (Pletora) - a blood disorder consisting of an increase in the volume of circulating blood Local blood and lymph disorders HYPEREMIA AND CONGESTION local increased volume of blood in a particular tissue or area. A. Hyperemia active process resulting from augmented tissue inflow because of arteriolar dilation; tissue is redder than surrounding areas because of engorgement with oxygenated blood 1. Skeletal muscle during exercise 2. Sites of inflammation B. Congestion passive process resulting from impaired outflow; systemic or local; tissue becomes blue-red (cyanotic), as worsening congestion leads to accumulation of deoxygenated hemoglobin 1. Systemic 2. Local C. Congestion and edema commonly occur together: congestion of capillary beds is related to development of edema D. Long-standing congestion (chronic passive congestion) results in stasis of poorly oxygenated blood and chronic hypoxia 1. May result in parenchymal cell degeneration, cell death, microscopic scarring 2. Capillary rupture may cause small hemorrhagic foci 3. Breakdown and phagocytosis of red cell debris may result in hemosiderin-laden macrophages Haemorrhage (Bleeding) the loss of blood from the circulatory system Ischemia a decrease in the blood supply to a bodily organ, tissue, or part caused by constriction or obstruction of the blood vessels Thrombosis blood clotting (coagulation) in a blood vessel in a living animal Embolus - a mass, such as an air bubble, a detached blood clot, or a foreign body, that travels through the bloodstream and lodges so as to obstruct or occlude a blood vessel Infarct - an area of tissue that undergoes necrosis as a result of obstruction of local blood supply, as by a thrombus or embolus Metastasis - transmission of pathogenic microorganisms or cancerous cells from an original site to one or more sites elsewhere in the body, usually by way of the blood vessels or lymphatics.

Interstitial fluid disorders 11

Dehydration (hypohydration) is defined as excessive loss of body water. Edema (Oedema) is an abnormal accumulation of fluid in the tissue. ( Categories: Increased Hydrostatic Pressure /Reduced Plasma Osmotic Pressure, /Lymphatic Obstruction / Sodium Retention / Inflammation) Hydrops - is an abnormal accumulation of fluid in the cavities (pleura, pericardium, or in the peritoneal cavity); eg: ascites, hydrothorax, hydropericardium, hydrocephalus Anasarca is severe, generalized edema with profound subcutaneous tissue swelling

Pulmonary congestion (hyperemia) and edema

Definition: is a circulatory disorder characterized by an excessive accumulation of blood and interstitial fluid in the lungs. Pulmonary edema is a frequent complication of many diseases and is therefore one of the most commonly encountered pulmonary abnormalities. If severe, pulmonary edema has a catastrophic effect on lung function by: - reducing pulmonary compliance, - blocking ventilation of the alveoli, - obstructing gas exchange across the alveolar septa, - reducing the surface area of the air-liquid interface in the alveoli - proteins present in the edema fluid interfere with surfactant function, Etiology: Active/hyperemia Pulmonary edema - inflammatory - increased venous hydrostatic pressure: chronic left heart failure, response increased blood volume, pulmonary venous oclusion (pneumonia) - increased permeability of the alveolar barrier: pneumonia, diffuse alveolar damage, endotoxemia/septicemia - impairment of active transport of fluid from distal airspaces: damage to type II pneumocytes or Clara cells, hypoxia (high altitude), oxygen and nytrogen radicals (increased by inflamation), halogenated Passive/congestion anesthetics, possibly lidocaine, malnutrition, high alveolar protein - chronic left heart content failure - reduced oncotic pressure : hypoproteinemia (uncommon) - lymphatic obstruction: neoplastic emboli in lymphatics or lymph nodes (rare) - neurogenic pulmonary edema secundary to brain trauma - acute upper airway obstruction: strangulation, hanging - hypoglicemia On gross examination, edematous lungs are wet, heavy, and do not completely collapse when the thorax is opened, and fluid oozes from the cut surface. Edema is prominent in the pleura and the pulmonary interstitium. In cattle and swine, the interlobular septa are obviously distended by clear fluid. Foam often fills the trachea and bronchi and flows from the nostrils, although this is a common incidental finding in horses and sheep dying of a variety of causes. The color of tissue is red or burgundy and consistency is increased. The thoracic cavity may contain excess fluid. Histologically: - hypertrophy of alveolar interstitial space due to excessive dilation of blood vessels 12

edema fluid is acidophilic, homogeneous, or faintly granular material filling alveoli, except for occasional discrete holes that represent trapped air bubbles. - presence of hemosiderin laden macrophages Histopathology is neither sensitive nor specific for detection of pulmonary edema: the protein in edema fluid can leach from sections during processing and be quite inconspicuous; conversely, pink material often fills the alveoli in autolysed carcasses or those euthanized with barbiturates. Therefore, gross examination is usually a more accurate indicator of the presence and severity of edema than hitological examination! Evolution : resorbtion; acute respiratory insufficiency - death; pulmonary fibrosis.

Muscle hemorrhage
Hemorrhage - Definition: represents a circulatory disorder characterized by the loss or outflow of blood from blood vessels (internal or external) Etiology: Per rexis (rupture) -traumatic injuries (knife, bullet, contusions a.o.) Aneurisms Aterosclerosis, calcinosis, hypertension Per diabrosis (erosion) Per diapedesis -Parasites (horse, cat) Toxemia, viremia, -increased gastric acidity - bacteriemia,, with endothelial ulcers tropism (CSF) -chemical drugs (NaOH) -Toxicity (ANTU, warfarin)

Classification of hemorrhages: - Petechia: 1- to 2-mm hemorrhages into skin, mucous membranes, or serosal surfaces - Purpura Slightly larger hemorrhages (more than 3mm) - Ecchymosis: Larger hemorrhages (>1 to 2 cm), typical after traumas Hematoma: a localized collection of extravasated blood Hemorrhagic diathesis: multiple hemorrhages in the whole body Gross lesions : swelled muscle, dark-red, with blood leaking on section Microscopically findings: - presence of multiple erythrocytes between myocytes and muscle fascicles - presence of siderophages (macrophages containing hemosiderin pigment) Evolution : hypovolemic shock; resorbtion; fibrosis; infection

White kidney infarct

Definition: Infarcts of the kidney are common lesions of localized coagulative necrosis produced by embolic or thrombotic occlusion of the renal artery or of one of its branches. The sequelae depend on whether the obstructing material is septic or bland and on the size and number of the vessels obstructed. Etiology: Thromboembolism: Occlusion of a blood vessel due to a thrombus (thrombotic endocarditis) Embolism: other foreign matter that gets stuck while traveling through the bloodstream (gas following intravenous injection) - Bland thrombi produce typical infarcts; 13

Septic thrombi produce abscesses that may heal, sequestrate, or discharge into the pelvis. Thrombosis of a trunk of a renal artery will produce total or subtotal necrosis of the kidney, the extent of the latter depending on the presence and efficiency of parahilar and capsular collaterals. If an arcuate artery is obstructed, there is necrosis of a wedge of both cortex and medulla. If an interlobular vessel is involved, infarction is limited to the cortex. The ease and the frequency with which the kidneys are infarcted result from their vascular architecture being of the "end-artery" type and the large volume of blood that continually traverses them. Gross lesions: Soon after total obstruction of a vessel, the related wedge of tissue is swollen and intensely cyanotic and it is congested by the blood that oozes into the vessels from collaterals. There is no sharp line between the infarcted zone and the adjacent normal tissue because in the narrow boundary zone there is an outer part in which blood continues to ooze slowly and an inner part that is more or less well served by diffusion from the viable tissue. In the outer part of the marginal zone, the red cells survive and circulation may be reestablished, but this zone persists for the first 2-3 days; it is usually referred to, apparently erroneously, as the zone of reactive hyperemia. The limit of useful diffusion determines the actual limit of the infarct, and it is here that dehemoglobinization begins, neutrophils accumulate, and the area of total necrosis begins. The dehemoglobinization begins from the periphery at about 24 hours and may be complete in 2-3 days, the infarcted area then being white. Before decoloration begins, the area that will be affected is outlined by a thin but distinct white line of leukocytes. Commonly, infarcts of various ages in a kidney indicate recurrent embolic episodes. Microscopically findings: 3 different areas: 1. central: coagulation necrosis (pale nuclei and cells) 2. leucocytes (PMN neutrophils and macrophages ) infiltrate 3. area with congestion and hemorrhage surrounded by normal tissue Evolution: The necrotic zone is progressively replaced by fibrous tissue, and healed infarcts persist as pale gray-white scars, wedge-shaped and much depressed below the surface. The scars may be difficult or impossible to distinguish grossly from focal healed pyelonephritis. .


Definition: A clot consisting of fibrin, platelets, red blood cells, and white blood cells that forms in a blood vessel or in a chamber of the heart in a living animal, and can obstruct the blood flow. Aetiology:


Local thrombosis - Virchow's triad: - Endothelial injury (e.g. trauma, atheroma) - Abnormal blood flow (loss of laminar flow resulting from stasis in veins or turbulence in arteries) (e.g. valvulitis, aneurysm) -Hypercoagulability (e.g. leukaemia, Factor V mutation )

Disseminated intravascular coagulation (DIC): -widespread microthrombi formation -hemorrhagic and ischaemic necrosis of tissue/organs (septicaemia, acute leukaemia, shock, snake bites, fat emboli from broken bones, or other severe traumas).

Virchow's triad in thrombosis.

Endothelial integrity is the most important factor. Injury to endothelial cells can alter local blood flow and affect coagulability. Abnormal blood flow (stasis or turbulence), in turn, can cause endothelial injury. The factors promote thrombosis independently or in combination (Robins and Cotran, Pathologic basis of disease)

Gross lesions

- must be differentiated from post-mortem blood clotting Post-mortem clott -non-adherent to the endothelial wall -shiny -elastic -regular surface (mold of the blood vessel) -homogenous colour (dark red)

Thrombus -adherent to the endothelial wall -mat -friable -irregular -non-homogenous colour

Microscopically findings: - in the vascular lumen, the thrombus mass has a globulous shape, formed of: - Fibrin filaments with concentric disposal - Blood cells (red blood cells, white blood cells, platelets) between the fibrin filaments - The thrombus area adherent to the wall: presence of good vascularised young connective tissue (fibroblasts, small blood vessels and colagen) - White blood cells barrier Evolution: If a patient survives the initial thrombosis, in the ensuing days to weeks thrombi undergo some combination of the following events: Propagation. Embolization. Dissolution (the result of fibrinolysis) Organization and recanalization (by the ingrowth of endothelial cells, smooth muscle cells, and fibroblasts) infection calcification, hyalinisation 15

Complications: Thrombi cause obstruction of arteries and veins , and are sources of emboli. Venous thrombi can cause congestion and edema in vascular beds distal to an obstruction, but they are far more worrisome for their capacity to embolize to the lungs and cause death. Arterial thrombi can embolize and cause downstream infarctions, a thrombotic occlusion at a critical site (e.g., a coronary artery) can have more serious clinical consequences.

Acute and passive liver congestion

Definition: is a circulatory disorder characterized by increase of blood in the venous system of the liver (increase in the venous blood pressure compared to portal pressure) Etiology: -formation of thrombus, abscess, neoplasm or parasites in the caudal cave vein -right heart failure, pericardial effusions, constrictive pericarditis -hepatic lobe torsion (local congestion) due to diaphragm hernia -broiler chicken ascites Gross lesions: Acute liver congestion -hypertrophy (round margins and distended Glisson membrane) -red dark color -marked lobular structure with distended central vein surrounded by a yellowish colour (steatosis) -blood present on the cut surface -regular surface -portal veins are dilated -erythrodyapedesis leading to red abdominal efusion, rich in fibrinogen (clots on the liver surface) Chronic liver congestion -hypertrophy with irregular and thicker surface (fine nodular surface) -opaque colour (due to fibrous connective tissue organized in fibrous plaques) -marked lobular structure with distended central vein surrounded by a yellowish color (steatosis) -blood present on the cut surface -increased consistency

In acute hepatic congestion, the central vein and sinusoids are distended; centrilobular hepatocytes can be frankly ischemic while the periportal hepatocytesbetter oxygenated because of proximity to hepatic arteriolesmay only develop fatty change. In chronic passive hepatic congestion the centrilobular regions are grossly red-brown and slightly depressed (because of cell death) and are accentuated against the surrounding zones of uncongested tan liver (nutmeg liver). Microscopically, there is centrilobular hemorrhage, hemosiderin-laden macrophages, and degeneration of hepatocytes. Because the centrilobular area is at the distal end of the blood supply to the liver, it is prone to undergo necrosis whenever the blood supply is compromised.


Microscopically findings: Acute liver congestion: -Central veins, spaces of Disse and central vascular sinusoids are dilated (filled with erythrocytes), compressing the hepatocytes which are atrophied -Mediolobular and periportal hepatocytes may present fatty change (hypoxic mechanism); Chronic liver congestion: -Central veins, spaces of Disse and central vascular sinusoids are dilated, compressing the hepatocytes which are atrophied and, with progression, will necrotize (loss of hepatocytes) - central hemorrhagic necrosis (compression and/or ischemic mechanism). -Central veins fibrosis -Reversed liver aspect -Presence of hemosiderin (erithrolysis) and macrophages engulfing this pigment (siderophages)

Differential diagnose: Infectious hepatitis of dogs (Rubarth) centrolobular necrosis, congestion, hemorrhage, no steatosis at the periphery Perilobular steatosis with other etiology Perilobular necrosis : rabbit calicivirus (haemorhagic disease of rabbits), ischemia no centrolobular severe congestion Evolution : - fibrosis - cirhosis - hepatic carcinoma - death by liver insufficiency.

DEFINITION: Inflammation represents a reaction of the connective-vascular tissue towards an agression designed to: - eliminate the agressive agent - repair the damaged tissue through cicatrisation Inflammation is THE defense reaction of an organism to an aggression (without it the survival would not be possible). The aggressive agents can be very diverse: Physique factors : cold, heat, radiations, trauma Chemical factors Pathogenic agents : bacteria, virus, parasites Immunologic events It represents as well an important cause of tissue lesions (from here the interest for the use of anti-inflammatory drugs destined to combat or regulate). CLASIFICATION Morphopatologic: 1. Alterative: Brutal action of factors (physical, chemical, biological) with a minimum vascular reaction. NECROSIS the main process. descuamative (cataral) - (if epithelium is affected) necrotic (tissue and parenchimatous organs): o liquefaction o coagulation 17

o caseification gangrenous (severe necrotic process with none or minimal reaction) o dry o humid o gassy 2. Exudative: Exudate = a pathological complex composed from a liquid fraction (plasma with different amounts of proteins) and a cellular component (blood cells). serous (high proteic content clots in contact with air) hemorrhagic (exudate is rich in red blood cells) purulent (suppurative)-(exudate rich in neutrophils and bacteria) o purulent catar o diffuse o abscess o phlegmon o empyema fibrinous (false membrane) - (exudate is rich in fibrinogen which converts to fibrin) o simple (exudate does not adhere to tissue) o fibrino-necrotic(diphtheroid)(exudate adheres to tissue) 3. Proliferative: are characterized by predomination of cell proliferation, with the presence of mononuclear cells (hystiocytes, lymphocytes, plasma cells, mast cells, macrophages/epitheloids, giant cells) polimorphonuclear (PMN) cells (neutrophils, eosinophils). They are produced especially by agents that act slowly. Epitheloid and giant cells originate from macrophages so they have phagocytotic and pinocytotic functions. Epitheloids are cells with large nucleus, rich in cytoplasm, without a clear demarcation of cell borders, due to cytoplasm elongations. Giant cells present numerous nuclei, with an abundant cytoplasm, and their morphology and nuclear pattern largely depends on the etiological agent. granulomatous (with macrophages and epithteloid-giant cells) o n foci (granuloma) o difuse interstitial o limpho-histiocitic o eozinophilic o fibrous o limpho-plasmocitic Evolution: - Peracute - Acute - Subacute - Chronic Etiology: Physique factors : cold, heat, radiations, trauma Chemical factors Pathogenic agents : bacteria, virus, parasites Immunologic events


ALTERATIVE INFLAMMATIONS Necrotic hepatitis (diffused and miliar)

Definition: An alterative inflammation of the liver characterized by the necrosis of the cells in the affected area and the presence of a leukocyte reaction. Etiology: - Chemical factors (CCl4), toxic factors (aflatoxins). - biological agents: viruses (Adenovirus DIH - dog infectious hepatitis, chicken, turkey, Calicivirus - haemorhagic disease of rabbit (HDR), Picornavirus - youngducks, Parvovirus young geese, Herpesvirus Aujeski disease), bacteria (Necrobacilosis, Leptospirosis, Clostridiosis, Campilobacteriosis, Salmonelosis, Pasteurelosis, Colibacilosis, Listeriosis, Chlamidiosis a.o.) and parasites (Trichomonas, Histomonas) Gross lesions: Diffuse (Rabbit Calicivirus) - lobulation evident - spread whitish color due to necrotized hepatocytes around the centrolobular area Large foci (Necrobacilosis Trichomonosis, Histomonosis) unique or multiple large necrotic foci (1-3cm) on the surface and in the parenchyma discoloration (yellow grayish area) friable and dry, surrounded by a congestive ring (red-violet) which delimits the healthy parenchyma Millar foci (fowl cholera, salmolesosis in young animals, Aujeski disease ) small (mm.), multiple, necrotic foci on the surface and in the hepatic parenchyma color: white-yellow

Microscopically findings: Diffuse necrotic hepatitis - destroyed liver architecture - coagulation necrosis mainly at the periphery of the lobules (cells are pale, with nuclei like shadows) - remains of necrotized cells - presence of inflammatory cells: mainly neutrophils and macrophages Miliar necrotic hepatitis -areas of pale color (coagulation necrosis) with inflamatory infiltrate, congestion and remains of the distructed cells

Evolution : depends on the etiological agent, extent of necrosis and animal resistance. The main possibilities of evolution are: - destruction of a large surface of the liver acute liver insufficiency death (DIH, HDR) - healing ad integrum (in case of small necrotic foci, and when the causing agent stops acting) - fibrosis cirhosis (larger areas of necrosis) - infection of the necrotic area (with formation of abscesses or gangrenes).


Chronic gastric ulcer (Chronic ulcerative gastritis)

Definition: is a excavation of the stomach surface due to mucosal necrosis which penetrates the muscularis mucosae and muscularis propria, produced by acid-pepsin aggression or by other factors. Gastroduodenal ulcer produces signs much less often in animals than in humans. The pathogenesis of peptic ulcer in both humans and animals in general seems to resolve into a relative imbalance between the necrotizing effects of gastric acid and pepsin on one hand, and the ability of the mucosa to maintain its integrity on the other . Impairment of mucosal integrity in the face of normal acid secretion is probably the predominant mechanism, although there are clear instances when hypersecretion of acid is causative. Etiology: 1. Factors implicated in hypersecretion of acid include: - abnormally high basal secretion, - increased histamine levels associated with mastocytosis or mastocytoma - Gastrinomas (Zollinger Ellison syndrome), rare gastrin-secreting tumors 2. Ulceration due to compromise of mucosal protective mechanisms attributed to: Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, phenylbutazone, indomethacin, naproxen, ibuprofen, flunixin meglumine, and pyroxicam. In humans, gastritis associated with Helicobacter pylori infection, and duodenal colonization with this agent, are associated with development of duodenal ulcer. Helicobacter-associated gastritis extending cranially in the stomach is associated with gastric ulcer. Similar associations between Helicobacter infection, gastritis, and peptic ulcer have not been demonstrated convincingly in domestic animals. Reflux of duodenal contents containing bile salts Glucocorticoids in high doses as antiinflammatory, immunosuppressive, or antineoplastic therapy "Stress"; trauma or major surgery; in dogs following spinal trauma Administration of methylprednisolone sodium succinate to dogs. Abomasal ulcers in cattle are common. Gastric ulcer in swine is usually restricted to the pars esophagea. In horses, ulcers in the stomach of.foals and adults are often found at autopsy incidental to some other disease process. Grossly, whatever the cause, the results of a breach of the gastric glandular mucosa have the potential to follow a common pathway to ulceration in all species . Acute superficial lesions, such as those associated with stress or following administration of aspirin, are often seen as areas of reddening and hemorrhage, especially along the margins of rugae in the fundic mucosa. Acid treatment of haemoglobin gives blood on the surface or in the gastric lumen a red-brown or black color. In some instances, melena, presumably the result of a recent episode of gastric bleeding, may be present in the lower intestine , with minimal gross evidence of hemorrhage or ulceration in the stomach. The microscopic lesion associated with hemorrhage of this type is often subtle; bleeding seemingly results from diapedesis, with minimal mucosal damage. Lesions of any genesis proceeding to gastric ulcer do so by progressive, often rapid, coagulative necrosis of the gastric wall. Ulcers vary in microscopic appearance depending on their aggression, and the point in their development at which they are intercepted: 20

Acute gastric lesions appear as erosions with superficial eosinophilic necrotic debris and loss of mucosal architecture to the depths of the foveolae, or as a depression in the mucosal surface with necrotic debris at the base. Necrosis usually extends rapidly to the muscularis mucosae, causing ulceration. - Subacute to chronic ulcers have a base and sides composed of granulation tissue of variable thickness and maturity, infiltrated by a mixed inflammatory cell population, and overlain by a usually thin layer of necrotic debris. The layer of granulation tissue may be thick and mature, or thinner, less mature, and with superficial evidence of recent necrosis. There is mucous metaplasia and hyperplasia in glands at the periphery of the ulcer, epithelial cells may gradually migrate across, closing the defect. Thrombosed arterioles and venules are often seen, associated with anemia or obvious hemorrhage. Signs associated with peptic ulcer include: variable appetite, abdominal pain, vomition, melena, and anemia. Evolution: Ulcers attaining the submucosa impinge on arterioles of increasing diameter, multiplying the risk of significant gastric hemorrhage. The ulcer may progress through the muscularis and serosa, culminating in perforation of the gastric wall with consecutive peritonitis or/and death. Perforating duodenal ulcer may instigate pancreatitis. Pyloric and duodenal stenosis has been associated with healing ulcers, as well as anemia.

EXUDATIVE INFLAMMATIONS Fibrinous pneumonia (Lobar pneumonia)

Definition: A predominantly exsudative inflammation of the lung produced mainly by bacterial agents. It is characterized by the formation at the level of epithelium, serosa and parenchyma of some false fibrin membranes (whitish with dirty-yellow nuances, sometimes brown if they are infiltrated with neutrophils). These membranes do not adhere to the deep plans, and can be easily detached or expectorated by cough (tracheo-brochial localisation). Etiology: The disease is produced by bacterial germs: Pasteurella spp., Mycoplasma spp., Bordetella spp, Haemophilus spp., Bordetella spp., Corynebacterium spp, Staphylococus spp.. Fibrinous pneumonia has a gradually evolution, both grossly and histologically. Due to the different stage evolution, the lung can present different aspects (stages) even from lobule to lobule, thus giving the mosaic aspect of the lung (grossly). The following stages, are representative for the evolution of fibrinous pneumonia in horses, where the different stages are easier recognized, due to the lungs anatomo-histology.


Gross lesions: Stage I - Pulmonary congestion and oedema - the lungs are wet, heavy, the colour is red or burgundy and consistency is increased - in trachea, bronchi and pulmonary tissue is present a pink or red foamy fluid

Microscopically findings: Stage I -hypertrophy of alveolar interstitial space due to excessive dilation of blood vessels; - in alveoli is present an homogenous acidophilic edema fluid and air bubbles

Stage II Stage II - Red hepatization consolidation of tissue into a liverlike mass, -presence of red (oxifil) fibrin masses in the alveolar lumen, with rare blood cells with a red-brown color -septal congestion Stage III - Gray hepatization Stage III - consolidation of tissue into a liverlike mass, with -presence of red fibrin masses in the a brown-graysh colour alveolar lumen, with abundhent leucocytes -mild septal congestion Stage IV - Resolution stage - Soft-pasty consistency, gray-yelowish colour - On section, a pus-like liquid is expressed More stages can co-exist on an animal Stage IV -fibrin is destroyed and alveolar content is represented by cells, neutrophils and macrophages, old/necrotized cells,

Evolution : - death-due to asfixia, septicemia or other complicatins - spontaneous resolution rarel - necrosis with incapsulation of the affected area - supuration - sclerosis - obstructive bronchiolitis *** In our slides we observe also a superposed bacterial infection. Thus, beside septal congestion and the red fibrin masses with mononuclear cells in the alveolar lumen, we also have present an important purulent exudate in the lumen of bronchioles and in the surrounding alveoles.

Purulent (suppurative) leptomeningitis

Definition: Inflammation of leptomeninges which is caused by a variety of purulent bacteria. Leptomeningitis can be classified according to etiology (e.g., bacterial, mycotic), according to duration (e.g., acute, chronic), and according to the type of exudates (e.g., fibrinous, purulent). Classification by type of exudate is very useful, not only because it indicates the expected histologic lesions, but also clinically because it indicates the possible etiology. Purulent meningitis is by far the most common meningitis in domestic animals, especially neonates. Purulent leptomeningitis may arise: 22

by direct extension from an adjacent structure. Extension from an epidural abscess or inflammation may result in diffuse leptomeningitis but, in most of the few cases of this origin, the leptomeningitis is local and overshadowed by the brain abscess that usually forms by local extension from a brain abscess, either by direct permeation or by spread in the Virchow-Robin spaces (in listeriosis and in association with very large cerebral abscesses) by hematogenous origin, thromboembolic lesions and leptomeningitis complicated by choroiditis, lymphogenous infection (rarely). Etiology: Lysteria spp., E. coli., Streptococus (suis, pneumonie), Staphylococcus, Haemophylus, Pneumococus, Salmonella spp., Mannheimia haemolytica and P. multocida. Once infectious agents gain access to the leptomeninges there is little resistance to spread in the meningeal spaces, and the inflammatory process becomes more or less diffuse in most cases. The apparent gross distribution of meningitis varies somewhat with the cause. In the first day or so of suppurative meningitis before exudation is clearly recognizable, the meninges may be faintly opaque and hyperemic. After a few days, the appearance of the brain and cord is typical. The basal cisterns that accumulate the most exudate are filled with creamy pus or with gray-yellow fibrinopurulent exudate. The extreme exudation in these cisterns is due in part to their large size but in part also to sedimentation of particulate exudate. The exudate is in the arachnoid spaces and there is little if any on the outer surface of this membrane. The arachnoid appears stretched. It is easy to overlook even copious exudates because their color is not very different from that of the brain . A useful clue is that even the largest basilar vessels and the trunk of the oculomotor nerve are partially or completely buried and obscured by exudate. Over the hemispheres the exudate is usually confined to the fissures, where the arachnoid space is wide, and spares the surfaces of the gyri, where the arachnoid space is narrow. The severe degree of exudation described above is what is usually seen in animals. On careful inspection by naked eye, almost every case of purulent meningitis can be detected but the microscope may be necessary to confirm some cases. The brain is swollen in every acute case of pyogenic meningitis, and the swelling is frequently severe enough to cause displacement with coning of the cerebellum. The edema affects the white matter. It is possible that obstruction of the meningeal orifices of VirchowRobin spaces by exudate and stasis of flow of meningeal fluid may contribute to the edema. The brain itself is normal except for softness and swelling and the rare cortical infarcts in the cerebrum or cerebellum. Microscopically, purulent meningitis does not differ in its character from pyogenic inflammation in other loose tissues, such as the lung. A few mononuclear cells are mixed with a very large number of neutrophils in the arachnoid spaces acompanied by hyperemia of meninges. The amount of fibrin in the exudate varies. There may be some infiltration for a short distance along the Virchow-Robin spaces about veins. The pia mater as a rule remains intact, and it is only in exceptional cases that some microbial activity is observed in the adjacent parenchyma, or the pia is eroded to allow neutrophils to invade the surface of the brain, showing spongy change or vacuolization due to edema. Evolution/Complications: meningitis spreads to the brain and cord. 23

Whether encephalitis develops by spread of meningitis may be largely a question of time. Internal hydrocephalus is a sequel to ependymitis and occlusion of the aqueduct, as a result of which the lateral and third ventricles are dilated. Chronic pyogenic leptomeningitis is rarely observed in animals. The process may sterilize itself or be sterilized by antimicrobials, but much of the injury is established in the early stages of the process and, once the diagnosis is evident clinically, death is the expected outcome. The early injury is exaggerated by the persistence of exudate even after the infection is controlled because there is no free drainage from the meningeal spaces. Healing occurs only after there has been considerable destruction of the meningeal framework with repair by fibrous tissue.

Pulmonary abscess
Definition: a collection of pus that has accumulated in a cavity formed by the tissue on the basis of an infectious process, usually caused by bacteria. Etiology: - Anaerobic and aerobic bacteria: Bacteroides, Fusobacterium species, Streptococcus spp., Staphylococcus, Klebsiella, Haemophilus, Pseudomonas,Nocardia, Escherichia coli, Streptococcus, Mycobacteria. - Fungi: Candida, Aspergillus. - Parasites: Entamoeba histolytica. Pulmonary abscesses usually arise either from chronic bronchopneumonia or from septic emboli lodging in the pulmonary vessels. A cranioventral location and associated bronchiectasis are evidence of origin from bronchopneumonia. Multiple, widely distributed abscesses usually indicate hematogenous origin and are often associated with an obvious source of septic emboli elsewhere in the body, such as endocarditis or hepatic abscesses with phlebitis of the hepatic vein in cattle. The occurrence of abscesses in other tissues supports a hematogenous route of infection. Other causes of pulmonary abscess include aerogenous fungal infections that often have a disseminated pattern, aspirated foreign bodies such as plant awns, direct traumatic penetration of the lung, and specific hematogenous infections such as caseous lymphadenitis and melioidosis. It is often impossible to determine the pathogenesis of isolated abscesses, if lesions are not identified in other tissues. Gross lesions: usually round or oval shape collection of pus, well delimited by fibrous membrane, with different colors (yellow, black, green-blue). Presence of purrulent material on the cut surface. Microscopically findings: There are 3 typical areas: 1. necrotic purrulent area in the centre with granular aspect(dead cells, neutrophils, and bacteria) 2. leucocyte barier (neutrophils and macrophages) 3. fibrous membrane Evolution: Abscesses may erode through the pleura to cause empyema, through blood vessels to cause massive blood loss, or into a bronchus to cause fatal airway obstruction or fulminant suppurative bronchopneumonia. Complications: septicemia, metastasis, membrane lysis (internal or external). Healing by fibrosis/calcification. 24


Taeniid tapeworms Taeniid cestodes are the most important tapeworms in domestic animals, not because of the effects of the adult worm in the carnivorous definitive host, but rather due to the metacestodes, or larval forms, in intermediate hosts. Single oncospheres hatch from the egg in the upper small intestine, penetrate the epithelium, and are carried in the portal blood to the liver. Some species of metacestodes migrate in the liver, eventually to enter the peritoneal cavity. Others persist to develop in the liver, while still others pass on to the heart, lungs, and systemic circulation, establishing in muscle or a variety of other sites and tissues. Metacestodes may occasionally be found in organs other than the site of predilection. Taeniid metacestodes assume four basic forms. - The cysticercus is a fluid-filled, thin-walled, but muscular cyst, into which the scolex and neck of a single larval tapeworm are invaginated. - The strobilicercus is a modification of this theme; late in larval development the scolex evaginates and is connected to the terminal bladder by a segmented strobila, so that it resembles a tapeworm, several centimeters long. - The coenurus is a single or loculated fluid-filled cyst, in which up to several hundred nodular invaginated scolices are present in clusters on the inner wall. Each scolex is capable of developing into a single adult cestode in the intestine of the definitive host. - The hydatid cyst is a uni- or multilocular structure, on the inner germinal membrane of which brood capsules develop. Within the brood capsules, invaginated protoscolices form. Brood capsules may float free in the cyst fluid, where they are termed "hydatid sand." Internal daughter cysts can develop. Release of brood capsules or protoscolices into tissues, as a result of rupture of the hydatid cyst, may lead to development of new cysts. The alveolar hydatid cyst proliferates by budding externally. Echinococcus spp. tapeworms occur in the small intestine of a number of species of carnivores, predominantly canids. In enzootic areas, the distinctive metacestodes, or hydatid cysts, are commonly found in normal or accidental intermediate hosts. Humans may accidentally become infected with the metacestode, and echinococcosis or hydatidosis is a significant public health problem where carnivores shedding Echinococcus eggs come in close contact with humans. The species are E. granulosus, E. multilocularis, E. oligarthus, and E. vogeli. The latter two involve sylvatic cycles in Central and South America, with felids and canids as definitive hosts respectively, and rodents as intermediate hosts in which polycystic hydatidosis occurs; E. uogeli may infect humans.The other two species may use domestic animals as definitive hosts, and will be considered further here. E. granulosus uses the dog and some other canids as the definitive host. The most widespread strain or genotype uses a sheep--dog cycle, and has been disseminated wherever there is pastoral husbandry of sheep. It is significant as a potential zoonosis in many parts of Eurasia and the Mediterranean region, some parts of the UK, North America, South America, continental Australia, and Africa. Eradication has been accomplished, or virtually so, in Iceland, New Zealand, and Tasmania. Other cycles affecting domestic animals include horse-; cattle-; camel-; pig-; water buffalo-; goat-, and human-dog. Sylvatic cycles include: in Eurasia 25

and North America, cervid-wolf~ in Argentina, hare-fox; in Sri Lanka, deer-jackal; in Australia, macropod- dingo. Not all cycles represent different genotypes. In the small intestine of the definitive host, protoscolices evaginate and establish between villi and in the crypts of Lieberkuhn. The scolex distends the crypt and the epithelium is gripped by the suckers and occasionally eroded, but there is little or no inflammatory response. The worms that develop are short, usually less than 6-7 mm long. They commonly have only 3-5 proglottids, the caudal gravid one making up almost half the length of the worm. Enteric signs are not normally encountered in dogs with intestinal hydatid tapeworms. Penetration of oncospheres released from eggs in the intestine of the intermediate host takes them into the subepithelial capillaries, or perhaps the lacteal. The majority probably migrate via the liver, some carrying on to the lungs and general circulation. However, those gaining the lacteal may bypass the liver, entering the vena cava with the lymph, and either are filtered out in the pulmonary circulation or are disseminated. Hydatid cysts occur most commonly in the liver and lung, with some strain and host species variation in the relative prevalence in these organs. In sheep they may be more common in lungs, while in cattle and horses, the liver is the usual site of establishment. Less commonly in domestic animals, the brain, heart, bone, and subcutaneous tissue may be sites of development of hydatid cysts. A single cyst, or up to several hundreds, may be present, displacing tissue in infected organs. Disease is rarely attributed to hydatidosis in animals, even in those heavily infected. However, strategic location of one or more cysts may lead to heart failure, bloat or central nervous signs. Condemnation of infected organs at meat inspection causes economic loss. Gross lesions: Hydatid cysts are usually spherical, turgid, and fluid-filled. They usually measure 5-10 cm in diameter in domestic animals; rarely, cysts in animals may be larger, but in humans hydatid cysts can become huge. On the other hand, some fertile cysts in equine livers may be as small as 2-3 mm across. The lining of fertile cysts is studded with small granular brood capsules, which contain protoscolices; and"hydatid sand," comprised of free brood capsules and protoscolices, is in the fluid. The lining of sterile cysts is smooth. Though the potential exists for development of internal daughter cysts, and rare exogenous budding by herniated cysts, most hydatid cysts in domestic animals are unilocular. However, they may be irregular or distorted in shape due to the variable resistance of parenchyma and portal tracts or bronchi and by the profiles of bone or other resistant tissues. Microscopically, immature hydatid cysts are surrounded by an infiltrate of mixed inflammatory cells, including giant cells and eosinophils. As they develop, a layer of granulation tissue, which may contain round cells and eosinophils, invests the cyst, and this evolves so that the inner portion of the fibrous capsule is comprised of mature collagenous connective tissue that is relatively acellular. Within this, and in close apposition, is the acellular lamellar hyaline outer layer of the hydatid cyst wall, comprised of a polysaccharideprotein complex, which, with time, may become hundreds of micrometers thick. The cyst is lined by the thin syncytial germinal layer from which the brood capsules form on fine pedicles. If the cyst is ruptured and protoscolices are released into tissue, secondary cysts may form from them. Evolution: Hydatid cysts may degenerate.The inner structures collapse, and the mass becomes caseous and may mineralize. Degenerate hydatid cysts grossly may resemble tuberculous lesions or metastatic squamous cell carcinoma. Death following the break (due to anaphylactic shock) could also occur, and paresis or paralysis due to nerve compression is another possibility.


This is a disease mainly of cattle, sheep, and pigs, leading to stomatitis, glossitis, lymphadenitis, and sometimes pyogranulomas in the wall of the forestomachs of ruminants. Actinobacillus lignieresii is part of the normal oral flora, and in cattle is associated with deep stomatitis. When introduced into the submucosa, it causes pyogranulomatous inflammatory loci centered on club colonies containing gram-negative coccobacilli. Morphologically similar lesions may be caused by a variety of organisms. Arcanobacterium pyogenes may be isolated from lingual ulcers and granulomas in lambs. Microscopic examination of these lesions reveals well-demarcated submucosal granulomas with plant fibers in the center, surrounded by a marked neutrophilic reaction. The organisms most likely gain entry after the mucosa is damaged by hard fibrous plant fibers from the weed lambsleeve sage (Salvia reflexa), present in the bedding. Actinomyces bovis, a gram-positive filamentous organism, causes pyogranulomatous mandibular and maxillary osteomyelitis in cattle, and mastitis in sows. Staphylococci may cause pyogranulomatous lesions (botryomycosis) in any species, especially mastitis in sows. Less common causes of similar microscopic lesions include Nocardia and the various agents associated with mycetomas Gross lesions: Actinobacillosis is typically a disease of soft tissue, spreading as a lymphangitis and usually involving the regional lymph nodes. This distinguishes it from actinomycosis, which causes bone lesions. The tongue is often involved in actinobacillosis, and the chronic condition produces clinical "wooden tongue." Entry of actinobacilli to the tongue may be gained through traumatic erosions along its sides, but often the primary lesion is in the lingual groove. Here, trapped grass seeds and awns may provoke the initial trauma. Lesions elsewhere in the soft tissue of the mouth may be attributed to disruption of the mucosa by similar types of insults, and eruption of, or abrasion by, teeth. Although actinobacillosis in cattle is best known as a disease of the tongue, the infection may occur in any of the exposed soft tissues, especially those of mouth and esophagus; occasionally it involves the wall of the forestomachs, the skin, or the lungs. Lesions in these sites resemble those described in the tongue. Actinobacillosis causes regional lymphadenitis. The cut surface of the node reveals small, soft yellow or orange granulomatous masses, which project somewhat above the capsular contour and which contain "sulfur" granules.There is also sclerosing inflammation of the surrounding tissues, which may cause adhesion to overlying skin or mucous membranes. The retropharyngeal and submaxillary nodes are most often affected, as well as the lymphoid tissues of the submucosa of the soft palate and pharynx. Involvement of the pharynx and the retropharyngeal lymph nodes may cause dyspnea and dysphagia. Microscopically, the lesion is a pyogranuloma, centered on a mass of coccobacilli, surrounded by radiating eosinophilic clubs made up of immune complexes. The club colonies, in turn, are surrounded by variable numbers of neutrophils, and are invested by macrophages or giant cells. Lymphocytic and plasmacytic infiltrates are present in the surrounding reactive fibrous stroma or granulation tissue. An individual inflammatory focus appears grossly as a nodular, firm, pale, fibrous mass a few millimeters to 1 cm in diameter, containing in the center minute yellow "sulfur" granules, which are the club colonies. Lymphogenous spread is common. Affected lymphatics are thickened, and nodules are distributed along their course. This distribution is best seen beneath the mucosa of the dorsum and the lateral surface of the tongue and often can be traced through to the pharyngeal lymphoid tissue. Some of these more superficial nodules erode the overlying epithelium, and coalescence may produce quite large ulcers. The most common form of lingual 27

actinobacillosis consists of granulation tissue in which are embedded many small abscesses surrounded by a dense connective tissue capsule. The epithelium overlying these large granulomas may be intact or ulcerated. Diffuse sclerosing actinobacillosis of the tongue (wooden tongue) is firm, because of extensive proliferation of connective tissue, which replaces the muscle fibers. Granulomatous nodules are sparsely scattered in the fibrous stroma. Oral actinobacillosis in swine causes lesions similar to those in cattle, including glossitis. Actinobacillosis may also occur sporadically or as outbreaks in sheep, but in this species the tongue seems to be exempt. The characteristic lesions in sheep occur in the subcutaneous tissue of the head, especially of the cheeks, nose, lips, and submaxillary and throat regions, and on the nasal turbinates. They may also occur on the soft palate and pharynx as complications of wounds received at drenching. The organism has been isolated from a horse with a greatly enlarged tongue. Evolution: fibrosis, fistulization, wooden tongue.

Bovine tuberculosis, caused by Mycobacterium bovis, is a chronic disease characterized by caseating granulomas in lung, lymph nodes, and other organs. Control programs have minimized the occurrence of bovine tuberculosis in many developed countries. The disease is rare in Canada, the USA, and Australia, although infected wildlife reservoirs remain and cases continue to occur in domestic livestock. Most recent reports of bovine tuberculosis in the USA and Canada have occurred in farmed cervids or in localized geographic areas. In most of Europe, fewer than 0.4% of herds are infected, but the prevalence is higher in Ireland, Spain, and Italy. In contrast, bovine tuberculosis is endemic in New Zealand and many, but reportedly not all, countries in Africa, Asia, Central and South America; 10-35% of herds are infected in many of these endemic areas. In many countries, the success of tuberculosis eradication schemes is complicated by wildlife reservoirs, which maintain infection and transmit disease to cattle. Many mycobacteria persist in soil for prolonged periods, and the infectivity of M. bovis is likely maintained for several weeks in the environment. However, because oral infections require high doses of bacilli, the importance of environmental survival in the epidemiology of disease is likely limited. The classical tubercle bacilli are - M. tuberculosis (human), - M. Bovis (bovine), and - M. avium (avian) . Two other closely related species are M. microti from voles and M. africanum. Differing strains of M. Avium are now commonly included with strains of the very closely related M. intracellulare as the M. avium-intracellulare complex. To avoid confusion surrounding the term tuberculosis, convention limits it to diseases caused by M. tuberculosis or M. bovis. The three main species of tubercle bacilli, M. tuberculosis, M. bovis, and M. avium, occur most frequently in their respective hosts, but cross-infections do occur and various other species of animals are affected. Bovine tuberculosis refers mainly to disease in cattle caused by Mycobacterium bovis, but the term is also used to describe the pathogenic effects of this agent in other hosts. The host range of M. bovis is broad, including cattle, deer, elk, bison, buffalo, goats, camels, 28

llamas, swine, elephants, rhinoceros, dogs, foxes, cats, mink, badgers, and nonhuman and human primates. Natural diseases most common in cattle, cervids, humans, and swine. M. avium causes mycobacteriosis chiefly in birds and is occasionally found in cattle, swine, horses, sheep, and monkeys. M. tuberculosis is chiefly responsible for tuberculosis in humans, and occasionally infects pigs, captive monkeys, dogs, cats, cattle, and psittacine birds. Transmision: Human infections with M. bovis are well documented, but are much less common than M. tuberculosis. Immunosuppressed individuals, such as those with the acquired immunodeficiency syndrome (AIDS), are at particular risk. Ingestion of milk from cows with mammary tuberculosis is a major route of infection in humans, typically inducing cervical lymphadenitis or other nonpulmonary forms of disease. This pattern of disease is of great historical importance as the impetus for identification of the tubercle bacillus and the subsequent pasteurization of milk, but infection from raw milk continues to occur in regions where bovine tuberculosis is common. Transmission from cattle to humans by aerosol or by contamination of cutaneous wounds also occurs, most frequently in those in close contact with infected cattle. Mycobacteria are nonmotile, nonspore-forming pleomorphic coccobacilli. They are gram-positive but almost unstainable by the simpler bacterial stains because of their high content of lipids. They are routinely stained with carbol-fuchsin, and then resist decoloration by inorganic acids. This property of acid-fastness of the stained bacilli depends on the amount and spatial arrangement of mycolic acids and their esters in the bacterial wall. In addition to the cell membrane and peptidoglycan layers found in other bacteria, the mycobacterial cell wall contains a large hydrophobic layer of mycolic acids, which bestows hydrophobicity on the cell wall, conferring environmental and antimicrobial resistance. The waxes and cell wall glycolipids are important inducers of the initial macrophage response and, together with peptidoglycan (muramyl dipeptide), are responsible for most of the adjuvant activity of mycobacteria that facilitates recruitment of antigen-presenting cells. Increased glycolipid content of mycobacterial cell walls, acid-fastness, and the amount of trehalose dimycolate (cord factor) in the cell wall are associated with increased virulence. Other glycolipids (mycosides) appear to form a barrier against lysosomal digestion and partly explain the ability of the organisms to survive after phagocytosis by macrophages. Intracellular survival is also facilitated by preventing fusion of phagosomes and lysosomes. The differing effectiveness of such mechanisms determines the relative ability of various mycobacteria to resist intracellular degradation. Tuberculoproteins are the other major category of immunoreactive substances in mycobacteria. They provide most of the antigenic determinants, but the adjuvant activity of the lipids and polysaccharides in the mycobacterial cell wall is needed for an animal to produce an immunologic response to these tuberculoproteins. Purified protein derivatives (PPD) from mycobacteria are capable of eliciting delayed-type hypersensitivity once the animal is sensitized, however, and this is the basis of tuberculin testing. Both tuberculoproteins and the adjuvant lipids are present in infection, and the result is the development of both humoral and cell-mediated immune responses. Humoral antibodies can be demonstrated by serologic techniques, but do not participate in the development of lesions or in the production of immunity. Cell-mediated responses are responsible for both aspects of the disease. The method of transmission influences the spectrum of lesions of bovine tuberculosis. Inhalation of droplet nuclei or dust particles containing M. bovis is the most common route of infection and leads to infection of the upper and lower airways. Oral infection requires a greater dose of bacilli than airborne infection to cause disease, and elicits lesions in the gut and associated lymph nodes. Transplacental transmission is a sequel of endometrial 29

tuberculosis, and leads to fetal lesions in hepatic and portal lymph nodes. Less common routes of infection include percutaneous inoculation, genital transmission, and intramammary infusion of contaminated pharmaceutical preparations. Important concepts in the pathogenesis of tuberculosis include the ability of mycobacteria to survive within macrophages, and the role of cellular immune responses in inciting granulomatous inflammation and enhancing the ability of macrophages to kill bacilli . Most animals that are infected with M. bovis do not develop clinical disease. The outcome of infection depends on bacterial factors, including the dose and virulence of infecting bacteria, but also on host factors, including the state of immune competence and heritable resistance to tuberculosis. Heritable variation in disease susceptibility has been identified in cattle and in deer. In the early phases of infection, bacilli are phagocytosed by macrophages and may be eliminated. Alternatively, infected macrophages may remain at the site of primary infection for prolonged periods before the disease progresses. An initial innate immune response develops at this site of primary infection, as macrophages secrete cytokines particularly tumor necrosis factor-or and the C-C chemokines that recruit additional macrophages and lymphocytes to the site. Macrophages stimulated by exposure to mycobacteria secrete interleukin-12, which skews the immune response to favor secretion of interferon-y and interleukin-2 by CD4+ T-helper-1 lymphocytes. These interferon-Tproducing T-helper lymphocytes signal the development of cell-mediated immunity, first detected at 14-28 days after infection by positive tuberculin skin test reactions. The arrival of these antigen-specific lymphocytes is crucial for host defense, activating macrophages and thus allowing them to overcome the block in phagosome maturation, and upregulate production of bactericidal products, including reactive nitrogen and oxygen intermediates and lysosomal enzymes, killing intracellular bacilli. Activated macrophages appear epithelioid, with abundant cytoplasm and indistinct cell borders, or form multinucleate giant cells. The cytokines tumor necrosis factor-alpha and interferon- gamma act synergistically to promote formation of the tuberculoid granuloma, a dynamic structure that prevents spread of infection to other sites in the lung, as well as animal-to-animal transmission, and represents a localized target for the immune response. Excessive tissue-damaging cell-mediated immune response, called delayed-type hypersensitivity, kills heavily infected macrophages, forming the caseous center of the granuloma. Matrix metalloproteinases released from activated macrophages are a likely cause of the characteristic cell necrosis and liquefaction of tissues in some lesions of tuberculosis. Bacilli within the caseous center do not multiply but may remain dormant as latent infections that may persist for years, until immunosuppression caused by diseases, drugs, hormones, or malnutrition, or other unidentified factors disturb the balance between host and agent, allowing proliferation of the pathogen and reactivation of the disease. Whether the delayed-type hypersensitivity reaction is benefidal or harmful to the host depends on the circumstances. On the one hand, the reaction to relatively small numbers of bacilli causes accelerated tubercle formation that enhances the killing of the organisms, and helps prevent reinfection or dissemination from the initial site of infection. On the other hand, the delayed-type hypersensitivity response to large amounts of mycobacterial antigen causes extensive cell necrosis and tissue destruction, which is seriously detrimental. Liquefaction, brought about by hydrolytic enzymes of macrophages and possibly neutrophils, is the most harmful response. The bacilli multiply extracellularly in the liquefied material and are available in large numbers for dissemination through cavities, vessels, and airways. In summary, the final determinants of the nature and intensity of lesions are the magnitude of the bacterial infection, the intensity and appropriateness of the immune response, and the modifying influences of the structure of the tissue involved. Gross or histologic lesions are absent in many cattle that react to tuberculin skin tests, and although M. bovis cannot be isolated from many of these cases, they are generally 30

considered to be infected for the purposes of epidemiology and control. Thorough examination of lymph nodes throughout the body is necessary before declaring a carcass free of visible lesions; only a single lesion is present in most cattle with gross lesions of tuberculosis. The distribution of lesions of bovine tuberculosis depends on the mode of transmission. In most cases, gross lesions are restricted to the respiratory tract and associated lymphoid tissues. Tubercles or craterous ulcers in gut or mesenteric lymph nodes suggest an oral route of infection, or ingestion of infected sputum that has been coughed up from the lung. Generalized disease is less common but well described. In respiratory infections, lesions are most common in retropharyngeal, bronchial, and mediastinal lymph nodes, and less frequent in mandibular and parotid lymph nodes and palatine tonsils. Lung lesions are detected in only 10-20% of cattle with gross lesions, andoften affect the caudal lobes. The classic gross lesion is the tubercle: a circumscribed, often encapsulated, 1-40 mm diameter, pale-yellow or white focus of granulomatous inflammation, often with caseous necrosis and~or mineralization. Larger lesions may contain liquefied or suppurative exudate and be mistaken for abscesses caused by pyogenic bacteria. Bacilli are released from expanding tubercles into the airways, and coughing up of infected sputum may spread the infection by ingestion to cause lesions in intestine or mesenteric lymph nodes, by adhesion to laryngeal or tracheal mucosa to incite ulcers or ulcerating tubercles, or by aspiration to seed secondary sites in the lung. Erosion of pulmonary tubercles through the pleura may result in implantation of bacilli throughout the pleural cavity, with development of multiple granulomas on pleural surfaces. Lymphatic spread has been suggested as an alternative route of pleural infection. Generalized lesions are reported in about 1% of animals with gross lesions of tuberculosis, and probably result from hematogenous dissemination of bacilli following erosion of the wall of a blood vessel by an expanding tubercle. Embolic lesions are most common in lung, and may involve lymph nodes, bone, liver, kidney, mammary gland, uterus, pleura, peritoneum, pericardium, and meninges . Lesions are rare in salivary gland, pancreas, spleen, brain, myocardium, or muscle. In some instances, presumably following substantial release of bacilli into the blood, the presence of innumerable tiny white loci justifies the term "miliary tuberculosis." In contrast, other carcasses display generalized lesions that are variable in size and degree of caseation or fibrosis, and imply a less catastrophic but more prolonged bacteremia. Erosion through serosal or mucosal surfaces by expanding tubercles spreads the infection by implantation on pleural, peritoneal, pericardial, or meningeal surfaces or along the airways, intestine, or urinary tract. Microscopically findings: Histologic features of the tubercle include: - (1) a central coagulum of caseous necrosis, consisting of eosinophilic homogeneous material with scant nuclear debris and a variable degree of mineralization; - (2) a mantle of macrophages and Langhans-type multinucleate giant cells; - (3) a capsule containing lymphocytes, clusters of neutrophils in some cases, and a rim of collagenous connective tissue in chronic lesions; and - (4) rare to numerous acid-fast bacteria within macrophages and giant cells of the mantle zone or extracellularly in the caseous core. The amount of fibrosis increases with time, and tends to be more prominent in individuals and species with greater resistance. The presence of neutrophils is highly variable, and their presence in large numbers is most common in cases with rapid multiplication of bacteria, numerous reactive lymphocytes, and easily distensible tissues. Tuberculosis in horses is often alimentary, with lesions in retropharyngeal and mesenteric lymph nodes and intestine. Intestinal infection may cause localized ulcers or thickened mucosal lesions reminiscent of Johne's disease in cattle. Tubercles in horses are 31

usually uniform, gray, smooth (lardaceous), with little caseation or mineralization but abundant fibrosis, and may resemble sarcomas. Tuberculosis in small ruminants is rare, but similar in most respects to the disease in cattle. Tuberculosis in swine is often systemic, and the morphology depends on the infecting pathogen. M. bovis produces caseous and mineralized tubercles similar to those that occur in cattle, and the lesions are often surrounded by a fibrous capsule. In the liver, there is a tendency for the caseous centers to liquefy. M. avium produces lesions that are proliferative in nature and consist of tuberculous granulation tissue resembling the lardaceous or sarcomatous lesions described in equine tuberculosis. The histologic appearance is of infiltration of macrophages, epithelioid cells, and Langhans' giant cells accompanied by extensive fibroplasia and numerous bacilli. Tuberculosis in dogs and cats usually appears as granulation tissue in which macrophages are scattered at random and giant cells are rare. Discrete tuberculous granulomas are uncommon, and composed principally of epithelioid cells surrounded by narrow zones of fibrous tissue in which there are scattered small collections of lymphocytes and plasma cells. Necrosis is often present in the centers of larger granulomas. Giant cells are rare. The presence of central necrosis and fairly small numbers of acid-fast bacilli in lesions of cats helps to distinguish lesions of tuberculosis from those of feline leprosy. The primary foci in the lungs of dogs develop in most cases in the dorsal part of the caudal lobes. Dissemination within the lungs occurs quite rapidly and is predominantly intrabronchial with the production of tuberculous bronchitis and bronchiolitis rather than bronchopneumonia. Pleuritis or peritonitis often accompanies primary infections in the lungs or intestine, respectively, with diffuse or fine nodular pleural thickening by granulation tissue containing few macrophages and bacilli. A thorough necropsy examination is the most sensitive method of detecting tuberculosis after death, as the likelihood of isolating M. bovis in culture is miniscule if gross lesions are not detected. Gross lesions of focal caseous lesions in lymph nodes or lung, or histologic detection of granulomas, particularly with central areas of necrosis and/or mineralization, should prompt an extensive and thorough search for acid-fast bacilli. A finding of low numbers of bacilli is more suggestive of bovine tuberculosis than of mycobacteriosis caused by M. avium. However, bacterial culture using egg-based or agar-based media enriched with serum or blood is the gold standard for definitive diagnosis of bovine tuberculosis, particularly if the diagnosis is likely to have a serious impact. Specimens should be collected using sterile technique, to avoid contamination with environmental mycobacteria that may overgrow M. bovis in culture. Immunohistochemical identification of M. bovis has been described. This procedure is more sensitive than examining acid-fast-stained sections, in terms of number of animals detected, staining intensity, and ease of detection, but the antibodies in current use cross-react with other mycobacteria as well as some gram-positive bacteria and fungi.

REPARATORY PROCESSES (REGENERATION AND REPAIR) Healing by Repair, Scar Formation and Fibrosis
If tissue injury is severe or chronic, and results in damage of both parenchymal cells and the stromal framework of the tissue, healing cannot be accomplished by regeneration. Under these conditions, the main healing process is repair by deposition of collagen and other ECM (Extracellular matrix) components, causing the formation of a scar. 32

In contrast to regeneration which involves the restitution of tissue components, repair is a fibroproliferative response that patches rather than restores the tissue. The term scar is most often used in connection to wound healing in the skin, but is also used to describe the replacement of parenchymal cells in any tissue by collagen, as in the heart after myocardial infarction. Repair by connective tissue deposition includes the following basic features: inflammation angiogenesis, migration and proliferation of fibroblasts, scar formation connective tissue remodeling. Cutaneous wound healing represents the prototype repair process. Suffice to say here that regardless of site, the inflammatory reaction elicited by the injury contains the damage, removes injured tissue, and promotes the deposition of ECM components in the area of injury, at the same time that angiogenesis is stimulated. However, if the damage persists, inflammation becomes chronic, leading to an excess deposition of connective tissue known as fibrosis. In most healing processes, a combination of repair and regeneration occurs. The relative contributions of repair and regeneration are influenced by: (1) the proliferative capacity of the cells of the tissue; (2) the integrity of the extracellular matrix (ECM); (3) the resolution or chronicity of the injury and inflammation. Because of the great importance of angiogenesis in processes other than wound healing, we start with a discussion of the mechanisms of angiogenesis before considering the steps of cutaneous wound healing. Angiogenesis is a fundamental process that affects physiologic reactions (e.g. wound healing, regeneration, the vascularization of ischemic tissues, and menstruation), and pathologic processes, such as tumor development and metastasis, diabetic retinopathy, and chronic inflammation. Therefore great efforts have been made to understand the mechanisms of angiogenesis, and to develop agents that have pro- or anti-angiogenic activity. VEGF (vascular endothelial growth factor) is the most important growth factor in adult tissues undergoing physiologic angiogenesis (e.g., proliferating endometrium) as well as angiogenesis occurring in chronic inflammation, wound healing, tumors, and diabetic retinopathy.

Cutaneous wound healing is divided into three phases: 1. inflammation, 2. proliferation, 3. maturation. These phases overlap, and their separation is somewhat arbitrary, but they help to understand the sequence of events that take place in the healing of skin wounds. - The initial injury causes platelet adhesion and aggregation and the formation of a clot in the surface of the wound, leading to inflammation. - In the proliferative phase there is formation of granulation tissue, proliferation and migration of connective tissue cells, and re-epithelialization of the wound surface. - Maturation involves ECM deposition, tissue remodeling, and wound contraction. Types of regeneration: 1. The simplest type of cutaneous wound repair is the healing of a clean, uninfected surgical incision approximated by surgical suture. Such healing is referred to as 33

healing by primary union or by first intention (prima intentionem). The incision causes death of a limited number of epithelial and connective tissue cells and disruption of epithelial basement membrane continuity. Re-epithelialization to close the wound occurs with formation of a relatively thin scar. 2. The repair process is more complicated in excisional wounds that create large defects on the skin surface, causing extensive loss of cells and tissue. The healing of these wounds involves a more intense inflammatory reaction, the formation of abundant granulation tissue (described below), and extensive collagen deposition, leading to the formation of a substantial scar, which generally contracts. This form of healing is referred to as healing by secondary union or by second intention (seconda intentionem). Despite these differences, the basic mechanisms of healing by primary (first intention) and secondary (second intention) union are similar. A large number of growth factors and cytokines are involved in cutaneous wound healing

Granulation tissue (Young connective tissue)

Formation of Blood Clot.

Wounding causes the rapid activation of coagulation pathways, which results in the formation of a blood clot on the wound surface. In addition to entrapped red cells, the clot contains fibrin, fibronectin, and complement components. The clot serves to stop bleeding and also as a scaffold for migrating cells, which are attracted by growth factors, cytokines and chemokines released into the area. Release of VEGF leads to increased vessel permeability and edema. However, dehydration occurs at the external surface of the clot, forming a scab that covers the wound. In wounds causing large tissue deficits, the fibrin clot is larger, and there is more exudate and necrotic debris in the wounded area. Within 24 hours, neutrophils appear at the margins of the incision, and use the scaffold provided by the fibrin clot to march in. They release proteolytic enzymes that clean out debris and invading bacteria.
Formation of Granulation Tissue.

Fibroblasts and vascular endothelial cells proliferate in the first 24 to 72 hours of the repair process to form a specialized type of tissue called granulation tissue, which is a hallmark of tissue repair. Grossly: The term derives from its pink, soft, granular appearance on the surface of wounds. Its characteristic histologic feature is the presence of new small blood vessels (angiogenesis) and the proliferation of fibroblasts . These new vessels are leaky, allowing the passage of plasma proteins and fluid into the extravascular space. Thus, new granulation tissue is often edematous. Granulation tissue progressively invades the incision space; the amount of granulation tissue that is formed depends on the size of the tissue deficit created by the wound and the intensity of inflammation. Hence, it is much more prominent in healing by secondary union. By 5 to 7 days, granulation tissue fills the wound area and neovascularization is maximal.
Cell Proliferation and Collagen Deposition.

Neutrophils are largely replaced by macrophages by 48 to 96 hours. Macrophages are key cellular constituents of tissue repair, clearing extracellular debris, fibrin, and other foreign material at the site of repair, and promoting angiogenesis and ECM deposition.


Migration of fibroblasts to the site of injury is driven by chemokines, and their subsequent proliferation is triggered by multiple growth factors. Macrophages are the main source for these factors, although other inflammatory cells and platelets may also produce them. Collagen fibers are now present at the margins of the incision, but at first these are vertically oriented and do not bridge the incision. In 24 to 48 hours, spurs of epithelial cells move from the wound edge (initially with little cell proliferation) along the cut margins of the dermis, depositing basement membrane components as they move. They fuse in the midline beneath the surface scab, producing a thin, continuous epithelial layer that closes the wound. Full epithelialization of the wound surface is much slower in healing by secondary union because the gap to be bridged is much greater. Concurrently with epithelialization, collagen fibrils become more abundant and begin to bridge the incision. The epidermis recovers its normal thickness and architecture, and surface keratinization.
Scar Formation.

The leukocytic infiltrate, edema, and increased vascularity largely disappear during the second week. Blanching begins, accomplished by the increased accumulation of collagen within the wound area and regression of vascular channels. Ultimately, the original granulation tissue scaffolding is converted into a pale, avascular scar, composed of spindleshaped fibroblasts, dense collagen, fragments of elastic tissue, and other ECM components. By the end of the first month, the scar is made up of acellular connective tissue devoid of inflammatory infiltrate, covered by intact epidermis.
Wound Contraction.

Wound contraction generally occurs in large surface wounds . The contraction helps to close the wound by decreasing the gap between its dermal edges and by reducing the wound surface area.
Connective Tissue Remodeling.

The replacement of granulation tissue with a scar involves changes in the composition of the ECM. The balance between ECM synthesis and degradation results in remodeling of the connective tissue framework an important feature of tissue repair.
Recovery of Tensile Strength.

Fibrillar collagens (mostly type I collagen) form a major portion of the connective tissue in repair sites and are essential for the development of strength in healing wounds. Net collagen accumulation, however, depends not only on increased collagen synthesis but also on decreased degradation. How long does it take for a skin wound to achieve its maximal strength? When sutures are removed from an incisional surgical wound, usually at the end of the first week, wound strength is approximately 10% that of unwounded skin. Wound strength increases rapidly over the next 4 weeks, slows down at approximately the third month after the original incision, and reaches a plateau at about 70% to 80% of the tensile strength of unwounded skin. Lower tensile strength in the healed wound area may persist for life

The adequacy of wound repair may be impaired by systemic and local host factors. Systemic factors include those listed below: Nutrition has profound effects on wound healing. Protein deficiency, for example, and particularly vitamin C deficiency, inhibit collagen synthesis and retard healing. Metabolic status can change wound healing. Diabetes mellitus, for example, is 35

associated with delayed healing, as a consequence of the microangiopathy that is a frequent feature of this disease. Circulatory status can modulate wound healing. Inadequate blood supply, usually caused by arteriosclerosis or venous abnormalities (e.g., varicose veins) that retard venous drainage, also impairs healing. Hormones such as glucocorticoids have well-documented anti-inflammatory effects that influence various components of inflammation. These agents also inhibit collagen synthesis. Local factors that influence healing include those listed here: Infection is the single most important cause of delay in healing, because it results in persistent tissue injury and inflammation. Mechanical factors, such as early motion of wounds, can delay healing, by compressing blood vessels and separating the edges of the wound. Foreign bodies, such as unnecessary sutures or fragments of steel, glass, or even bone, constitute impediments to healing. Size, location, and type of wound . Wounds in richly vascularized areas, such as the face, heal faster than those in poorly vascularized ones, such as the foot. As we have discussed, small incisional injuries heal faster and with less scar formation than large excisional wounds or wounds caused by blunt trauma.

Complications in wound healing can arise from abnormalities in any of the basic components of the repair process. These aberrations can be grouped into three general categories: - (1) deficient scar formation, - (2) excessive formation of the repair components, - (3) formation of contractures. Inadequate formation of granulation tissue or assembly of a scar can lead to two types of complications: wound dehiscence and ulceration. Excessive formation of the components of the repair process can give rise to hypertrophic scars and keloids. The accumulation of excessive amounts of collagen may give rise to a raised scar known as a hypertrophic scar; if the scar tissue grows beyond the boundaries of the original wound and does not regress, it is called a keloid Exuberant granulation is another deviation in wound healing consisting of the formation of excessive amounts of granulation tissue, which protrudes above the level of the surrounding skin and blocks re-epithelialization (this process has been called, with more literary fervor, proud flesh). Excessive granulation must be removed by cautery or surgical excision to permit restoration of the continuity of the epithelium. Finally (fortunately rarely), incisional scars or traumatic injuries may be followed by exuberant proliferation of fibroblasts and other connective tissue elements that may, in fact, recur after excision. Called desmoids, or aggressive fibromatoses, these lie in the interface between benign proliferations and malignant (though low-grade) tumors. The line between the benign hyperplasias characteristic of repair and neoplasia is frequently finely drawn. Contraction in the size of a wound is an important part of the normal healing process. An exaggeration of this process gives rise to contracture and results in deformities of the wound and the surrounding tissues. Contractures are commonly seen 36

after serious burns and can compromise the movement of joints.


Deposition of collagen is part of normal wound healing. However, the term fibrosis is used more broadly to denote the excessive deposition of collagen and other ECM components in a tissue. As already mentioned, the terms scar and fibrosis are used interchangeably, but fibrosis most often indicates the deposition of collagen in chronic diseases. The basic mechanisms that occur in the development of fibrosis associated with chronic inflammatory diseases are generally similar to the mechanisms of skin wound healing The persistence of injury leads to chronic inflammation, which is associated with the proliferation and activation of macrophages and lymphocytes, and the production of a plethora of inflammatory and fibrogenic growth factors and cytokines. TGF- is practically always involved as an important fibrogenic agent , regardless of the original cause. It is produced by most of the cells in granulation tissue and causes fibroblast migration and proliferation, increased synthesis of collagen and fibronectin, and decreased degradation of ECM due to inhibition of metalloproteinases. Fibrotic disorders include diverse diseases such as liver cirrhosis, systemic sclerosis, fibrosing diseases of the lung (idiopathic pulmonary fibrosis, pneumoconioses, and drug-, radiation-induced pulmonay fibrosis), chronic pancreatitis, glomerulonephritis, and constrictive pericarditis.

Bone regeneration Bone callus

Traumatic and nontraumatic fractures are some of the most common pathologic conditions affecting bone. In the case of perfect immobilisation of the 2 fractured ends, a fracture can be healed by formation of bone callus. Fractures are classified as complete or incomplete; closed (simple) when the overlying tissue is intact; compound when the fracture site communicates with the skin surface; comminuted when the bone is splintered; displaced when the ends of the bone at the fracture site are not aligned. pathologic fracture - if the break occurs in bone already altered by a disease process, stress fracture is a slowly developing fracture that follows a period of increased physical activity in which the bone is subjected to new repetitive loadsas in sports training. Bone is unique in its ability to repair itself; it can completely reconstitute itself by reactivating processes that normally occur during embryogenesis. This process involves regulated expression of a multitude of genes and can be separated into overlapping stages with particular molecular, biochemical, histologic, and biomechanical features, described next. 1. Immediately after fracture, rupture of blood vessels results in a hematoma, which fills the fracture gap and surrounds the area of bone injury. The clotted blood provides a fibrin mesh, which helps seal off the fracture site and at the same time creates a framework for the influx of inflammatory cells and ingrowth of fibroblasts and new capillary vessels. Simultaneously, degranulated platelets and migrating inflammatory cells release PDGF (Platelet-derived growth factor), TGF- (Transforming growth factor), FGF (Fibroblast growth factors), and interleukins, which activate the osteoprogenitor cells in the periosteum, medullary cavity, and surrounding soft tissues and stimulate osteoclastic and osteoblastic activity. Thus, by the end of the 37

first week the hematoma is organizing, the adjacent tissue is being modulated for future matrix production, and the fractured ends of the bones are being remodelled. This fusiform and predominantly uncalcified tissue - called SOFT-TISSUE CALLUS or PROCALLUS - provides some anchorage between the ends of the fractured bones but offers no structural rigidity for weight bearing. 2. Subsequently, the activated osteoprogenitor cells deposit subperiosteal trabeculae of woven bone that are oriented perpendicular to the cortical axis and within the medullary cavity. In some cases the activated mesenchymal cells (fibroblasts/fibrocytes) in the soft tissues and bone surrounding the fracture line also differentiate into chondroblasts that make fibrocartilage and hyaline cartilage. In an uncomplicated fracture, the repair tissue reaches its maximal girth at the end of the second or third week, which helps stabilize the fracture site. The newly formed cartilage along the fracture line undergoes enchondral ossification (such as normally occurs at the growth plate), forming a network of bone that connects to the reactive trabeculae deposited elsewhere in the medullary cavity and beneath the periosteum. In this fashion the fractured ends are bridged by a BONY CALLUS, and as it mineralizes the stiffness and strength of the callus increases to the point that controlled weight bearing can be tolerated. 3. In the early stages of callus formation an excess of fibrous tissue, cartilage, and bone is produced. If the bones are not perfectly aligned , the volume of callus is greatest in the concave portion of the fracture site. As the callus matures and is subjected to weight-bearing forces, the portions that are not physically stressed are resorbed , and in this manner the callus is reduced in size until the shape and outline of the fractured bone have been re-established. The medullary cavity is also restored, and after this has been completed it may be impossible to demonstrate the site of previous injury. Direct metaplasia: transformation of fibrous tissue (fibroblasts, fibrocytes and colagen fibers) directly into bone tissue. Indirect metaplasia: transformation of fibrous tissue into cartilaginous tissue (chondroblats and chondrocytes) and these into bone tissue (osteoblasts, osteocytes, osteoclasts). Evolution: With a good imobilisation restitutio ad integrum. The sequence of events in the healing of a fracture can be easily impeded or even blocked. For example, displaced and comminuted fractures frequently result in some deformity, and inadequate immobilization permits constant movement at the fracture site, so that the normal constituents of callus do not form, resulting in delayed union and nonunion. If a nonunion allows too much motion along the fracture gap, the central portion of the callus undergoes cystic degeneration, and the luminal surface can actually become lined by synovial-like cells, creating a false joint or pseudoarthrosis. A serious obstacle to healing is infection of the fracture site, which is a risk in comminuted and open fractures. The infection must be eradicated before bony union can be achieved. Generally, young animals, in whom most uncomplicated fractures are found, near perfect reconstitution is the norm. In older age groups in whom fractures tend to occur on a background of some other disease (e.g., osteoporosis and osteomalacia), repair is more often imperfect and may require mechanical immobilization (e.g., placement of stabilizing pins).

TUMORS PATHOLOGY Nomenclature of tumors


Oncology - is a branch of medicine that deals with tumors (cancer). - the expression tumor disease, cancer disease and neoplasm are used. Tumor a pathological swelling, whether of inflammatory, cystic, edematous or other nature. Cancer has been used since the antiquity = crayfish. Neoplasm - is composed of the Greek prefix neo- (new) and plasis (formation). Benign tumors the characteristic have led to the designation good nature tumor. Malignant tumors - the characteristic have led to the designation bad nature tumor. Metastasis (change a place) cells are detached from primitive tumors and they can be carried by blood or lymph towards other organs, where they will develop secondary tumors.

Characteristic of benign/malign tumors

CHARACTERISTICS OF BENIGN TUMORS Growth type Growth speed Structure Mitosis Evolution Metastasizing Local consequences General consequences Spontaneous evolution Evolution after removal Expansive Low Typical Rare Local No Variable (compression) None (exception: secretory tumors) Usually favorable No recurrences MALIGN Infiltrating Rapid Atypical (anaplasia) Numerous Local + General Yes Severe (infiltration, necrosis) Constant (generalization phase) Always fatal Common recurrences

Epithelial tumors The term used for the benign tumors is composes by: organs+ adenoma - hepatoma or liver adenoma, breast adenoma, The term used for the malign tumors is composes by: organs+ carcinoma - breast carcinoma, lung carcinoma, spinocelular carcinoma,. Skin tumors are relatively frequent, especially in dogs, horses, cattle and cats Incidence is variable Classification of skin tumors is difficult due to the complex structure, as well as to the ectodermal and mesodermal origin of skin components, to which structural and physiological peculiarities of the skin in different animal species and breeds are added. Etiology - the possibility of the intervention of intrinsic and extrinsic risk factors is considered, such as: hormonal conditions, 39

genetic and immunological factors, solar radiation, ionizing radiation, viral factors, chemical factors

EPITHELIAL TUMORS Squamous cell carcinoma (SCC)

Squamous cell carcinoma is a highly malignant neoplasm, frequently associated with solar dermatosis, being the tumor of the cells of the malpighian layers from the epidermis; with varying degrees of keratinocyte (squamous cell) differentiation. It is a relatively common, locally invasive and occasionally metastatic neoplasm of most domestic species. Etyology, localisation and affected species: Sunlight is probably the most important carcinogenic stimulus for these tumors and accounts for the preference of squamous cell carcinoma for the eyelid and conjunctiva of cattle and horses, the ear pinna of cats and sheep, and the vulva of cattle, goats, and recently sheared sheep. Chronic exposure to sunlight has also been proven to cause squamous cell carcinoma of the relatively hairless, poorly pigmented abdominal and juxtanasal skin of dogs. The progression from solar keratosis to carcinoma occurs over several years In addition to sunlight, carcinogens contained in tobacco, coal tar and soot, arsenic, and smegma have been shown experimentally or by epidemiologic inference to cause squamous cell carcinoma of skin and other tissues. Gross lesions: Squamous cell carcinomas are usually firm, white, poorly demarcated dermal masses that are ulcerated and streaked with red. In some locations (eye, penis) they are raised and papillary even though the surface is ulcerated. Chronic inflammation accompanies many of these tumors, particularly those of the ear pinna and nail bed. In these instances, the reddening, crusting and ulceration of the inflammatory lesion may hide the tumor. Microscopic examination. SCCs are recognized microscopically by identifying malignant epithelial cells demonstrating various degrees of differentiation towards keratinocytes. In invasive squamous cell carcinomas, tumor cells breach the basement membrane to form trabeculae, nests and cords within the dermis that are usually contiguous with the epidermis in at least one area. The tumor cells most resemble those of normal stratum spinosum but have vesicular nuclei with one or multiple very prominent nucleoli. Cytoplasm is usually abundant and eosinophilic. Keratinization within such cords or islands results in laminated keratin "pearls" surrounded by tumor cells. With increasing anaplasia, tumors exhibit wide variation in nuclear size, decreasing cytoplasmic mass, increased basophilia, and disappearance of intercellular bridges. Keratinization may be limited to only individual tumor cells and mononuclear or even multinucleated giant tumor cells may be present. The high malignancy forms are composed of undifferentiated cells, large, round, atypical cells with eosinophilic cytoplasm. In the typical squamous cell carcinoma, the tumor cells spread through the dermis as slender anastomosing cords, with some cells falling off the cords to remain as apparently isolated islands in the dermal stroma. Tumor cell invasion is usually associated with marked 40

desmoplasia (prolifetation of fibrous tissue). Mitotic figures are usually numerous and are in proportion to the degree of anaplasia. Evolution: Its metastatic potential is low, with certain qualifications depending on location. Those initiated by sunlight are slow to metastasize, then usually only to local lymph nodes. In contrast, those originating on the canine digit may be more prone to metastasize, but even these are cured by amputation in virtually all but the most neglected cases.

Trichoblastoma - Ribbon Type

HAIR FOLLICLE TUMORS Hair follicle tumors are generally rare in animals, the only species in which they are frequent being the dog. - extremely rare in the cat, (fewer than 1% of all skin tumors) - Histologically distinct types, in decreasing order of frequency, include - Trichoblastomas (benign neoplasms of follicular germinative cells) - Trichoepitheliomas (One of multiple small, benign nodules, mostly on the skin of the face, derived from basal cells of hair follicles enclosing keratin pearls) - Pilomatrixomas (benign appendageal tumor with differentiation toward hair cells) - Two rare forms also exist: tricholemmomas and trichofolliculomas, also exist. In general, hair follicle tumors are benign and have an excellent prognosis after surgical excision. Trichoblastoma is a benign tumor derived from the primitive hair germ of embryonic follicular development. There are ribbon, trabecular, granular, and spindle cell trichoblastomas. In dogs, these tumors were formerly classified as basal cell tumors. Types: 1.Spindle cells trichoblastoma 2.Granular cells trichoblastoma 3.Trabecular trichoblastoma 4.Ribbon trichoblastoma Gross aspects: The ribbon trichoblastoma is a small, dermal to subcutaneous tumor. Microscopically findings: - long cords of pale eosinophilic epithelial cells that may branch with nuclei arranged in a palisade way, perpendicular to the long axis of the columns. - nuclei are hyperchromatic and the number of mitosis is variable. - nuclei of tumors arranged in cords often palisade perpendicular to the long axis of the cord. - in the central islands are present ratiating cells with eosinophilic cytoplasm. - Abundant collagen that may appear hyalinized accompanies the tumor cells. Evolution: Recurrence occurres rarely; occasionally metastasis to regional lymph nodes and pulmonary

Papillary carcinoma of the mammary gland


Mammary tumors, at least in dogs and to a certain extent in cats, have many similarities to breast neoplasms in women. Mammary gland tumors are frequent in dogs and cats, appearing extremely sporadically in other domestic animals. In bitches, the incidence of mammary tumors is estimated at 50% of all neoplasms in this species, of which approximately 60% are benign and 40% malignant. The mean onset age for mammary tumors is between 10 and 11 years. Incidence is higher in certain breeds, such as: Poodle, English Spaniel, Brittany Spaniel, English Setter, Pointer, Fox Terrier, Boston Terrier and Cocker Spaniel; incidence is lower in Chihuahua and Boxer breed. Mammary tumors in the bitch are hormone dependent, and the risk of appearance increases after each estrous cycle. Mammary tumor cells, either benign or malignant, have estrogen and progesterone receptors. These hormones induce the hypertrophy of the mammary parenchyma, which is obvious after estrus. The higher tumor incidence in the posterior mammary gland pairs is correlated with the higher gland volume and abundant secretion during the lactation period. If before the first cycle the risk of tumor appearance is 0.5%, it reaches 8% after the first cycle and over 26% after the second or more estrous cycles. In dogs, approximately 40% of all mammary tumors are located in the inguinal mammary glands and appear shortly after estrus. A similarity between human breast tumors and mammary tumors in bitches is found regarding incidence, behavior and histological origin. The appearance of mammary tumors in bitches corresponds to the development of these tumors in women. The risk of developing these tumors increases starting with the age of 6 years in bitches and 40 years in women (the age of 2 years in dogs is equivalent to the age of 24 years in humans, then every year after the age of 2 corresponds to 4 years in humans). ypical and atypical lobular and ductal hyperplastic lesions have been present in 73.63% of cases in dogs and 56.25% in cats, at the periphery of neoplastic mammary nodules. These changes can be considered precancerous; benign precancerous lesions from the periphery of malignant neoplasms suggest multicentric histogenesis, and evolution is in successive stages, with a continuity in time of the oncogenic system. In conclusion, benign hyperplastic lesions, associated with both benign and malignant tumors, are considered as precancerous stages. Histologically, benign and/or hyperplastic lesions are found in the proximity of a malignant tumor. Benign tumors: fibroadenomas (benign mixed tumors), simple adenomas, benign mesenchymal tumors. Malignant tumors: solid carcinomas, tubular adenocarcinomas, papillary carcinomas, anaplastic carcinomas, sarcomas, carcinosarcomas (malignant mixed tumors). Mammary tumors in cats are particularly frequent, especially at the mean age of 10 14 years. Siamese cats have a higher risk, and they can develop mammary tumors even at a young age. In this species, mammary tumors are less hormone-dependent, early ovariohysterectomy being only partially protective. Malignant neoplasms are found in a much higher proportion compared to neoplasms in bitches. In decreasing order, incidence is appreciated as follows: adenocarcinomas, then carcinomas and sarcomas. Metastases appear early and in a high proportion in lymph nodes and lungs, being also detected in the pancreas, kidneys, central nervous system and, more rarely, in the heart, liver and jejunum. Gross lesions: Clinically, mammary tumors appear as single or multiple nodules in the parenchyma, with or without the involvement of nipples. They can be located in any of the eight glands, and benign and malignant forms can coexist. Approximately 2/3 of mammary tumors are found in glands 4 and 5, probably due to the more abundant parenchyma at this level. On clinical examination, tumors are either benign or malignant, they can be small, firm, with well circumscribed nodules, which makes impossible the differentiation between benignity and malignancy. Rapid growth, local tissue invasion and ulceration are 42

characteristic of malignancy. Inflamed mammary carcinomas appear as diffuse swellings, with the multiple involvement of the congeneric gland, being painful and warm. Peripheral edema is present due to the obstruction of lymphatic vessels and retrograde growth. Macroscopically, carcinoma is characterized by rapid growth, doubling its volume in a short time, with local invasion, infiltrating the surrounding normal tissue. Sometimes, mammary neoplasms are delimited, a capsule appearing on palpation, but they present fibrous adhesions to the epidermis and the muscle fasciae or the neighboring muscles, and they cannot be freely moved. The skin is frequently ulcerated and the tumor invades the lymphatic vessels and lymph nodes, skin and the adjacent gland on the same side. Mammary neoplasms can have diameters between 2 and 20 cm, and round, ovoid, discoid, fungiform or poorly defined shapes. The tumor extends rapidly and occupies the whole gland, as well as adjacent glands, and carcinomas can coexist with benign tumors in the same gland and/or the neighboring glands. Microscopically findings: The tumor is formed by columnar or cuboid cells, arranged in tubules under a sessile papillary form. The neoplastic cells present a higher pleomorphism and a high mitotic index, necrotic foci, lymphocytic and plasma cell and granulocytes infiltration. Diagnosis is established based on clinical examination, supplemented by blood and serological profile. Radiographic thoracic and abdominal examination can evaluate the presence of metastases in the lungs and the increase in volume of lymph nodes. Fine needle aspiration for cytologic examination is not recommended, since it cannot differentiate with certainty a benign from a malignant tumor. Evolution: Metastases frequently develop by lymphatic route, and also, by venous route. In the case of carcinomas, the lymphatic route is the most important, towards the axillary and inguinal lymph nodes, and fine lymphatic vessels enter the thoracic cavity, facilitating lung metastases, as well as the abdominal cavity, with the possible dissemination of neoplasms in the liver and other parenchymatous organs. Less affected sites by metastasis are the long bones and the skeleton. It is noteworthy that lung metastases can be evidenced several months before the mammary neoplasm can be clinically detected. Radiographically, lung neoplasms can be identified in a proportion of 65 up to 97%, depending on the size and delimitation of nodules. Prognosis is directly related to the tumor size. Treatment, in both dogs and cats, in the absence of metastases and inflammation, consists of surgical removal. Chemotherapy in mammary neoplasms can be applied under the form of drug combinations, such as cyclophosphamide, vincristine and methotrexate or as postoperative adjuvant treatment.Mixed therapy in mammary neoplasms in dogs and cats has been less used, compared to breast tumors in women. The treatment of mammary tumors in dogs and cats cannot be considered a solved problem, as long as approximately 80% of subjects with carcinomas have recurrences that result in death. Ovariectomy or ovariohysterectomy will be carried out prophylactically in bitches before the first cycle and as curative therapy in young cats with multicentric fibroadenomatosis.



Soft tissue neoplasms (connective tissue tumors) relatively frequent in domestic animals In cats, the second position of all neoplasms diagnosed, and in dogs, they are the third most frequent tumors, after skin tumors and melanomas - Malignant connective tumors, sarcomas, show an extremely high morphological heterogeneity - Sarcomas of intermediate malignancy - Benign tumors (-oma) Classification: - connective tissue tumors proper: hard, soft fibroma and myxoma; nodular fasciitis; fibrosarcoma; hemangiopericytoma; predominantly cellular sarcomas; fibrohistiocytoma; equine sarcoid; tumor-like lesions: cutaneous fibrous polyp, keloid and hyperplastic scars, calcinosis circumscripta; - adipose tissue tumors: lipoma, liposarcoma; - muscle tissue tumors: leiomyoma, leiomyosarcoma; rhabdomyoma; rhabdomyosarcoma; - blood and lymphatic vessel tumors: hemangioma; malignant hemangioendothelioma or hemangiosarcoma; glomus tumors; lymphangioma; lymphangiosarcoma; synovial tumors; tumor-like lesions; - mesenchymal tumors of peripheral nerves; - mastocytoma; - mesothelioma; histiocytic tumors; - mixed tumors; - unclassified tumors.

Poorly melanotic MELANOMA

Definition: malign tumor of melanocytes (melanocytoma - benign form). Etiology: multifactorial determinats and favoring factors (genetic predisposition in Lipitan horse breed, Duroc swine breed; dogs: Boxer, Airdale terrier, Cocker spaniel, Scottish terrier and Boston terrier). Tumors derived from melanocytes or melanoblasts are of neuroectodermal origin. They have been reported in most species of domestic animals and many wildlife species, although they are most common in dogs, horses, and some breeds of swine. Localisation: skin, oral mucosa and intraocular; hyperpigmented regions and regions with lack of hair (lips, tale base, foreskin of the penis). In dogs, melanomas in the oral cavity and non-haired skin of the lip are almost invariably malignant. Those of the nailbeds also are frequently malignant, whereas cutaneous tumors are more commonly benign. In horses, melanomas occasionally occur as congenital tumors, however they are most common in older gray horses with a site predilection for the perineum, genital area, and distal limbs. Melanomas are uncommon in cats and are often amelanotic. Melanomas in cattle may occur as a congenital lesion, or they may occur at any age. Most are benign in cattle, although occasional tumors are malignant. Melanocytic tumors are uncommon in goats and sheep and are generally pigmented. Very aggressive tumors, metastasis (blood or lymph) in almost any organ or tissue!!! Gross lesions: - Shape: nodular or multinodular 44

- Color : Brown-black, dependent on the grade of cell differentiation - Consistency: wood-like Symptomatic lesions usually are about 3 or 4cm in diameter when discovered. They grow rapidly; necrosis and ulceration are common, as is invasion of bone by gingival tumors. Over 70% metastasize to the regional lymph nodes. An approximately equal number spread via hematogenous and lymphatic routes to more distant sites, especially the lungs, where they may be evident at necropsy, but too small to be detected radiographically. On section: black (ink-like) liquid Microscopically findings: Malignant melanomas can be composed of a variety of cell morphologies including spindle cells, epithelioid cells, a mixture of spindle cells and epithelioid cells, signet-ring cells, or balloon cells (clear cells). In addition, the cells can be heavily pigmented or amelanotic and form bundles, sheets, nests, and whorled patterns. Focal areas of chondroid or osseous metaplasia within the tumor may be seen on rare occasion. The most common types of malignant melanoma are composed of epithelioid cells, a mixture of epithelioid and spindle cells, or spindle cells alone, forming an unencapsulated mass in the dermis or subcutis. Cytoplasm is generally moderate to abundant, and the degree of pigmentation is highly variable, from darkly pigmented to amelanotic. Occasional multinucleated cells can be present. Evolution: In malignant melanoma, like in other forms of neoplasms, the following treatment methods are used: -the surgical method, -radiotherapy -chemotherapy. -immunotherapy has been recently experimented with encouraging results, especially in the case of malignant melanoma. The median survival time for untreated dogs is reported as 65 days, and survival following treatment is little better, at about 3 months.

Osteoblastic productive OSTEOSARCOMA

This malignant tumor is the most common primary neoplasm of the appendicular skeleton in dogs and cats. In general, it is a rapidly progressive tumor with early metastasis to the lungs leading to early mortality. Most osteosarcomas arise from within bones, particularly in the metaphyseal regions of long bones, and are referred to as central osteosarcomas. Less commonly, osteosarcomas arise in the periosteum or even in extraskeletal tissues. Osteosarcomas occasionally arise in soft tissues of dogs and cats, in the absence of a primary bone lesion in the mammary gland, but may also arise in the gastrointestinal tract, subcutaneous tissues, spleen, urinary tract, liver, skin, muscle, eye, and thyroid gland. They also arise in the esophagus in association with Spirocerca lupi infestation. In general, extraskeletal osteosarcomas occur in older dogs than skeletal osteosarcomas (mean age 10.611.5 years) and show no apparent predilection for large breeds. Osteosarcoma accounts for approximately 80% of primary bone tumors in dogs and 70% in cats. In dogs, the mean age of occurrence is around 7.5-8 years, but the range is broad and animals less than 2 years of age are sometimes affected. The tumor occurs predominantly in large and medium-sized breeds and has a strong site preference. A hereditary basis for the formation of OS has been suspected, based primarily on the (large) breed prevalence of the disease as well as the subjective assessment of increased 45

incidence in some related families. Males are reported to be slightly more frequently affected than females with the exception of the Saint Bernard, rottweiler, and Great Dane. Osteosarcomas occasionally occur at sites of chronic irritation and repair, such as those associated with osteomyelitis, bone infarcts, or the presence of an internal fixation device. In such cases, the tumor may originate from the diaphyseal region of long bones, or other locations not normally considered predilection sites for osteosarcoma. The mean age of osteosarcoma in cats is 10.5 years (range 3-18 years) and there is no apparent breed predisposition. Unlike dogs, most osteosarcomas in cats arise in the diaphyses of long bones, rather than the metaphyses. Osteosarcomas are rare in domestic animals other than dogs and cats, but are reported occasionally in horses, cattle and sheep. In these species, the tumor generally involves bones of the head, particularly the mandible. The gross and radiographic appearance of central osteosarcoma varies markedly, depending on the behavior of the tumor cells and the matrix they produce. Some subtypes are predominantly lytic, some are productive, while others comprise a mixture of both destructive and proliferative elements. An increased volume of the affected bone is found, and in section, congestion, edema appears, with the presence of osteofibrous tissue. Concomitant muscular atrophy develops, and regional lymph nodes are enlarged and hard. Fracture at the tumor site is not an uncommon complication, sometimes very soon after the development of the tumor, but in most cases, in advanced forms. Rhinorrhagia frequently appears when osteosarcoma is located in the nasal bones. Osteosarcomas in cats are located in the posterior limbs (tibia and femur); they develop slowly, and metastases occur late, after the diagnosing of the disease, with pulmonary and renal locations. Juxtacortical osteosarcoma in cats is usually located in the long bones of the extremities and cranial bones, frontal bone and mandible Productive tumors frequently provoke a more marked periosteal reaction than the osteolytic tumors. Osteosarcomas of long bones commonly, perhaps invariably, erode cortical bone but although they tend to invade the epiphysis rather than the diaphysis, they rarely penetrate the adjacent articular cartilage. Osteosarcomas may be subclassified according to the predominant histologic pattern. poorly differentiated osteosarcoma osteoblastic osteosarcomas chondroblastic osteosarcomas fibroblastic osteosarcomas telangiectatic osteosarcoma giant cell osteosarcomas Subclassification of osteosarcomas can be justified in that it may lead to the identification of correlations of osteosarcoma subtype with prognosis, and susceptibility to therapy. Although cytology is usually less reliable than histology in the diagnosis of mesenchymal tumors, central osteosarcomas can often be diagnosed with confidence on examination of fine-needle aspiration biopsies or imprints prepared from tissue biopsy samples. The histologic appearance of osteosarcomas varies markedly, but the production of osteoid and/or tumor bone by malignant osteoblasts is a common factor. The tumor matrix may also contain variable quantities of cartilage and collagen, but if tumor osteoid is present


then the tumor is classified as osteosarcoma. This reflects the greater malignant potential of malignant osteoblasts than either chondroblasts or fibroblasts. Osteoblastic osteosarcomas are recognizable by the presence of cells with features of anaplastic osteoblasts (spindle-shaped cells resembling fibroblasts or plump, oval or rounded cells with basophilic cytoplasm and eccentric, hyperchromatic nuclei, more closely resembling nonneoplastic osteoblasts) throughout much of the tumor. The tumor cells have hyperchromatic, often eccentric nuclei and variable quantities of basophilic cytoplasm. Mitotic figures are often very common. The cell borders are often angular and there may be a pale Golgi zone adjacent to the nucleus. Osteoblastic osteosarcomas may be further subclassified into nonproductive and productive osteosarcomas depending on the quantity of tumor bone produced. Moderately productive osteoblastic osteosarcoma is the most common subtype of osteosarcoma in dogs. Radiographically, there is a mixed pattern of destruction and production. In some cases with abundant tumor bone formation, differentiation of tumor bone from reactive bone may be difficult or impossible. Differential diagnose: chondrosarcomas osseous metaplasia of multipotential mesenchymal cells in tumors of nonosseous origin, such as mammary carcinoma Thin strands of osteoid may closely resemble collagenous fibrous tissue Fibrin in areas of hemorrhage may also be mistaken for osteoid but is not birefringent. Formation of endosteal and periosteal new bone is a feature of a variety of inflammatory and neoplastic bone lesions. Distinguishing between osteosarcoma and an early fracture callus presents a challenge. Evolution: The prognosis for all subtypes is very poor. Hematogenous metastasis to the lungs commonly occurs early in the disease. Vascular invasion can sometimes be detected at the tumor margins. Pulmonary metastases are detected (10% of dogs) at the time of initial diagnosis and it is likely that most dogs with osteosarcoma will eventually develop metastases if their lives are prolonged by surgery or other forms of treatment.

Cutaneous vasoformative tumors are common in dogs, occasional in cats, horses, cattle and uncommon in other species. The majority are benign in dogs and horses whereas malignant tumors are more common in cats. Hemangioma and hemangiosarcoma (HSA) are tumors of vascular endothelial origin. Vascular tumors may be associated with thrombocytopenia, disseminated intravascular coagulation, and other hemostatic abnormalities. Definition: Hemangioma is a benign neoplasm of blood vessel endothelium that can originate in the dermis or subcutis. The tumor is usually a solitary, well-circumscribed, fluctuant to firm, blue to red-black, slowgrowing mass. Cutaneous hemangioma in dogs usually occurs in older animals (mean, 9-10 years) without apparent sex predilection. Benign cutaneous vascular lesions in horses frequently occur in animals less than 1 year of age and some are congenital, 47

Location: The tumor can occur anywhere but lightly pigmented, sparsely haired ventral abdominal and inguinal skin may be predisposed (limbs, flanks, neck, face, scrotum and perineum; in organs - more frequently located on the oral mucosa, spleen, liver, lung and heart). Etiology: Chronic solar damage has been suggested as a cause of dermal hemangiomas in this location and they may be multiple. Gross lesions: The lesions are most commonly located on the limbs and present as a cauliflower or nodular mass (usually between 0.5 and 3.0 in diameter) or diffuse skin thickening which may become alopecic and ulcerated. The lesions may recur following excision. In some instances they are too extensive to be excised, necessitating euthanasia of the affected animal. Cutaneous hemangiomas usually occur in adult and aged cattle; congenital hemangiomas have been reported also and these are frequently multiple. Microscopically, hemangiomas consist of nonencapsulated dermal or subcutaneous masses composed of blood-filled channels lined by a single layer of flattened, mature endothelium. Mitotic figures are rare. Subcutaneous tumors are usually wellcircumscribed, while those in the dermis may not be as well defined and may incorporate adnexal structures within the mass. The tumors are classified as capillary or cavernous depending on the size of the vascular spaces. The cavernous type is more common in dogs. The vascular channels are usually separated by collagenous septa that contain variable numbers of mast cells, lymphoid cells, and hemosiderin-laden macrophages. Occasional vascular channels contain fibrin thrombi. Solar-induced dermal hemangiomas of glabrous skin are located in the superficial dermis and may be associated with solar elastosis. Differential diagnose: Cutaneous melanoma. Evolution: Surgical excision is curative. In case of tumors located in parenchymatous organs, death may occur by internal hemorrhage.

Definition: a rare malignant tumor of fibroblasts, with the involvement of other mesenchymal cells and collagen. Species affected: Is common in dogs and cats and uncommon in other domestic species. Age and location: In dogs, they usually occur in older animals and are most common on the trunk and limbs. Gross lesions: They usually arise in the subcutis and are poorly circumscribed masses of variable size that may be soft to firm in consistency. Large tumors are often ulcerated and alopecic. Macroscopically, large variations in sizes from several centimeters to impressive distorting formations. Usually, there are single, nodular, multinodular tumors, with dermal or subcutaneous location, adherent to subjacent tissues, sometimes ulcerated. In section, they appear poorly delimited, without a capsule, with firm or soft consistency, friable and bleeding, being lobulated and gray-white, with hemorrhagic and/or necrotic areas. Eextremely different locations in any body region, the limbs, the trunk and the interscapular area being more frequently affected. It frequently produces lymph node and pulmonary metastases (more often in cats than in dogs). Fibrosarcoma is the most common malignant mesenchymal tumor of cats, and three forms of fibrosarcoma have been recognized - virus-induced (rare - Feline sarcoma virus (FeSV) is the cause of multicentric fibrosarcoma in cats usually less than 5 years of age. FeSV is a 48

replication-defective retrovirus that requires Feline leukemia virus (FeLV) as a helper virus. The genetic recombination of the two viruses produces an acutely transforming virus that induces multiple simultaneous rapidly growing fibrosarcomas after a short incubation period.) - solitary in older cats (much more common) - post-vaccinal (interval between vaccination and tumor development is 3 months to 3.5 years. The mechanism of tumor development is unknown) Microscopically: fibrosarcomas consist of interlacing and intersecting bundles of immature fibroblastic cells. The tumors show a great deal of variation with respect to cellular pleomorphism and density, mitotic activity, and amount and maturity of collagen. Multinucleated giant cells are seen in many fibrosarcomas but are not numerous. A structure usually formed by fibroblasts, collagen and reticulin fibers is found (whirl / swirl apect). Tumor cells are fusiform, but they can also be stellate, separated by scarce collagen bundles. Nuclei are anisomorphic, with prominent nucleoli. The cell cytoplasm is poorly colored, varying in shape and size, cell margins are difficult to distinguish. Myxomatous microfoci, bone or cartilaginous metaplasias may be detected in the tumor mass. Highly vascularised, capillaries have fine walls, which determine the presence of numerous hemorrhagic foci. The tumor presents a rapid infiltrative growth. Differential diagnose: by immunohistochemistry from other spindle cell tumors: - peripheral nerve sheath tumor - leiomyosarcoma - rhabdomyosarcoma - amelanotic malignant melanoma - spindle cell carcinoma - malignant schwannoma - malignant fibrous histiocytoma - leiomyosarcoma - spindle cell forms of amelanotic melanoma - squamous cell carcinoma and others. Evolution: Most fibrosarcomas recur locally and metastasize infrequently. Wide surgical excision prolongs the interval to recurrence but often fails to remove the tumor completely. Radiation therapy and chemotherapy are under evaluation as adjunctive treatment to prevent local recurrence and systemic spread, respectively.