Liver Flashcards
Blood supply to liver
Portal circulation (70-80%)
Hepatic artery (30-20%)
Classic lobule
Centrilobular region: at center of hexagon (central vein - blood out of liver, bile in)
Midzonal region: middle region
Periportial region: (portal triad, blood into liver, bile out)
Hepatic acinus
Zonal model
Zone 1 ~ periportal
Zone 2 ~ midzonal
Zone 3 ~ centrilobular
Portal triad
Portal venule
Hepatic arteriole
Bile ductule
Indicators of liver injury
Leakage enzymes (cytosolic) - ALT (dogs/cats), AST (liver and muscle), SDH (large animals)
Inducible enzymes (membrane bound) - ALP (dogs/cats), GGT- liver and biliary (all species)
Kupffer cells
Macrophages living in space of Disse
Phagocytize RBCs, accumulate iron
Also phagocytize bacteria, endotoxin, apoptosis cells, etc.
Can accumulate ceroid/lipofusin (wear and tear pigment)/lipid
Lipogranuloma
Fatty cyst
Accumulate in macrophage??
Stellate cells
Vitamin A metabolism
May —> myfibroblasts —> fibrosis
Between sinusoids and hepatocytes in space of Disse
Liver function
Protein synthesis (albumin, fibrinogen, clotting factors, globulins)
Bile metabolism/transport
Bilirubin metabolism
Drug metabolism
Conversion of toxic compounds of GI origin (i.e. NH3)
Lipid/CHO
Sequelae of hypoalbuminemia
Ascites
Sequelae due to coagulopathy
Hemorrhage
Primary photosensitization
Photodynamic compound that can’t be excreted goes to skin (e.g. St John’s wort)
Secondary (hepatogenous) photosensitization
Follows colestasis in herbivores
Phylloerythrin (catabolism of chlorophyll) or other photodynamic compound accumulates
Congenital porphyria
Hereditary defect in heme metabolism —> photosensitization
Hyperbilirubinemia
Leads to icterus/jaundice
Types of icterus
Prehepatic
Hepatic
Post hepatic
Prehepatic icterus
Caused by hemolysis
Causes vary (immune-mediated, infectious, trauma, metabolic, toxin, etc)
Increased unconjugated bilirubin
Hepatic icterus
Liver disease comprises ability to uptake/excrete bilirubin
Increased conjugated and unconjugated bilirubin
Posthepatic icterus
Bile duct obstruction —> increased conjugated bilirubin
Hepatoencephalopathy
Inability to detox NH3 —> travels to brain and produces neurological signs
Reaction to liver injury
Hydropic or vacuolar degeneration
Glycogen accumulation
Fatty change/lipidosis
Storage disorders
Necrosis
Inflammation
Bile stasis
Vacuolar hepatopathy
Reversible injury
- hepatocellular swelling
- glycogen accumulation
- hepatic lipidosis
Hepatocellular swelling
Cells accumulate water due to inability to maintain fluid/ionic homeostasis
First sign of must injury
Swelling with pale staining cytoplasm
Glycogen accumulation
Hepatocytes swelling with clear cytoplasm, WITHOUT displacement of nucleus from cell center
Usually midzonal
Orangey hue to liver
Steroid hepatopathy
ONLY in dogs
Associated with glucocorticoids —> accumulation of glycogen in hepatocytes
Hepatic lipidosis
Vacuoles of lipid in cytoplasm of hepatocytes
Yellowy liver
Mechanisms of fatty Change in liver
Over-ingestion of fats or carbs (leading to FA synthesis)
Mobilization of fatty stores
Decreased oxidation of FAs
Decreased apoprotein in synthesis
Decreased export of lipoproteins
Tension lipidosis
Lipid accumulations at edges of liver due to anoxic environment created by tension
Feline fatty liver syndrome
Hepatic lipidosis in cats - usually a larger cat going off feed
Storage disorders
Accumulations in hepatocytes/Kupffer cells due to inherited metabolic disorders
Need to identify storage product and enzyme deficiency/defective gene for definitive diagnosis
Requirements for definitive diagnosis of storage disorder
Identification of storage product and enzyme deficiency / defective gene
Canine copper-associated hepatopathy
Accumulation of copper in hepatocytes, overlap with chronic hepatitis
Cu accumulates in centrolobular hepatocytes —> necrosis and inflammation —> chronic hepatitis/cirrhosis
Breeds with predilection for copper-associated hepatopathy
Bedlington terrier
West highland white terrier, Dalmatian (familial association)
Doberman pinschers, labs, cocker spaniels (breed predisposition)
Stain for detecting Cu
Rubeanic acid stain
Types of necrosis
Liquefactive
Coagulative
Patterns of necrosis
Focal
Multifocal
Confluent
Bridging
Massive
Piecemeal
Pattern of necrosis indicating infectious agents
Multifocal random
Pattern of necrosis indicating toxic or nutritional cause
Massive
Pattern of necrosis indicated toxic or hypoxic cause
Zonal
Hepatitis
Inflammation of liver parenchyma
Cholangitis
Inflammation of bile ducts
Cholangiohepaitits
Inflammation of bile ducts with extension into liver parenchyma
Cholecystitis
Inflammation of the gall bladder
Choledochitis
Inflammation of the larger/common bile ducts
Bile stasis / colestasis
Bile in canaliculi or bile ducts
Intracellular or extra/post-hepatic
Due to toxins, inflammation, duct obstruction
Often with Hyperbilirubinemia
Inc in inducible enzymes in circulation
Pyrollizidine alkaloid toxicosis
Specific toxic insult in horses —> bile stasis
Sequelae of necrosis and inflammation
Regeneration > fibrosis > bile duct hyperplasia
Cirrhosis
Cirrhosis
severe diffuse (bridging) hepatic fibrosis with nodular regeneration and bile duct hyperplasia
Fibrosis and nodular regeneration
Bands of fibrosis between nodules of normal (restored) hepatic tissue
Often seen with chronic hepatitis
Visualization of fibrosis with Masson’s trichrome or Van Gieson’s stain
Sequelae of cirrhosis
Portal hypertension —> multiple acquired portosystemic shunts —> Ascites
Loss of hepatic function —> insufficiency —> failure—> coagulopathy, Hyperbilirubinemia, hepatoencephalopathy, edema, Ascites, photosensitization
Congenital liver disease
Hereditary Hyperbilirubinemia
Storage diseases
Peritoneal-pericardial diaphragmatic hernia
Vascular shunts (common)
Biliary abnormalities
Biliary cysts
Nodules will be greenish or yellowish in color
Can be multifocal or focal
Traumatic insult to liver
Displacement through hernia
Rupture
Hematoma from blunt trauma
Lobar torsion (may occur with trauma)
Factors predisposing liver to rupture
Hepatitis
Neoplasia
Fatty liver
Amyloidosis
Amyloidosis
Eosinophilic material in space of Disse
Atrophy of adjacent hepatocytes, dilation of sinusoids; Lugol’s iodine to see amyloid (black)
Increases friability of liver
Can be associated with inflammatory conditions (secondary/reactive amyloid), breed predisposition
Can hemorrhage with biopsy
Vascular causes of liver injury
Congestion
Infarction
Portal thrombi
Portosystemic shunts/vascular anomalies
Passive congestion in liver
Secondary to CHF
Can form fibrosis
“Nutmeg” liver - blood pooling and loose
Congenital portosystemic shunt
Often leads to hepatic hypoplasia/microhepatica
Typically a single, less tortuous shunt
Small stature, anesthetic intolerance, behavior abnormalities, head pressing, seizures, GI signs, …
Acquired portosystemic shunt
Tend to be multiple, extra-hepatic, tortuous
Ascites may develop
Associated with cirrhosis, portal hypertension
Intrahepatic portosystemic shunt more frequently found in
Large breed dogs (patent ductus venosus)
Extrahepatic portosystemic shunt more frequently found in
Small breed dogs, cats, ferrets
Primary portal vein hypoplasia
Microvascular dysplasia
Non-cirrhosis portal hypertension
Congenital
Peliosis hepatis (telangiectasia)
Dilation of small groups of sinusoids
Generally incident finding
Primarily in cattle/cats
Causes of inflammatory liver disease
Viral
Bacterial
Fungal
Parasitic
Idiopathic (serum hepatitis in horse, chronic hepatitis in dogs, lobular dissecting hepatitis)
Cholangitis
Infectious canine hepatitis
Canine adenovirus 1
Rare due to vaccination
Edema blue eyes
Necrosis/inflammation of liver
(Also caused turkey spotted kidney)
Viral causes of hepatitis
CAV-1 (dogs)
Herpesviruses (mammals, birds)
Coronaviruses (FIP virus, murine coronavirus)
Rift Valley fever (ruminants)
Bacterial causes of hepatitis
Clostridium spp
Salmonella spp
Leptospirosis
Mycobacteria spp
Parasitic causes of hepatitis
Protozoa (T. Gondii, N. Caninum, Eimeria stiedae)
Nematodes (larval migrans, Ascaris suum)
Cestodes (cysts in liver)
Trematodes (Fasciola spp, Fascioloides spp)
Tyzzer’s disease
C. Piliforme (Gram NEGATIVE clostridium)
Obligate intracellular
K9, Equine
Fibrinous cholecystitis
Caused by Salmonella
Inflammation of gall bladder
Clostridium hemolyticum
Bacterial cause of hepatitis
Focally extensive, bacillary haemoglobinuria
Clostridium novyi
Infectious necrotic hepatitis / black disease
In cattle / sheep
Proliferate in area of ischemia often associated with a liver fluke
Liver abscesses
Common in cattle
Associated with omphalitis
Often Fusobacterium necrophorum in large animals
Also Salmonella, Lepto, Mycobacteria
Multifocal necrosis
Granulomatous hepatitis can be caused by
Mycobacterium spp
Histoplasma capsulatum (fungi)
Eimeria stediae
Causes severe proliferative hepatitis in rabbits
Proliferative colangitis
Milk spot liver caused by
Ascarid migration in pigs (A. suum)
Hepatic tremadoiasis
Fasciola hepatica - bovine
Opisthorchis felineus - felin
Serum hepatitis / Theiler’s disease
(Small friable) Dish rag liver in horses with severe diffuse centrilobular necrosis
Historically associated with administration of xenobiotics, vaccines, idiopathic
Most recently suggests Equine parvovirus hepatitis
Acute massive necrotizing hepatitis
Chronic Canine Hepatitis
Chronic inflammation of liver (often periportal)
Lymphocytes, plasma cells, few neutrophils
Most canine hepatitis is idiopathic
Approximately 1/3 associated with excess Cu
Chronic (lymphocytic) Cholangitis in cats
Chronic inflammation of bile duct/ductules
Often associated with IBD/pancreatitis (triaditis)
Idiopathic
Histologically may overlap with small cell lymphoma —> immunohistochemistry may be needed
Lobular dissecting hepatitis
Rare idiopathic inflammatory disease
Young to middle aged large breed dogs
Mixed inflammation with fibroplasia throughout sinusoids (separates hepatocytes)
Poor prognosis
Acute neutrophilic (Suppurative) Cholangitis
Believed to involve ascending bacterial infection, in rare occasions, obstruction of extrahepatic bile ducts
Cats > dogs
Histo: onion skin like lesions, looser/more clear space than lymphocytic Cholangitis
Predictable (e.g. toxin)
Dose-dependent
Idiosyncratic
Individual response (i.e. dose independent toxin)
Direct toxin
Toxic as ingested
Indirect toxin
Toxic as metabolized
Mechanisms of hepatoxicity
DNA damage (alkylation, intercalating)
RNA damage (binding RNA polymerase, impair RNA transcription)
Inhibition of lysosomal enzymes
Production of free radicals - membrane damage
Canalicular damage —> bile stasis/icterus
Stimulation of apoptosis
Idiopathic
Manifestation of liver toxicity
No morphological abnormalities (biochem only)
Fatty change / lipidosis
Cell swelling
Bile stasis
Necrosis
Examples of toxins
Pharmaceuticals (NSAIDs, phenobarbital)
Plants
Mushrooms
Algae
Acute copper toxicity results in liver disease in … grazing on pasture high in … and low in …
Often associated with a stressful event
Sheep
Cu
Mo
Hepatosis dietetica
Liver disease in swine attributed to Vit E / Se deficiency
Pathogenesis of Hepatosis dietetica
Lack of antioxidants —> massive centrilobular necrosis by ROS damage
Hepatosis dietetica is seen in combination with what cardiovascular disease?
Mulberry heart disease
Hepatocutaneous syndrome is associated with what other disease condition
Superficial necrolytic dermatitis (severe keratosis of paws/nose)
Cystic mucosal hyperplasia of the gall bladder
Incidental finding
Nodular hyperplasia
Incidental finding
Most dogs >10 will develop 0.5 to 10 cm nodules
Hepatocellular adenoma
Single large mass
Uncommon, but present in dogs; rare in other species
Cholangiocellular (biliary) cystadenoma
Green or yellow tumor in liver
Singular or multifocal
Gall bladder adenoma
Occurs uncommonly in dogs
Hepatocellular carcinoma
Uncommon in dogs (rarely metastatic)
Rare in other species
Cholangiocellular (bile duct) carcinoma
Biliary duct tumor
Umbilicated lesions
Highly infiltrative and metastatic
Uncommon, but both dogs and cats
Metastatic tumors affecting the liver
Lymphosarcoma
Metastatic (pancreatic) carcinoma
Diffuse mast cell tumor
Histiocytic sarcoma
Hemangiosarcoma
Gall bladder lesions
Cystic mucosal hyperplasia
Mucocele
Infarction / cholecystitis
Choleliths (stones)
Mucocele
Kiwi fruit ultrasound
Accumulation of inspissated bile and/or mucin in gall bladder
Idiopathic
May lead to obstruction / rupture
Cholelithiasis
Infrequent
May lead to obstruction
Cholecystitis
Secondary to pressure necrosis/inflammation with obstruction or ascending bacterial infection
