Patterns of Hepatobiliary & Pancreatic Disease in Dogs & Cats Flashcards
what are the 7 critical functions of the liver
- bilirubin metabolism
- bile acid metabolism
- carbohydrate metabolism
- lipid metabolism
- xenobiotic metabolism (bioactivation, detoxification)
- protein synthesis (albumin, globulins, apoproteins, clotting factors)
- immune function
describe the architecture of the liver
what is the zonal organization of the hepatic lobule
periportal area (zone 1)
midzonal area (zone 2)
centrilobular area (zone 3)
describe how the zonal organization of the hepatic lobulue
what is shown here
PV = portal vein
LP = limiting plate
BD = bile duct
HA = hepatic artery
LV = lymphatic vessel
what are the functions of fenestrated endothelial cells
dynamic filter of plasma proteins, solutes and particulate matter
what is the function of kupffer cells
phagocytosis
what are the functions of stellate cells
lipid and vitamin storage, fibrosis (reparative response to injury through myofibroblast transformation and fibrosis)
how is bilirubin metabolized (10)
- senescent erythrocytes
- phagocytozed by macrophages in splee, bone marrow, and liver
- globin portion degraded within macrophages (constituents returned to the amino acid pool)
- heme Fe transferred to Fe-binding proteins such as trasnferrin for recycling
- remaining portion of heme
- biliverdin
- bilirubin (circulating bound to albumin)
- uptake by hepatocytes
- glucuronydation
- bile excretion
what are the ezymes that are secreted as inactive proenzymes (6)
- trypsin
- chymotrypsin
- collagenase
- phospholipase
- elastases
- carboxypeptidases
what are the enzymes that are secreted as active enzymes
amylase
lipase
what are the liver vascular anomalies in the dog (3)
- portosystemic shunts (PSSs)
- congenital extrahepatic shunts
- intrahepatic shunts
what is a congenital extrahepatic shunts
shunting from portal vein or major tributaries (left gastric or splenic veins, less commonly gastroduodenal or mesenteric veins) to the caudal vena cava (portocaval shunt) or to the azygous vein (portoazygous shunt)
what are intrahepatic shunts
located in left hepatic division
persistent patent fetal ductus venosus
what type of hepatic shunts are common in large breed dogs
typically large intrahepatic shunts
usually patent ductus venosus, but sometimes large intrahepatic communications
what hepatic shunts are common in small breed dogs
single large extrahepatic shunts between portal vein and vena cava or azygous vein
how do acquired portosystemic shunts occur (4)
- chronic liver disease
- periportal fibrosis
- portal hypertension
- development of multiple tortuous shunting vessels
what is shown here
acquired portosystemic shunt
multiple tortuous shunting vessels
what is primary portal vein hypoplasia
affected extrahepatic or intrahepatic portal vein (or both) accompanied by portal hypertension with a development of multiple collateral portosystemic shunts
what is congenital hepatoportal microvascular dysplasia
without accompanying macroscopic portosystemic shunts
what breeds is congenital hepatoportal microvascular dysplasia seen in
- cairn terriers
- yorkies
- maltese
what are histological features of portosystemic shunts (5)
- hepatocellular atrophy
- closely and unevenly spaced portal triads
3. portal triads with attenuated or absent portal vein profiles
4. proliferation/reduplication or portal arterioles
- possible bile duct proliferation
what histological change is seen here
proliferation of portal arterioles
absence of portal vein
what are the clinical presentation of congenital shunts (3)
- failure to thrive
- neurological signs (hepatic encephalopathy)
- history of depression, convulsions, and other nervous signs exacerbated by a high protein diet, and may be alleviated by dietary control
what are the presenting signs of acquired shunts
with chronic liver disease resulting in portal hypertension
- elevation of liver enzymes serum levels
- possible ascites
what are the toxins implicated in hepatic encephalopathy (11)
- ammonia
- aromatic amino acids
- bile acids
- decreased alpha ketoglutaramate
- endogenous benzodiazepines
- false neurotransmitters
- GABA
- glutamine
- phenol
- short chain fatty acids
- tryptophan
what type of virus is canine adenovrius 1
DNA virus
what tropism does canine adenovirus have
for endothelium, mesothelium and hepatocytes
what is the clinical presentation of canine adenovirus 1 (5)
- fever
- vomiting and melena (in severe cases)
- abdominal pain
- corneal opacity (edema) in chronic cases (possible spontaneous resolution)
- rare peracute cases –> sudden death without clinical manifestations
what are some gross pathological changes to the liver caused by canine adenovirus 1 (4)
- granular appearance of serosal surface
- scattered petechial or blotchy serosal hemorrhages
- liver enlarged (but with sharp edges) and friable
- fibrin strands on liver surface, particularly between lobules
what other gross pathological changes can be seen in the rest of the GI tract following canine adenovirus 1 (3)
- small amounts of blood tinged fluid the abdomen
- gallbladder wall thickening (edema)
- hemorrhages in other organs (kindey, lung) variable
what is the likely cause of these pathological changes
dog CAV-1 infection
what is changes are seen here and what is the likely cause
fibrin tags on liver lobes
gall bladder wall thickened by edema
CAV-1 infection
what histopathological changes are seen here and what is the likely cause
hepatocellular necrosis and loss
intranuclear viral inclusion bodies
dog CAV-1 infection
what can cause chronic hepatitis in dogs (3)
- viruses
- bacteria
- toxins
what is copper associated with in dogs
implicated in progressive necro-inflammatory canine liver disease with breed related susceptibility
what are inflammatory infiltrates dominated by in chronic hepatitis in dogs (2)
- CD3+
- T-cells
what damages does chronic hepatitis in dogs cause to the liver (2)
- hepatocellular necrosis and loss
- progression to parenchymal collapse and fibrosis
what mechanisms might contribute to chronic hepatitis in dogs
immune mediated/autoimmune mechanisms
what type of inflammation does a primary hepatopathy cause (5)
moderate to marked inflammatory inflitrate of
- lymphocytes
- plasmacytic
- neutrophilic
- granulomatous
- eosinophilic
what type of damage does a primary hepatopathy cause
necrosis/apoptosis
+/- ductular proliferation
+/- fibrosis
what is the clinical scenario with primary hepatopathies (2)
- moderate to severe increased ALT
- +/- abnormal function tests
what type of infiltrate does chronic hepatitis cause (4)
mild to moderate inflammatory infiltrate
- lymphcytic
- neutrophilic
- granulomatous
- eosinophilic
what damage is seen in chronic hepatitis (3)
- necrosis/apoptosis
- portal-portal or portal-central fibrosis with lobular architechture distortion
- regenerative nodules (micronodular or macronodular)
whta is the clinical scenario with chronic hepatitis (6)
- increased total serum bile acids
- hyperbilirubinemia
- hypoalbuminemia
- +/- ascites
- acquired portosystemic shunts
- portal hypertension
what type of inflammation does a secondary hepatopathy cause (4)
mild to moderate portal inflammation
- lymphocytic
- plasmocytic
- neutrophilic
- granulomatous
is there necrosis/apoptosis with a secondary hepatopathy
no
is there fibrosis with a secondary hepatopathy
no
is there architechtural remodelling with a secondary hepatopathy
no
what is the clinical scenario of a secondary hepatopathy
- ALT/ALP 3x upper limit of normal
- normal function tests
what are the most common causes of canine chronic hepatitis
- immune
- toxic –> copper
- infectious is uncommon
what are the most common clinical signs of chronic hepatitis (13)
- decreased appetite
- lethargy/depression
- icterus
- ascites
- PU/PD
- vomiting
- diarrhea
- hepatic encephalopathy
- melena
- abdominal pain
- gingival bleeding
- hematochezia
- hemoperitoneum
what are the clinical pathologies that are most commonly seen in chronic hepatitis (8)
- increase ALT
- increased ALP
- increased ASP
- increased GGT
- increased total serum bile acids
- decreased BUN
- decreased albumin
- decreased cholesterol
what is consistently seen in hematology and clinical chemistry in chronic hepatitis
increased ALT and ALP
in most cases increased in AST, GGT, bilirubin and resting BAs
decreased albumin and urea
increased PT and PTT
what histological changes are seen in chronic hepatitis (5)
- portal and parenchyma inflammation (mainly lymphocytes and plasmacells)
- hepatocyte necrosis/apoptosis associated with inflammation
- variable periportal to bridging fibrosis
- copper accumulation in the periportal regions (secondary to cholestasis)
- no infectious agents (viruses or bacteria) identified
what is DLA
dog leukocyte antigen
central role in control of the immune system
regulation/presentation of self and non self antigens to the immune system
what is DLA involved in with chronic hepatitis
associated with susceptibility/resistence to chronic hepatitis in english springer spaniels
increased risk of chronic hepatitis
what is copper essential for
cofactor for enzymes and cellular functions
what is copper homeostasis regulated by (4)
- uptake in the GI tract
- intra and extra cellular trafficking system
- distribution through the body (bound to ceruloplasmin)
- cellular storage (metallothionein) and excretion (mainly in the bile)
what breed has genetic basis for copper associated canine liver disease
bedlington terriers
autosomal recessive gene deletion which has an important role in copper biliary excretion
what other breeds have a predisposition of copper associated liver disease (5)
- dobermann
- west highland white terrier
- skye terrier
- dalmation
- lab retriever
how is copper associated liver disease diagnosed
- determination of copper levels in fresh liver tissue sample
- histopathology, special strains (Rhodanin/rubeanic acid)
where is primary copper accumulation in the liver
centrilobular
where is the secondary to chronic liver injury copper accumulation
secondary is mainly periportal
what are the clinical signs of copper associated chronic hepatitis (10)
- exercise intolerance
- depression
- anorexia
- vomiting
- weight loss
- polyuria/polydipsia
- icterus
- diarrhea
- ascites
- salivation
what are the clinical findings with copper assocaited with chronic hepatitis in dogs (2)
- hemolysis from Cu release into blood (only bedlington terriers)
- serum biochemistry abnormaities (increase in ALT higher than ALP)
what are toxic causes of liver disease in dogs (3)
- xylitol
- amanitin
- microcystin-LR (from blue green algae)
what are therapeutic drugs that can cause liver disease in dogs (4)
- trimethoprim-sulfonamide
- mebendazole (antiparasitic)
- anticonvulsant drugs (primidone, phenytoin, phenobarbital)
- carprofen
what causes endogenous steroid induced hepatopathy
cushing’s syndrome
how does cushing’s disease lead to steroid induced hepatopathy
hyperadrenocorticism (possibly related to ACTH secreting pituitary tumour) –> sustained increased levels of circulating glucocorticoids
intracytoplasmic accumulation of glycogen and fluid –> marked hepatocellular swelling/vacuolation
what is shown here in the liver
marked hepatocellular swelling/vacuolation from endogenous steroid induced hepatopathy
what are the types of steroid induced hepatopathy
- iatrogenic: prolonged admin of corticosteroids
- endogenous: cushing’s
what is suppurative cholangitis/cholangiohepatitis common in
mature/aged cats 11-15 years
less common in dogs
what is the acute phase of suppurative cholangitis/cholangiohepatitis (2)
- inflammation and degeneration of bile ducts
- inflammation extending into lobules and periportal hepatocyte necrosis
what is the subacute phase of suppurative cholangitis/cholangiohepatitis
- cholangiohepatits with mixed inflammation + bile duct proliferation and variable periportal to bridging fibrosis
what is the chronic stage of suppurative cholangitis/cholangiohepatitis
concentric periportal fibrosis and pseudolobule formation
what is the pathogenesis of suppurative cholangitis/cholangiohepatitis
biliary tract inflammation assocaited with ascending bacterial infection
what is the most common bacteria involved in suppurative cholangitis/cholangiohepatitis
E. coli
where are the bacteria present in suppurative cholangitis/cholangiohepatitis
portal vessels, sinusiods and parenchyma than the bile ducts
what age does lymphocytic cholangitis/cholangiohepatits most common occur in cats
>4 years
what does lymphocytic cholangitis/cholangiohepatits lead to
progression to prominent fibrosis with cholestasis and possible icterus
what is gallbladder mucocele in dogs
gallbaldder distention with accumulated mucoid secretion
possible extension and accumulation of bile laden mucus into cystic, hepatic and common bile ducts –> variable extrahepatic obstruction
what can occur with severe cases of gallbladder mucocele in dogs
distention with abnormal semisolid accumulations of mucus
possible ischemic necrosis and rupture
what histopathological changes can be seen with gallbladder mucocele
hyperplasia of mucus secreting glands
formation of mucus filled cysts
what is the etiopathogenesis of gallbladder mucocele (3)
- decreased gallbladder motility
- bile stasis
- altered bile compostition and viscosity
what breed is juvenile pancreatic atrophy commonly seen in
german shepherds
what is the etiology of juvenile pancreatic atrophy
preceded by intense inflammatory cell infiltration dominated by CD*+ T-lymphocytes (atropic lymphocytic pancreatitis)
presumed autoimmune process against acinar cells
what is exocrine pancreatic insufficiency (EPI) caused by in dogs
juvenile pancreatic atrophy
what is exocrine pancreatic insufficiency (EPI) caused by in cats
chronic pancreatitis
what occurs with clinical onset of exocrine pancreatic insufficiency
85%-90% of secretory capacity is lost
how is exocrine pancreatic insufficiency diagnosed
serum levels of trypsin like immunoreactivity (TLI)
what are the clinical features of exocrine pancreatic insufficiency (3)
- diarrhea and chronic weight loss despite voracious appetite
- possible steatorrhea (fat in feces) due to inadequate digestion and assimilation of lipids
- malassimilation of nutrients (lack of direct digestive action of pancreatic enzymes and lack of activation of intestinal enzymatic activities)
what is the pathogenesis of acute pancreatic necrosis
activation of trypsinogen to trypsin within acinar cells
trypsin then causes activation of pancreatic enzymes which causes autodigestion of the pancreas
what are the early lesions in acute pancreatic necrosis
necrosis and inflammation at the periphery of affected lobules
with variable involvement of adjacent adipose and connective tissue
what do elastase and phospholipase A enzyme activation cause in acute pancreatic necrosis
expansion of the area of pancreatic necrosis
what do lipases cause in acute pancreatic necrosis
hydrolysis and necrosis of peripancreatic fat
what are the effects of the acute pancreatic enzymes
trypsin, phospholipase A, elastase, lipase and colipase –>
damage the walls of the local blood vessels –>
increased vascular permeability –>
edmea, hemorrhage, thrombosis
how is the complement cascade activated in acute pancreatic necrosis (4)
the enzymatic tissue necrosis + superimposed ischemic necrosis
- local activation of the complement cascade
- release of cytokines TNF-alpha, IL-1. IL-6, IL-8 and platelet-activating factor (PAF)
- leukocyte chemotaxis into the area
- amplification of pancreatic damage via the generation ROS and additional cytokine release
what are the systemic effects of acute pancreatic necorsis (7)
- cytokines, NO and activated digestive enzymes are released into the circulation
- consumption of circulating protease inhibitors
- activation of kinin system, coagulation, fibrinolytic system, complement
- systemic inflammatory response
- hypotension
- hypovolemic shock
- DIC
- multiple organ failure
what does the release of activated enzymes, vasoactive peptides, inflammatory mediators and embolic debris into the systemic circulation (3)
- multifocal hepatocellular necrosis
- pulmonary edema and acute interstitial pneumonia
- myocardial injury with arrhythmias
what can lead to acute renal failure from acute pancreatic necrosis
microvascular thrombosis in DIC
tubular degeneration induced by hypotension/hypoperfusion
what are complications that can occur in acute pancreatic necorsis due to the systemic effects (4)
- portal vein thrombosis
- pulmonary thromboembolism
- physical obstruction of the extrahepatic bile duct or duodenum
- intestinal ileus (intestinal paralysis)
what factors increase the risk for acute pancreatic necrosis (8)
- middle aged to old dogs
- overweight or obese
- nutrtitional factors (amount and quality of dietary lipids)
- breeds: mini schnauzer, yorkie, mini poodles, non-sporting/non-working breeds
- females > males
- hyperadrenocorticism
- hypothyroidism
- hypercalcemia
what is acute pancreatitis
inflammation with ductal and lobular distribution
what is acute pancreatitis in dogs
reflux of bacteria or activated enzymes and bile salts from the intestine
what is acute pancreatitis in cats
frequently associated with Toxoplasmosis
what is chronic pancreatitis
extension of inflammatory process starting in the ducts
what is chronic pancreatitis frequently associated with (3)
- ascending infection with intestinal bacteria
- migration of flukes
- migrating larvae of strongylus equinus and strongylus edentatus in horses
what causes granulomatous/pyogranulomatous pancreatitis
systemic fungal infections
feline infectious peritonitis
what are biomarkers used for pancreatitis/pancreatic necrosis (2)
- canine pancreas-specific lipase (cPSL)
- canine pancreatic elastase-1 (cPE-1)
what is feline pancreatitis commonly associated with
concurrent disease in other organ systems
what are frequent co morbidities associated with feline pancreatits
hepatic lipidosis
inflammatory liver disease (ILD)
bile duct obstruction
diabetes mellitus
inflammatory bowel disease (IBD)
vitamin deficiencies (B12/cobalamin, folate, K)
intestinal lymphoma
nephritis
pulmonary thromboembolism
pleural and peritoneal effusions
what is triaditis
concurrent inflammation of the pancreas, liver and small intestine
what are the clinical features of triaditis
anorexia, weight and muscle mass loss, diarrhea, vomiting, icterus, hepatomegaly, thickened intestine, pancreatic mass, abdominal pain, abdominal effusion, pyrexia, hypothermia, tachypnea, dyspnea and shock
what are the clinical chemistry abnormalities in triaditis
liver enzymes elevation (ALT, AST< GGT, ALP) + bilirubin increase (hepatobiliary disease)
eleveated pancreatic lipase serum levels (pancreatitis)
decreased cobalamin, folate and albumin (IBD or intestinal lymphoma)
