Digestive System Pathology Lecture #3 Updated Fall 2024 PDF

Pathology of the Digestive System Manar AbdelMageed, PhD 3  Oral cavity – Teeth Salivary glands Digestive Esophagus System Stomach Pathology Intestine Liver and Pancreas  Oral cavity – Teeth...

Pathology of the Digestive System Manar AbdelMageed, PhD 3  Oral cavity – Teeth Salivary glands Digestive Esophagus System Stomach Pathology Intestine Liver and Pancreas  Oral cavity – Teeth Salivary glands Digestive Esophagus System Stomach Pathology Intestine Liver and Pancreas Liver The traditional structural unit of the liver is a lobule – a hexagonal structure containing a central vein at the center and portal triads at the angles (periphery). Within the portal triads there are bile ducts, branches of portal vein, hepatic artery, nerves and lymphatics. Liver The functional unit is the acinus which is centered around the portal triad with the central vein at the periphery. Hepatocytes located near portal triads receive the highest concentrations of oxygen, nutrients and hormones. The acinus is divided into three zones (Zones 1,2 & 3) Liver Liver Circulatory disturbances Chronic venous congestion (CVC) = Nutmeg liver Causes: 1. Right side heart failure 2. Caudal vena cava thrombosis 3. Obstruction or compression of hepatic veins Grossly: The liver is enlarged and shows enhanced reticular pattern on cut section resembling nutmeg Microscopically: 1. Centrilobular area (Zone 3)  persistent hypoxia  Hepatocytes necrosis and sinusoids congested 2. Midzonal area (Zone 2) partial hypoxia  degeneration (fatty change) 3. Periportal area (Zone 1) Relatively normal and healthy 4. Fibrosis around central veins 5. Hemosiderosis Liver Circulatory disturbances Chronic venous congestion (CVC) = Nutmeg liver Causes: 1. Right side heart failure 2. Caudal vena cava thrombosis 3. Obstruction or compression of hepatic veins Grossly: The liver is enlarged and shows enhanced reticular pattern on cut section resembling nutmeg Microscopically: 1. Centrilobular area (Zone 3)  persistent hypoxia  Hepatocytes necrosis and sinusoids congested 2. Midzonal area (Zone 2) partial hypoxia  degeneration (fatty change) 3. Periportal area (Zone 1) Relatively normal and healthy 4. Fibrosis around central veins 5. Hemosiderosis Liver Circulatory disturbances Telangiectasis or Peliosis hepatis Is the presence of focal areas in the liver in which sinusoids are dilated and filled with blood. Common in cattle and old cats and HAS NO CLINICAL SIGNIFICANCE. Pathogenesis: Two possible mechanisms: Either localized weakness of the reticulin framework and subsequent dilation of the sinusoids OR death and loss of hepatocytes with subsequent extension of the sinusoids Grossly: Dark red areas, irregular in shape but usually well circumscribed, and ranging from pinpoints to many centimeters in diameter Microscopically: Multiple, dilated, blood-filled spaces lined by endothelium. Liver Circulatory disturbances Infarction Infarction of the liver is uncommon because of the dual blood supply to the liver (from the hepatic artery and portal vein). However, thrombosis or compression of an intrahepatic branch of the hepatic artery caused by embolism, neoplasia, or sepsis can result in a localized infarct. In ruminants, hemorrhagic infarcts can be secondary to mycotic rumenitis. Torsion of individual lobes occurs in swine and dogs (also mink and rabbits), and the resultant infarction can cause death due to shock and hemorrhage. Liver of a rabbit that had died from a liver lobe torsion. The caudal lobe has twisted around so the blood supply was cut off ischemia  infarction. Liver Circulatory disturbances Shunt = ‫تغيير مسار‬ A vascular abnormality where blood from the portal circulation bypass ‫ يتجاوز‬the liver and Portosystemic shunts flow directly into the systemic circulation. It can be acquired or congenital. Congenital portosystemic shunts Liver Circulatory disturbances Shunt = ‫تغيير مسار‬ A vascular abnormality where blood from the portal circulation bypass ‫ يتجاوز‬the liver and Portosystemic shunts flow directly into the systemic circulation. It can be acquired or congenital. Congenital portosystemic shunts Occurs in all species but most often in dogs and cats. The shunt is either intrahepatic or extrahepatic in location but usually limited to a single large-caliber vessel. Typically, intrahepatic shunts involve failure of closure of the ductus venosus at birth usually in large breeds of dogs. On the other hand, extrahepatic shunts such as portal vein to caudal vena cava anastomosis, occur more often in smaller breeds of dogs. Affected animals are typically stunted (small in size, as it can’t metabolize nutrients delivered from the intestine) and frequently develop signs of hepatic encephalopathy due to hyperammonemia (will be discussed later). Grossly: 1. The liver is small, but normal in color 2. The urinary bladder contain green ammonium biurate crystals 3. There is no ascites. Microscopically: 1. Portal areas show collapse of portal veins (small or absent) and reduplication of hepatic arterioles (compensatory hypertrophy) 2. Atrophy of hepatic lobules. Liver Circulatory disturbances Shunt = ‫تغيير مسار‬ A vascular abnormality where blood from the portal circulation bypass ‫ يتجاوز‬the liver and Portosystemic shunts flow directly into the systemic circulation. It can be acquired or congenital. Congenital portosystemic shunts Normal liver Intrahepatic shunt Extrahepatic shunt Liver Circulatory disturbances Shunt = ‫تغيير مسار‬ A vascular abnormality where blood from the portal circulation bypass ‫ يتجاوز‬the liver and Portosystemic shunts flow directly into the systemic circulation. It can be acquired or congenital. Congenital portosystemic shunts Congenital intrahepatic shunt, persistent Congenital extrahepatic portocaval shunt patentductus venosus in a dog. in a cat. Liver Circulatory disturbances Shunt = ‫تغيير مسار‬ Congenital portosystemic shunts L Portal areas are abnormal because they lack a portal vein and contain numerous A single anomalous vessel (arrow) small-caliber arterioles (arrows) that connects the portal circulation with the systemic circulation Green Ammonium Biurate Crystals in the Urinary Bladder. Liver Circulatory disturbances Shunt = ‫تغيير مسار‬ A vascular abnormality where blood from the portal circulation bypass ‫ يتجاوز‬the liver and Portosystemic shunts flow directly into the systemic circulation. It can be acquired or congenital. Acquired portosystemic shunts Mostly caused by chronic liver diseases that lead to portal hypertension The shunts tend to be multiple, small and tortuous. Ascites is common in conditions that develop acquired shunts because of the associated portal hypertension. Liver Metabolic & Nutritional disturbances Fatty liver = Hepatic lipidosis / steatosis Is accumulation of neutral fat inside hepatocytes Causes: 1- Dietary causes: Excessive fat in diet Anorexia in obese animals Cobalt and Vit B12 deficiency  white liver Yellow, enlarged, rounded border, tense capsule, disease in sheep and goats due to anemia greasy cuts ection and float in formaline 2- Toxic and hypoxic injury  decreased oxidation and metabolism of fatty acids 3- Ketosis: In pregnant and lactating animals, there is a continuous demand for glucose and amino acids, and ketosis results when fat metabolism (which occurs in response to the increased energy demands) becomes excessive. Common in dairy cattle during peak lactation and during late gestation in ewes (= pregnancy toxaemia) 4- Feline fatty liver syndrome: In stressed obese cats  anorexia  increased mobilization of fat Vacuolated (microsteatosis) and Signet ring appearance (macrosteatosis) Liver Metabolic & Nutritional disturbances Glycogen accumulation Accumulation of glycogen inside hepatocytes In liver, glucocorticoids increase glycogen storage Glucocorticoid-induced hepatocellular degeneration (steroid hepatopathy) occurs when excessive levels of endogenous (Hyperadrenocorticism)or exogenous glucocorticoids cause increased accumulation of glycogen in hepatocytes. Glucocorticoids induce glycogen synthetase enhancing hepatic storage of glycogen. The disease occurs in dogs and is frequently iatrogenic (due to prolonged treatment with steroids). In severe cases, the liver is enlarged and pale, but otherwise grossly unremarkable. Microscopically, affected hepatocytes are swollen and have extensive cytoplasmic vacuolation. Liver Metabolic & Nutritional disturbances Chronic copper toxicosis in sheep Occurs as a result of the presence of 3 ENVIRONMENTAL FACTORS acting alone or together: 1. Excessive copper intake (Contamination of water or food) 2. Diet low in molybdenum (which antagonizes copper uptake from the GIT). 3. Hepatotoxins Grazing on fields containing hepatic phytotoxins such as pyrrolizidine alkaloids (Heliotropium, Crotalaria, Senecio) Inside hepatocytes, Cu Cu This can result in massive copper is stored in Cu release of copper from lysosomes. damaged hepatocytes, which Cu Once the when taken up in circulation, lysosomal storage Cu can lead to a hemolytic crisis capacity is exhausted, copper Sheep are the most susceptible breaks into the species to chronic copper cytoplasm where it toxicity, because their liver cells Cu is cytotoxic ROS (produces ROS) and have a high affinity for copper causes membrane Cu and they excrete copper into damage (lipid the bile at a very low rate, Cu Biliary excretion is an important step peroxidation) and Cu leading to a build-up of liver in copper homeostasis necrosis copper concentration over time Liver Metabolic & Nutritional disturbances Chronic copper toxicosis in sheep Lesions: 1- Massive hepatic necrosis 2- Jaundice 3- Gun metal blue kidney 4- Dark color of urine (hemoglobinuria) Liver Metabolic & Nutritional disturbances Nutritional diseases of the liver Hepatosis dietetica (In pigs) A syndrome of acute hepatic necrosis in young, rapidly growing pigs. Caused by vitamin E and/or selenium deficiency  oxidative injury. The lesion is centrilobular to massive hepatic necrosis and hemorrhage. White liver disease (In Sheep) Is caused by insufficiency of cobalt intake. Cobalt is a necessary cofactor in the synthesis of vitamin B12 and other enzymes, and deficiency of this vitamin leads to anemia. Affected livers are pale and fatty most likely Hepatosis dietetica in a pig. due to anemia Liver Hepatobiliary injury and response Patterns of hepatocellular degeneration and necrosis Cellular degeneration and/or necrosis in the liver occur in one of four morphologic patterns: Random, Zonal, Bridging or Massive Random hepatocellular degeneration and necrosis Single cell necrosis or Multifocal necrosis (scattered randomly throughout the liver). There is no predictable location within liver lobules. It is typical of many infectious agents (viruses, bacteria, certain protozoa). Grossly: The lesions appear as discrete, pale or dark-red foci, sharply delineated from the normal parenchyma. The size varies from less than 1 mm to several mm. Equine Herpesvirus Hepatitis, Hepatic Single cell necrosis can’t be seen grossly Necrosis, Liver, Foal. Note the randomly Microscopically: distributed gray-to-white foci of random The affected cells are degenerate or hepatocellular necrosis caused by equine necrotic and there may be inflammation. herpesvirus. Liver Hepatobiliary injury and response Patterns of hepatocellular degeneration and necrosis Periportal Zonal hepatocellular degeneration and necrosis Zonal change affects hepatocytes within defined areas of the hepatic lobule and leads to enhanced lobular pattern on the capsular and cut surfaces. Specific forms of zonal change include: Centrilobular degeneration & necrosis Paracentral degeneration & necrosis Midzonal degeneration & necrosis Periportal degeneration & necrosis Centrilobular Midzonal Paracentral Liver Hepatobiliary injury and response Centrilobular degeneration and necrosis Circumferentially around the central vein This is a common lesion because zone 3 hepatocytes receive the least oxygenated blood and are therefore more susceptible to hypoxia. Also, they have the greatest enzymatic activity (Cytochrome P450) capable of activating compounds into toxic forms. The most common causes of centrilobular zonal change are: 1. Severe anemia 2. Congestion due to right side heart failure 3. Indirect toxins that need activation by Cytochrome P450 (e.g: CCL4) Liver Hepatobiliary injury and response Paracentral degeneration and necrosis Paracentral cellular degeneration involves only a wedge of parenchyma around the central vein because only the outer margin of one diamond shaped acinus is affected. Possible cause: Ischemic lesion or infarct produced by an occlusion of a terminal portal venule, such as may occur in disseminated intravascular coagulation (DIC). Liver Hepatobiliary injury and response Midzonal degeneration and necrosis This is uncommon change affecting hepatocytes in the middle portion of the lobule (zone 2). It has been reported in pigs and horses with aflatoxicosis. Liver Hepatobiliary injury and response Periportal degeneration and necrosis This is also an uncommon and involves zone 1 hepatocytes. It is most often caused by toxins which do not require metabolism to cause injury (e.g. Yellow phosphorus) and thus damage to hepatocytes in the first zone is encountered. Liver Hepatobiliary injury and response Bridging necrosis This is the result of confluence of areas of necrosis and implies increased severity of the lesion. The links can be central to central, portal to portal, or central to portal. Liver Hepatobiliary injury and response Massive necrosis It involves necrosis of all hepatocytes within a lobule or contiguous lobules but not necessarily necrosis of the whole liver. In the acute stage, the liver has a mosaic appearance of dark red areas (necrosis and hemorrhage) intermingled with greyish or yellow areas (surviving hepatocytes). If the animal survives to a chronic stage, the necrotic areas collapse and are replaced by fibrous tissue; the liver becomes smaller and has a wrinkled capsule (postnecrotic scarring). Massive hepatic necrosis is seen in hepatosis dietetica of pigs (vitamin E/Selenium deficiency), migrating helminth parasites in several species and blue-green algae poisoning. Liver Hepatobiliary injury and response Note: Reticular pattern A gross appearance of liver seen when each single lobule is affected in the same way e.g: centrilobular necrosis, periportal necrosis Liver Hepatitis Inflammation of the liver According to the cause: Infectious and Toxic (non-infectious) According to the time course: Acute and chronic According to the exudate: Suppurative and non-suppurative Cholangitis is inflammation targeting the biliary ducts. It can be acute or chronic. Cholangiohepatitis involves the biliary ducts and hepatic parenchyma. Liver Hepatitis  Causes of Infectious hepatitis  Bacterial: 1. Corynebacterium spp & Trueperella pyogenes  Suppurative hepatitis in ruminants (The formed abscesses are well-encapsulated and contain a thick viscous green pus) 2. Fusobaterium necrophorum  liver abscesses (Chemical ruminitis!) 3. Cl. novyi & Cl. hemolyticum  necrotic hepatitis in sheep and cattle 4. Salmonellosis  focal granulomatous hepatitis 5. Leptospirosis  necrotic hepatitis and jaundice  Viral: 1. Canine infectious hepatitis  centrilobular hepatic necrosis 2. Herpes viruses (BHV-1 and EHV-1)  multifocal necrotic hepatitis Liver Hepatitis  Parasitic: 1. Fascioliasis 2. Migrating ascarid larvae (Milk spot liver) 3. Hydatid disease (Echinococcosis)  Causes of toxic hepatitis: 1. Plant toxins and blue green algae 2. Mycotoxins: Aflatoxins 3. Drugs and chemicals: acetaminophine toxicosis in cats, excessive administration of corticosteroids, organophosphorus toxicity 4. Copper toxicosis Liver General responses of liver to injury Responses of the liver to different injurious agents that cause destruction of hepatic parenchyma include: (1) Regeneration of parenchyma (2) Biliary hyperplasia (3) Replacement by fibrosis. The outcome of any given hepatic injury reflects the nature and duration of the injury. Liver General responses of liver to injury Regeneration The liver has a very good regenerative ability. As much as 3/4 of the functional mass of the liver must be removed before signs of dysfunction appear, and the liver can quickly (within 6-7 days!) regenerate as much as 60% of its mass without apparent ill-effect. Normal lobules Regeneration without fibrosis occurs if the original fibrous and reticulin framework is intact, there is adequate supply of blood, and there is free drainage of bile. Regeneration involves mostly the replication of mature hepatocytes adjacent to areas of cell loss or stem cells No further injury residing in the portal area (oval cells) The process is perfectly orchestrated where proliferation of hepatocytes is stimulated by growth factors, including transforming growth factor alpha (TGFα) and hepatocyte Acute injury Regeneration of growth factor (HGF) among others and once the lobule is normal lobules adequately regenerated the process is controlled by other mediators such as TGFβ which stops replication of hepatocytes. The outcome of regeneration is a normally functional lobule Liver General responses of liver to injury Biliary hyperplasia & ductular reaction Formation of new bile ductules either from the hepatic bipotential progenitor cells (oval cells) at the edge of the portal areas or via proliferation of already existing mature biliary epithelium Causes: 1. Any disease which obstructs bile drainage; Cholestasis. 2. Hepatotoxicity (e.g: aflatoxin poisoning) where it can be an attempt to regenerate hepatocytes Ductular Reaction, Goat. Ductular reaction is characterized by the proliferation of basophilic progenitor cells (arrows) forming poorly defined small-caliber ducts that may lack a distinct lumen. Liver General responses of liver to injury Fibrosis Hepatic fibrosis is an overall increase in the ECM (extracellular matrix) within the liver When the liver is injured, stellate cells (Ito cells) go through a progressive phenotypic change from the typical lipid-storing cell to a cell with a myofibroblastic appearance and function  deposition of collagen and ECM Note : The loss of endothelial fenestrations and the increased connective tissue beneath the endothelial cells leads to a condition termed capillarization of the sinusoids and is responsible for diminished hepatic function. Liver General responses of liver to injury Fibrosis Within the hepatic lobule, the site of fibrosis can be indicative Bridging fibrosis of the type of insult. For example: Centrilobular fibrosis can be indicative of: Central-central Central-portal 1. Chronic toxic injury by indirect toxins that require metabolism by cytochrome P450 to be injurious e.g: CCl4 2. Chronic passive hepatic congestion from long-standing right- sided heart failure Periportal fibrosis be indicative of: Normal lobules Progressive fibrosis Chronic toxic injury by small group of toxicants that affect the periportal hepatocytes because they do not require metabolism by cytochrome P450 enzymes to produce an injurious metabolite e.g Yellow phosphorus. Repeated Bridging fibrosis, which is analogous to bridging necrosis, implies injury fibrosis that extends from one portal tract to another (Biliary fibrosis) or from portal tracts to central veins or one central vein to another. Acute injury Early fibrosis Liver General responses of liver to injury Fibrosis Chronic Extrahepatic Cholestasis, Cholelithiasis, Liver, Centrilobular fibrosis (cardiac fibrosis), most Horse. There is reduplication of bile ducts (arrows) and severe at the center of the lobe in chronic passive extensive fibrosis (F) throughout the portal tract (biliary congestion in a dog. fibrosis) as a consequence of prolonged stasis and subsequent leakage of bile. Liver General responses of liver to injury Cirrhosis = End-stage liver A diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally and functionally abnormal regenerative nodules Causes: 1. Chronic toxicity 2. Chronic cholangitis and/or biliary obstruction 3. Chronic congestion (right side heart failure) 4. Inherited disorders of metal metabolism (copper or iron) 5. Chronic hepatitis 6. Idiopathic Grossly: The entire liver is small, firm, and irregular consisting of nodules of regenerating parenchyma separated by fibrous bands, which appear as depressions on the surface. It can be micronodular, macronodular or mixed. Liver General responses of liver to injury Cirrhosis = End-stage liver A diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally and functionally abnormal regenerative nodules Microscopically: 1. Regenerative nodules surrounded by connective tissue septa 2. The regenerative nodules do not retain the normal histological arrangement of hepatic lobules 3. The haphazardly arranged bands of fibrous connective tissue contains numerous blood vessels, hyperplastic bile ducts and mononuclear inflammatory cells 4. Venus and atriovenus shunts between the central vein and the portal vein or the hepatic artery can be seen The end-stage liver obviously cannot perform its normal functions, so the clinical manifestations of hepatic failure occur in affected animals. Regenerative nodule lacking the normal architecture of the hepatic lobules Liver Manifestations of hepatic failure Hepatic failure Hepatic failure refers to a clinical syndrome that results from inadequate liver function. It indicates massive reduction of the amount of liver cells or Manifestations of hepatic failure: decrease in their functionality. Loss of normal liver Hepatic encephalopathy function can occur as a consequence of either acute Coagulopathy (bleeding tendencies) or chronic liver damage. Hypoalbuminemia Vascular and hemodynamic alterations (e.g., acquired portosystemic shunts) Edema, ascites (secondary to hypoalbuminemia and/or portal hypertension) Hepatocutaneous syndrome Photosensitization Icterus (hyperbilirubinemia) Liver Manifestations of hepatic failure Hepatic encephalopathy (HE) Nervous manifestations mainly due to increased ammonia in the blood (Hyperammonemia) seen in hepatic insufficiency or portal- systemic blood shunting Most ammonia in the body forms when protein is broken down by bacteria in the intestines. The liver normally converts ammonia into urea, which is then eliminated in urine. Ammonia levels in the blood rise when the liver is not able to convert ammonia to urea Neurologic manifestations range from depression and other Alzheimer type II astrocytosis behavioral changes to mania, convulsions and coma Microscopically; the hallmark of HE is Alzheimer type II astrocytosis, in which astrocytes are enlarged and arranged in pairs, triplets or quartets with swollen nuclei, surrounded by clear edematous cytoplasm. Liver Manifestations of hepatic failure Coagulopathy (bleeding tendencies) Widespread ecchymoses and petechiae can accompany hepatic failure The process is multifactorial, complex and not very well understood Possibly due to Impaired synthesis of clotting factors, fibrinogen, prothrombin, etc Liver Manifestations of hepatic failure Hypoalbuminemia Hypoalbuminemia can occur in association with chronic liver disease and not acute hepatic failure because of the long half-life of albumin (dog - 8 days, cattle 21 days) It occur due to decreased hepatic production of albumin by the damaged liver Hypoalbuminemia together with the possible portosystemic shunts in end stage liver will lead to production of Ascites Liver Manifestations of hepatic failure Vascular and hemodynamic alterations Chronic damage to the liver and fibrosis can produce an increased amount of vascular resistance through the liver. This results in hemodynamic alterations such as portal hypertension, acquired portosystemic shunts, and ascites. Ascites: Increased hydrostatic pressure within the hepatic vasculature may cause transudation of fluid into the peritoneal cavity to produce ascites. Transudation of fluid into the peritoneal cavity is enhanced by the decreased colloid osmotic pressure of plasma resulting from hypoalbuminemia (due to reduced hepatic synthesis of plasma proteins). Acquired Portosystemic Ascites associated with chronic liver disease (end-stage liver) occurs most Anastomoses, Abdomen, Dog. commonly in the dog and cat, occasionally in sheep, and rarely, in the horse The numerous prominent veins that are present over the surface of and cattle. the kidney allow blood within the portal venous system to bypass the liver and directly enter the systemic circulation. Liver Manifestations of hepatic failure Hepatocutaneous syndrome Aka: Superficial necrolytic dermatitis. This is a rare disease of middle-age or older dogs characterized by crusting, erosions, and scaling of the skin. Lesions are distributed symmetrically over the face, footpads and inguinal area especially at mucocutaneous junctions. It is most commonly associated with chronic liver disease, but the mechanism of cutaneous injury is not understood. Liver Manifestations of hepatic failure Photosensitization Refers to inflammation of skin (usually unpigmented) because of the action of ultraviolet light on photodynamic compounds (compounds that can absorb light) that have become bound to dermal cells. Activation of these photodynamic agents by UV light leads to production of reactive oxygen species and induced inflammation of the skin (dermatitis) Hepatic photosensitization (secondary photosensitization) occur in herbivorous animals with hepatic dysfunction or biliary obstruction where Phytoporphyrins (formerly known as phylloerytherins); the photodynamic catabolite of chlorophyll that is normally excreted in bile is now elevated in the blood and circulating the body to reach the skin and when activated by UV light induce dermatitis. Lesions: hair loss, erythema, and necrosis Liver Manifestations of hepatic failure Disturbances of bile flow and hyperbilirubinemia (icterus, jaundice) Elevated levels (> 2 mg/dl) of bilirubin in blood (hyperbilirubinemia) can produce icterus (Yellow discoloration of mucosa, adipose, and elastic tissues such sclera and aorta) Causes of hyperbilirubinemia can be prehepatic, hepatic and post hepatic as follows: a. Prehepatic – Overproduction of bilirubin as a consequence of hemolysis, (especially intravascular hemolysis), which overwhelms the liver's ability to remove bilirubin from plasma and to secrete conjugated bilirubin into bile. b. Hepatic - Decreased uptake, conjugation or secretion of bilirubin, as in severe hepatocellular injury. Often seen with hepatotoxins. c. Posthepatic - Reduced outflow of bile ( cholestasis) following mechanical obstruction of bile ducts (extrahepatic cholestasis) or impairment of flow within canaliculi (intrahepatic cholestasis). In severe cholestasis the liver has a yellowish or greenish brown discoloration. Histologically, the canaliculi are distended with bile which may also be present in Kupffer cells and as extracellular bile lakes. Liver Manifestations of hepatic failure Disturbances of bile flow and hyperbilirubinemia (icterus, jaundice) Canalicular bilirubin. Distention of canaliculi by bile pigment Liver Developmental anomalies and miscellaneous changes Congenital cysts Occur in all species. They probably arise from bile ducts (ductal plate malformations) or the hepatic capsule. They are usually incidental findings and should be distinguished from parasitic cysts, particularly Cysticerci (larvae of Taenia spp). Congenital polycystic disease occurs in humans, dogs (Cairn terriers) and cats (Persian and Persian X); associated with congenital cysts in liver and kidney  Liver Developmental anomalies and miscellaneous changes Tension lipidosis This is a discrete pale area of hepatic lipidosis in the liver, usually adjacent to the insertion of the mesenteric attachment (occurs in cattle and horses). It is proposed that these attachments impede blood supply to the subjacent hepatic parenchyma by exerting tension on the capsule resulting in hypoxia. Tension Lipidosis (Steatosis), Liver, Cut Surface, Cow. Note the area of fatty change (F), the ligamentous attachment adjacent to the affected portion (arrowhead), and the areas of telangiectasis (arrows). Liver Developmental anomalies and miscellaneous changes Capsular fibrosis Capsular fibrosis is the presence of discrete fibrous tags or plaques on the diaphragmatic surface of the liver and on the adjacent diaphragm of the horse. The tags most likely represent resolution of non-septic peritonitis rather than parasitic migration. Infectious diseases of the liver (Infectious hepatitis) Liver Infectious canine hepatitis The etiology is canine adenovirus 1 (CAV-1) Can be fatal in young puppies The virus has tropism for hepatocytes, vascular endothelium, and renal epithelium, producing acute necrosis, minimal inflammation, and characteristic large intranuclear inclusion bodies. Gross appearance o Paint-brush hemorrhages and ecchymoses on serous membranes. o The liver is enlarged, friable and finely mottled. o The wall of the gall bladder is markedly edematous. o Hemorrhages often occur in the brain and lung and the kidney may have hemorrhagic infarcts. o Some dogs recovering from the disease develop transient immune complex uveitis (type III hypersensitivity) and corneal edema (= blue eye). Liver Infectious canine hepatitis The etiology is canine adenovirus 1 (CAV-1) Can be fatal in young puppies The virus has tropism for hepatocytes, vascular endothelium, and renal epithelium, producing acute necrosis, minimal inflammation, and characteristic large intranuclear inclusion bodies. Histological appearance o Centrilobular hepatic necrosis from ischemia and individual hepatocellular necrosis. o Large amphophilic intranuclear inclusion bodies in hepatocytes, endothelial cells and Kupffer cells. o Endothelial damage and hemorrhages in other organs. Liver Herpesvirus infections Herpesvirus infections of the liver typically occur in neonates and fetuses. The abortigenic herpesviruses include equine herpesvirus 1 (EVR), bovine herpesvirus 1 (IBR), canine herpesvirus 1, and pseudorabies virus. The characteristic lesion is multifocal, randomly distributed, small (