Liver and pancreatic disease Flashcards

Question

Chronic hepatitis is characterized by?

Answer 1

Chronic hepatitis is characterized by hepatocellular apoptosis or necrosis, a variable mononuclear or mixed inflammatory infiltrate, regeneration, and fibrosis. The proportion and distribution of these components vary widely, and it is necessary to include in the diagnosis the activity (determined by the quantity of inflammation and extent of hepatocellular apoptosis and necrosis) and the stage of the disease (determined by the extent and pattern of fibrosis and the possible presence of architectural distortion) as well as the possible etiology.

Answer 2

Toxic liver injury may develop after direct impact with the hepatocytes or after metabolic transformation by the liver from nontoxic substances to toxic metabolites. Toxins are often plant and fungal products, drugs, or chemicals, and they may cause a predictable dose-dependent injury or an idiosyncratic non–dose-dependent reaction in a minority of exposed animals. Toxic hepatic injury varies considerably with the type of reaction, dose, and duration of exposure to the toxin and includes no morphological abnormalities (biochemical only), hepatocellular swelling, steatosis and necrosis, cholestasis, inflammation and fibrosis.

Answer 3

Hepatic abscesses are usually caused by bacterial infections reaching the liver by several routes, as portal umbilical veins (particularly seen in newborn animals), ascending infection of the biliary system, and by direct contact and penetration of the liver capsule; in adult animals the infection may be caused by Yersinia spp., Nocardia asteroides, and Actinomyces spp. Hepatic abscesses may develop in association with central necrosis of hepatocellular neoplasms.

Answer 4

Hepatic granulomas may occur in both primary liver disease or in generalized disease. They consist of multifocal aggregation of activated macrophages, mostly infiltrated by lymphocytes and plasma cells, and fibroblasts, and they may be surrounded by collagen fibers. Infectious causes for hepatic granulomas in dogs and cats include mycobacterial infection, systemic mycoses, opportunistic fungal infections, migrating nematode larvae, and schistosomiasis. In dogs, diffuse granulomatous inflammation of the liver may be also caused by Leishmania infection and Bartonella spp. in cats it may be caused by Cytauxzoon felis infection.

Answer 5

Hepatic metabolic storage disorders, usually associated with inherited but sometimes acquired metabolic enzyme deficiencies, can vary in morphologic appearance. Most commonly it occurs with findings of clear vacuoles, vacuoles with granular or hyaline material, or pigmented granules in hepatocytes and/or Kupffer cells and macrophages. Administration of some xenobiotics (e.g., griseofulvin) may induce an acquired storage disease known as erythropoietic protoporphyria.

Answer 6

1. Hepatocellular neoplasia: (I) nodular hyperplasia (as distinguished from regenerative nodules seen in macronodular cirrhosis of the liver) (II) hepatocellular adenoma and (III) hepatocellular carcinoma 2.Cholangiocellular neoplasia: (I) cholangiocellular adenoma (II) cholangiocellular carcinoma (biliary carcinoma), and (III) mixed hepatocellular and cholangiocellular carcinomas. 3. Hepatic carcinoids (and hepatoblastoma): Hepatic carcinoids are thought to originate from preexisiting neuroendocrine cells in the epithelium. 4. Primary vascular and mesenchymal neoplasia includes hemangiosarcoma, lymphangioma, lymphangiosarcoma, fibrosarcoma, leiomyosarcoma, malignant mesenchymoma, osteosarcoma, and rhabdomyosarcoma. Except for hemangiosarcoma, these are extremely rare in dogs and cats.

Answer 7

carbohydrate, lipid, and protein metabolism; detoxification of metabolites and xenobiotics; storage of vitamins, trace metals, fat, and glycogen; fat digestion; and immunoregulation. The clinical signs, physical findings, and clinicopathologic abnormalities that accompany hepatic disease reflect deficiencies in these varied functions. The liver, however, has a tremendous reserve capacity to perform these functions. Thus the appearance of relatively specific signs of hepatobiliary disease such as icterus, hypoglycemia, bleeding tendencies, hepatic encephalopathy (HE), or ascites, which reflect exhaustion of the liver's functional reserves, occurs late in disease progression

Answer 8

Early clinical signs of hepatic disease—such as intermittent anorexia, polyuria/polydipsia (PU/PD), vomiting, and lethargy—are also common with disease in other organ systems.

Answer 9

Strong breed predispositions and the occurrence of several recognizable clinical syndromes that accompany hepatobiliary disease, including gastrointestinal ulceration, hepatic encepalopathy, tissue jaundice, coagulopathies, and ascites

Answer 10

Recent ingestion of a known hepatotoxic substance or treatment with a potentially hepatotoxic drug. Stunted growth, prolonged response to anesthesia, or drug intolerance in a young animal, particularly in a predisposed breed, suggests the presence of a PSVA. A recently stressed obese cat that becomes anorexic is a classic history for a cat with idiopathic hepatic lipidosis.

Answer 11

The gastrointestinal, renal, neurologic, and/or hematopoietic systems. In addition, a rare dermatological syndrome, called superficial necrolytic dermatitis, marked by ulcerative crusting dermatitis of the face and distal extremities, accompanies a unique form of chronic liver disease in dogs and cats known as hepatocutaneous syndrome

Answer 12

Hematemesis, abdominal pain, and/or melena.

Answer 13

HE is a neurological condition associated with failure of the liver to detoxify inhibitory neurotoxins generated in the intestinal tract. The clinical signs are those of diffuse cerebral disease. HE is most often seen with PSVA or with hepatopathies associated with acquired portosystemic shunts but may also accompany acute fulminant hepatic failure.

Answer 14

In acute failure the neurological signs of HE can be confused with those associated with hypoglycemia, which commonly accompanies severe acute hepatic failure. Cerebral edema, an ominous consequence of fulminant hepatic failure, can also cause neurological signs mimicking HE. The signs include disorientation, stupor, and coma, and a neuroexcitatory component to the neurological findings may be observed.

Answer 15

One of several important differential diagnoses for the presence of abdominal fluid accumulation is hepatobiliary disease. Ascites may accompany primary or metastatic hepatobiliary neoplasia, or it can signal the presence of bile peritonitis from rupture of the gallbladder or biliary tract. Portal hypertension (PH) due to increased portal venous blood flow or increased resistance to portal blood flow can lead to ascites.

Answer 16

PH can be prehepatic (obstruction of the portal vein or its branches prior to entering the liver), intrahepatic (obstruction of microscopic portal vein tributaries, sinusoids, or small hepatic veins) or posthepatic (obstruction within hepatic veins, cranial vena cava, or right atrium). In chronic inflammatory/fibrotic liver disease, intrahepatic PH may develop from capillarization of the hepatic sinusoidal endothelium.

Answer 17

(1) psychogenic polydipsia (2) alterations in portal vein osmoreceptors (3) decreased hepatic urea production, resulting in disruption of the renal medullary concentration gradient (4) potassium depletion (5) stimulation of thirst centers due to HE (6) increased endogenous cortisol levels associated with increased adrenal production or decreased hepatic degradation.

Answer 18

Ammonia biurate stones form due to chronic hyperammonemia and hepatic processing of uric acid.

Answer 19

The most significant physical finding that should prompt a consideration of hepatobiliary disease is icterus, a yellow discoloration of mucous membranes associated with accumulation of bilirubin. Pale mucous membranes, abdominal enlargement due to ascites or hepatomegaly, and poor body-condition score might be other findings on physical examination of animals with hepatobiliary disease.

Answer 20

Direct stimulation of chemoreceptor trigger zone Gastroduodenal ulceration Concurrent intestinal inflammatory disease

Answer 21

Extrahepatic bile duct obstruction

Answer 22

Gastroduodenal ulceration Coagulopathy

Answer 23

Hyperbilirubinemia

Answer 24

Portal hypertension Avid renal sodium and water retention Hypoalbuminemia

Answer 25

Blood loss from coagulopathy or GI bleeding Anemia of chronic disease

Answer 26

Evaluation of serum values of hepatobiliary enzymes—such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transpeptidase (GGT)—are used to screen for hepatobiliary disease. Consistent increases in serum enzyme concentrations occur following hepatobiliary injury. Although these serum enzymes have a high sensitivity for the detection of hepatobiliary disease, their interpretation is hampered by lack of specificity for hepatobiliary disease. The central role that the liver has in drug metabolism, its high blood flow, and its anatomical juxtaposition between the gastrointestinal tract and the systemic circulation make it uniquely sensitive to secondary injury. Thus there are several clinical conditions in which liver enzymes may be increased but in which clinically significant hepatobiliary disease may not be present

Answer 27

Although the magnitude of serum enzyme elevation is usually proportional to the severity of active hepatobiliary damage, the degree of elevation is not predictive of hepatobiliary functional capacity. Marked increases in serum enzymes may indicate substantial hepatobiliary injury, but the liver has tremendous regenerative capacity. Thus enzyme values do not indicate prognosis.

Answer 28

In severe, end-stage chronic liver disease, serum enzymes may be normal or only mildly increased, because replacement of hepatocytes by fibrosis and/or prolonged enzyme leakage can deplete total liver enzyme content.

Answer 29

Exposure to some hepatotoxins, such as aflatoxin and microcystin, may not be associated with elevation in serum transaminase values due to toxin-associated inhibition of enzyme gene transcription and/or biosynthesis. Thus a single serum enzyme determination should never be used to establish a prognosis. The prognostic value of serum enzymology is improved by following sequential serum enzyme determinations, especially in conjunction with a hepatic function test or hepatic biopsy.

Answer 30

ALT is a liver-specific cytosolic enzyme. The largest increases in serum ALT, a leakage enzyme, are seen with hepatocellular necrosis and inflammation. The magnitude of ALT elevation is roughly proportional to the number of injured hepatocytes.

Answer 31

The serum half-life in dogs is around 2.5 days. There are no published values for the half-life of feline ALT. In an acute insult, the finding of a 50% decrease in sequential serum ALT determinations over the course of the enzyme's half-life is considered a good prognostic sign. In dogs, serum ALT may also increase with severe muscle necrosis.

Answer 32

Serum AST is more sensitive than serum ALT in the detection of hepatobiliary disease, although it is considerably less specific, because significant amounts of AST are also contained in muscle. In instances where serum AST is much higher than serum ALT, a muscle source should be explored. Alternatively, since AST is present within the mitochondria as well as the cytosol, an elevated AST/ALT ratio may be indicative of acute severe irreversible injury.

Answer 33

ALP's low specificity is associated with the presence of several isoenzymes and its unique sensitivity to drug induction.

Answer 34

The liver, kidney, intestine, bone, and placenta.

Answer 35

The intestinal, kidney, and placental isoenzymes do not contribute to serum ALP due to their short half-life. An exception is in late-term feline pregnancy, where the placental ALP isoenzyme represents a significant source of the serum enzyme.

Answer 36

Increased osteoblastic activity associated with growing bones in young animals or with pathologic conditions, such as osteomyelitis or osteosarcoma, can increase serum B-ALP. These conditions typically cause mild increases in the total serum ALP.

Answer 37

A liver isoenzyme (L-ALP) and a corticosteroid-induced isoenzyme (C-ALP). In cats, there is only a liver isoenzyme.

Answer 38

In the dog and cat, L-ALP is a membrane-bound enzyme found on hepatocyte canalicular membranes and luminal surfaces of biliary epithelial cells.

Answer 39

Canine C-ALP is a hyperglycosylated form of the isoenzyme produced by hepatocytes and is also located on the hepatocyte canalicular membrane.

Answer 40

The serum half-life of both L-ALP and C-ALP in the dog is 70 hours. The half-life of the cat liver isoenzyme is only 6 hours.

Answer 41

Increases in serum ALP in the dog and cat are the result of increased de novo synthesis and/or elution of the enzyme from cellular membranes.

Answer 42

Exposure of dogs to excess endogenous or exogenous corticosteroids increases serum ALP.[28],[29]. Serum ALP elevation in corticosteroid-treated dogs is accompanied by changes in hepatic morphology, which include a ballooning enlargement of hepatocytes and development of intracytoplasmic hepatic vacuolation due to glycogen accumulation. In some studies, focal areas of hepatocyte necrosis have been described. In dogs treated with prednisone, these morphologic changes begin by day two and gradually progress in severity as corticosteroid treatment continues. A similar vacuolar hepatopathy can develop in dogs in the absence of exposure to exogenous or endogenous cortisol, presumably due to low-grade cortisol excess from chronic illness.

Answer 43

Chronic corticosteroid exposure due to hyperadrenocorticism or iatrogenic hypercortisolism from parenteral, oral, or topical corticosteroid administration is consistently associated with increases in C-ALP. Serum C-ALP also increases in chronically ill animals, apparently from long-term endogenous cortisol excess. While highly sensitive for the detection of exposure to corticosteroids, the specificity of isoenzyme analysis is very low, and many dogs with hepatobiliary disease also have increases in serum C-ALP

Answer 44

In dogs, corticosteroids increase serum ALT. In most dogs, drug induction results in mild (fourfold) increases in ALT; but in some individuals, increases approach those seen with acute hepatocellular injury. Whether these larger elevations in serum ALT activity represent enzyme induction or are reflective of possible corticosteroid hepatotoxicity is still unclear. Serum AST is marginally affected by corticosteroids.

Answer 45

Phenobarbital may induce either L-ALP and/or C-ALP. Interpretation of serum ALP elevations in dogs on phenobarbital is complicated by the fact that this drug is a hepatotoxin. Overall, the existing literature supports the observation that mild to moderate increases in ALP (up to five times the upper limit of normal) and ALT (up to two times the upper limit of normal) may reflect enzyme induction. However, increases in GGT and AST are seldom due to induction and may be suggestive of primary liver disease.

Answer 46

The magnitude of serum ALP elevations in feline hepatobiliary disease are not as great as those in dogs due to the short half-life of feline ALP, and because feline hepatic stores of ALP are less than in dogs. Thus feline serum ALP is a less sensitive indicator of hepatic disease than serum ALP in dogs.

Answer 47

Hepatobiliary conditions associated with intrahepatic or extrahepatic cholestasis.

Answer 48

GGT is present in many tissues, although serum GGT concentrations are primarily derived from the liver. Hepatic GGT is located on the hepatocyte canalicular membrane.

Answer 49

Serum elevations in GGT are most common with cholestatic disorders and are associated with increased de novo synthesis as well as membrane elution. In dogs, moderate to marked increases in GGT are seen with intrahepatic and extrahepatic cholestasis, while mild elevations are seen with acute hepatocellular injury.

Answer 50

Hypoalbuminemia, which may decrease plasma oncotic pressure. Bleeding tendencies may be associated with coagulation protein deficiencies HE can be the result of ammonia retention.

Answer 51

The liver is the exclusive site of albumin synthesis.

Answer 52

Because synthesis occurs at 33% of maximum capacity, and the serum half-life of albumin is 8 to 9 days, serum hypoalbuminemia is most often seen in chronic hepatic disorders, such as cirrhosis and PSVA.

Answer 53

In cirrhotic dogs, serum hypoalbuminemia, PH, and avid sodium and water retention lead to the development of ascites. In ascitic animals, serum hypoalbuminemia may reflect both third-part sequestration of albumin in the abdominal fluid as well as hepatic synthetic failure.

Answer 54

Protein-losing enteropathies protein-losing nephropathies exudative cutaneous lesions vasculitis, acute blood loss. Inadequate nutrition can curtail hepatic albumin synthesis. Because albumin is a negative acute-phase reactant, systemic inflammatory disease may shut down hepatic albumin synthesis.

Answer 55

Globulins The serum globulin fraction is composed of immunoglobulins and nonimmunoglobulins. Because the liver synthesizes many of the nonimmunoglobulins, including α-globulins and β-globulins, hepatic synthetic failure can be accompanied by hypoglobulinemia. However, since many nonimmunogloblins are acute-phase reactants whose hepatic production is increased in response to systemic inflammatory disease, early chronic inflammatory liver disease may be accompanied by hyperglobulinemia.

Answer 56

Immunoglobulins are not synthesized in the liver but may be increased in chronic inflammatory hepatic disease. A polyclonal increase in γ-globulins has been documented in chronic canine hepatic disease and is seen in 50% of cats with chronic cholangiohepatitis.

Answer 57

Hypergammaglobulinemia in chronic liver disease may be associated with enhanced systemic immunoreactivity due to abnormal Kupffer cell processing of portal antigens or secondary to autoantibody production.

Answer 58

Coagulation Proteins The liver has a vital role in hemostasis. Hepatocytes synthesize all coagulation factors, except factor VIII, as well as being critical inhibitors of coagulation and fibrinolysis (antithrombin III, antiplasmin) and fibrinolytic proteins (plasminogen).

Answer 59

The liver is also responsible for clearance and catabolism of activated coagulation factors, plasminogen activators, and breakdown products of fibrinolysis, such as fibrin degradation products (FDP).

Answer 60

II, VII, IX, X, and protein C.

Answer 61

The prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, and FDPs.

Answer 62

Hepatic synthetic failure Vitamin K deficiency The presence of a consumption coagulopathy, such as disseminated intravascular coagulation (DIC).

Answer 63

Since more than 70% depletion of any factor must be present to show prolongation of coagulation times, it is not surprising that many more dogs had abnormalities in the concentration of coagulation factors than had prolongation of PT or PTT.

Answer 64

Prolongation of PT is the first coagulation abnormality seen with vitamin K deficiency, because factor VII has the shortest plasma half-life. Vitamin K is a cofactor in the carboxylation and resultant activation of factors II, VII, XI, X, and protein C.

Answer 65

When prolongation of PT followed by response to parenteral vitamin K supplementation (which usually occurs within 24 to 48 hours) is used to diagnosis vitamin K deficiency, from 50% to 75% of cats with naturally occurring hepatobiliary disease have vitamin K deficiency.[44]

Answer 66

Chronic bile duct obstruction interrupts the enterohepatic circulation of bile acids, resulting in intestinal bile acid deficiency that in turn causes malabsorption of fat-soluble vitamin K. Oral antibiotics alter the normal intestinal bacterial flora, resulting in the destruction of vitamin K–generating bacteria. Inadequate dietary consumption of vitamin K, although rarely a primary cause of vitamin K deficiency, may be contributory, especially in disorders that cause prolonged anorexia, such as feline idiopathic hepatic lipidosis.

Answer 67

Despite the presence of abnormalities in coagulation tests, spontaneous hemorrhage in animals with hepatic disease is rare. This may be due to concurrent abnormalities in the anticoagulant system, including a failure of hepatic synthesis of antithrombin or plasmin.

Answer 68

Prolongation of PT, PTT, decreased fibrinogen, thrombocytopenia, and increased FDPs, all of which may accompany hepatic failure or vitamin K deficiency.

Answer 69

Early in liver disease, fibrinogen concentrations may be normal to increased (fibrinogen is an acute-phase reactant); but as hepatic function deteriorates, fibrinogen levels typically decrease due to a decrease in synthesis.

Answer 70

Increases in FDPs may represent impaired hepatic clearance of FDPs.

Answer 71

Low protein C activity has been documented in dogs with hepatobiliary disease.[47]

Answer 72

Both quantitative and qualitative platelet defects accompany hepatobiliary disease. Many dogs with chronic hepatitis have mild thrombocytopenia (120,000 to 150,000). The reason for thrombocytopenia is unknown, and it is rare in cats with hepatobiliary disease unless DIC is present. Dogs with hepatobiliary disease have qualitative defects in platelet aggregation.

Answer 73

The liver is responsible for detoxifying ammonia, which is generated primarily in the gastrointestinal tract through bacterial degradation of amines, amino acids, and purines; by the action of bacterial urease on urea; and by intestinal catabolism of glutamine.

Answer 74

Ammonia is detoxified either by enzymatic conversion to urea in the mitochondrial urea cycle or by consumption in the synthesis of glutamine. Urea is then normally excreted by the kidneys. Ammonia, which escapes hepatic metabolism, enters the systemic circulation where other tissues—including the kidney, muscle, brain, and intestines—detoxify it by the formation of glutamine.

Answer 75

Hepatic synthetic failure or shunting of portal blood away from the liver may result in hyperammonemia. Because the urea cycle typically operates at only 60% capacity, hepatic synthetic failure must be fairly advanced for blood ammonia concentrations to rise. And because shunting of portal blood directly deposits ammonia in the systemic circulation, blood ammonia concentrations are more sensitive in detection of this disorder.

Answer 76

Elevated fasting blood ammonia levels have a sensitivity of 100% and 86% for detection of congenital or acquired PSVA in dogs with a high overall specificity (89%). Fasting hyperammonemia occurs less often with chronic parenchymal disease, being abnormal in about half of dogs with chronic hepatitis. Hyperammonemia also occurs in animals with urea-cycle enzyme deficiencies and pathologic conditions that result in decreased availability of urea-cycle substrates.

Answer 77

Decreases in BUN are thought to arise secondary to decreased urea production in the atrophied liver. Decreased BUN is not specific for liver disease, because it can be influenced by hydration status, dietary protein content, gastrointestinal hemorrhage, glomerular filtration rate, and fluid or solute diuresis.

Answer 78

Bilirubin is a yellow pigment formed in the reticuloendothelial cell system (RES) by the enzymatic processing of heme.

Answer 79

Bilirubin released from RES cells is not water soluble and is transported in plasma reversibly bound to albumin. This unconjugated bilirubin is extracted by the liver and conjugated by esterification with glucuronic acid. Water-soluble conjugated bilirubin is actively secreted against a concentration gradient into the bile.

Answer 80

Bilirubin in bile makes its way to the intestinal tract, where it is either excreted unchanged in the feces or is converted to urobilinogen by the action of enteric bacteria. Most urobilinogen is further degraded into the brown-pigmented stercobilins. The absence of stercobilins in the feces results in pale-colored acholic stools. Small amounts of urobilinogen enter the portal venous system and undergo enterohepatic circulation. The majority is reexcreted into the bile, but a small amount is secreted in the urine.

Answer 81

Icterus is the clinical manifestation of bilirubin retention within tissues. Although less sensitive than serum liver enzyme activities for detection of hepatobiliary disease, serum hyperbilirubinemia is more specific. Hyperbilirubinemia occurs when an abnormality in the processing of bilirubin exists, and it can be divided into three categories: prehepatic, hepatic, and posthepatic.

Answer 82

Prehepatic hyperbilirubinemia is associated with increased production of bilirubin due to the need to process large amounts of heme, such as occurs during severe hemolytic anemia. It is readily differentiated from hepatic and posthepatic causes by determining hematocrit.

Answer 83

Hepatic hyperbilirubinemia is associated with impaired hepatic uptake, conjugation, or excretion of bilirubin. It is seen in hepatic disorders in which severe intrahepatic cholestasis develops. Hepatic hyperbilirubinemia may also accompany severe extrahepatic infections. In this condition, referred to as the cholestasis of sepsis, which occurs in both dogs and cats, circulating cytokines directly inhibit hepatocyte bilirubin transport.

Answer 84

Posthepatic hyperbilirubinemia is associated with interruption of flow within the extrahepatic bile ducts.

Answer 85

The differentiation of hepatic and posthepatic icterus can be quite challenging clinically and yet is extremely important, because these conditions demand different interventional strategies. Posthepatic hyperbilirubinemia usually requires surgical decompression of the biliary tract, whereas hepatic hyperbilirubinemia is typically treated medically. The clinical differentiation between hepatic and posthepatic hyperbilirubinemia is best made by ultrasound evaluation of the biliary system, combined with careful consideration of clinical history, physical examination, and ancillary laboratory testing.

Answer 86

During prolonged cholestasis, excess conjugated bilirubin may become irreversibly bound to albumin. These so-called biliproteins are clinically significant in that they are measured as direct reacting bilirubin, but their half-life approximates that of albumin. Their presence can result in persistently elevated serum bilirubin weeks after the resolution of the underlying cholestatic liver disorder.

Answer 87

Bile acids are synthesized exclusively in the liver from cholesterol. After conjugation to either taurine or glycine, bile acids are excreted into bile, where they are collected, stored, and concentrated in the gallbladder.

Answer 88

After ingestion of a meal, cholecystokinin release stimulates gallbladder contraction and the release of bile acids into the intestine. In the intestinal lumen, bile acids aid in the solubilization and absorption of fats.

Answer 89

When the bile acids reach the ileum, they are efficiently transported back into the portal circulation, from which they are reextracted by the hepatocyte sinsusoidal bile acid transporter. This enterohepatic circulation of bile acids operates at 98% efficiency.

Answer 90

Disruption of the enterohepatic circulation of bile acids results in increases in the concentration of total serum bile acids (TSBAs).

Answer 91

Increased portal vein bile acid concentrations are reflected in a transient elevation in TSBA. This endogenous challenge to the enterohepatic circulation of bile acids is used clinically. In a typical bile acid test, TSBAs are determined after a 12-hour fast; a test meal is fed, and postprandial TSBA is determined 2 hours later.

Answer 92

Urine bile acids may be used as a diagnostic test for hepatobiliary disease in the dog and cat. The excretion of water-soluble bile acids in urine reflects the TSBA concentration during the period of urine formation, such that persistently elevated TSBA results in elevated urine bile acid levels.

Answer 93

These include the completeness of gallbladder emptying The rate of gastric emptying Intestinal transit rate The efficiency of ileal bile acid reabsorption, The frequency of enterohepatic cycling.

Answer 94

Inadequate fat or amino acid content in the test meal or consumption of an insufficient amount of food can result in failure of cholecystokinin release and gallbladder contraction. The presence of concurrent disease that delays gastric emptying may result in failure to stimulate gallbladder contraction. Alterations in intestinal transit time, so that the movement of conjugated bile acids to the ileum is delayed, can result in less than optimum timing for determination of the postprandial values. Severe ileal disease can result in decreased bile acid reabsorption and inadequate challenge to the enterohepatic circulation. The presence of small bowel overgrowth leads to bacterial deconjugation and decreased ileal absorption of bile acids.

Answer 95

When interdigestive gallbladder contraction occurs during the course of the fast preceding the test. It may also be associated with individual variations in gastric emptying, response to cholecytokinin release, and intestinal transit time.

Answer 96

more than 70% of hepatic function must be lost before hypoglycemia occurs, which happens most often in acute fulminant hepatic failure and in small-breed dogs with PSVA.

Answer 97

It is an early feature of xylitol toxicosis in dogs. The initial drop in blood glucose is associated with insulin hypersecretion but is later associated with hepatic failure.

Answer 98

Up to 35% of dogs with congenital PSVA experience episodes of hypoglycemia. In these dogs hypoglycemia may be due to impaired hepatic glucose production, decreased hepatic glycogen stores, and/or reduced responsiveness to glucagon. Inadequate glycogen stores may reflect immaturity of the carbohydrate-metabolizing enzyme systems, or it may be a consequence of chronic stimulation of glycogenolysis.

Answer 99

Increased glucose utilization by the tumor or Secretion of an insulin-like growth factor that inhibits gluconeogenesis and promotes glycogenolysis. Insulin levels, when measured, have been normal.

Answer 100

In dogs, a glycogen-debranching enzyme (type IIIa in Curly-Coated Retrievers and German Shepherds) and glucose-6-phosphate (type 1a in Maltese) have been associated with fasting hypoglycemia and the development of hepatomegaly due to glycogen accumulation.[65-67] These diseases are diagnosed by tissue-specific enzyme assays.

Answer 101

The liver has several functions in lipid metabolism. Plasma fatty acids released from adipose tissue are extracted by hepatocytes and are either converted to triglycerides or undergo mitochondrial β-oxidation.

Answer 102

Triglycerides are either stored or packaged as very low-density lipoproteins and are released into the vasculature.

Answer 103

The liver also extracts chylomicron remnants and low-density lipoproteins from plasma. This is the major route by which cholesterol enters into the liver, although the liver is also capable of cholesterol synthesis.

Answer 104

Hepatic cholesterol can be esterified, packaged, and secreted in lipoproteins or stored in the liver. The majority of unesterified (free) cholesterol in the liver undergoes biliary excretion.

Answer 105

In the dog and cat, EHBDO is accompanied by increases in serum cholesterol. Hypercholesterolemia is associated with increased hepatic synthesis and/or decreased biliary excretion of cholesterol.

Answer 106

Hypocholesterolemia occurs in approximately 62% of dogs and 67% of cats with PSVA and may be due to decreased cholesterol synthesis or increased incorporation of cholesterol into bile acids. Hypocholesterolemia also occurs with late-stage chronic liver disease in dogs.

Answer 107

About 50% of dogs and 15% of cats with PSVA have ammonia biurate crystalluria. Repeated examination of fresh urine specimens may be necessary to document the presence these crystals.

Answer 108

Uric acid, a byproduct of purine nucleotide catabolism, is converted to allantoin by hepatic urate oxidase. In hepatic disease, a deficiency of this enzyme may lead to hyperuricemia. In the presence of concurrent hyperammonemia, increased concentrations of both ions appear in the urine, resulting in the precipitation of ammonia biurate crystals.

Answer 109

Bilirubinuria indicates the presence of conjugated bilirubin in urine. Bilirubinuria in the dog is not abnormal, because dogs have a low renal threshold for bilirubin, and their renal tubular epithelium is capable of bilirubin production. However, cats have a high renal threshold for bilirubin, and their kidneys do not produce it. Bilirubinuria in cats, therefore, is always abnormal and suggests the presence of a hepatobiliary or hemolytic disorder.

Answer 110

a hepatobiliary or hemolytic disorder.

Answer 111

Anemia may be present in dogs or cats with hepatobiliary disease. Regenerative anemia is most often associated with blood loss. Although spontaneous bleeding associated with a coagulopathy is rare in dogs and cats with hepatic disease, blood loss may occur after provocative procedures or secondary to gastrointestinal ulceration.

Answer 112

Nonregenerative anemia, a more common finding in hepatic disease, is usually normocytic-normochromic and is often associated with inefficient utilization of systemic iron stores (anemia of chronic disease).

Answer 113

A microcytic, hypochromic, nonregenerative anemia is suggestive of chronic gastrointestinal blood loss.

Answer 114

Erythrocyte microcytosis occurs in dogs and cats with congenital PSVA,[65] in dogs with acquired shunting secondary to cirrhosis, and in some cats with idiopathic hepatic lipidosis. Studies investigating the cause of this microcytosis in dogs with PSVA have documented a relative iron deficiency, which may be associated with impaired iron transport. Target cells and poikilocytes may be seen in dogs and cats with hepatic disease. These morphologic changes may be associated with alterations in the erythrocyte plasma membrane lipoprotein content, resulting in altered cell deformability.

Answer 115

Since prednisone needs to be metabolized into prednisolone by the liver, it is logical to use prednisolone in cases of liver disease. Prednisolone can thus be regarded as the treatment of first choice for idiopathic chronic hepatitis. Corticosteroids have antiinflammatory effects but also antifibrotic and choleretic effects. Their principle indication, however, is immunomodulation. For stimulation of choleresis, UDCA (Ursodeoxycholic Acid) is much more effective, and the weak effect on formation of fibrosis does not justify the use of corticosteroids for treatment of fibrosis without mononuclear inflammation.

Answer 116

For cases in which a defect in copper metabolism is known, leading to copper storage and associated hepatotoxicity, specific chelating therapy instead of steroids is indicated.

Answer 117

Glucocorticoids are contraindicated for infectious diseases of the liver and biliary system. They should be reserved for chronic hepatitis with mononuclear inflammation for which no infectious etiology is known and in the absence of copper accumulation. Acute hepatitis may be caused by toxins, viruses, and so on, but the specific etiology remains unknown in most cases. In the author's experience, about 20% to 30% of the cases of acute hepatitis become chronic. Most acute hepatitis cases recover spontaneously without treatment, or with only symptomatic support (antiemetics, fluid therapy).

Answer 118

iatrogenic Cushing disease and gastrointestinal hemorrhage. In such cases H2 receptor antagonists may be given to reduce gastric acid production.

Answer 119

If immunosuppression is the desired action of therapy, and glucocorticoids lead to unacceptable adverse effects, azathioprine is the alternative drug. By combining azathioprine and glucocorticoids, the steroid doses can be much reduced, so side effects can be avoided or made acceptable.

Answer 120

Bone marrow suppression

Answer 121

UDCA is one of the natural bile acids in the enterohepatic circulation. Bile acids are produced and conjugated in the liver and are kept very efficiently in the enterohepatic cycle. The primary bile acids, those primarily formed in the liver, are transformed by intestinal bacteria into secondary and tertiary bile acids, so that a mixture of bile acids circulate.

Answer 122

The less hydrophilic, the more toxic the specific bile acid tends to be. The most toxic bile acid is lithocholic acid, and the hydrophilic UDCA is nontoxic in concentrations encountered in normal or diseased liver.

Answer 123

Toxic bile acids have a number of negative effects. They induce the apoptosis of hepatocytes by activation of the Fas receptor, which activates intracellular signaling of the apoptosis pathway. Liver cell necrosis is also induced by altered permeability of the mitochondrial membrane due to high concentrations of bile acids. Disruption of the mitochondrial electron-transport chain leads to formation of free radicals and oxidative damage to the cells.

Answer 124

1. UDCA has been shown to prevent cells from entering the apoptosis pathway and to prevent mitochondrial damage. 2. Induction of an increased bile flow by UDCA. Active bile acid excretion into the bile canaliculi by hepatocytes is one of the main mechanisms by which bile is formed, because excretion of bile acids against a huge concentration gradient is followed by water, building the flow of bile. Addition of external bile acids to the pool induces the need for hepatocytes to excrete more bile acids, thereby enhancing the bile flow and the efflux of toxic bile acids. (The enhanced bile flow explains also why UDCA is contraindicated in cases of extrahepatic bile duct obstruction). 3. Modulating the immune system in different ways, resulting in reduction of the immune response, which may be favorable in cases where autoimmunity is part of the trigger for ongoing disease. 4. Increase the production of glutathione (GSH) and metallothionein in hepatocytes, which could help prevent oxidative damage.

Answer 125

Chronic, severe cholestatic diseases, such as destructive cholangitis in dogs and lymphocytic cholangitis in cats. In addition, the WSAVA Liver Standardization Group has defined UDCA as the most appropriate drug to compare with glucocorticoids to find the best treatment of idiopathic chronic hepatitis.

Answer 126

Oxidative stress and damage of cells by free-oxygen radicals is one of the disease mechanisms that has been extensively studied in recent years. Factors such as reduced blood perfusion, inflammatory reactions, and accumulation of copper or iron in the liver may be incriminated in the development of hepatocyte necrosis and hepatitis.

Answer 127

Copper toxicosis exerts its toxic effect, resulting in chronic hepatitis or hemolysis specifically by oxidative damage caused by free copper in the cell. Oxidation is also the principal mechanism by which phalloidin, produced by the mushroom Amanita phalloides, and acetaminophen (Paracetamol) cause severe, sometimes fulminant liver failure. Oxidative stress is also a key step in the pathogenesis of ethanol-associated liver injury in man.

Answer 128

The main sources of free radicals are hepatocyte mitochondria, cytochrome P450 enzymes, and endotoxin-activated macrophages (Kupffer cells)

Answer 129

Free radicals take up electrons from neighboring molecules, which causes oxidative damage to lipids, proteins, and DNA.

Answer 130

The normal cellular defense mechanisms against oxidative stress are superoxide dismutase (SOD), catalase, and GSH peroxidase. Depletion of GSH may cause exhaustion of part of the cellular defense and do oxidative damage. Nutritional vitamins C and E act also as free-radical scavengers.

Answer 131

It is logical to separate liver diseases in which oxidation is the principle event leading to tissue damage and inflammation, such as Amanita and acetaminophen intoxication and copper storage diseases, and liver diseases such as viral or idiopathic hepatitis, in which oxidative stress is one factor in a series of events, but not the key factor.

Answer 132

Direct elimination of free copper by copper-chelating drugs such as penicillamine. There are no reports on the effect of antioxidant therapy in copper storage diseases of dogs, so there is no basis to recommend such therapies in addition to chelating drugs. The only event in copper storage diseases in which use of antioxidants is logical is hemolytic crisis

Answer 133

Vitamin C, vitamin E, silymarin, and S-adenosyl-L-methionine (SAMe). In addition, zinc and UDCA have antioxidant function.

Answer 134

These vitamins are normally synthesized by dogs and cats, whereas humans cannot make vitamin C (ascorbate).

Answer 135

S-Adenosyl-L-Methionine: SAMe is a natural metabolite in the hepatocytes. It is a precursor for cysteine, one of the amino acids of GSH, which forms one of the main defense mechanisms of the cell against intoxications; depletion causes oxidative stress. Depletion might occur by exhaustion due to exposure to toxic substances.

Answer 136

The precursor of SAMe is methionine, which is activated by SAMe synthetase. Theoretically, deficient capacity of this liver enzyme as a consequence of liver disease could cause inadequate production of SAMe and GSH. SAMe is nontoxic, and administration of exogenous SAMe could restore deficient GSH in the hepatocytes.

Answer 137

Silymarin, or silibinin, is the active component extracted from the fruit of Silybum marianum, commonly known as milk thistle. It appears to be a strong free-radical scavenger, increasing cellular SOD. There are many reports on its protective and even life-saving action on the liver after intoxication with the mushroom toxin phalloidine and acetaminophen, which exert their toxic effects by oxidation. In dogs the typical oxidative changes in the mitochondria can be prevented in experimental intoxication with these toxins. Treated dogs had much lower elevated liver enzymes, reduced prolonged prothrombin times. In conclusion, there is no evidence that antioxidants have a beneficial effect in liver diseases not primarily caused by oxidative damage; until there is evidence from randomized, double-blind, placebo-controlled studies, they do not yet deserve a place in routine medication.

Answer 138

Increased lipid peroxidation in hepatocytes activates the mesenchymal hepatic stellate cells (HSCs). Transforming growth factor beta-1 (TGF-β) is the principal and most potent fibrogenic cytokine, and it is produced by Kupffer cells and HSCs. HSCs are also the primary target cells that produce extracellular collagen matrix.

Answer 139

Specific drugs to inhibit TGF-β are not yet clinically available. Presently the reduction of lipid peroxidation, which reduces HSC activation, is the only clinically available method of stoping fibrongenesis of the liver. One certain way to stop fibrogenesis of the liver to prevent cirrhosis is to treat the underlying disease and thereby stop progression of fibrosis. In veterinary and human medicine, colchicine is the only specific drug used to stop and reduce fibrosis. It is thought to act via stimulation of collagenase activity. The disadvantage is that side effects have been reported, such as vomiting, diarrhea, and neurological signs.

Answer 140

Storage of opper in the liver can induce oxidative damage due to free intracellular copper. Copper toxicosis in Bedlington Terriers has been the historic example of this form of chronic hepatitis, which is caused by a deletion in the COMMD1 gene. There are a number of forms of chronic hepatitis in different breeds that have been attributed to copper storage as the causative factor. (Bedlington Terriers, Skye Terriers,Dalmatians, West Highland White Terriers and Turkish Shepherds, Labrador Retrievers) Copper may also accumulate as a result of impaired biliary excretion secondary to cholestatic diseases. Thus, hepatitis in Dobermans and Labrador Retrievers may be a primary copper metabolic disease or secondary copper accumulation due to intrahepatic cholestasis in the course of hepatitis. In light of this, all of the above breeds must have primary copper storage diseases.

Answer 141

Excessive copper is generally stored and encapsulated in the hepatocyte lysosomes and cannot be reached by chelating drugs. Since it is the free cytoplasmatic, and not the lysosomal, copper that causes oxidative damage, quantitative copper measurements do not necessarily reflect the success of chelating or other therapy.

Answer 142

Only diseases in which copper accumulation is the primary defect require specific anticopper medication. If copper accumulates as the consequence of a cholestatic disease, specific treatment of the underlying disease will reduce the amount of free cellular copper. The rationale for additional chelating medication has never been proven for such diseases. Chelating drugs should be used with some care, since dogs treated for long chelators can develop disease due to copper deficiency.

Answer 143

1. Chelating drugs can actively bind free extracellular copper, upon which the complex is excreted into the urine by the kidneys. Chelators bind free copper actively, and thus are an effective way to remove the free intracellular copper that causes the hepatic damage. At present there are two copper chelators available. D-penicillamine has been the first drug successfully used. The alternative copper-chelating drugs are 2,3,2- and 2-2-2-tetramine tetra hydrochloride. 2. Zinc. In the intestinal tract, zinc induces metallothionein in the enterocytes. This protein binds copper, and the complex is sequestered with the senescent enterocyte into the intestinal lumen. Zinc should be used as a preventive drug to avoid accumulation of free copper in the liver. 3. The third potential form of medication for copper storage diseases is by giving antioxidants.

Answer 144

Ascites typically is a late sign of decompensation in the course of chronic liver disease, such as chronic hepatitis, cirrhosis, and portal vein hypoplasia (syn. microvascular dysplasia) in dogs. Cats very rarely have ascites due to chronic liver disease.

Answer 145

The portal blood pressure is only high enough to cause ascites without hypoalbuminemia in cases of acute complete obstruction of the portal vein by thrombosis and congenital arteriovenous fistulas. Whatever the cause is, in all liver disease associated with ascites, the high portal pressure may also lead to formation of portosystemic collateral vessels and various grades of hepatic encephalopathy (HE).

Answer 146

The potential risk for HE brings the need to use diuretics with caution. The main complicating factors by which HE may quickly aggravate—even to comatose forms, which may be lethal—are alkalosis and hypokalemia.

Answer 147

Only the nonionized NH3 form of ammonia penetrates cellular (neuronal) membranes. In any form of alkalosis, the reaction equilibrium (NH3 + H+ ↔ NH4+) shifts to the left. Therefore ammonia is much more toxic in alkalosis.

Answer 148

In hypokalemia, the plasma potassium is replenished by a shift of potassium from the cells in exchange with sodium and hydrogen ions. The resulting hydrogen shift causes alkalosis in the extracellular fluid and acidosis in the cells, so that ammonia can easily penetrate cells. Intracellularly it becomes ionized, in which form it cannot leave the cell. Blood ammonia, which is the best parameter to monitor HE, may then be surprisingly low in relation to the severity of the HE, because most of it is trapped inside the cells. This cellular ammonia trap is easily activated with the use of most diuretics. It is therefore better to use potassium-sparing, aldosterone-receptor–antagonizing diuretics, such as spironolactone. If a dog eats well enough to have an adequate supply of alimentary potassium to substitute the renal loss, loop diuretics such as furosemide can be used. Combinations of furosemide and aldactone may be very effective to treat ascites. It is important to monitor blood pH and potassium and to correct potassium deficiency.

Answer 149

The most risky period with respect to ascites and HE is when free fluid is accumulating. In a relatively short period of several days or weeks, the newly formed abdominal free fluid can account for more than the entire circulating volume. In this period the renin-angiotensin-aldosterone system is highly activated, resulting in sodium and water retention and potassium loss. Intravenous fluid therapy and potassium compensation is necessary when the dog does not eat and drink sufficiently. Complete paracentesis of the ascitic fluid is the best stimulation to avoid complications of HE.

Answer 150

A low-sodium diet may help to keep the ascites controlled.

Answer 151

Ammonia and aromatic amino acids are the two main factors. Both require portosystemic collateral circulation, either congenital or acquired due to chronic portal hypertension, to reach the systemic circulation and the blood-brain barrier. The reserve capacity of the liver in dogs is enough to prevent HE in liver disease without collateral circulation

Answer 152

In cats that cannot make the essential amino acid arginine, HE may occur without shunting as a result of fasting. These cats often develop hepatic lipidosis simultaneously; both lipidosis and HE are a manifestation of their inability to synthesize several essential amino acids. There are large variations in susceptibility to these effects among different cats.

Answer 153

Arginine is an essential intermediate of the hepatic urea cycle, and deficiency causes inadequate detoxification of ammonia.

Answer 154

Should have reduced protein content with specific reduction of sources of aromatic amino acids. Very strict reduction of proteins may be counterproductive; it has clearly been shown in dog studies that prevention of catabolism—that is, negative energy balance—is more important than strict maintenance of low protein intake. Another important factor is that lactulose and soluble fiber in the diet may help very efficiently to reduce ammonia uptake from the large intestines.

Answer 155

Ammonia is metabolized by the colonic bacterial flora to produce acids that reduce the pH of colonic content. Ammonia is then present in the ionic form, which is not absorbed and thus is lost with the feces.

Answer 156

There are well-balanced commercial liver-support diets that meet these requirements for adequate energy content, sufficient reduction of protein with special emphasis on aromatic amino acids, and the presence of soluble fiber. These diets also contain low copper and sodium. Because in these cases, not only HE but also ascites may form, with interrelated metabolic complications as described above. Low copper is not necessary in relation with HE or ascites, but it is important in the management of those forms of canine hepatitis that are thought to be caused by copper metabolic diseases.

Answer 157

Since the disaccharide molecule is metabolized in the colon into multiple smaller molecules that increase the osmotic content of the colon and attract water into the feces. The best guideline for use of lactulose for management of HE is to give just enough twice daily to attain a slightly softer stool. The combination of diet and lactulose is often sufficient to manage chronic HE for many years in patients in which the underlying cause cannot be treated (inoperable portosystemic shunts, arteriovenous fistula, portal vein hypoplasia, or inactive cirrhosis). Specific commercial liver-support diets based on soy protein has recently been proven to be most effective

Answer 158

Catabolism, dehydration, alkalosis, hypokalemia, and formation of ascites. Sudden high intestinal ammonia production in the face of portosystemic collateral circulation may also cause sudden aggravation of HE. This may be caused by intestinal bleeding from gastroduodenal ulcers, which may be associated with chronic liver disease. Blood is the most ammoniagenic protein, and in sudden deterioration, it may be important to examine and treat possible gastrointestinal bleeding.

Answer 159

Measurement of blood pH, potassium, and ammonia; correction of hypokalemia and hypovolemia; and intravenous feeding to correct catabolism. It should be understood (see Treatment of Ascites) that the blood level of ammonia and potassium are reflections, but not exact representations, of what is going on in the neurons.

Answer 160

The neuronal GABA/benzodiazepine receptor system, which suppresses neuronal activity. For this reason extreme care should be taken with any sedation or anesthesia exploiting this receptor system. If necessary, inhalation anesthesia is most safe, because it exploits different receptors and does not depend on the liver function.

Answer 161

Liver lipidosis Having a shared metabolic basis, feline hepatic lipidosis and nonportosystemic HE require essentially the same therapy. General rules concerning the influence of hypokalemia and alkalosis also apply for HE in cats and will not be repeated here.

Answer 162

Catabolism leads to decreased insulin–glucagon ratio in the circulation, which stimulates hormone-sensitive lipase to release fatty acids. The liver is the main place for their metabolism, and one of the principle routes by which the liver can make fat stores suitable for utilization in other tissues is by the formation of very low-density lipoproteins (VLDL). One aspect of this complex metabolic disorder is the unavailability of essential amino acids. These are necessary for different liver functions, such as formation of apoproteins for composition of VLDL—in which form accumulating triglycerides can be exported from the liver cells—and the urea cycle, in which arginine is essential.

Answer 163

To restore the energy balance and supplement amino acid deficiencies, especially arginine and taurine. L-carnitine may also be an important factor, because it may help the hepatocytes to exploit fatty acids in beta oxidation. This is the only form of HE requiring high instead of low protein feeding. Multivitamins. Force-feeding. Otherwise a gastrostomy tube is most adequate for long-term force-feeding without stress for the cat.

Answer 164

Since the risk for HE is a contraindication for drugs activating the GABA/benzodiazepine receptor system, overstimulation of which is part of the pathogenenis of HE.

Answer 165

Insulin resistance. This insulin resistance implies that very large doses of insulin would be needed, with the inherent risk for sudden hypoglycemia. A benefit of treatment with insulin has never been demonstrated, and it is advised to restrict the therapy to forced feeding.

Answer 166

Because they stimulate lipolysis and fatty acid accumulation in the liver, induce catabolism, and increase the risk for hyperglycemia.

Answer 167

Neutrophilic or lymphocytic cholangitis and hepatic lymphosarcoma are the most frequent hepatobiliary diseases causing lipidosis.

Answer 168

To prevent disease.

Answer 169

1. Metabolic diseases affecting the liver, such as steroid hepatopathy and lipidosis of the liver as occurs with diabetes or that induced by catabolism in fasting cats 2. Systemic diseases secondarily involving the liver, including hypoxic necrosis of the liver and nonspecific reactive hepatitis due to endotoxemia 3. Primary hepatitis (chronic or acute) of toxic, viral, or unknown etiology; copper storage diseases with secondary hepatitis; and the end-stage of each form of chronic hepatitis—cirrhosis.

Answer 170

Acute and chronic hepatitis (including lobular dissecting hepatitis) Copper-associated hepatitis in dogs Cirrhosis in dogs Hepatic abscesses in dogs Liver lipidosis in cats.

Answer 171

prednisolone, azathioprine

Answer 172

Oxidative intracellular damage may in theory be part of the pathogenesis of many liver diseases, however, a positive effect of antioxidants has never been shown in acute idiopathic hepatitis. Acute hepatitis in dogs is almost never caused by bacterial infection, therefore there is no need to treat for an infectious agent with antibiotics. As a routine, idiopathic acute hepatitis, which is a histopathologic diagnosis, does not need specific treatment. Supportive care may be indicated. The most important point in making the diagnosis of acute idiopathic hepatitis is that the disease may progress into chronic hepatitis. Usually recovery from acute idiopathic hepatitis takes place in about 3 weeks. Beginning forms of chronic hepatitis can be treated very successfully with prednisolone preventing advanced fibrosis or cirrhosis.

Answer 173

It is important to ask the pet owner if acetaminophen or mushroom toxins (phalloidin) may have been ingested recently. These toxic forms of hepatitis are caused by oxidative damage and require specific treatment. Phalloidin intoxication should be treated with silymarin. Any other antioxidant therapy, such as SAMe, should also be useful, but reports have focused on silymarin Supportive care, induction of vomiting in very acute intoxication, and measures to prevent or reduce HE are also indicated. Many dogs die within 1 week due to liver and kidney failure.

Answer 174

Acetaminophen intoxication should be treated similarly to phalloidin intoxication. There are several reports on the favorable effect of SAMe treatment for acetaminophen intoxicationbut the classical treatment is with the combination of N-acetylcysteine, vitamin C and cimetidine. Historically, acetaminophen and phalloidin intoxication have had different treatments, but it is logical to expect good effect from both silymarin and SAMe in conjunction with symptomatic therapy. Dogs with acetaminophen intoxication may develop hemolysis, and a blood transfusion may be required.

Answer 175

Leptospirosis is an acute disease primarily of the kidneys, but it causes also a nonspecific reactive hepatitis with intrahepatic cholestasis. Icterus is therefore common, although the symptoms arise mainly from acute nephritis. Each dog with acute disease displaying icterus together with acute renal failure should be treated immediately with ampicillin or amoxicillin clavulanate. If the diagnosis is confirmed by high IgM titer, antibiotics are continued until kidney function is restored. Of course the acute renal failure should also be treated with fluid therapy.

Answer 176

Liver abscesses are rare in dogs and cats. Treatment is by surgical removal of the abscess after pretreatment with antibiotics. The choice for specific antibiotics should be based on culture of an ultrasound-guided fine needle aspirate. Staphylococcus and Clostridium are most common Chronic hepatitis is one of the most common liver diseases in dogs. In most cases it is not possible to indicate a cause (idiopathic hepatitis). The inflammatory cells are lymphocytes and plasma cells, indicating that at least part of the pathogenesis may be immune mediated. The only well-documented therapy is with glucocorticoids. Prednisolone should be given until the inflammation (liver cell necrosis and infiltration with inflammatory cells) has recovered completely. Severe fibrosis or cirrhosis may require lifelong support by dietary measures and lactulose. Copper-associated forms of hepatitis: If there is active hepatitis, treatment should be with copper-chelating drugs such as penicillamine. Prevention of clinical disease in early diagnosed cases, or maintenance therapy when chelation therapy has stopped the inflammation, can be achieved with zinc salts Dobermans, especially females 5 to 7 years old, may display a specific form of hepatitis, called Doberman hepatitis. The prognosis of this disease has generally been reported to be bad. However, there are recent results of studies in Dobermans indicating that copper is the primary cause of hepatitis in these dogs. We have treated Doberman hepatitis only with penicillamine, and this has resulted in complete remission of the disease. Loblular dissecting hepatitis is a very severe form of hepatitis, developing very rapidly and usually lethal within 2 to 4 weeks. There is very pronounced fibrosis, which is the reason that, despite the acute course, this disease is classified under the chronic forms of hepatitis. Medication with immunosuppressive drugs is usually without success, and there is no report of a successful medical treatment for this disease.

Answer 177

Destructive Cholangitis in Dogs: This is strictly not a form of hepatitis but an idiosyncratic reaction in dogs, nearly always to drugs containing sulfonamides. Necrosis of the smaller intrahepatic bile ductules is the result, and these dogs display extremely severe intrahepatic cholestasis. The first action is immediate withdrawal of the sulfonamide medication. The necrosis of the intrahepatic bile ductules is irreversible, and the only hope is that it is possible to save and exploit the remaining biliary system. In our experience it is essential to start treatment with UDCA immediately. Long-term reaction in the liver: Chronic cholestasis may induce chronic damage to the liver with continuous loss of functional hepatocytes and activation of the deposition of fibrous tissue. This may finally produce porto-portal bridging fibrosis in the liver (biliary fibrosis) which, although the architecture of the liver lobules remains intact, can give rise to portal hypertension. Ascites and formation of acquired portosystemic shunting may result.

Answer 178

In the vast majority of cases, Escherichia coli is cultured, but staphylococci or other bacteria may also be identified. It may in some cases be an infection superimposed on preexisting bile duct obstruction associated with cholelithiasis, pancreatic, or intestinal disease. Bile duct obstruction requires surgical decompression and antibiotic medication guided by culture of bile. True, uncomplicated neutrophilic cholangitis is an acute disease characterized only by bacterial infection of the bile ducts as evaluated with the combination of bile culture, liver histology, and ultrasonography. Uncomplicated neutrophilic cholangitis responds quickly to antibiotic therapy. Amoxicillin clavulanate, amoxicillin, or ampicillin may be the first choice treatment until the results of culture become available.

Answer 179

The chronic bile duct inflammation of lymphocytic cholangitis causes irregularly distended fibrotic bile ducts that are prone to secondary bacterial infection. In patients with obstruction, treatment with UDCA is contraindicated, whereas it is one of the most useful medications for lymphocytic cholangitis. In most cases the difference can only be seen with histologic examination of a liver biopsy; the two diseases have different histologic characteristics. Liver fluke eggs may also be visible histologically in the bile ducts but should also be evaluated with fecal examination. There is rarely any response to even very long term, high-dose glucocorticoid medication. UDCA may be the only generally advised drug for which there is at least a theoretical basis for use. As outlined earlier, it has beneficial effects on cholestatic diseases in different ways.

Answer 180

CH refers to canine hepatic disease that is chronic—that is, lasting more than 4 to 6 months—that has hepatocellular apoptosis or necrosis associated with an inflammatory infiltrate (often mixed, but predominately lymphoplasmacytic), and typically progresses to fibrosis and cirrhosis.[1] The etiology, if known, should be included as an adjective (e.g., drug-induced CH, copper-associated CH); otherwise the CH is termed idiopathic.

Answer 181

CH has various causes including copper, drugs, or infectious agents, and there are familial tendenciesand there are familial tendencies. Breeds reported to have an increased frequency of CH include Doberman Pinscher, Bedlington Terrier, West Highland White Terrier, Cocker Spaniel, Dalmatian, Skye Terrier, Standard Poodle, Labrador Retriever, German Shepherd Dog, Scottish Terrier, English Springer Spaniel, and Beagle.

Answer 182

Immune mechanisms may be important in some dogs and CD3+ lymphocytes were the most common hepatic lymphoid cells of dogs with CH in two studies. Antinuclear antibodies (ANAs) and antibodies to liver membrane proteins have occasionally been found in dogs with CH, but the ANA is extremely nonspecific. Major histocompatibility complex class II antigen expression on hepatocytes from Dobermans with CH, but not unaffected control dogs, has also been suggested to support an immune mechanism

Answer 183

Hepatic copper has been associated with CH in Boxers and Anatolian Shepherds. In Bedlington Terriers inability to excrete copper into the biliary tract causes formation of reactive oxygen species (hydroxyl radicals), which produce CH and ultimately cirrhosis. Copper also accumulates secondary to cholestasis, inflammation, and increased dietary copper intake, but cholestasis and inflammation seemingly cause relatively minor increases in hepatic copper. Fanconi syndrome has been found in dogs with copper-associated CH; however, it was not clear whether copper was responsible for the renal dysfunction.

Answer 184

Iron can accumulate in the liver of dogs with hepatic disease. Iron accumulated in Kupffer cells and macrophages but not hepatocytes. Iron accumulation seems secondary to inflammation, necrosis, and/or copper accumulation. It has been hypothesized that iron accumulation in the hepatic parenchyma may aggravate preexisting hepatic damage

Answer 185

Alpha-1 antitrypsin (α1-AT), also known as alpha-1 protease inhibitor, might cause canine CH. As hepatocytes accumulate α1-AT, they die and attract mononuclear cells whose cytokines cause production of more α1-AT.

Answer 186

Finding hypoalbuminemia and/or hypocholesterolemia suggests either hepatic insufficiency (cirrhosis) or protein-losing enteropathy.

Answer 187

Hepatic insufficiency Decreased protein intake, Excessive loss due to polyuria All of which occur in dogs with CH.

Answer 188

Anemia of chronic disease, sometimes with microcytosis, leukocytosis, and/or thrombocytopenia. Approximately to of patients have prolonged PT and PTT

Answer 189

A modified transudate or a low protein transudate associated with fibrosis or cirrhosis.

Answer 190

Copper chelation therapy typically involves penicillamine. Penicillamine also has antiinflammatory effects, and it inhibits fibrosis. Penicillamine therapy causes vomiting in approximately 30% of treated animals, but administering it with food may decrease such side effects

Answer 191

Hemolytic anemia, and blood zinc concentrations need to be checked periodically

Answer 192

Inflammatory cells cause hepatocellular necrosis, which creates space (hepatocyte dropout) that is filled by more inflammatory cells. The liver's response to necrosis is to produce hepatocytes and bile duct epithelium. However, lysosomal proteases and radicals released by inflammatory cells disrupt normal hepatic extracellular matrix (ECM) and cellular membranes, causing release of substances such as transforming growth factor-β, which attract collagen-producing cells (Ito cells). Fibrosis causes ECM modification, and hepatocytes growing on it may have functional alterations.

Answer 193

Is when bridging fibrosis causes permanent hepatic distortion, regenerative nodules, and portocentral vascular anastomoses. Fibrosis cutting across acinar zones causes micronodular cirrhosis. Fibrosis dividing the liver into groups of acini with more than one portal tract within each nodule causes macronodular cirrhosis. Fibrosis only surrounding bile ducts causes biliary cirrhosis. Excess collagen production limits the ability of vessels and sinusoids to distend, increasing resistance to blood flow. As cirrhosis persists, the type of collagen laid down may be less susceptible to collagenase activity, making it harder to remove

Answer 194

Prednisolone, azathioprine, penicillamine, zinc, and vitamin E appear to inhibit or delay fibrosis.

Answer 195

Colchicine, a microtubule assembly inhibitor, increases collagenase activity

Answer 196

Bedlington Terriers have a high incidence of an autosomal recessive metabolic defect in biliary copper excretion. The gene responsible for this defect: COMMD1. Bedlingtons homozygous for the trait progressively accumulate copper in their livers, possibly beginning in utero. Initially, affected dogs asymptomatically accumulate copper in the centrolobular region (zone 3). When hepatic copper reaches 1500 to 2000 ppm, it is also found in zones 1 and 2 (midzonal and periportal areas), and histologic damage becomes evident. Once sufficient copper has accumulated in the liver, otherwise insignificant stress may trigger acute hepatic necrosis, which may be complicated by acute hemolysis and renal failure due to release of large amounts of copper.

Answer 197

Hepatic histopathology. Accumulation of copper in lysosomal granules is the first histologic abnormality. As hepatic copper levels increase, random areas of focal inflammation occur. Inflammatory infiltrates extend out from portal triads as disease progresses, with occasional bridging necrosis and some fibrosis. Finally cirrhosis occurs. Hepatic copper levels increase until about 6 years of age but then begin to decrease, possibly because copper-laden hepatocytes are replaced with scar tissue or regenerative nodules. Hepatic iron concentrations are also increased.

Answer 198

These patients have altered copper excretion into the bile. Clinical presentation and clinical pathology findings are as described under CH, but PU/PD, splenomegaly, neutrophilic leukocytosis, normal to increased PCV, and bleeding may be more common than in affected patients of other breeds. Many patients presenting with clinical illness die within weeks of the first signs of disease Current thought is that copper is responsible for hepatic damage in Doberman hepatitis; but the pathogenesis is different than in Bedlington terriers with immune mechanisms playing a role. Hepatic iron concentrations tend to be increased

Answer 199

Canine adenovirus 1 Parovirus Findings varies between different studies. Some have hypothesized that the viral infection initiates a self-perpetuating inflammatory hepatic disease.

Answer 200

Inflammatory cells found diffusely throughout the hepatic lobule, as opposed to primarily in periportal regions, plus collagen and reticulin fibers dissecting around small groups or single hepatocytes. Copper may be found in the liver but appears to be a secondary event. Hepatic enzymes are typically increased, and ascites from portal hypertension is probably the most common presenting clinical sign. This syndrome appears most commonly in neonatal and juvenile dogs (mean of 11 months old in one series).

Answer 201

Trimethoprim/sulfadiazine phenobarbital diethylcarbamazine-oxibendazole amiodarone carprofen although they are usually relatively mild and do not closely resemble CH

Answer 202

Mixed periportal (zone 1) inflammatory infiltrates, with inflammation usually extending through and into the bile ducts. Bacterial infections must be eliminated, usually by cytology or culture of bile. Serum bilirubin, ALT, SAP, and serum bile acids tend to be higher than expected with CH, but one cannot discriminate between CH and cholangiohepatitis based upon laboratory values. Drugs can sometimes be responsible.

Answer 203

Edema and sinusoidal congestion with occasional, mild neutrophilic and eosinophilic infiltrates. Serovar grippotyphosa has been suggested to cause CH.

Answer 204

macrophages

Answer 205

Dogs with leishmaniasis seldom have clinical signs of hepatic disease. Biochemical changes (e.g., hypoalbuminemia, increased SAP, hyperbilirubinemia) are occasionally found, but histologic changes are common. Most infected dogs have granulomatous or pyogranulomatous portal infiltrates.

Answer 206

Nonsuppurative hepatitis has been reported in dogs with babesiosis. However, classic signs of babesiosis, such as anemia and fever are typical, and the hepatic lesions are usually not confused with primary hepatic disease.

Answer 207

........they have a predominantly neutrophilic infiltration or whether the inflammatory infiltrate is predominantly lymphocytic in nature. (It has been postulated that lymphocytic cholangitis and neutrophilic cholangitis may be essentially part of the same disease syndrome, with lymphocytic cholangitis representing a chronic stage of an earlier neutrophilic cholangitis. However, in contrast to neutrophilic cholangitis, lymphocytic cholangitis occurs more often in young cats, with more than 50% of cases in cats younger than 4 years of age........) A small proportion of cats with inflammatory liver disease show a mixed-cell infiltrate consisting of both neutrophils and lymphocytes.

Answer 208

Lymphocytic cholangitis, neutrophilic cholangitis, and cholangitis associated with liver fluke. These different forms broadly correlate with different clinical presentations, and this classification system has some practical relevance to the management of affected cats

Answer 209

These include infectious diseases such as feline infectious peritonitis (FIP), protozoal infections (most notably toxoplasmosis), bartonellosis, and hepatotoxicities particularly associated with drugs including diazepam and tetracyclines.

Answer 210

Inflammatory disruption of the limiting plate to involve hepatic parenchyma is not a consistent feature and, if present, is usually an extension of a primary cholangitis.

Answer 211

A primarily neutrophilic infiltrate within the bile duct lumen and/or epithelium, although there may also be a range of inflammatory cells including lymphocytes and plasma cells. Neutrophilic cholangitis can be further divided into acute and chronic phases: In the acute stage there may be disruption of the limiting plate with infiltrate extending into the portal areas. The neutrophilic inflammation may extend to the hepatic parenchyma and may result in hepatic abscesses. Periportal necrosis is common. The bile ducts themselves show necrosis and degeneration. Fibrosis and bile duct proliferation may occur in the more chronic stages, together with a more mixed inflammatory infiltrate in portal areas with neutrophils, lymphocytes, and plasma cells.

Answer 212

Pancreatitis, characterized histologically by periductal infiltration, acinar degeneration, fibrosis, and nodular hyperplasia. The extent of the pancreatitis is generally mild. Inflammatory bowel disease (IBD)

Answer 213

Ascending infection of the biliary tract from the intestine

Answer 214

The pancreatic and bile ducts are joined before entering the duodenum and this may predispose to concurrent development of pancreatitis and neutrophilic cholangitis. It is possible that the presence of IBD may predispose to ascending infection. In triaditis the predominant clinical features are most often associated with the cholangitis, with the pancreatitis and IBD being identified as complications.

Answer 215

There is a consistent infiltration of small lymphocytes in and restricted to the portal areas, often associated with variable portal fibrosis and biliary ductular proliferation. Lymphocytes centering around bile ducts or present in the biliary epithelium may be seen. In a proportion of these cases with lymphocytic cholangitis, solitary plasma cells and eosinophils may also be present. A distinct pathologic process that has also been noted in cats is that of lymphocytic portal hepatitis. It is not clear whether what has been termed lymphocytic portal hepatitis is a distinct separate entity or a variant of lymphocytic cholangitis.

Answer 216

IBD and pancreatitis have been reported to be common in cases described as lymphocytic portal hepatitis. Pancreatitis has been recognized in combination with lymphocytic cholangitis, but previous reports do not reveal any evidence of a striking associations. The etiology of lymphocytic cholangitis is unknown, although an immune-mediated mechanism is believed to contribute to the pathogenesis.

Answer 217

Liver fluke infestation resulting in chronic cholangitis is commonly encountered in cats in endemic areas. The fluke lifecycle requires two intermediate hosts; water snails; and a variety of fish. Cats become infected by ingestion of raw fish. Following ingestion flukes migrate from the intestine, up bile ducts and into the liver. This results in dilated large bile ducts with papillary projections and periductal and portal fibrosis. A mixed mild to moderate inflammatory infiltrate may be present within bile ducts and portal areas. Liver flukes and eggs may be present within bile ducts, but these are rarely evident.

Answer 218

(Rarely, another underlying primary cause of cholelithiasis may be identified. For example, pyruvate kinase deficiency, an inherited hemolytic disorder encountered in Somali and Abyssinian cats, has been reported to cause bilirubin cholelithiasis associated with chronic haemolysis) Rarely, another underlying primary cause of Gallstones can be radiolucent, although calcification is a common feature

Answer 219

(1) jaundice and (2) progressive ascites, with jaundice appearing to be more common. Occasionally both clinical signs are present. However, in some cats the only reported clinical sign is progressive weight loss despite a normal or increased appetite, and in others hepatomegaly is detected as an incidental finding with minimal clinical signs reported.

Answer 220

An increase in liver enzymes (ALT, ALP, and GGT) and bile acids that can be severe is usually seen. Bilirubin levels may be increased, frequently corresponding with jaundice. . Serum globulin levels are often raised. (may reflect an increase in γ globulins) The most consistent change on hematology is lymphopenia (mild anemia etc might also be seen) If ascitic fluid is present, abdominal paracentesis will show this to be clear to yellow tinged. It is generally thick with a high protein content, the majority of which is globulin. Histopathology is required to make a definitive diagnosis.

Answer 221

Corticosteroids are the mainstay of treatment used based on countering immune-mediated damage to the liver. Other immunosuppressive agents are occasionally used (e.g., cyclosporine, chlorambucil, methotrexate, cyclophosphamide). Colchicine may be used. Choleretics, SAMe, and nutritional support may be helpful.

Answer 222

...anorexic, lethargic, and pyrexic. Jaundice is usually present and is caused by intrahepatic cholestasis, sometimes with extrahepatic biliary obstruction. There may also be evidence of abdominal pain and resentment on abdominal palpation, as well as vomiting and ptyalism.

Answer 223

Increases in ALT and bilirubin. Cholestatic enzymes, ALP, and γGT are usually but not always increased, and usually raised fasting or postprandial (or both) serum bile acid concentrations are found. The most common finding on hematology is leukocytosis with neutrophilia and left shift. There may be suppression of hepatic production of clotting factors in the form of prolonged clotting times and increased PIVKA levels. The principal abnormalities on imaging are related to the extrahepatic biliary tract. Evidence of gallbladder distension usually exists, and the bile duct may appear prominent.

Answer 224

Escherichia coli is the most frequently isolated organism, but a mixed growth of other organisms that constitute the normal small intestinal bacterial flora (most commonly Enterococcus spp., Streptococcus spp., Clostridium spp., and Bacteroides spp.) are frequently found, reflecting ascending infection from the gut. Cholecystectomy may be necessary in some cases to remove inspissated bile.

Answer 225

It should be broad spectrum, be bactericidal, achieve therapeutic levels in bile, and not require hepatic metabolism for activation or excretion

Answer 226

Buprenorphine generally provides good analgesia. Choleretics are of value in promoting bile flow, and this is indicated if extrahepatic biliary obstruction is not present. The beneficial effects of ursodeoxycholic acid include changing the composition of the bile acid pool by reducing the proportion of hydrophobic bile acids that have toxic effects on hepatocellular membranes in addition to potential antiinflammatory, immunomodulatory, and antifibrotic properties. Vitamin K supplementation is indicated if defects in clotting function are identified. S-adenosyl-L-methionine (SAMe): One beneficial effect is believed to be the restoration of glutathione levels that are reduced in liver disease, leading to increased oxidative damage and exacerbation of liver disease. Other beneficial effects may be to increase levels of cysteine and taurine, which are required for bile acid conjugation and a cytoprotective effect

Answer 227

The portal vein and the systemic circulation, bypassing the hepatic sinusoids and liver parenchyma.

Answer 228

Normally, blood draining the spleen, pancreas, stomach, and intestine enters the portal vein, perfuses the liver through the sinusoidal network, and finally drains through the hepatic veins into the caudal vena cava (CVC).

Answer 229

Trophic hormones (intestinal and pancreatic), nutrients, bacterial products, and intestinal-derived toxins. The ductus venosus

Answer 230

When blood bypasses the liver, trophic factors (particularly insulin and glucagon) are not available to encourage hepatic growth, resulting in poor hepatic development, deficient protein production, reticuloendothelial dysfunction, altered fat and protein metabolism, hepatic atrophy, and eventually liver failure.

Answer 231

Impaired hepatic function, hepatic encephalopathy, chronic gastrointestinal (GI) signs, lower urinary tract signs, coagulopathies, and delayed growth. These problems are the result of the body accumulating both exogenous and endogenous toxins that are normally metabolized or eliminated by the liver, as well as the failure of normal hepatic function (e.g., gluconeogenesis, urea cycle, uric acid cycle, glycogenolysis).

Answer 232

In dogs, the ductus venosus carries oxygenated maternal blood from the placenta to the fetal systemic circulation, bypassing the hepatic circulation. This fetal vessel located on the left side of the liver normally closes by approximately 3 to 10 days of age.

Answer 233

Closure is initiated by blood pressure changes after umbilical venous flow ceases. There is evidence in some species that thromboxane or various adrenergic compounds can stimulate contraction of the musculature of the ductus venosus and may aid in the vessel's closure.

Answer 234

Abnormal vessel patency, or other abnormal developments in the vitelline venous system, results in congenital intrahepatic PSS (IHPSS). The majority of IHPSSs are not necessarily subsequent to a patent ductus venosus, and the cause of other left, right, and central divisional IHPSS or EHPSS is currently unknown.

Answer 235

The portal vein is formed by the confluence of the cranial and caudal mesenteric veins, providing up to 80% of the blood and 50% of the oxygen content to the liver, with the remainder being supplied by the hepatic arterial blood. Blood from the GI tract, spleen, and pancreas is drained by their respective veins, which join the portal vein. The portal vein enters the liver branching into left and right vessels that supply the various liver lobes. (The main right branch supplies the right lateral and caudate process of the caudate lobe, and the main left branch supplies all other lobes, giving off a central branch that supplies the right medial lobe). In the cat, the portal vein separates directly into left, central, and right branches.

Answer 236

The portal vein branches into smaller venules where the blood enters the parenchyma via the portal triads. That blood travels through the hepatic sinusoids, is cleansed by the reticuloendothelial system, and then drains into the central veins that converge to form larger hepatic venules and ultimately hepatic veins that empty into the CVC. When the path is interrupted by an anomalous vessel, blood is diverted away from the liver, traveling the path of least resistance, reaching the systemic circulation prior to transversing the hepatic circulation.

Answer 237

(1) congenital IHPSSs and EHPSSs (2) disorders associated with abnormal hepatic blood flow or portal hypertension, currently termed primary hypoplasia of the portal vein (PVH) (3) disturbances in outflow.

Answer 238

These are termed PVH with portal hypertension and PVH without portal hypertension. Examples of PVH with portal hypertension include noncirrhotic portal hypertension (NCPH) and hepato-portal fibrosis/venoocclusive disease. PVH without portal hypertension was previously termed microvascular dysplasia (MVD).

Answer 239

PSSs can either be congenital or acquired in nature. Congenital PSS most commonly occurs as a single vessel that provides direct vascular communication between the portal venous supply and the systemic venous circulation (CVC or azygous veins), bypassing the liver. This commonly occurs as a single intrahepatic or extrahepatic communication (80%).

Answer 240

Intrahepatic portocaval shunts Extrahepatic portocaval shunts Extrahepatic portoazygous shunts Portal vein atresia with resultant multiple portal-cabal anastomoses Hepatic arteriovenous malformations (HAVMs), and microintrahepatic PSS (PVH without portal hypertension, formally termed microvascular dysplasia).

Answer 241

Approximately 25% to 33% of congenital PSSs are intrahepatic (IHPSSs) in both dogs and cats. Most IHPSSs occur in larger-breed dogs, whereas most EHPSSs occur in smaller breeds. Some EHPSSs, like splenocaval shunts, may be associated with less severe clinical signs because splenic blood is not of GI origin and less portal blood is being shunted away from the liver. Dogs with IHPSSs generally have the largest volume of diverted portal blood, allowing them to develop more severe clinical signs at an earlier age than those with EHPSSs or PVH.

Answer 242

Secondary to chronic portal hypertension in which increased portal pressures lead to the opening of fetal, vestigial blood vessels. These have also been seen as congenital abnormalities. These vessels provide an alternative to handle an increase in the hydrostatic pressure present within the portal system.

Answer 243

Hepatic fibrosis (cirrhosis) Portal vein hypoplasia with portal hypertension (congenital NCPH) or HAVMs.

Answer 244

When there is intraabdominal portal hypertension with a patent portal vein and a noncirrhotic liver. The underlying cause of this condition is unknown but speculations include severe, diffuse intrahepatic vascular malformations without concurrent cirrhosis, resulting in portal hypertension and multiple EHPSSs.

Answer 245

This is a microscopic malformation of the hepatic microvasculature. It is characterized by small intrahepatic portal vessels, portal endothelial hyperplasia, portal vein dilation, random juvenile intralobular blood vessels, and central venous hypertrophy and fibrosis. These lesions may allow for abnormal communications between the portal and systemic circulation at a microvascular level. This can occur as an isolated disease, or in combination with macroscopic PSS.

Answer 246

HAVM is a rare condition of multiple high-pressure arterial and low-pressure venous communications. This condition, previously termed hepatic arteriovenous fistula, is more appropriately named a malformation because most are composed of numerous communications (malformation) rather than a single communication (fistula). They are usually congenital and have been described in both dogs and cats

Answer 247

HE is a neuropsychiatric syndrome involving a number of neurologic abnormalities that occurs when more than 70 % of liver function is lost. The healthy liver serves a filtration function against a multitude of neurotoxic substances that are absorbed across the GI barrier. When liver function is altered, the liver cannot appropriately perform its role in substance clearance or metabolism, permitting toxic substances to enter the systemic circulation. This results in dramatic effects on other organs, particularly the central nervous system (CNS), creating an encephalopathic state. Multiple aspects of CNS metabolism have been implicated in the pathophysiology of HE.

Answer 248

Ammonia, tryptophan, glutamine, aromatic amino acids, short-chain fatty acids, gamma-aminobutyric acid (GABA), and endogenous benzodiazepines

Answer 249

Impede neuronal and astrocyte function, cause astrocytes to swell Depress electrical activity Inhibit membrane pumps or ion channels, Increase intracellular calcium concentrations, Interfere with neuronal oxidative metabolism.

Answer 250

Ammonia may be considered most important because increased concentrations trigger a sequence of metabolic events implicated in HE. Ammonia is the easiest substance to measure in animals, and treatment to decrease ammonia seems to reduce signs of HE.

Answer 251

Ammonia is normally produced by GI flora and converted in the normal liver to urea and glutamine via the urea cycle. Ammonia is exitotoxic; it is associated with an increase release of glutamate, the major excitatory neurotransmitter of the brain, and overactivation of glutamate receptors, mainly N-methyl-D-aspartate receptors. This has been implicated as a cause of HE-induced seizures. With chronicity, the inhibitory factors surpass the excitatory stimulus, causing signs more suggestive of coma or CNS depression. These inhibitory factors include GABA and endogenous benzodiazepines.

Answer 252

Neuroinhibition, although excitatory phenomenon like seizures, aggression, and hyperexcitability can occur.

Answer 253

The combination of Systemic toxins (e.g., nonsteroidal antiinflammatory drugs (NSAIDs), high-protein meals) and Metabolic derangements (hypoglycemia, dehydration, hypokalemia, alkalemia, GI ulceration, problems with stored blood transfusions, constipation, and drugs [sedatives, analgesics, benzodiazepines, antihistamines]).

Answer 254

In cats, EHPSSs are more commonly identified, though IHPSSs have been reported

Answer 255

before 1-2 years

Answer 256

“Failed to thrive” since birth, is small in stature (or the runt of the litter), has weight loss or failure to gain weight, has anesthetic intolerance, is dull or lethargic at times, and displays “bizarre” behavior, stargazing, head pressing, staring into walls or corners, random barking, intermittent blindness, pacing or aggression). Some pets have a history of dysuria. A complaint of polyuria and polydipsia (PU/PD) is common in dogs.

Answer 257

Poor medullary concentration gradient due to a low blood urea nitrogen (BUN) Increased renal blood flow Increased ACTH secretion and associated hypercortisolism Psychogenic polydipsia from HE.

Answer 258

The central nervous, The GI The urinary systems

Answer 259

Due to decreased urea production, increased ammonia excretion, and decreased uric acid metabolism, formation of ammonium urate calculi are common and can be associated with bacterial urinary tract infections

Answer 260

Mild to moderate, microcytic, normochromic, nonregenerative anemia (The cause of the microcytic anemia is not fully understood, although studies suggest a defective iron-transport mechanism, decreased serum iron concentrations, decreased total iron-binding capacity, and increased hepatic iron stores in Kupffer cells. This may suggest iron sequestration). Erythrocyte target cells are common on morphology evaluation in dogs and poikilocytes in cats. Leukocytosis, due to inadequate hepatic endotoxin and bacteria clearance from the portal circulation

Answer 261

Most are due to decreased hepatic synthesis: low albumin, low BUN, hypocholesterolemia, and hypoglycemia. In cats hypoalbuminemia is uncommon but low BUN and creatinine are common. Excess serum liver enzyme activities are also common. These are usually mild to modest increases (twofold to threefold) in alkaline phosphatase (ALP) and alanine aminotransferase (ALT). These abnormalities are typical of any hepatic vascular anomaly. Interestingly, the ALP is typically higher than the ALT in dogs with PSSs, likely due to the contribution of bone isoenzyme in growing animals. Hepatic organelle injury and increased release or decreased elimination of canalicular ALP has also been proposed

Answer 262

A low urine specific gravity (>50% are hyposthenuric or isosthenuric) and ammonium biurate crystalluria. The low specific gravity likely results from the polydipsia, as well as the poor medullary concentration gradient that occurs with the low BUN subsequent to a deficient urea cycle. Hyperammonuria, also resulting from the deficient hepatic urea cycle, combined with hyperuricacidemia due to a deficiency in hepatic purine and pyrimidine metabolism (uric acid cycle), results in excessive ammonia and urate excretion in the kidneys. These compounds can precipitate into crystals or stones in the kidney or bladder. Ammonium biurate crystalluria is common. Proteinuria is often seen in dogs with PSSs, suspected to be secondary to glomerular sclerosis or another underlying glomerulopathy.

Answer 263

Fasting (12 hour) and 2-hour postprandial serum bile acid (SBA) is the test of choice for evaluating liver function in animals suspected as having PSSs. Bile acids are synthesized in the liver from cholesterol and, following conjugation, are secreted into the bile canaliculi and stored in the gallbladder until released into the duodenum.

Answer 264

They aid lipid absorption via intestinal fat emulsification and metabolism, are reabsorbed from the ileum, transported into the portal venous system, and extracted by hepatocytes for recirculation.[60-63] Production, excretion, and enterohepatic recirculation are all evaluated through bile acid concentrations.

Answer 265

The timing of the gallbladder contraction, the rate of intestinal transport, the degree of bile acid deconjugation in the small intestine, the rate and efficiency of bile acid absorption in the ileum, the portal blood flow, and the function of the hepatocyte uptake and canalicular transport.

Answer 266

Inappropriate sample timing, other hepatobiliary diseases/cholestasis, glucocorticoid or anticonvulsant therapy, tracheal collapse, seizures, and GI disease. Falsely lowered results can occur with delayed intestinal absorption from prolonged transport time, lack of gallbladder contraction, inadequate food intake/delayed gastric emptying, and malabsorption or maldigestion. Gallbladder contraction can occur between meals, resulting in higher preprandial than postprandial bile acid levels.

Answer 267

The shunting of the reabsorbed SBA (serum bile acids) to the systemic circulation. When false-negative test results are suspected, an ammonia tolerance test can be obtained. Two samples are evaluated: prior to and 30 minutes following ammonium chloride administration This test has been documented to have a sensitivity of 95% to 100% for hepatic insufficiency. The test should be considered carefully and is contraindicated in animals with HE. Ammonia concentrations are not as sensitive (62% to 88% PSS animals are abnormal) as the SBA test. Both false-positive and false-negative baseline ammonia levels have been documented, making a high ammonia level supportive, but not diagnostic, for PSSs

Answer 268

Due to an enzyme deficiency (ornithine transcarbamylase) in the urea cycle, has been reported. Other causes of hyperammonemia in young animals include methylmalonic acidemia, other urea cycle enzyme deficiencies, and urethral obstruction-induced hyperammonemia. These conditions are not associated with PSSs.

Answer 269

(I, II, V, IX, X, XI, XIII [and VIII via the liver vascular endothelium]), 65% to 80% factor loss before prolongation in PT and PTT is observed. Animals with chronic liver disease, as with PSSs, typically have prolongation only in the PTT, whereas animals with acute liver disease may have prolongations in both PT and PTT. The prolonged PTT in PSSs is suspected to be due to a variety of factors: impaired hepatic synthesis, qualitative abnormalities, and clearance of coagulation factors (Interestingly, the deficient factors include those involved in the common (Factors II, V, and X) and extrinsic pathways (Factor VII), leading one to expect the PT to be prolonged as well. One speculation is a factor XII deficiency that can cause prolongation in PTT alone without resultant symptomatic bleeding.) Dogs with PSSs have abnormally low platelet counts preoperatively, which is worse postoperatively. No decrease in platelet count was low enough to cause clinical bleeding. This may be supportive of a postoperative consumptive coagulopathy.

Answer 270

Unless there is severe hypoproteinemia, severe GI bleeding, or portal hypertension associated with HAVM, NCPH, or acquired multiple EHPSS (chronic liver disease/cirrhosis). Typically the fluid for any of these conditions would be a pure transudate that is clear and relatively acellular with total protein <1000 nucleated cells/µL.

Answer 271

Due to potassium depletion from chronic diarrhea or decreased intake, and hypokalemia may also contribute to HE

Answer 272

Metabolic acidosis may contribute to HE and should be corrected slowly with fluid therapy and, rarely, sodium bicarbonate. It is important to verify that concurrent respiratory acidosis does not exist prior to sodium bicarbonate therapy. Glucose should be supplemented in the IV fluids, particularly in young puppies with PSS, where glycogen stores and gluconeogenesis are minimal.

Answer 273

Feeding nothing PO, cleansing enemas with warm water and/or lactulose, oral lactulose therapy, antibiotic therapy (metronidazole, ampicillin, or neomycin), and anticonvulsant therapy if necessary.

Answer 274

With low-dose midazolam (a benzodiazepine that is preferred to diazepam due to the lack of propylene glycol as a carrying agent, which requires liver metabolism).

Answer 275

It promotes the acidification of colonic contents, trapping ammonia in the form of ammonium, while decreasing bacterial numbers and eliminating ammonium and bacteria in the feces. The osmotic effect will result in catharsis, reducing fecal transit time and exposure to bacteria for proliferation and ammonia production.

Answer 276

Antibiotics, such as metronidazole, neomycin, or ampicillin, will decease GI bacterial numbers, allowing for a reduction in ammonia production as well. Metronidazole and ampicillin also decrease risk of bacterial translocation and systemic infections. In pets with signs of bleeding or anemic, packed red blood cells, whole blood, or fresh frozen plasma may be of benefit. If there is evidence of HE, fresh whole blood is preferred as stored blood contains a decreased number of clotting factors and elevated ammonia levels, potentially worsening HE.

Answer 277

.....protein of high biologic value (enough to meet the animal's needs, but not to encourage HE)

Answer 278

Acid receptor blockade (famotidine or omeprazole) with sucralfate.

Answer 279

Ascites is rarely seen in animals with PSSs unless there is severe hypoalbuminemia. If ascites is due to poor oncotic pressures, colloidal therapy should be considered. If ascites is due to portal hypertension, diuretic therapy and low sodium diets should be considered. Additional sodium sources (particular treats) may exacerbate the ascites and should be avoided. Spironolactone is the initial diuretic of choice for its potassium-sparing effects. Furosemide may be necessary as well but should be used with caution because it potentiates further hypokalemia.

Answer 280

antiinflammatory, immunomodulatory, and antifibrotic Promoting choleresis

Answer 281

Antioxidant and free radical scavenging properties of silymarin. Specifically, it has been shown to inhibit lipid peroxidation of hepatocyte and microsomal membranes and protect against gene damage by suppression of hydrogen peroxide, super-oxide, and lipoxygenase. Silymarin also increases hepatic glutathione content, appears to retard hepatic collagen formation, and has hepatoprotective effects through inhibition of Kupffer cell function.

Answer 282

xenobiotics. Intrinsic hepatotoxicity results from the direct action of a xenobiotic or its metabolite on vital cell targets (e.g., acetaminophen). Many damage zone 3 and the most common pathophysiologic response is necrosis without an inflammatory infiltrate. Although we think of drug-metabolizing enzymes in their role of detoxifying xenobiotics and toxins, they may also enhance the toxicity of some.

Answer 283

Schematic illustrating acinar versus lobular structure of liver. Acinus describes a 3-D cone-shaped unit that receives blood from the portal vein (PV) and hepatic arteriole (HA), which flows through the parenchyma toward the terminal hepatic venule (THV). The zones reflect different areas of susceptibility to bloodborne toxins versus hypoxia. The lobule centers around a THV and is bordered by triads of a bile ductile (BD), PV and HA. The parenchyma around the portal triads is affected by processes occurring in these three structures, especially the biliary tree. 

Answer 284

immune-mediated mechanisms. Because the liver has an enormous regenerative capacity, replacement of lost hepatocytes may mask detection of drug-induced injury. The outcome of intrinsic and idiosyncratic xenobiotic hepatotoxicity varies widely, ranging from cell survival to apoptosis or complete cytolytic necrosis. Nutritional status affects xenobiotic toxicity, with obesity favoring the accumulation of lipid-soluble toxic metabolites as opposed to anorexia or protein: calorie restriction in which there is a reduction of hepatic glutathione (GSH) concentrations that can augment hepatotoxicity associated with oxidant injury.

Answer 285

Drug-induced liver injury can mimic all forms of spontaneous liver disease involving hepatocellular necrosis, changes consistent with toxic hepatitis, steatosis or lipidosis, and cholestasis (canalicular stasis ± periportal inflammation). Xenobiotic-induced hepatic necrosis may be zonal (often zone 3) or panlobular.

Answer 286

Diffuse or multifocal hepatic necrosis and degeneration with or without canalicular cholestasis. While hepatic acinar structure is maintained, areas of necrosis and degeneration are surrounded by viable hepatocytes and an inflammatory infiltrate (neutrophils, macrophages, or eosinophils). Illness can range from asymptomatic increases in transaminases to signs of overt liver failure and jaundice.

Answer 287

Abnormal accumulation of triglycerides (TG) in the hepatocyte cytoplasm within membrane-bound vesicles in either a macrovesicular or microvesicular pattern. Microvesicular steatosis reflects severe metabolic disruptions associated with abnormal mitochondrial function and impaired TG egress from the endoplasmic reticulum and Golgi apparatus. When diffuse, this lesion often accompanies inflammation and hepatocellular necrosis.

Answer 288

Disrupted bile production or flow and may present as a periportal inflammatory lesion causing hepatocanalicular cholestasis or a less obtrusive canalicular dysfunction without inflammation and necrosis. Clinical evidence of this form of injury involves sequential increases in alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) activity, and development of hyperbilirubinemia.

Answer 289

Antimicrobials: Sulfonamide reactions are the best recognized examples in dogs: causing acute parenchymal damage with moderate to severe increases in ALT activity, acute cholestasis associated with jaundice, or a combination of these responses. Also tetracyclines can induce hepatocellular lipid retention, as well as fulminant hepatic failure in both dogs and cats.

Answer 290

Phenobarbital, Phenytoin, and Primidone Phenibarbital: Initial clinical signs of phenobarbital hepatopathy include sedation and ataxia caused by impaired drug metabolism. With severe liver injury, anorexia, jaundice, ascites, and coagulopathy are variably recognized. Diazepam-associated hepatotoxicity in cats is an idiosyncratic reaction causing panlobular hepatocellular necrosis sparing the biliary epithelium.

Answer 291

Administration of a combination heartworm-hookworm preventative containing diethylcarbamazine and oxibendazole has been associated with lethal hepatotoxicity in dogs.

Answer 292

Methimazole can cause cholestatic hepatotoxicity; this usually occurs within the first month of therapy and is suggested by increased transaminases, ALP, and jaundice. Liver injury is reversible if the drug is discontinued. Because metabolism of toxic intermediates involves GSH, it is postulated that cats with subnormal hepatic GSH concentrations may be at increased risk for methimazole hepatotoxicity. Additionally, because catabolism and protein deficiency states can enhance hepatic GSH depletion, some symptomatic hyperthyroid cats may be at higher risk for methimazole toxicity. For example, cats with preexisting gut or liver disease associated with GSH depletion (e.g., cholangitis, cholangiohepatitis) may be predisposed.

Answer 293

Nonsteroidal antiinflammatory drugs (NSAIDs) can be associated with idiosyncratic hepatotoxicity, as well as dose-dependent GI bleeding and exacerbation of renal insufficiency. Virtually all NSAIDs are capable of causing some form of liver injury. Histologic lesions vary within and between NSAID drug classes. Although hepatocellular injury (necrosis) is most common, cholestatic injury, mixed cholestatic/necrotic injury, steatosis, and granulomatous inflammation also are recognized (human). Because many toxic metabolites are normally detoxified by GSH, some metabolites of NSAIDs become more toxic when hepatic GSH stores are depleted (e.g., animals with preexisting chronic necroinflammatory and cholestatic liver disease). Aspirin and phenylbutazone are directly hepatotoxic

Answer 294

Some dogs have occult hepatic injury yet lack clinical signs. Modest to markedly increased transaminase activity, exceeding the increases in ALP activity, are common. Renal toxicity (granular casts, glucosuria in the absence of hyperglycemia, and proteinuria) may also develop

Answer 295

Acetaminophen is primarily metabolized in the liver by sulfation and glucuronidation; conjugated products are water soluble and subsequently eliminated in urine. Conjugation with GSH or cysteine protects the liver from toxicity through renal excretion of mercapturic or cysteine conjugates. If an individual is both GSH and cysteine deficient this can cause lethal cellular injury. Mitochondrial effects reduce cellular ATP and impair availability of mitochondrial GSH, resulting in cellular oxidation and hepatocyte death. Species sensitivity to acetaminophen hepatotoxicity reflects NAPQI formation and their inherent susceptibility to either hepatotoxicity or hematotoxicity. Dogs have an apparent predisposition to acetaminophen-induced liver injury likely related to their intrinsically low hepatic GSH concentrations. Dogs surviving initial hepatotoxicity also can develop hematotoxicity, whereas cats are relatively resistant to hepatotoxicity.

Answer 296

N-acetylation. Cats, having higher hepatic GSH concentrations but whose red blood cells (RBCs) are more susceptible to oxidation due to the orientation of their hemoglobin sulfhydryl groups, are more susceptible to hematotoxicity. Cats also demonstrate signs consistent with endothelial toxicity (facial edema, pulmonary edema). Treatment involves removal of acutely ingested drug and administration of a thiol donor to supplement cysteine and restore circulating and liver GSH.

Answer 297

CCNU can cause delayed, cumulative, dose-related, chronic hepatotoxicity that is irreversible and that can be fatal.

Answer 298

Aflatoxin (like aflatoxin-contaminated dog food). The sugar substitute xylitol (most commonly found in baked goods, desserts, toothpaste, other oral care products): dogs can experience marked insulin release with potential for subsequent hypoglycemia. At a dose >0.5 g/kg acute severe fulminant hepatic failure occurs. Sago Palms or cycads are often used as ornamental plants, houseplants, or bonsai. Cycad neurotoxicosis and hepatotoxicosis have been described in many animals. Natural or Herbal Remedies.

Answer 299

A neutral copper balance is achieved through biliary copper excretion. Consequently, any metabolic abnormality that interferes with normal copper egress from the liver or compromises bile management (e.g., cholestasis) can result in hepatocellular copper accumulation. Both copper and iron are known to accumulate in liver tissue of dogs and cats with necroinflammatory liver disorders, where they enhance hepatic vulnerability to oxidant injury.

Answer 300

Because copper is a transition metal, it has both prooxidant and antioxidant effects. Pathologic hepatocellular copper retention is well described in the Bedlington Terrier as an autosomal recessive trait resulting in the deletion of the COMMD1 (MURR-1) gene

Answer 301

Because hepatocytes depleted of GSH have increased susceptibility to iron-mediated lipid peroxidation and because high hepatic iron is associated with subnormal vitamin E availability and a reduced tissue GSH/GSSG balance, supplementation with both vitamin E and thiol donors is recommended

Answer 302

Associated with the precursor protein amyloid A (AA), an amino terminal fragment of the acute-phase protein, serum amyloid A (SAA). This protein accumulates secondary to sustained acute-phase reactions associated with chronic inflammatory, infectious, or neoplastic processes or as a familial trait. In systemic amyloidosis, clinical signs vary according to the extent of tissue involvement. In familial AA amyloidosis of Chinese Shar-Pei dogs and Abyssinian cats, most clinical signs reflect renal involvement.

Answer 303

Diffuse hepatic amyloid deposition in cats predisposes to spontaneous liver lobe fracture owing to increased organ fragility and coexistent symptomatic coagulopathy due to inhibition or deficiency of specific factors, binding of ionized calcium, or vitamin K deficiency. Cats present following acute death or with hypothermia from hypovolemic, hemorrhagic shock associated with massive hemoabdomen. A regenerative anemia, Howell-Jolly bodies due to amyloid impaired splenic function, “stress” leukocytosis, poikilocytes, thrombocytopenia, and abnormally prolonged clotting times are common. Although an increased ALT may be observed, some cases lack biochemical features indicating hepatic involvement.

Answer 304

In Chinese Shar-Pei dogs with amyloid secondary to “Shar-Pei fever,” colchicine is used. Colchicine attenuates inflammatory responses by reducing tumor necrosis factor receptor externalization, inflammatory mediator release, neutrophil recruitment, and deposition of amyloid fibrils.

Answer 305

Lipoprotein lipase (LPL) regulates the dispersal of fatty acids to muscle and adipose. Feline familial LPL deficiency, an autosomal recessive trait, disturbs fat metabolism leading to hypertriglyceridemia, hyperchylomicronemia, and systemic sequela including hepatic lipid accumulation. Affected cats have a more than tenfold increase in circulating TG yet normal total cholesterol concentration. Affected kittens do not exhibit clinical signs other than fasting lipemia

Answer 306

development of diffuse vacuolar hepatopathy (hepatocellular TG and glycogen) or biliary mucocele. Biliary mucocele formation may reflect the influence of hypercholesterolemia on bile composition but is augmented by cystic epithelial hyperplasia of the gallbladder wall and possibly gallbladder dysmotility.

Answer 307

In the developmental stage, biliary mucoceles are asymptomatic and serendipitously discovered during abdominal ultrasonography. Symptomatic patients present for signs reflecting necrotizing cholecystitis or are investigated for persistent high ALP activity. The appearance of a “kiwi fruit” echo image within the gallbladder lumen is diagnostic for a firm, well-established mucocele; however, sludge within the gallbladder and accompanying peritonitis are more common changes. In dogs with gallbladder inflammation or ischemia, a thickened wall or a wall with a bilaminar or trilaminar appearance may be observed. The latter pattern seemingly predicts risk of gallbladder rupture. Surgical removal is indicated, with urgency depending on clinical evidence of necrotizing cholecystitis (hyperbilirubinemia, high liver enzymes, cranial abdominal pain, leukocytosis, bilaminar or trilaminar wall). Underlying causes include disorders causing hyperlipidemia or hypercholesterolemia (hypothyroidism, protein-losing nephropathy, diabetes mellitus, hyperadrenocorticism, sex hormone adrenal hyperplasia, and idiopathic hyperlipidemia).

Answer 308

.High-dose glucocorticoid administration usually induces a significant increase in ALP and ALT activity within 2 to 3 days if given by injection and within 1 to 2 weeks if given orally. Individual variation in response, different potencies of glucocorticoid agents, and route of exposure (endogenous, parenteral, oral, cutaneous, ocular) influence changes in hepatic morphology, clinicopathologic features, and clinical signs. Typically, increased ALP and GGT activities develop in parallel as these enzymes undergo induction and subsequent release from sinusoidal and canalicular membranes. A similar scenario occurs in dogs with adrenal hyperplasia syndromes, where high steroid sex hormone or high cortisol production occurs. Clinical assessment may fail to disclose an underlying health problem or cortisol values consistent with classic hyperadrenocorticism in a dog with a prominent vacuolar hepatopathy and high ALP activity (often with modestly increased SBA concentrations).

Answer 309

the rate of hepatic synthesis exceeds their dispersal into the systemic circulation or their use in fatty acid oxidation. Hepatic TGs are synthesized from fatty acids delivered from the systemic circulation (dietary lipids, adipose stores) and from de novo hepatic synthesis. Overnutrition augments hepatic fat accumulation; feeding a high proportion of dietary carbohydrates may have an inhibitory influence on mitochondrial fat oxidation favoring hepatic fat accumulation. Feline obesity predisposes to development of HL: In inappetant obese cats, release of fatty acids from their ample peripheral adipose stores challenges the liver's capacity for fat utilization and dispersal.

Answer 310

Hormone-sensitive lipase (HSL, promoting adipocyte lipolysis) and LPL (promoting fat uptake into adipocytes) directly influence adipocyte fat metabolism.

Answer 311

Norepinephrine, epinephrine, growth hormone, glucagon, corticosteroids, and thyroxin increase HSL activity, whereas insulin inhibits it. Because cats release catecholamines readily, stress may augment HSL activation. Because this effect is enhanced in the absence of insulin, occult or overt hepatic TG accumulation in unregulated diabetics is common. Although LPL promotes fat uptake into adipocytes in the well-fed condition, during starvation, LPL activity declines and HSL increases, creating a hormonal balance favoring hepatocellular fat accumulation. In this way, an obese individual undergoing self-imposed starvation (anorexia) has increased risk for peripheral fat mobilization and excessive hepatic TG retention.

Answer 312

The fate of fatty acids in the liver includes utilization in beta-oxidation, conversion to phospholipids, and use in formation of various lipid-containing moieties (TG, cholesterol esters, lipoproteins).

Answer 313

A key in TG dispersal is via formation of very low density lipoproteins (VLDL). A variety of subcellular activities regulate VLDL formation and dispersal, including lipid transport through subcellular compartments, packaging with apoprotein, formation of secretory particles and vesicles, and expulsion into the perisinusoidal space. Impairment at any step or imbalance between lipoprotein components may compromise this process favoring hepatic TG accumulation. The essential interaction of fatty acids and L-carnitine at mitochondrial membranes influences both the intraorganelle activation of fatty acids and their availability for beta-oxidation

Answer 314

Theoretical explanation for regional carnitine deficiency in cats with hepatic lipidosis: Increased delivery of long-chain free fatty acids requires carnitine for transport across organelle walls. Supplementation with L-carnitine appears to hasten clinical recovery in cats with hepatic lipidosis.

Answer 315

Deficiency of hepatocellular GSH in cats with HL may reflect intramitochondrial GSH insufficiency where it is necessary for redox-balance to sustain continued energy production. Finding hepatic GSH deficiency in cats with HL implicates dysfunction of the transsulfuration pathway with diminished SAMe availability. Additionally, B12 deficiency is a common feature in HL cats secondary to primary gut disease. Perhaps B12 deficiency and dysfunction of the transmethylation pathway may be a causal factor. Because.............. increases fatty acid oxidation in normal and obese cats, and in cats with modeled HL, it is reasonable to include it in treatment.

Answer 316

Hematologic features include a nonregenerative anemia and a stress leukogram reflecting the primary illness causing anorexia. Poikilocytosis is common and may reflect altered RBC membrane lipids, metabolism, or oxidative stress affecting cell membrane flexibility. Biochemical changes reflect cholestasis and, to a lesser degree, altered hepatocellular membrane permeability and viability. Most cats have a markedly increased ALP activity with lesser magnitudes of increase in transaminases. Rarely, a cat with HL will have high transaminases with only modest ALP activity. Finding high GGT activity in a cat with HL increases suspicion of underlying pancreatitis, pancreatic neoplasia, cholangiohepatitis, major bile duct obstruction, cholelithiasis or choledochitis, or biliary tree neoplasia. Hyperbilirubinemia and high serum bile acid concentrations are common. Hypokalemia reflects inappetence and is significantly associated with failure to survive if uncorrected. Hypochloremia may reflect vomiting. Hypophosphatemia reflects intercompartmental shifts in phosphate and most commonly heralds onset of a refeeding syndrome. Urinalysis typically reports urobilinogen with bilirubin pigmenturia and bile crystalluria. Ultrasound evaluation characteristically shows a hyperechoic hepatic parenchyma. Aspirat from the liver

Answer 317

Provision of a balanced, high-protein feline diet delivering adequate energy (goal feeding of 40 to 60 kcal/kg/day). Cats with HL are often deficient in vitamin K as proven by PIVKA (proteins induced in vitamin K absence or antagonism) testing or prothrombin time (PT) tests. Lack of dietary intake, altered intestinal bacterial flora subsequent to antimicrobial treatment, and impaired vitamin K epoxidase cycle associated with hepatic dysfunction are underlying causes. Supplement with 250 to 500 mg L-carnitine per day. Fat-soluble vitamin deficiency is suspected in severe HL. Most critical is vitamin K.

Answer 318

Normal lysosomes degrade cellular and extracellular macromolecules, providing amino acids, fatty acids, nucleic acids, and carbohydrate residues for reuse. Primary lysosomes, derived from the Golgi apparatus, may fuse with other membrane-bound vesicles forming secondary lysosomes. Storage diseases are defined by the nature of the lysosomal hydrolase deficiency and resultant accumulated metabolic substrates or products. Disorders are suspected based on clinical signs, including progressive neurologic dysfunction, ocular abnormalities, visceromegaly (including hepatomegaly), and skeletal abnormalities; signs may overlap clinically with nonlysosomal storage disorders. Different disorders may be associated with hepatocellular or Kupffer cell storage product accumulation. The mucopolysaccharidoses (MPSs) and disorders associated with interrupted catabolism of oligosaccharides can be crudely determined by specific urine tests. Treatment is limited for these disorders.

Answer 319

Ischemic injury and hypovolemia reduce hepatic perfusion and impair macrophage function; interrupted choleresis enables enteric opportunists to invade hepatic structures. Infection, sepsis, and endotoxemia also cause hepatic injury and cholestasis.

Answer 320

a nonregenerative anemia (chronic inflammation), leukopenia, or leukocytosis associated with a left shift and toxic change in neutrophils. Biochemical abnormalities include increased transaminase and ALP activities and variable hyperbilirubinemia. Sepsis-induced biochemical jaundice is encountered especially in cats, but sepsis-related hypoglycemia is rare in this species.

Answer 321

Infectious canine hepatitis caused by adenovirus type 1 is a unique pathogen because it is the only recognized virus with primary tropism for the liver. Recently, virulent calicivirus forms have presented as devastating but restricted outbreaks in several centers.

Answer 322

Granulomatous hepatic inflammation is an uncommon diagnosis characterized by multiple discrete and sharply defined nodular infiltrates consisting of aggregates of macrophages (± epithelioid cells). It is surrounded by, or intermixed with, lymphocytes and plasma cells. Lesions may be focal, multifocal, or diffuse. Underlying causes include many infectious agents. Noninfectious disorders that may associate with hepatic granulomatous or pyogranulomatous lesions include drug reactions, lymphangiectasia, histiocytosis or histiocytic neoplasia, lymphosarcoma, immune-mediated inflammation, and copper-associated hepatic necrosis. Immune-mediated inflammation may be associated with a positive antinuclear antibody test

Answer 323

Hepatocellular, bile duct, mesenchymal, and neuroendocrine. In cats, benign tumors are more common, whereas in dogs, tumors are more often malignant.

Answer 324

Hepatic tumors metastasize first to regional lymph nodes and then lung, and peritoneum in the dog and peritoneum in the cat. Biliary tumors in the cat may extend into the pancreas. Metastatic extension to brain, spinal cord, bone, kidney, adrenal gland, and spleen is less common in each species.

Answer 325

Lymphoreticular neoplasia

Answer 326

Including chronic lethargy, inappetence, dehydration, PU/PD, and fever. Less commonly, vomiting, diarrhea, jaundice, and ascites (dogs) may develop. PU/PD is more commonly linked to primary liver tumors (up to 50% of dogs). Rarely, neurologic signs develop in dogs reflecting hypoglycemia or hepatic encephalopathy.

Answer 327

Hypoglycemia may be a dominant marker of large tumor mass (metabolic consumption) or reflect paraneoplastic phenomena such as production of an insulin-like substance. Hypoalbuminemia, more common in dogs than cats, may reflect a negative acute phase response, catabolism and poor nutritional intake, or hepatic insufficiency.

Answer 328

The gallbladder is a reservoir where bile is stored, modified, and eventually expelled. Bile is formed in the hepatocytes and is actively secreted into the bile canaliculi. From the canaliculi, bile flows to the interlobular ducts and ultimately to the lobar ducts. The lobar ducts give rise to the left and right hepatic ducts. The cystic duct is an offshoot of the hepatic ducts and travels toward the gallbladder. The cystic duct is an important landmark in that it distinguishes the otherwise continuous hepatic ducts from the common bile duct.

Answer 329

Cholesterol, lecithin, phospholipids, and bile salts.

Answer 330

Bile emulsifies fat and neutralizes acid in partially digested food. The synthesis of bile acids and their secretion provides an important method for the excretion of cholesterol.

Answer 331

When the gallbladder contracts, bile is released into the common bile duct and enters the duodenum through the sphincter of Oddi. In the dog, the common bile duct joins the minor pancreatic duct at the major duodenal papilla. In the cat, the common bile duct joins the major pancreatic duct before entering the duodenum.

Answer 332

mucosa, lamina propria, smooth muscle, and serosa

Answer 333

The rounded apical and most distended part of the gallbladder is designated the fundus. The middle portion of the gallbladder comprises the body and the neck tapers into the cystic duct.

Answer 334

Gallbladder contraction is primarily initiated by cholecystokinin, a peptide hormone secreted in the duodenum in response to fats and proteins entering the small intestine. Vagal parasympathetic innervation also plays an important role in contraction. Gastrin and motilin are involved in contraction, but their exact role is not completely understood in the domestic animal.

Answer 335

Somatostatin, released by the pancreas and gastrointestinal epithelium in response to fats in the small intestine, is a potent inhibitor of gallbladder contraction and facilitates gallbladder filling. Vasoactive intestinal peptide (VIP), nitric oxide, and pancreatic polypeptide cause gallbladder relaxation

Answer 336

Varied precipitated bile components. In the dog, cholesterol, bilirubin, and mixed stones have been reported. Calcium-based stones are rare due to the ability of the canine gallbladder to absorb free calcium in bile. Feline choleliths contain cholesterol, bilirubin derivatives, and calcium salts.

Answer 337

Cholesterol is strongly hydrophobic, necessitating transport in micelles to remain suspended in solution. When there is an imbalance between bile salts and cholesterol, bile becomes more viscous. Supersaturation occurs, leading to the formation of gallstones. Various abnormalities may promote supersaturation and cholelithiasis. These include gallbladder dyskinesia, hypercholesterolemia, hypertriglyceridemia, hyperbilirubinemia, endocrine disease, cholesterol absorption, and transport defects in the gallbladder. Gallstones may cause obstruction or inflammation of the gallbladder or can be incidental findings on abdominal ultrasound. If the obstruction is severe, the gallbladder or bile duct ruptures, leading to bile peritonitis

Answer 338

Choledocholiths, stones in the common bile duct, may either be primary or secondary. Primary stones develop directly in the common bile duct. Secondary stones are more common and form in the gallbladder, later passing into the common bile duct.

Answer 339

A stress leukogram is the most common finding. However, a neutrophilic leukocytosis with a left shift is typical in patients with biliary rupture. Mild to moderate nonregenerative anemias are common in patients with chronic disease. The total bilirubin, ALP, and GGT are commonly elevated. Bilirubinuria is often evident and generally precedes clinical jaundice. Due to the short half-life of ALP in the cat (6 hours compared with 72 hours in dogs), even mild increases are significant. ALT and AST elevations, when present, are less dramatic than rises in ALP and GGT. Mild hypercholesterolemia occurs with cholestasis and severe elevations are observed with biliary obstruction. Azotemia occurs secondary to dehydration and vomiting. Hypoalbuminemia and hypoglycemia may occur if sepsis or endotoxemia are present. (Abdominal radiographs are often of limited diagnostic value because most stones do not contain sufficient calcium to be visualized; use US).

Answer 340

Bile stasis, gallbladder mucoceles, ascending bacterial or parasitic diseases, and biliary neoplasia. In addition, infarction and hematogenous spread of bacteria may be involved. Choleliths are concurrently identified in some patients. Some patients with cholecystitis develop necrotizing cholecystitis. Cholecystitis may be either acute or chronic in nature. Mild cases are often asymptomatic. The predominant symptoms of moderate to severe acute cholecystitis include anorexia and vomiting, with abdominal pain and fever. Similar to cholelithiasis, laboratory findings vary widely with cholecystitis. Most clinicopathologic changes are consistent with cholestasis or posthepatic biliary disease

Answer 341

Biliary cystadenoma and biliary adenocarcinoma (cholangiocarcinoma).(however both are rarely seen)

Answer 342

The clinical signs of parasitic biliary disease depend on the degree of liver injury and biliary obstruction. Many cats are asymptomatic carriers. Weight loss, anorexia, and vomiting are the most common complaints in symptomatic cats. Jaundice and abdominal distention

Answer 343

Predisposing factors include dyslipidemias, dysmotility of the gallbladder, endocrine disease, and exogenous steroid administration. (Breed predispositions include Shetland Sheepdogs, Cocker Spaniels, and Miniature Schnauzers. Mucoceles occur most commonly in older canine patients). Potential complications of mucoceles include extrahepatic bile duct obstruction, cholecystitis, necrotizing cholecystitis, bile peritonitis, and pancreatitis.

Answer 344

Surgery Medical therapy for gallbladder mucoceles has been successful in seven patients and in particular those with hypothyroidism. A combination therapy of cholerectics and antibiotics are most frequently attempted. Cholerectics, such as ursodiol and SAMe, alter the microenvironment of the gallbladder and increase bile flow. Care should be taken in patients with biliary obstruction because cholerectics may induce rupture of the gallbladder or biliary tree.

Answer 345

pancreatitis. Contrary to previous reports, chronic pancreatitis appears to be more common than acute pancreatitis. Other diseases of the exocrine pancreas, such as exocrine pancreatic insufficiency, pancreatic neoplasia, or fluid accumulations of the exocrine pancreas, occur less frequently.

Answer 346

Chronic pancreatitis is associated with pancreatic fibrosis and atrophy. Acute and chronic pancreatitis cannot be differentiated clinically and it is crucial to recognize that either acute or chronic pancreatitis may be associated with neutrophilic or lymphocytic-plasmacytic infiltration. Either can be associated with systemic complications and either can be associated with local complications, such as pancreatic necrosis and pancreatic fluid accumulations. However, chronic pancreatitis is less commonly associated with local and systemic complications and is usually a milder disease process.

Answer 347

Hyperlipidemia and hypertriglyceridemia (cause or an effect?) Hereditary pancreatitis is well-documented in humans Drugs?? L-asparaginase, azathioprine, estrogen, furosemide, potassium bromide, salicylates, sulfonamides, tetracyclines, thiazide diuretics, and vinca alkaloids. Iatrogenic hypercalcemia zinc toxicosis Obese animals (hypothyroidism and hyperadrenocorticism) Obstruction of the pancreatic duct system Reflux of duodenal juice into the pancreatic ducts can also cause pancreatitis. Under normal circumstances such reflux is unlikely to occur because the duct opening is surrounded by a specialized compact smooth mucosa over the duodenal papilla and is equipped with an independent sphincter muscle. However, these protective mechanisms may fail in situations where there is abnormally high duodenal pressure, for example, during vomiting or after blunt trauma to the abdominal cavity. Surgical manipulation and blunt abdominal trauma are also potential causes of pancreatitis Severe pancreatic ischemia due to severe dehydration or during shock Pancreatitis has been recognized as a potential complication of canine babesiosis Autoimmune mechanisms

Answer 348

Proteolytic and phospholipolytic enzymes are synthesized, stored, and secreted in the form of inactive zymogens. These zymogens are activated by enzymatic cleavage of a small peptide (the activation peptide) from the amino terminal of the polypeptide chain. Under physiologic conditions, activation of these zymogens occurs in the duodenum. Also, premature activation of zymogens is inhibited by their segregation from lysosomal enzymes. Furthermore, should significant activation occur, acinar cells contain a specific trypsin inhibitor, pancreatic secretory trypsin inhibitor (PSTI, also known as SPINK 1), that is synthesized, stored, and secreted together with trypsinogen. Thus, whenever premature activation of trypsinogen to trypsin occurs, PSTI is believed to inhibit trypsin activity, blocking a chain reaction of enzyme activation. Pancreatic juice reaches the duodenum through the pancreatic duct, which only allows for unidirectional flow. This unidirectional flow is important in preventing pancreatic enzymes from causing damage to the acinar cells. Finally, plasma protease inhibitors, including α1-proteinase inhibitor and α2-macroglobulins, scavenge proteases that may have reached the vascular space. Once all of these protective mechanisms have been surpassed, damage to acinar cells occurs.

Answer 349

tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-2, IL-6, IL-8, IL-10, interferon-α (IFN-α), IFN-β, nitric oxide (NO), and platelet-activating factor (PAF).

Answer 350

thrombocytopenia. Several different findings when analyzing blood, but no finding on complete blood count, serum chemistry profile, or urinalysis is specific for pancreatitis.

Answer 351

amylase and lipase activities, serum trypsinlike immunoreactivity (cTLI), pancreatic lipase immunoreactivity (cPLI), trypsin-α1-proteinase inhibitor complexes, and serum and urinary trypsinogen activation peptide (TAP) Serum amylase and lipase activities have been used to aid in diagnosing canine pancreatitis for decades, despite studies repeatedly showing a lack sensitivity and specificity. Many cell types of the body synthesize and secrete lipases, enzymes that hydrolyze lipids. Assays for serum lipase activity are not specific for pancreatic lipase, but immunoassays that quantify canine pancreatic lipase (cPLI) are specific for pancreatic exocrine function and for pancreatitis. Two small studies have reported a sensitivity of serum cPLI concentration for canine pancreatitis of about 82%. Thus, serum cPLI concentration is the most sensitive and specific test for canine pancreatitis currently available.

Answer 352

Until recently, metoclopramide, a dopamine inhibitor, was widely used. However, the effect of metoclopramide on splanchnic perfusion remains in question and the use metoclopramide in dogs with pancreatitis may not be wise. Dolasetron and ondansetron, both 5-HT3 antagonist, are effective antiemetic agents in dogs. Maropitant, an NK1 antagonist, can be used.

Answer 353

Many dogs have mild forms of chronic pancreatitis. Often, these dogs have concurrent conditions, most notably IBD. Little is known about appropriate therapy for these dogs and management is often limited to evaluation and treatment of the concurrent condition. Serum calcium and triglyceride concentrations should always be evaluated in order to identify any risk factors that can potentially be addressed. Also, use of ultra-low-fat diets is recommended.

Answer 354

A pancreatic pseudocyst is a collection of sterile pancreatic fluid enclosed by a wall of fibrous or granulation tissue. It is considered a complication of pancreatitis. A pancreatic abscess is a circumscribed collection of pus, usually in close proximity to the pancreas. This is considered a complication of pancreatitis. A bacterial infection may or may not be present.

Answer 355

The most common cause of EPI in dogs is pancreatic acinar atrophy (PAA), which is almost exclusively seen in German Shepherd Dogs, Rough-Coated Collies, and Eurasians. (an autosomal recessive trait?) The second most common cause of EPI in dogs is chronic pancreatitis. As with other organs, chronic inflammation can lead to atrophy and fibrosis, which ultimately can lead to destruction of enough exocrine pancreatic mass to cause clinical signs of EPI. (Another potential cause of EPI is an obstruction of the pancreatic duct by a tumor, which, if complete, can lead to lack of digestive enzymes in the small intestinal lumen, despite their normal production. Long term, an obstructed pancreatic duct can lead to either pancreatitis, pancreatic atrophy, or both. This can lead to clinical signs of EPI. Obstructions of the pancreatic duct have been described in humans but have never been conclusively demonstrated in dogs). Pancreatic aplasia and hypoplasia could also cause clinical signs of EPI and these conditions are sometimes suspected when EPI is diagnosed at an early age, but no case has been conclusively demonstrated in a dog.

Answer 356

Pancreatic secretory products and pancreatic enzymes are crucial for digestion of food. When pancreatic acinar cells are lacking, regardless of the cause, maldigestion ensues. It is important to note that the GI tract is highly redundant and for most pancreatic digestive enzymes there are other enzymes with the same function that are synthesized and secreted by other organs. Also, the exocrine pancreas has a huge functional reserve. It has been estimated that clinical signs of EPI only occur if more than 90% of exocrine pancreatic function have been lost. Maldigestion leads to undigested food components in the intestinal lumen. This leads to diarrhea, proliferation of the small intestinal microflora, and weight loss. These clinical signs are not solely due to maldigestion. Deficiency of other pancreatic functions may also play a role: -For example, the pancreas secretes large quantities of bicarbonate necessary to buffer gastric acid. -The pancreas is believed to synthesize and secrete trophic factors that help maintain normal GI mucosa. -The exocrine pancreas also is the major source of intrinsic factor in the dog.

Answer 357

As a result, all pancreatic digestive enzymes are lacking. Rarely, a single enzyme may be lacking. Lack of a single enzyme, however, even if complete, most likely would not lead to clinical signs. Pancreatic lipase is an exception because pancreatic lipase deficiency has been reported as a cause of clinical signs of EPI in humans and in one dog.

Answer 358

EPI can be subclinical, and isolated dogs with severely decreased serum cTLI concentrations without any clinical signs may be seen. Dogs with severely decreased pancreatic size on exploratory laparotomy have been demonstrated to not have clinical signs. The most consistent clinical sign in dogs with EPI is weight loss. Loose stools are also commonly observed, but watery diarrhea is rather uncommon. Often, these dogs have a poor hair coat, borborygmus, and flatulence. Many dogs with EPI show an increased appetite, coprophagia, or even pica.

Answer 359

Based on the demonstration of a lack of exocrine pancreatic function: Serum canine TLI concentration remains the gold standard for the diagnosis of EPI in dogs. An assay for the measurement of serum pancreatic lipase immunoreactivity in dogs (cPLI) has been developed and validated. The PLI assay is highly species specific and measures the mass concentration of pancreatic lipase in serum. Pancreatic lipase is much larger than trypsinogen and is also positively charged. Pancreatic lipase is thus repelled from the glomerular membrane and is only slowly excreted by the kidneys. Therefore, a larger residual amount of pancreatic lipase remains in the vascular space and the assay is thus less sensitive for EPI

Answer 360

While feeding a low-fat diet has been recommended by some, experimental studies have shown that dogs treated with pancreatic enzyme supplements do not digest fat normally. Fat restriction would, therefore, increase risk of fat-soluble vitamin and essential fatty acid deficiencies. Therefore, a high-quality maintenance diet would be best. However, diets with high fiber content should be avoided because dietary fiber may interfere with fat absorption. One study demonstrated that 82% of dogs with EPI are cobalamin deficient. Therefore, dogs with EPI should be evaluated for cobalamin deficiency and, if identified, supplementation is necessary. Serum concentrations of most fat-soluble vitamins have also been shown to be decreased in dogs with EPI. However, fat-soluble vitamin supplementation has not been investigated and oversupplementation with fat-soluble vitamins may cause side effects. It has been reported that dogs with EPI also commonly have SIBO. Tylosin is recommended for the treatment of SIBO but other antibiotic agents, such as metronidazole or oxytetracycline, can also be used.

Answer 361

Neoplastic diseases of the exocrine pancreas can be primary or secondary. Primary neoplastic diseases of the exocrine pancreas can be classified as benign or malignant. Pancreatic adenomas are usually benign primary solitary tumors. Adenomas can be differentiated from pancreatic nodular hyperplasia by the presence of a capsule. Pancreatic adenocarcinoma is a primary malignant tumor of the exocrine pancreas. Clinical presentation: A variety of nonspecific changes may be seen on a complete blood count and/or a serum chemistry profile. Increases in serum hepatic enzyme activities are commonly identified.[104] Hyperglycemia, when present, is related to concurrent destruction of pancreatic beta cells. Serum activities of lipase and amylase have not been commonly reported, but some are increased, in dogs with pancreatic adenocarcinoma

Answer 362

(Figure 283-1 Pathogenesis of feline exocrine pancreatic disease)

Answer 363

Characterized by pancreatic acinar cell and peripancreatic fat necrosis (>50% of the pathology), with varying amounts of inflammation, hemorrhage, mineralization, and fibrosis. Inflammation may be present, but necrosis is the predominant feature.

Answer 364

Neutrophilic inflammation accounts for >50% of the pancreatic pathology. Necrosis may be present, but neutrophilic inflammation is the predominant feature. ASP is less common than ANP, appears to affect younger animals, and may have a differing pathogenesis.

Answer 365

Lymphocytic inflammation, fibrosis, and acinar atrophy. Necrosis and suppuration may be present in small amounts, but lymphocyte infiltration is the predominant feature. Antemortem differentiation of chronic pancreatitis (CP) and ANP cannot be made on the basis of clinical, clinicopathologic, or imaging findings. histopathology remains the only dependable method of differentiating these two disorders. Chronic nonsuppurative pancreatitis and ANP may vary in their pathogeneses or they may represent a continuum of disease from necrosis to inflammation and fibrosis

Answer 366

Nodules of pancreatic acinar or duct tissue are distributed throughout the pancreatic parenchyma. (Fibrosis, inflammation, necrosis, and hemorrhage are not features of this condition). The clinical significance of this lesion is unknown. Pancreatic nodular hyperplasia is often detected at the time of routine abdominal ultrasonography or as an incidental finding at necropsy.

Answer 367

Pancreatic adenocarcinoma

Answer 368

A nonepithelial-lined cavitary structure containing fluid, pancreatic cells, and/or enzyme. Rarely seen in cats (and dogs)

Answer 369

A circumscribed collection of purulent material involving the right or left lobe of the pancreas. Like pseudocyst, pancreatic abscessation appears to be a complication of pancreatitis in humans and dogs. The incidence and significance of this lesion in the cat are unknown.

Answer 370

Atrophy may result from degeneration, involution, necrosis, or apoptosis of the exocrine pancreas. Most cats with this condition are believed to have end-stage CP. The endocrine portion of the gland may or may not be involved in the same process. Exocrine pancreatic insufficiency is the clinical syndrome that results from losing >95% of exocrine pancreatic function. Affected animals develop a classic maldigestion syndrome characterized by weight loss, steatorrhea, and diarrhea

Answer 371

Concurrent biliary tract pathology has a known association with ANP in the cat. Cholangitis is the most important type of biliary tract disease for which an association has been made, but other forms of biliary tract pathology (e.g., stricture, neoplasia, and calculus) have known associations. The pathogenesis underlying this association is not entirely clear but relates partly to the anatomic and functional relationship between the major pancreatic duct and common bile duct in this species. Unlike the dog, the feline pancreaticobiliary sphincter is a common physiologic and anatomic channel at the duodenal papilla. Mechanical or functional obstruction to this common duct readily permits bile reflux into the pancreatic ductal system. Like concurrent biliary tract disease, inflammatory bowel disease (IBD) is an important risk factor for the development of ANP in cats. Several factors appear to contribute to this association: (1) high incidence of IBD; (2) clinical symptomatology of IBD; (3) pancreaticobiliary anatomy, and (4) intestinal microflora. Bacteria readily proliferate in the feline small intestine because of differences in gastrointestinal motility and immunology. If chronic vomiting with IBD permits pancreaticobiliary reflux, a duodenal fluid containing a mixed population of bacteria, bile salts, and activated pancreatic enzyme would perfuse the pancreatic and biliary ductal systems. Ischemia (e.g., hypotension, cardiac disease) is a cause or consequence of obstructive pancreatitis in the cat. Inflammation and edema reduce the elasticity and distensibility of the pancreas during secretory stimulation. Sustained inflammation increases pancreatic interstitial and ductal pressure, which serves to further reduce pancreatic blood flow, organ pH, and tissue viability Obstruction of the pancreatic duct (e.g., neoplasia, pancreatic flukes, calculi, duodenal foreign bodies) is associated with the development of ANP in some cats. Pancreatic ductal obstruction has marked effects on pancreatic acinar cell function. During ductal obstruction, ductal pressure exceeds exocytosis pressure and causes pancreatic lysosomal hydrolases to colocalize with digestive enzyme zymogens within the acinar cell. Infectious agents (Toxoplasma gondii, feline herpesvirus I, feline infectious peritonitis) have been implicated in the pathogenesis of feline ANP, although none have been reported as important causes of ANP. Virulent calici viral infections have been reported in multiple cat households or research facilities. Pancreatic and liver fluke infections. Trauma Organophosphate Poisoning (such as treatment for ectoparasites) Idiosyncratic Drug Reactions: Therapy with azathioprine, l-asparaginase, potassium bromide, and trimethoprim sulfa drugs have been associated with the development of ANP in the dog. Similar associations have not been made in the cat. (Hypercalcemia) (Nutrition (High-fat feedings and obesity have been associated with the development of pancreatitis in the dog, but similar associations have not been made in the cat)

Answer 372

Digestive zymogens, which initiate protein, carbohydrate, and lipid digestion; Bicarbonate and water, which serve to neutralize pH in the duodenum Intrinsic factor, which facilitates cobalamin (vitamin B12) absorption in the distal ileum; Antibacterial proteins, which regulate small intestinal bacterial flora. Digestive zymogens are secreted primarily by acinar cells, while bicarbonate, water, intrinsic factor, and antibacterial proteins are secreted primarily by ductal cells.

Answer 373

With acute pancreatic necrosis, premature activation of digestive zymogen within pancreatic acinar cells leads to acinar cell necrosis (trypsin, chymotrypsin, carboxypeptidase), hemorrhage (elastase digestion of blood vessel elastin fibers), and fat necrosis and saponification (lipase digestion of pancreatic, peripancreatic, and mesenteric fat). With exocrine pancreatic insufficiency, affected cats develop severe nutrient maldigestion, acid injury to the duodenal mucosa, cobalamin and fat soluble vitamin malabsorption, and bacterial proliferation in the gut. A large body of experimental, and some clinical, evidence suggests that the initiating event of acute pancreatitis is the premature activation of digestive zymogens within the acinar cell. Premature activation of digestive zymogen results in acinar cell necrosis and pancreatic autodigestion. A variety of inflammatory mediators and cytokines, interleukins, nitric oxide, and free radicals are involved in the further evolution of pancreatic acinar cell necrosis and inflammation, which can affect the outcome

Answer 374

Serum trypsinlike immunoreactivity (TLI) mainly measures trypsinogen but also detects trypsin and some trypsin molecules bound to proteinase inhibitors. Serum TLI concentration is the diagnostic test of choice for feline exocrine pancreatic insufficiency because it is highly sensitive and specific. The use of this test in the diagnosis of feline ANP is less useful. Serum trypsinogen-like immunoreactivity (TLI) concentrations are transiently elevated in experimental feline acute pancreatitis, but increases in clinical cases are less consistent. The poor sensitivity (i.e., 33%) of this test precludes its use as a definitive assay for feline ANP.

Answer 375

When trypsinogen is activated to trypsin, a small peptide, trypsinogen activation peptide (TAP), is split from the trypsinogen molecule. Under normal conditions, activation of trypsinogen takes place only in the small intestine and TAP is undetectable in the blood. During pancreatitis, trypsinogen is activated prematurely in pancreatic acinar cells and TAP is released into the vascular space. Urine TAP assays have shown some promise in experimental models of feline pancreatitis, whereas serum TAP assays have shown some utility in preliminary clinical

Answer 376

Abnormal increases in fPLI have been cited in preliminary reports of feline ANP, but the true sensitivity and specificity of fPLI in the diagnosis of feline ANP have not yet been reported. As with fTLI assays, there are likely many false positives and false negatives with fPLI in the diagnosis of feline ANP.

Answer 377

Chronic Nonsuppurative Pancreatitis, Exocrine Pancreatic Insufficiency Hepatic Lipidosis Diabetes Mellitus

Answer 378

As with dogs, clinical signs reported in cats with EPI include weight loss, soft voluminous feces, and ravenous appetite. Affected cats may have an antecedent history of recurring bouts of acute pancreatitis (e.g., anorexia, lethargy, vomiting) culminating in CP and EPI

Answer 379

Several studies have related severe CP to the development of diabetes mellitus. ANP per se may not necessarily be a risk factor for the development of diabetes mellitus, but disease progression to the chronic nonsuppurative form may increase that risk.

Liver and pancreatic disease Flashcards

(404 cards)