Patterns of Hepatobiliary & Pancreatic Disease in Dogs & Cats

Question 1

what are the 7 critical functions of the liver

Answer 1

1. bilirubin metabolism
2. bile acid metabolism
3. carbohydrate metabolism
4. lipid metabolism
5. xenobiotic metabolism (bioactivation, detoxification)
6. protein synthesis (albumin, globulins, apoproteins, clotting factors)
7. immune function

Question 2

describe the architecture of the liver

Answer 2

Question 3

what is the zonal organization of the hepatic lobule

Answer 3

periportal area (zone 1)

midzonal area (zone 2)

centrilobular area (zone 3)

Question 4

describe how the zonal organization of the hepatic lobulue

Answer 4

Question 5

what is shown here

Answer 5

PV = portal vein

LP = limiting plate

BD = bile duct

HA = hepatic artery

LV = lymphatic vessel

Question 6

what are the functions of fenestrated endothelial cells

Answer 6

dynamic filter of plasma proteins, solutes and particulate matter

Question 7

what is the function of kupffer cells

Answer 7

phagocytosis

Question 8

what are the functions of stellate cells

Answer 8

lipid and vitamin storage, fibrosis (reparative response to injury through myofibroblast transformation and fibrosis)

Question 9

how is bilirubin metabolized (10)

Answer 9

1. senescent erythrocytes
2. phagocytozed by macrophages in splee, bone marrow, and liver
3. globin portion degraded within macrophages (constituents returned to the amino acid pool)
4. heme Fe transferred to Fe-binding proteins such as trasnferrin for recycling
5. remaining portion of heme
6. biliverdin
7. bilirubin (circulating bound to albumin)
8. uptake by hepatocytes
9. glucuronydation
10. bile excretion

Question 10

what are the ezymes that are secreted as inactive proenzymes (6)

Answer 10

1. trypsin
2. chymotrypsin
3. collagenase
4. phospholipase
5. elastases
6. carboxypeptidases

Question 11

what are the enzymes that are secreted as active enzymes

Answer 11

amylase

lipase

Question 12

what are the liver vascular anomalies in the dog (3)

Answer 12

1. portosystemic shunts (PSSs)
2. congenital extrahepatic shunts
3. intrahepatic shunts

Question 13

what is a congenital extrahepatic shunts

Answer 13

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)

Question 14

what are intrahepatic shunts

Answer 14

located in left hepatic division

persistent patent fetal ductus venosus

Question 15

what type of hepatic shunts are common in large breed dogs

Answer 15

typically large intrahepatic shunts

usually patent ductus venosus, but sometimes large intrahepatic communications

Question 16

what hepatic shunts are common in small breed dogs

Answer 16

single large extrahepatic shunts between portal vein and vena cava or azygous vein

Question 17

how do acquired portosystemic shunts occur (4)

Answer 17

1. chronic liver disease
2. periportal fibrosis
3. portal hypertension
4. development of multiple tortuous shunting vessels

Question 18

what is shown here

Answer 18

acquired portosystemic shunt

multiple tortuous shunting vessels

Question 19

what is primary portal vein hypoplasia

Answer 19

affected extrahepatic or intrahepatic portal vein (or both) accompanied by portal hypertension with a development of multiple collateral portosystemic shunts

Question 20

what is congenital hepatoportal microvascular dysplasia

Answer 20

without accompanying macroscopic portosystemic shunts

Question 21

what breeds is congenital hepatoportal microvascular dysplasia seen in

Answer 21

1. cairn terriers
2. yorkies
3. maltese

Question 22

what are histological features of portosystemic shunts (5)

Answer 22

1. hepatocellular atrophy
2. closely and unevenly spaced portal triads

3. portal triads with attenuated or absent portal vein profiles

4. proliferation/reduplication or portal arterioles

5. possible bile duct proliferation

Question 23

what histological change is seen here

Answer 23

proliferation of portal arterioles

absence of portal vein

Question 24

what are the clinical presentation of congenital shunts (3)

Answer 24

1. failure to thrive
2. neurological signs (hepatic encephalopathy)
3. history of depression, convulsions, and other nervous signs exacerbated by a high protein diet, and may be alleviated by dietary control

Question 25

what are the presenting signs of acquired shunts

Answer 25

with chronic liver disease resulting in portal hypertension 1. elevation of liver enzymes serum levels 2. possible ascites

Question 26

what are the toxins implicated in hepatic encephalopathy (11)

Answer 26

1. ammonia 2. aromatic amino acids 3. bile acids 4. decreased alpha ketoglutaramate 5. endogenous benzodiazepines 6. false neurotransmitters 7. GABA 8. glutamine 9. phenol 10. short chain fatty acids 11. tryptophan

Question 27

what type of virus is canine adenovrius 1

Answer 27

DNA virus

Question 28

what tropism does canine adenovirus have

Answer 28

for endothelium, mesothelium and hepatocytes

Question 29

what is the clinical presentation of canine adenovirus 1 (5)

Answer 29

1. fever 2. vomiting and melena (in severe cases) 3. abdominal pain 4. corneal opacity (edema) in chronic cases (possible spontaneous resolution) 5. rare peracute cases --\> sudden death without clinical manifestations

Question 30

what are some gross pathological changes to the liver caused by canine adenovirus 1 (4)

Answer 30

1. granular appearance of serosal surface 2. scattered petechial or blotchy serosal hemorrhages 3. liver enlarged (but with sharp edges) and friable 4. fibrin strands on liver surface, particularly between lobules

Question 31

what other gross pathological changes can be seen in the rest of the GI tract following canine adenovirus 1 (3)

Answer 31

1. small amounts of blood tinged fluid the abdomen 2. gallbladder wall thickening (edema) 3. hemorrhages in other organs (kindey, lung) variable

Question 32

what is the likely cause of these pathological changes

Answer 32

dog CAV-1 infection

Question 33

what is changes are seen here and what is the likely cause

Answer 33

fibrin tags on liver lobes gall bladder wall thickened by edema CAV-1 infection

Question 34

what histopathological changes are seen here and what is the likely cause

Answer 34

hepatocellular necrosis and loss intranuclear viral inclusion bodies dog CAV-1 infection

Question 35

what can cause chronic hepatitis in dogs (3)

Answer 35

1. viruses 2. bacteria 3. toxins

Question 36

what is copper associated with in dogs

Answer 36

implicated in progressive necro-inflammatory canine liver disease with breed related susceptibility

Question 37

what are inflammatory infiltrates dominated by in chronic hepatitis in dogs (2)

Answer 37

1. CD3+ 2. T-cells

Question 38

what damages does chronic hepatitis in dogs cause to the liver (2)

Answer 38

1. hepatocellular necrosis and loss 2. progression to parenchymal collapse and fibrosis

Question 39

what mechanisms might contribute to chronic hepatitis in dogs

Answer 39

immune mediated/autoimmune mechanisms

Question 40

what type of inflammation does a primary hepatopathy cause (5)

Answer 40

moderate to marked inflammatory inflitrate of 1. lymphocytes 2. plasmacytic 3. neutrophilic 4. granulomatous 5. eosinophilic

Question 41

what type of damage does a primary hepatopathy cause

Answer 41

necrosis/apoptosis +/- ductular proliferation +/- fibrosis

Question 42

what is the clinical scenario with primary hepatopathies (2)

Answer 42

1. moderate to severe increased ALT 2. +/- abnormal function tests

Question 43

what type of infiltrate does chronic hepatitis cause (4)

Answer 43

mild to moderate inflammatory infiltrate 1. lymphcytic 2. neutrophilic 3. granulomatous 4. eosinophilic

Question 44

what damage is seen in chronic hepatitis (3)

Answer 44

1. necrosis/apoptosis 2. portal-portal or portal-central fibrosis with lobular architechture distortion 3. regenerative nodules (micronodular or macronodular)

Question 45

whta is the clinical scenario with chronic hepatitis (6)

Answer 45

1. increased total serum bile acids 2. hyperbilirubinemia 3. hypoalbuminemia 4. +/- ascites 5. acquired portosystemic shunts 6. portal hypertension

Question 46

what type of inflammation does a secondary hepatopathy cause (4)

Answer 46

mild to moderate portal inflammation 1. lymphocytic 2. plasmocytic 3. neutrophilic 4. granulomatous

Question 47

is there necrosis/apoptosis with a secondary hepatopathy

Answer 47

no

Question 48

is there fibrosis with a secondary hepatopathy

Answer 48

no

Question 49

is there architechtural remodelling with a secondary hepatopathy

Answer 49

no

Question 50

what is the clinical scenario of a secondary hepatopathy

Answer 50

1. ALT/ALP 3x upper limit of normal 2. normal function tests

Question 52

what are the most common causes of canine chronic hepatitis

Answer 52

1. immune 2. toxic --\> copper 3. infectious is uncommon

Question 53

what are the most common clinical signs of chronic hepatitis (13)

Answer 53

1. decreased appetite 2. lethargy/depression 3. icterus 4. ascites 5. PU/PD 6. vomiting 7. diarrhea 8. hepatic encephalopathy 9. melena 10. abdominal pain 11. gingival bleeding 12. hematochezia 13. hemoperitoneum

Question 54

what are the clinical pathologies that are most commonly seen in chronic hepatitis (8)

Answer 54

1. increase ALT 2. increased ALP 3. increased ASP 4. increased GGT 5. increased total serum bile acids 6. decreased BUN 7. decreased albumin 8. decreased cholesterol

Question 55

what is consistently seen in hematology and clinical chemistry in chronic hepatitis

Answer 55

increased ALT and ALP in most cases increased in AST, GGT, bilirubin and resting BAs decreased albumin and urea increased PT and PTT

Question 56

what histological changes are seen in chronic hepatitis (5)

Answer 56

1. portal and parenchyma inflammation (mainly lymphocytes and plasmacells) 2. hepatocyte necrosis/apoptosis associated with inflammation 3. variable periportal to bridging fibrosis 4. copper accumulation in the periportal regions (secondary to cholestasis) 5. no infectious agents (viruses or bacteria) identified

Question 57

what is DLA

Answer 57

dog leukocyte antigen central role in control of the immune system regulation/presentation of self and non self antigens to the immune system

Question 58

what is DLA involved in with chronic hepatitis

Answer 58

associated with susceptibility/resistence to chronic hepatitis in english springer spaniels increased risk of chronic hepatitis

Question 59

what is copper essential for

Answer 59

cofactor for enzymes and cellular functions

Question 60

what is copper homeostasis regulated by (4)

Answer 60

1. uptake in the GI tract 2. intra and extra cellular trafficking system 3. distribution through the body (bound to ceruloplasmin) 4. cellular storage (metallothionein) and excretion (mainly in the bile)

Question 61

what breed has genetic basis for copper associated canine liver disease

Answer 61

bedlington terriers autosomal recessive gene deletion which has an important role in copper biliary excretion

Question 62

what other breeds have a predisposition of copper associated liver disease (5)

Answer 62

1. dobermann 2. west highland white terrier 3. skye terrier 4. dalmation 5. lab retriever

Question 63

how is copper associated liver disease diagnosed

Answer 63

1. determination of copper levels in fresh liver tissue sample 2. histopathology, special strains (Rhodanin/rubeanic acid)

Question 64

where is primary copper accumulation in the liver

Answer 64

centrilobular

Question 65

where is the secondary to chronic liver injury copper accumulation

Answer 65

secondary is mainly periportal

Question 66

what are the clinical signs of copper associated chronic hepatitis (10)

Answer 66

1. exercise intolerance 2. depression 3. anorexia 4. vomiting 5. weight loss 6. polyuria/polydipsia 7. icterus 8. diarrhea 9. ascites 10. salivation

Question 67

what are the clinical findings with copper assocaited with chronic hepatitis in dogs (2)

Answer 67

1. hemolysis from Cu release into blood (only bedlington terriers) 2. serum biochemistry abnormaities (increase in ALT higher than ALP)

Question 68

what are toxic causes of liver disease in dogs (3)

Answer 68

1. xylitol 2. amanitin 3. microcystin-LR (from blue green algae)

Question 69

what are therapeutic drugs that can cause liver disease in dogs (4)

Answer 69

1. trimethoprim-sulfonamide 2. mebendazole (antiparasitic) 3. anticonvulsant drugs (primidone, phenytoin, phenobarbital) 4. carprofen

Question 70

what causes endogenous steroid induced hepatopathy

Answer 70

cushing's syndrome

Question 71

how does cushing's disease lead to steroid induced hepatopathy

Answer 71

hyperadrenocorticism (possibly related to ACTH secreting pituitary tumour) --\> sustained increased levels of circulating glucocorticoids intracytoplasmic accumulation of glycogen and fluid --\> marked hepatocellular swelling/vacuolation

Question 72

what is shown here in the liver

Answer 72

marked hepatocellular swelling/vacuolation from endogenous steroid induced hepatopathy

Question 73

what are the types of steroid induced hepatopathy

Answer 73

1. iatrogenic: prolonged admin of corticosteroids 2. endogenous: cushing's

Question 74

what is suppurative cholangitis/cholangiohepatitis common in

Answer 74

mature/aged cats 11-15 years less common in dogs

Question 75

what is the acute phase of suppurative cholangitis/cholangiohepatitis (2)

Answer 75

1. inflammation and degeneration of bile ducts 2. inflammation extending into lobules and periportal hepatocyte necrosis

Question 76

what is the subacute phase of suppurative cholangitis/cholangiohepatitis

Answer 76

1. cholangiohepatits with mixed inflammation + bile duct proliferation and variable periportal to bridging fibrosis

Question 77

what is the chronic stage of suppurative cholangitis/cholangiohepatitis

Answer 77

concentric periportal fibrosis and pseudolobule formation

Question 78

what is the pathogenesis of suppurative cholangitis/cholangiohepatitis

Answer 78

biliary tract inflammation assocaited with ascending bacterial infection

Question 79

what is the most common bacteria involved in suppurative cholangitis/cholangiohepatitis

Answer 79

E. coli

Question 80

where are the bacteria present in suppurative cholangitis/cholangiohepatitis

Answer 80

portal vessels, sinusiods and parenchyma than the bile ducts

Question 81

what age does lymphocytic cholangitis/cholangiohepatits most common occur in cats

Answer 81

\>4 years

Question 82

what does lymphocytic cholangitis/cholangiohepatits lead to

Answer 82

progression to prominent fibrosis with cholestasis and possible icterus

Question 83

what is gallbladder mucocele in dogs

Answer 83

gallbaldder distention with accumulated mucoid secretion possible extension and accumulation of bile laden mucus into cystic, hepatic and common bile ducts --\> variable extrahepatic obstruction

Question 84

what can occur with severe cases of gallbladder mucocele in dogs

Answer 84

distention with abnormal semisolid accumulations of mucus possible ischemic necrosis and rupture

Question 85

what histopathological changes can be seen with gallbladder mucocele

Answer 85

hyperplasia of mucus secreting glands formation of mucus filled cysts

Question 86

what is the etiopathogenesis of gallbladder mucocele (3)

Answer 86

1. decreased gallbladder motility 2. bile stasis 3. altered bile compostition and viscosity

Question 87

what breed is juvenile pancreatic atrophy commonly seen in

Answer 87

german shepherds

Question 88

what is the etiology of juvenile pancreatic atrophy

Answer 88

preceded by intense inflammatory cell infiltration dominated by CD\*+ T-lymphocytes (atropic lymphocytic pancreatitis) presumed autoimmune process against acinar cells

Question 89

what is exocrine pancreatic insufficiency (EPI) caused by in dogs

Answer 89

juvenile pancreatic atrophy

Question 90

what is exocrine pancreatic insufficiency (EPI) caused by in cats

Answer 90

chronic pancreatitis

Question 91

what occurs with clinical onset of exocrine pancreatic insufficiency

Answer 91

85%-90% of secretory capacity is lost

Question 92

how is exocrine pancreatic insufficiency diagnosed

Answer 92

serum levels of trypsin like immunoreactivity (TLI)

Question 93

what are the clinical features of exocrine pancreatic insufficiency (3)

Answer 93

1. diarrhea and chronic weight loss despite voracious appetite 2. possible steatorrhea (fat in feces) due to inadequate digestion and assimilation of lipids 3. malassimilation of nutrients (lack of direct digestive action of pancreatic enzymes and lack of activation of intestinal enzymatic activities)

Question 94

what is the pathogenesis of acute pancreatic necrosis

Answer 94

activation of trypsinogen to trypsin within acinar cells trypsin then causes activation of pancreatic enzymes which causes autodigestion of the pancreas

Question 95

what are the early lesions in acute pancreatic necrosis

Answer 95

necrosis and inflammation at the periphery of affected lobules with variable involvement of adjacent adipose and connective tissue

Question 96

what do elastase and phospholipase A enzyme activation cause in acute pancreatic necrosis

Answer 96

expansion of the area of pancreatic necrosis

Question 97

what do lipases cause in acute pancreatic necrosis

Answer 97

hydrolysis and necrosis of peripancreatic fat

Question 98

what are the effects of the acute pancreatic enzymes

Answer 98

trypsin, phospholipase A, elastase, lipase and colipase --\> damage the walls of the local blood vessels --\> increased vascular permeability --\> edmea, hemorrhage, thrombosis

Question 99

how is the complement cascade activated in acute pancreatic necrosis (4)

Answer 99

the enzymatic tissue necrosis + superimposed ischemic necrosis 1. local activation of the complement cascade 2. release of cytokines TNF-alpha, IL-1. IL-6, IL-8 and platelet-activating factor (PAF) 3. leukocyte chemotaxis into the area 4. amplification of pancreatic damage via the generation ROS and additional cytokine release

Question 100

what are the systemic effects of acute pancreatic necorsis (7)

Answer 100

1. cytokines, NO and activated digestive enzymes are released into the circulation 2. consumption of circulating protease inhibitors 3. activation of kinin system, coagulation, fibrinolytic system, complement 4. systemic inflammatory response 5. hypotension 6. hypovolemic shock 7. DIC 8. multiple organ failure

Question 101

what does the release of activated enzymes, vasoactive peptides, inflammatory mediators and embolic debris into the systemic circulation (3)

Answer 101

1. multifocal hepatocellular necrosis 2. pulmonary edema and acute interstitial pneumonia 3. myocardial injury with arrhythmias

Question 102

what can lead to acute renal failure from acute pancreatic necrosis

Answer 102

microvascular thrombosis in DIC tubular degeneration induced by hypotension/hypoperfusion

Question 103

what are complications that can occur in acute pancreatic necorsis due to the systemic effects (4)

Answer 103

1. portal vein thrombosis 2. pulmonary thromboembolism 3. physical obstruction of the extrahepatic bile duct or duodenum 4. intestinal ileus (intestinal paralysis)

Question 104

what factors increase the risk for acute pancreatic necrosis (8)

Answer 104

1. middle aged to old dogs 2. overweight or obese 3. nutrtitional factors (amount and quality of dietary lipids) 4. breeds: mini schnauzer, yorkie, mini poodles, non-sporting/non-working breeds 5. females \> males 6. hyperadrenocorticism 7. hypothyroidism 8. hypercalcemia

Question 105

what is acute pancreatitis

Answer 105

inflammation with ductal and lobular distribution

Question 106

what is acute pancreatitis in dogs

Answer 106

reflux of bacteria or activated enzymes and bile salts from the intestine

Question 107

what is acute pancreatitis in cats

Answer 107

frequently associated with Toxoplasmosis

Question 108

what is chronic pancreatitis

Answer 108

extension of inflammatory process starting in the ducts

Question 109

what is chronic pancreatitis frequently associated with (3)

Answer 109

1. ascending infection with intestinal bacteria 2. migration of flukes 3. migrating larvae of strongylus equinus and strongylus edentatus in horses

Question 110

what causes granulomatous/pyogranulomatous pancreatitis

Answer 110

systemic fungal infections feline infectious peritonitis

Question 111

what are biomarkers used for pancreatitis/pancreatic necrosis (2)

Answer 111

1. canine pancreas-specific lipase (cPSL) 2. canine pancreatic elastase-1 (cPE-1)

Question 112

what is feline pancreatitis commonly associated with

Answer 112

concurrent disease in other organ systems

Question 113

what are frequent co morbidities associated with feline pancreatits

Answer 113

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

Question 114

what is triaditis

Answer 114

concurrent inflammation of the pancreas, liver and small intestine

Question 115

what are the clinical features of triaditis

Answer 115

anorexia, weight and muscle mass loss, diarrhea, vomiting, icterus, hepatomegaly, thickened intestine, pancreatic mass, abdominal pain, abdominal effusion, pyrexia, hypothermia, tachypnea, dyspnea and shock

Question 116

what are the clinical chemistry abnormalities in triaditis

Answer 116

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)