Hepatobiliary System PDF

Hepatobiliary System Anatomy / Portals of Entry / Defenses / Mechanisms of Liver Injury / Gall Bladder Disorders Biography of a Liver Largest internal organ in body Adult carnivores: 3% to 4% of body weight Adult omnivores, small ruminants: 1.5% - 2% of body weight Large herbivores...

Hepatobiliary System Anatomy / Portals of Entry / Defenses / Mechanisms of Liver Injury / Gall Bladder Disorders Biography of a Liver Largest internal organ in body Adult carnivores: 3% to 4% of body weight Adult omnivores, small ruminants: 1.5% - 2% of body weight Large herbivores: 1% of the body weight Location: Central cranial abdomen (monogastrics) Ruminants: displaced to the right by rumen Lobation: varies among species https://commons.wikivet.net/images/thumb/0/0e/Pig_Liver_Topography.jpg/300px-Pig_Liver_Topography.jpg  Blood Supply Nutritional supply Hepatic artery: 20-30% blood flow Functional supply Draining Portal vein : 70-80% blood flow (from GI) ***High source of microbe/ toxin exposure! http://ib.bioninja.com.au/options/option-d-human-physiology/d3-functions-of- the-liver/liver-blood-flow.html  Functional Subunit of the Liver Liver > Lobe > Lobuleor subunit live What’s in a lobule? Hexagonal structure Cords of Hepatocytes Central vein Portal triads Bile ductule Portal vein branches Hepatic artery branches Lymphatics and nerves http://ib.bioninja.com.au/options/option-d-human-physiology/d3-functions-of-the-liver/liver-structure.html Functional Subunit of the Liver Blood Flow within the Lobule Bile flow flows AWAY from CV towards PT Histologic Perspective Discontinuous capillaries Space of Disse with Stellate cell “Ito” Where is the Space of Disse? Too small to see on “normal” microscopy! Portals of Entry and Connection to Lesion Distribution Hematogenous (viral, bacterial, fungal, etc) Hepatic artery Don’t forget from the portal supply too! Umbilical vein Random, multifocal embolicshowering Ascending infections (bacterial) Centered around biliary tree Penetrating wounds Discrete (focally extensive) Multiple “layers” involved Defense (Innate) Mechanisms Reticulin: Sinusoidal scaffold (BM): contains collagen types III, IV, XVIII and (ECM) components supports the sinusoidal endothelial cells Stellate cells (“Ito” cells) Synthesize collagen, other ECM components Lie in Space of Disse Store Vit A Initiate hepatic fibrosis Liver growth and regeneration (secretion of growth factors) Kupffer cells Lie in sinusoids Phagocytosis / Antigen presentation Many more! http://memecrunch.com/meme/ZTQP/liver-employee-of-the-month/image.jpg A Blurb on Bile Bile flows opposite blood flow from Away central Bile= water, cholesterol, bile acids, bilirubin, inorganic ions Bile acids: synthesized from cholesterol; conjugated to prevent precipitation into calculi reabsorbed from ileum, extracted from portal blood, resecreted into bile via enterohepatic circulation (95% recycled!) Interruption of process -> fat malabsorption and deficiency of fat-soluble vitamins Bile Function Excretory (body’s waste products, such as surplus cholesterol, bilirubin, and metabolized xenobiotics) Bile acids facilitate lipid digestion galbladder asyoueat contract Buffers to neutralize the acid pH of the ingesta from stomach Liver functions Understanding “normal” is key to understanding abnormal! Production and excretion of bile Bilirubin metabolism Carbohydrate metabolism Lipid metabolism Xenobiotic metabolism https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcT0mcKL- CIsoTT0vSwT1Wlc7XRWWUPSbU6hvKJiKSSLDDf0bJMe cytochrome P450 enzymes of SER of hepatocytes: major site of metabolism Protein and urea synthesis albumin; variety of transport proteins; lipoproteins; clotting factors; fibrinolysis proteins; acute phase proteins; complement proteins conversion of ammonia into urea Immune function Acute phase proteins, Kupffer cells, transport of IgA produces factors 1 Acute Hepatitis Inflammation: “itis” neutrophils! (sometimes few lymphocytes if viral) 1 macrophages Necrosis Apoptosis (Pic): Herpesviral hepatitis (acute): Equine Herpesvirus: What does it all mean? Pattern? Color? Cream foci Red foci? or hemorrhage vasculitis Areas of palor? inflammation necrosis Herpes 1 virus aherpesvirus Chronic Hepatitis Name a feature of chronic lesions (hint: cream colored and strong!) F-F-F-F-…… Fibrosis Change in players: neuts are no longer! 2nd string players: Macs, lymphocytes, plasma cells Regenerative changes: What type of cell adaptation would this be? hyperplasiahypertrophy Focal chronic changes: not life altering Diffuse chronic changes: LIVER FAILURE Different types of chronic hepatitis Granulomatous macrophages Chronic suppurative Chronic active https://noahsarkive.cldavis.org/cgi-bin/show_image_info_detail.cgi?image=F00371 Cirrhosis End stage liver +/- Nodular regeneration FIBROSIS! (CHRONIC) Lumpy bumpy Loss of function All affects blood flow -> often leads to shunting of blood Whats causes this? TNTC!!! This is end stage…so whatever caused it has been going on for a while But…commonly: Chronic congestion Chronic toxins Chronic inflammation Copper tox (Bedlington Terriers) mine a storeexcesscopper  gen What about the GB? What’s it all mean? Cholestasis: Disturbance in bile flow Intra or extrahepatic ainer outsidelinecompressing.in.net Also a cause of icterus (post hepatic cause) Cholecystitis or Inflammation a a.rs Cholangitis Inflammationofbin.net Can be intra or extrahepatic https://www.wpclipart.com/cartoon/animals/o ctopus/octopus_simple_green.png.html Cholangiohepatitis Let’s add some modifiers. What do you suppose they mean? Lymphocytic cholangitis Cats > 4ys, Unk etiology: possibly autoimmune? Suppurative cholangitis Type of inflamm cells? Et. Agt? How would you diagnose? Bilirubin Metabolism: Refresher from Physio More Gall Bladder terminology Hyperbilirubinemia: incr. concentration of conjugated / unconjugated bilirubin in blood Icterus/jaundice: Pre hepatic / hepatic/ post hepatic causes yellow tissues secondary to hyperbilirubinemia Takes time! You can have hyperbilirubinemia without icterus! Physiologic icterus in horses: due to inappetence (decr. bilirubin uptake by liver) why Additional Terminology Necrosis Vs Apoptosis (review) Biliary Hyperplasia: Proliferation of mature biliary cells Ductular reaction: “Oval cells” proliferation of progenitor cells (can become bile ductule epithelium or hepatocytes) Regeneration Hyperplasia (proliferation) Hepatocytes, bile duct epithelium, sinusoids Nodular Regeneration of the liver can regain Replace lost mass Ain’t pretty Not as functional Cirrhosis Gall Bladder Disorders Cholelithiasis Bile concretions (choleliths, gallstones) Ruminants +/- obstructions no Horses getthis Cystic Mucinous Hyperplasia of GB Dogs, sheep Usually incidental Spongy Cysts, polypoid masses containing mucous Gallbladder Mucocele Small breed dogs Shetland sheepdogs Gall bladder filled with jelly-like mucous Hyperplastic GB mucosa Etiology: unk (Cushinoid dogs have higher incidence) Ass’d with: Obstruction GB rupture Thrombosis of GB Hepatobiliary System Liver Disease Patterns / General Disorders of Domestic Animals / Terminology of Geographical Patterns of Lesions Recognizing patterns can help with determining differentials! Random Bacteria toxins virussome Fungus Bridging degen & necrosis a.usweconnectingwadamant Massive degen & necrosis Lobular (entire lobule) Acinar (CV to CV) Zones Centrilobular (Zone 3) Midzonal (Zone 2) Periportal (Zone 1 )  Things to remember! Although lesions can begin as a pattern discussed prior…. They happen in real time They grow! They coalesce! So may hinder ability to appreciate the initial pattern if the lesion /disease has been around for a while Random patterns No preference of destruction (apoptosis, necrosis) Many etiologies Virus Bacteria Fungal Parasitic (protozoal) Bridging vs Massive Necrosis Bridging: coalescing lesions with adjacent lobules Massive: Entire lobule +/- contiguous lobules affected  Zonal Patterns (NOT Random) Usually produce an enhanced gross lobular pattern But need histo to determine which zone is affected (cannot see this with the naked eye) pariportal Midzonal Central lobular Case: 1 10 day old calf Pale mm Distended abdomen Coughing , slow moving Died: necropsy pics are next! What do you see? (Describe- do not diagnose!) Bronchil pneumonia pulmonary edema ID organs describe lesions Lesion related or not? Which came first? Can you give a morph for each lesion? ftp.IY.ummc.fi iI sareasorfinrosons Heart I thought this lecture was on liver?? - well, here you go….. Morph: hepatomegaly, chronic passive congestion Related or unrelated to heart and lung? What is the lesion histologically? Know what to expect! Need to understand anatomy /physio first! Here is the histo….. Now explain why here…. central lobular hepatocytes coagulative Necrosis Due to hypoxia CV http://www.niehs.nih.gov/research/atniehs/labs/lep/path-support/core-support/liverpath/necrotic/ Blood Flow within the Lobule Bile flow flows AWAY from CV towards PT  Centrilobular Hepatocytes: A Double Whammy! Prone to injury during a diseased state Why? Toxins: Uber metabolically active cells here (CP450 system) Metabolites to more toxic metabolites sus to Injury Blood flow Think location! Heart failure -> Blood flow is compromised https://www.kelsopr.com/public-relations-agency-blog/pr-double-whammy-in-the-times-for-solicitors-neglectassist Gross Lesion: Reticular Pattern in the Liver Does it mean anything important? http://rivista-cdn.reptilesmagazine.com/images/cache/cache_3/cache_1/cache_9/Normal-reticulated-python50-ca3f9913.jpeg?ver=1531063081&aspectratio=1.6 https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjksJvHrdbdAhUEU98KHUy7DMoQjRx6BAgBEAU&url=https%3 A%2F%2Fanimals.mom.me%2Fdifference-between-masai-reticulated-giraffes-3135.html&psig=AOvVaw1piIlEQxu2AOiNMzNSLL7R&ust=1537971795220522 Guide to Reticular pattern lesion is happening in Nextlobule insamepiece NOT specific for any one disease BUT….gives you insight! Reticular pattern: Wherever the lesion is in the lobule, other lobules have the same lesion location http://www.cfsph.iastate.edu/DiseaseInfo/ImageDB/RHD/RHD_003.jpg https://noahsarkive.cldavis.org/cgi-bin/show_image_info_detail.cgi?image=F32365 Back to our Case… Although it may not look like it now…. If observed early enough, this liver could have had a reticular pattern grossly Here, lesions have been developing We refer to this lover as a “Nutmeg Liver” due to chronic passive congestion ( toxins are another common cause of NL)  Reticular vs. Nutmeg Liver Pattern: Main difference is chronicity NL commonly observed with chronic passive congestion https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcTm4sknzL- NSTtLYDAvzdOWf2j_jCBBOhc-_8UWYlmMNfap_EBl https://encryptedn0.gstatic.com/images?q=tbn:ANd9GcQteQEL7tBEklWEfiCxRtjj447i6bmoW uOGrmAg5EpqR9qlfybn https://vet.uga.edu/ivcvm/courses/vpat5215/digestive/images/f02448.jpg Patterns and Specific Disease Examples Periportal degeneration / necrosis: Some toxicities (phosphorus) Midzonal degeneration / necrosis Aflatoxins (Po and Eq) C/L Degeneration / necrosis: ****perfusion problems Anemia Not enough Bloodflow Rt side heart failure Toxins / drugs Disorders of Domestic Animals: Biliary Cysts Congenital All domestic species (esp dogs, cats, pigs) Incidental (usually) Single, multiple and fluid filled Congenital (inherited) polycystic disease Liver, kidney, +/- pancreas WHW terriers, Persians (PKD1,2 gene defect) Can be silent or clinical DDX: parasitic cysts (cysticerci) https://noahsarkive.cldavis.org/cgi-bin/show_image_info_detail.cgi?image=F21174 Capsular Fibrosis Pathologic? Abnormal, not usually pathologic (not currently causing disease now) BUT gives info because: Commonly from resolution of nonseptic peritonitis Also thought might be from previous parasite migration Recovered chronichealing by  Portosystemic Shunts Acquired Portal hypertension (abscess, tumors, cirrhosis, congestive heart failure, etc) Congenital Intrahepatic shunt Failure of closure ductus venosus (connects umbilical vein to vena cava) Large breed dogs Extrahepatic shunt Porto-caval, portal- azygous vein shunt more common types Small breed dogs and cats What would you expect the liver to look like? * think about function! Atrophy smaller PSS Sequelae: Hepatic encephalopathy Hyperammonemia Ammonuim biurate crystals in urine Dueto Bypass of liver whichcausesbuildup of Ammonium https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiD6r-z- 9jdAhVhTt8KHZIABr0QjRx6BAgBEAU&url=https%3A%2F%2Fwww.mysecondhome.com%2Fblog%2Fwhat-is-head-pressing-in-dogs-cats%2F&psig=AOvVaw1KvF5w-R-s33_kUzyOr91d&ust=1538061414476960 Metabolic Disturbances: Lipidosis (Steatosis) When lipid metabolism goes wrong: Triglyceride accumulation in hepatocytes > rate of degradation or release as lipoproteins=> Lipidosis up cannot keep **NOT a specific disease entity**many diseases can cause this High fat or carbohydrate diet Increased metabolism of fat Lactation, starvation, endocrine disorders Abnormal hepatocyte function -> leading to accumulation of triglycerides in cells fat getting cannot process Decreased apoprotein synthesis-> Decreased export of lipoproteins Secretory defects of hepatocytes (impaired secretion of lipoprotein) Increased glucose / insulin concentrations Putting the P-h-a-t in Fatty Liver: The Who and the How Cobalt/ Vit B deficiency: “White liver disease”: sheep, goats usuallyyellow Ketosis , Bovine fatty liver syndrome High energy demands (obese, late gestation right before or after parturition) Feline fatty liver syndrome Obese, anorexic cats -> hepatic failure Hepatocellular Steatosis: donkeys, ponies, mini horses Overweight, pregnant, lactating Baby got back! Fatty livers: Swollen with rounded borders Pale Friable Greasy on cut surface shouldbeunder Ribcage Might present as a reticular pattern! Gross Path: DDXs for pale, swollen livers Lipid (Hepatic lipidosis) Hepatocytes contain lipid vacuoles Glycogen (Steroid induced hepatopathy, diabetes, glycogen storage diseases) Hepatocytes contain glycogen and water Hepatic amyloidosis Ducks Spaces of Disse contain amyloid (also basement membranes of other organs) Red Congo Glycogen Hepatopathy Glucose stored in hepatocytes as glycogen (normal) Excessive accumulation of glycogen Midzonal distribution Enlarged, rounded borders, pale, NONGREASY Diseases causing metabolic disturbances Diabetes Steroid induced Iatrogenic Cushings Glycogen Storage diseases Hepatic Amyloidosis IEtagism Can affect many organs! Liver Kidney (if in liver and kidney, renal failure usually manifests before liver) nasal mucosa Not a single disease entity! Many disease can manifest to this Amyloidosis Types AL amyloid Primary amyloidosis Secreted in B cell proliferative disorders AA amyloid Secondary or reactive amyloidosis (consequence of prolonged inflammation) AA synthesized from SAA by liver Hereditory amyloidosis (familial amyloidosis) Shar Pei Abyssinian cats ß-amyloid Beta pleated sheet- deposition in Alzheimer’s (also found in old dogs) blood vessels, basement membranes, spaces of disse, spleen  Iodine stain: Fresh tissue Special stain: Formalin fixed tissue Congo red (board question!) Apple green birefringence under polarized light Amyloidosis Why it is a big deal: Deposition of material that cannot be broken down (formation of beta pleated sheet) Compression, occlusion of spaces (space of disse) Organs most affected Kidney (mesangium, BM): glomerulonephropathy = protein loss Liver (space of disse): birds Spleen ( red pulp, PAL sheaths) Many others Copper Toxicosis 1983–present copper-plated zinc Liver stores copper normally! Sequestered to prevent toxicosis Liver: bound to metallothionein, stored in lysosomes Toprinttoxicosis In serum: Cu bound to ceruloplasmin Suspect Copper deficiency / toxicity? TAKE Serum and A LIVER SAMPLE! Excess copper-> free radicals (ROS) Damage RBCs Oxidative intravascular hemolysis Penny-loafers! Ha!  All species affected! High Cu diet Overcorrection for Cu deficiency Cu in sprays, fertilizers Sheep, ruminants, pigs Normal Cu, low Molybdenum Mo antagonizes copper uptake Metabolic disorders of Cu Bedlington terriers (MURR1, COMMD1 gene defect) Familial copper retention: Dobermans, Labrador retrievers, Skye terriers, West Highland white terriers, Dalmatians Liver stores Cu-> insult to liver-> massive release of Cu into circulation Sheep are susceptible: they accumulate Cu faster than other species Hepatotoxic phytotoxins (pyrrolizidine alkaloid plants Crotalaria, Senecio, Heliotroptium) https://www.memecreator.org/meme/one-does-not-simply-get-cu-toxicosis-by-ingesting-lots-of-copper How do we know it’s copper in those hepatocytes? Rhodanine Staining Other Hepatic Accumulations Bile pigments Hemosiderin: iron containing pigment (blood) derived from ferritin Local / systemic excess of iron breakdown of RBCs Hemosiderosis: abundant hemosiderin in tissues no organ dysfunction Hemochromatosis: increased storage of iron with organ dysfunction Melanin: melanosis nut to Monomaman poorama.uainfantinematinee to damage connessing tissue Lipofuscin: wear and tear pigment, nonpathologic, age related Ceroid: pathologic, looks like lipofuscin, peroxidation of fat Parasitic hematin: “fluke exhaust”  Hemosiderin – Prussian Blue Stain Lipofuscinosis – Schmorl’s Stain Fluke exhaust from parasitic migration Hepatobiliary System Viral / Bacterial / Parasitic / Fungi Specific Viral Hepatic Diseases Herpesvirus EHV-1 BHV-1 CHV-1 Caprine herpesvirus FHV-1 ILT: Gallid herpesvirus-1 Pseudorabies (Suid herpesvirus-1) What do they all have in common? Alphaherpesviruses! Cytolytic (Random necrosis) Variable inflammation Persistant, latent Fast replicating INIB Abortogenic (fetuses and neonates commonly affected) Most severe before thermoregulation capability of animal Not Liver specific (it is a virus, afterall) Liver, lung, spleen especially Herpesviral infections Infection routes Transplacental Ascending into the uterus Contact with infected littermates Oronasal secretions from dam FIP Mutated feline coronavirus Liver often involved (multisystemic) Pyogranulomatous vasculitis Fatal Wet form Type III hypersensitivity Dry form Type IV hypersensitivity Infectious Canine Hepatitis Canine adenovirus-1 Subclinical Dogs enter portal circulation (opportunistic bacteria) -> necrosuppurative hepatitis  Leptospirosis ZOONOTIC > 23 antigenically distinct pathogenic serogroups >200 serovars Each serovar differs with species & organs affected and severity of disease Many causing IV hemolysis Enter mucous membranes / broken skin Shed in urine Systemic disease / Abortions Centrilobular areas (IV hemolysis! Perfusion) +/- icterus Dissociation of hepatocytes = friable liver Warthin Starry Stain http://d2r2ijn7njrktv.cloudfront.net/apnlive/uploads/2018/05/15151115/Scientists-a-step-closer-to-potential-vaccine- against-Leptospirosis.jpg Mycobacterium Granulomas Mycobacterium bovis Mycobacterium avium-intracellulare complex Gross – random granulomas modular Lung / Liver. Mycobacteriosis in Python molurus Acid-fast positive PCR http://www.scielo.br/scielo.php?script=sci_ arttext&pid=S1678-91992016000100320 Parasitic diseases Nematodes, Cestodes, Trematodes Ascaris Suum Random! Milk spots (fibrosis) Abscesses/ granulomas Stephanurus dentatus: pig Strongylus spp.: horse Dirofilaria immitis Caval syndrome Dirofilaria immitis Dogs Vena caval syndrome (DIC, intravascular hemolysis, acute hepatic failure) Severe passive congestion from blocked caudal vena cava Hypersensitivity to antigens? Cestodes Cysts Taenia hydatigena – dogs Cysticercus tenuicollis – horses, ruminants, pigs Echinococcus granulosus – dogs, sheep, cattle http://dora.missouri.edu/wp-content/uploads/2013/01/CESTODES-WITH-A-RAT-INTERMEDIATE-HOST.jpg Trematodes Ruminants Fasciola hepatica Fascioloides magna Parasite hematin Secondary Clostridial disease! (perfect anaerobic environment!!!) Clostridium haemolyticum C. novyi Dogs Heterobilharzia americana – shistosome granulomatous lesions (liver, mesentery, pancreas, more) Location can help with ID of parasite! Thick bile ducts: prolferative cholangiohepatitis : “pipe stem” liver F. hepatica: (adults) bile ducts F. magna: (adults) BD & parenchyma Fungal Ruminants: Aspergillus Zygomycetes Mucor, Absidia, Rhizopus Systemic fungi! Blastomyces dermatiditis Coccidiodes immitis iii Histoplasma capsulatum Cryptococcus neoformans Staining: PAS, GMS, Mucicarmine specificforc ryptococcus Hepatobiliary System Toxins  TOXINS Love Liver! Why? Examples: Cyanobacteria Plants Pyrrolizidine alkaloid plants Cycads palmtree Mycotoxins Aflatoxin Phomopsin Sporidesmin Mushrooms Chemicals Xylitol Phosphorus A Double Whammy! Metals / Nutrients C/L necrosis: perfusion , CP450 Drugs centrionnar Common Patterns of Liver to Hepatotoxins C/L necrosis! (most common) Cytochrome P450 system In SER of hepatocytes metabolize lipid soluble chemicals into water-soluble compounds for excretion from the body in bile or urine (biotransformation) Periportal Random Hepatocellular apoptosis Hepatotoxic Agents Cyanobacteria (Blue-green algae) Microcystis Affects Livestock > dogs, cats Late summer / early fall Toxin: Microcystin LR Hemorrhage and necrosis (GI, liver) C/L to massive necrosis (+sinusoidal endothelial necrosis) https://img.apmcdn.org/85b6095501ef430c476475f1a3fb3abe8d9fb0c5/uncropped/8b4f7d-20170816-algaebloom01.jpg Pyrrolizidine Alkaloid Plants Senecio, Cynoglossum, Amsinckia, Crotalaria Mostly chronic intoxication Pigs > cattle, horses > sheep, goats Fibrotic liver Characteristic histologic features: Megalocytosis (prevention of cell division , but not DNA synthesis, biliary proliferation, fibrosis, +/- nodular regeneration DDX: aflatoxins, nitrosamines Cycads Contain cycasin, macrozamin -> deconjugated by intestinal bacteria -> toxic metabolite= methylazoxymethanol Liver, GI, neurotoxin Acute : C/L necrosis nzpalms.co.nz Chronic: Cattle: megalocytosis , nuclear hyperchromasia, varying fibrosis, GI disease progressive proprioceptive deficits in the hind limbs Acute: sheep > other species Dogs can also be intoxicated by cycads Cholestatic Plant Intoxications Photosensitization common sequelae Lantana Lantadena A, B, C Chronic cholestasis Brassicca (turnip, kale) Unk toxin Mimics sporidesmin Cholangiectasis, peribiliary fibrosis Mycotoxins (fungal toxins) Aflatoxins: Aspergillus flavus -> aflatoxin B1 Corn, peanuts, cottonseed, commercial dog food Carcinogen, toxin, teratogen Pigs > dogs> horses > calves > birds (ducks, turkeys) > adult horses & cattle Firm, pale liver Histo: steatosis, biliary hyperplasia, C/L to bridging necrosis / fibrosis, cellular atypia of hepatocytes (megalocytosis) Phomopsin: Lupine plants Cattle, sheep, horses Chronic: atrophic, fibrotic liver +++mitoses, H/C necrosis, biliary hyperplasia Mushrooms (Amanita sp.) – toxin: cyclopeptides Small liver, C/L to massive necrosis, steatosis, hemorrhage Death Sporidesmin (toxin) : Pithomyces chartarum (fungus) grows in dead ryegrass Sheep > cattle plan Necrosis: epithelium biliary ducts with minimal inflammation Cholestasis-> failure to excrete phylloerythrin -> photosensitization (lesions predominantly on head)= “ facial eczema” Left lobe of the liver (increased proportion of blood draining from SI), most severely affected +/- atrophy and fibrosis. “boxing glove” liver Hepatotoxic Chemicals Xylitol Artificial sweetener hypoglycemia Acute toxin: dogs hyperinsulinemia, hypoglycemia Icterus, liver failure, seizures C/L or midzonal to massive necrosis White Phosphorus Rodenticide PERIPORTAL necrosis (unusual pattern for a toxin) Does not need CP450 Metals / Mineral / Nutritional deficiencies/ toxicities Iron Copper Hepatosis dietetica (Vit E/ Sel def) http://www.greenhome.com/wordpress/wpcontent/uploads/2016/07/xylitol.jpg Hepatotoxic Drugs MANY! Cats > dogs to intoxication by many chemicals (cats are relatively deficient in hepatic glucuronyltransferase activity) Acetaminophen (cats) > dogs Carprofen (varies among canine breeds) Anticonvulsants—primidone, phenytoin, and phenobarbital (dogs) Hepatosis Dietetica Vit E/ Selenium def Free radical (oxidative damage) leads to necrosis Young, rapid growing pigs C/L to massive necrosis Equine Serum Hepatitis Horses with injection of biologic (contains equine serum) equine antisera: tetanus antitoxin or pregnant mare serum gonadotropin Possible infectious etiology Fast clinical course and death Hepatic encephalopathy, icterus Dish rag liver: massive necrosis (loss of structural integrity) https://www.google.com/search?q=dishrag&source=lnms&tbm=isch&sa=X&ved=0ahUKEwiIvaaRyeXdAh XHnuAKHUEaAx8Q_AUIDigB&biw=1440&bih=758#imgrc=v_O9DHt6Cnpy_M: Raised (Nodular) Liver Lesions Hepatic Neoplasia (just a few……) Primary neoplasia ( arising from the liver) Hepatocellular adenoma Can be confused with nodular regeneration grossly Metastatic neoplasia (very common!) Hepatocellular carcinoma Often solitary, well demarcated (but malignant!) Easily confused grossly with adenoma Lymphoma Additional Tumors of the Liver Lymphoma (usually metastasized from another organ) Hemangioma / sarcoma Melanoma Lymphoma Biliary Neoplasia Cholangiocellular adenoma Biliary epithelium neoplastic cells Biliary cystadenoma (a variant) Cholangiocellular carcinoma Biliary epithelium neoplastic cells Umbilicated lesions we ussion arresse outrigger Metastasis common https://noahsarkive.cldavis.org/cgi-bin/show_image_info_detail.cgi?image=F55643