Veterinary Hepatology Chapter 280
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Questions and Answers

What is one of the roles of the liver in the body?

  • Regulation of kidney function
  • Pumping of blood through the heart
  • Synthesis of clotting factors (correct)
  • Production of hormones

    • Which breed of dog is most commonly associated with copper storage disease?

  • Golden Retriever
  • Labrador
  • Bedlington Terrier (correct)
  • Poodle

    • What is the term for the accumulation of free fluid in the abdomen?

  • Ascites (correct)
  • Hypertension
  • Hypoalbuminemia
  • Icterus

    • What is the term for the yellow discoloration of the skin and mucous membranes?

    <p>Icterus</p> Signup and view all the answers

    What is the primary cause of portal hypertension in liver disease?

    <p>Chronic hepatitis with fibrosis</p> Signup and view all the answers

    What is the classification of Portal hypertension based on its location?

    <p>Prehepatic, sinusoidal, and postsinusoidal</p> Signup and view all the answers

    What is the primary cause of acute Hepatic Encephalopathy (HE)?

    <p>Fulminant liver failure</p> Signup and view all the answers

    What is the term for the superficial necrolytic dermatitis seen in liver disease?

    <p>Hepatocutaneous syndrome</p> Signup and view all the answers

    What is the characteristic of Alanine Aminotransferase (ALT) in dogs?

    <p>Half-life of 48-60 hours</p> Signup and view all the answers

    What is the level of bilirubin at which clinical icterus is typically seen?

    <p>Above 3</p> Signup and view all the answers

    What is the term for the congenital anomaly in which the portal vein does not develop properly?

    <p>Portal vein hypoplasia</p> Signup and view all the answers

    What is the characteristic of Aspartate Aminotransferase (AST) in cats?

    <p>Half-life of 77 minutes</p> Signup and view all the answers

    What is the characteristic of Alkaline Phosphatase (ALP) in cats?

    <p>Only the liver ALP contributes to serum measurement</p> Signup and view all the answers

    What is the characteristic of Gamma-Glutamyl Transpeptidase (GGT) in cats with hepatic lipidosis?

    <p>GGT elevation is lower than ALP elevation</p> Signup and view all the answers

    What is the purpose of bile acids in the digestive system?

    <p>To solubilize fats in the small intestine</p> Signup and view all the answers

    What is the consequence of loss of 75% of liver function?

    <p>Hypoglycemia</p> Signup and view all the answers

    What is the typical range for bile acids in a fasting blood sample?

    <p>15 mcmol/L</p> Signup and view all the answers

    What is the characteristic of bilirubin in bile duct obstruction?

    <p>Conjugated bilirubin in plasma binds irreversibly with albumin</p> Signup and view all the answers

    What is the function of protein C in the coagulation pathway?

    <p>To degrade factors Va and VIIIa</p> Signup and view all the answers

    What is a common cause of hypofibrinogenemia in liver disease?

    <p>Diffuse liver disease</p> Signup and view all the answers

    What is the primary cause of chronic Hepatic Encephalopathy (HE) in cats?

    <p>Hepatic lipidosis</p> Signup and view all the answers

    What is the characteristic of posthepatic causes of Portal hypertension?

    <p>Obstruction in larger vessels like the caudal vena cava or the right atrium</p> Signup and view all the answers

    What is the primary function of the liver in ammonia detoxification?

    <p>To convert ammonia to urea</p> Signup and view all the answers

    What is the significance of a prolonged PT in a patient with liver disease?

    <p>All of the above</p> Signup and view all the answers

    What is the primary use of ultrasound in liver disease?

    <p>To evaluate bile ducts and gallbladder</p> Signup and view all the answers

    What is the significance of a small liver on imaging studies?

    <p>Portosystemic shunting</p> Signup and view all the answers

    What is the advantage of CT angiography in diagnosing portosystemic shunting?

    <p>It improves diagnostic accuracy</p> Signup and view all the answers

    What is the primary limitation of fine-needle aspiration biopsy in liver disease?

    <p>Low cellularity</p> Signup and view all the answers

    What is the typical dosage of prednisolone in dogs with chronic hepatitis?

    <p>1-2 mg/kg PO q 24 h</p> Signup and view all the answers

    What is the purpose of repeating liver biopsy 6 weeks after starting treatment with prednisolone?

    <p>To assess the patient's response to treatment</p> Signup and view all the answers

    What is the mechanism of action of zinc in the treatment of copper toxicosis?

    <p>Zinc induces the synthesis of metallothionein, which binds copper with a higher affinity than zinc</p> Signup and view all the answers

    What is the reference interval for the hepatic copper concentration in healthy dogs?

    <p>500-1000 mcg/g</p> Signup and view all the answers

    What is the dosage of trientine for dogs not tolerating penicillamine due to GI side effects?

    <p>10-15 mg/kg PO q12 hr</p> Signup and view all the answers

    What is the purpose of feeding a copper-restricted diet in dogs with copper toxicosis?

    <p>To reduce the absorption of copper from the GI tract</p> Signup and view all the answers

    What is the dosage of lactulose in dogs and cats with hepatic encephalopathy?

    <p>1-3 mL per 10 kg body weight q 6-8 h</p> Signup and view all the answers

    What is the characteristic of azathioprine in dogs with chronic hepatitis?

    <p>It is a purine analog that can be used as an immunosuppressant</p> Signup and view all the answers

    What is the function of S-adenosyl methionine (SAMe) in the treatment of liver disease?

    <p>To increase hepatic glutathione and have anti-oxidant and anti-inflammatory properties</p> Signup and view all the answers

    What is the primary use of N-acetylcysteine (NAC) in the treatment of liver disease?

    <p>To treat acetaminophen toxicity</p> Signup and view all the answers

    What is the dosage of cyclosporine in dogs with chronic hepatitis?

    <p>5 mg/kg PO BID</p> Signup and view all the answers

    What is the effect of silymarin on cytochrome P450 activity in humans?

    <p>It decreases cytochrome P450 activity</p> Signup and view all the answers

    What is the purpose of copper staining and quantification in liver biopsy specimens?

    <p>To identify copper accumulation</p> Signup and view all the answers

    What is the role of ursodeoxycholic acid (ursodiol) in the treatment of liver disease?

    <p>It has choleretic, cytoprotective, and immunomodulatory effects</p> Signup and view all the answers

    Which breed of dog is associated with autoimmune chronic hepatitis?

    <p>Doberman Pinscher</p> Signup and view all the answers

    Why is prednisolone preferred over prednisone in the treatment of liver disease in dogs?

    <p>Because prednisolone is converted to prednisone in the liver</p> Signup and view all the answers

    What is the effect of silymarin on free radicals in the treatment of liver disease?

    <p>It scavenges free radicals</p> Signup and view all the answers

    What is the benefit of delivering silymarin with phosphatidylcholine?

    <p>It improves the bioavailability of silymarin</p> Signup and view all the answers

    What is the effect of S-adenosyl methionine (SAMe) on hepatic glutathione levels?

    <p>Increases</p> Signup and view all the answers

    What is the primary use of N-acetylcysteine (NAC) in the treatment of liver disease?

    <p>To treat acetaminophen toxicity</p> Signup and view all the answers

    What is the effect of silymarin on cytochrome P450 activity in humans?

    <p>Decreases</p> Signup and view all the answers

    What is the benefit of delivering silymarin with phosphatidylcholine?

    <p>Increases bioavailability</p> Signup and view all the answers

    What is the role of ursodeoxycholic acid (ursodiol) in the treatment of liver disease?

    <p>Choleretic</p> Signup and view all the answers

    Why is prednisolone preferred over prednisone in the treatment of liver disease in dogs?

    <p>Because prednisone is converted to prednisolone in the liver</p> Signup and view all the answers

    What is the effect of silymarin on free radicals in the treatment of liver disease?

    <p>Decreases</p> Signup and view all the answers

    What is the benefit of using vitamin E in the treatment of liver disease?

    <p>Antioxidant effect</p> Signup and view all the answers

    What is the purpose of repeating liver biopsy 6 weeks after starting treatment with prednisolone?

    <p>To evaluate the degree of hepatic inflammation and adjust the treatment plan</p> Signup and view all the answers

    What is the mechanism of action of zinc in the treatment of copper toxicosis?

    <p>It induces increased synthesis of metallothionein by enterocytes which binds copper with a higher affinity than zinc</p> Signup and view all the answers

    What is the reference interval for the hepatic copper concentration in healthy dogs?

    <p>1000 mcg/g</p> Signup and view all the answers

    What is the dosage of lactulose in dogs and cats with hepatic encephalopathy?

    <p>1-3 mL per 10 kg body weight q 6-8 h</p> Signup and view all the answers

    What is the characteristic of azathioprine in dogs with chronic hepatitis?

    <p>It is a purine analog that can be used to treat chronic hepatitis</p> Signup and view all the answers

    What is the purpose of feeding a copper-restricted diet in dogs with copper toxicosis?

    <p>To reduce the amount of copper absorbed from the gastrointestinal tract</p> Signup and view all the answers

    What is the dosage of prednisolone in dogs with chronic hepatitis?

    <p>1-2 mg/kg PO q 24 h</p> Signup and view all the answers

    What is the mechanism of action of penicillamine in the treatment of copper toxicosis?

    <p>It combines with copper and allows it to be mobilized from the liver and excreted in the urine</p> Signup and view all the answers

    What is the purpose of trientine in the treatment of copper toxicosis?

    <p>It is used as a second-line treatment for dogs not tolerating penicillamine due to GI side effects</p> Signup and view all the answers

    What is the characteristic of cyclosporine in dogs with chronic hepatitis?

    <p>It is a T-cell inhibitor that has been used with some success in chronic hepatitis</p> Signup and view all the answers

    Study Notes

    Hepatobiliary Disease

    Roles of the Liver

    • Immunoregulation
    • Synthesis of clotting factors
    • Storage of vitamins, trace minerals, glycogen, blood, triglycerides
    • Detoxification of toxins
    • Metabolism of carbs, proteins, lipids
    • Liver has remarkable regenerative capacity after loss of functional tissue

    Breed Predispositions

    • Copper storage diseases: Labrador, Doberman, Dalmatian, Skye Terrier, West Highland White, Bedlington (COMMD1 mutation), Siamese cats
    • Idiopathic chronic hepatitis: Labrador, Poodle, Doberman, American and English Cocker Spaniels, English Springer Spaniels
    • Amyloidosis: Abyssinian, Oriental, Siamese cats and Shar-Pei dogs
    • Congenital extrahepatic portosystemic shunts: Yorkie, Havanese, Pug, Maltese, mini Schnauzer
    • Congenital intrahepatic portosystemic shunts: Irish Wolfhound, Labrador, Golden Retriever, Australian Shepherd
    • Portal vein hypoplasia or microvascular dysplasia: Maltese, Yorkie, Cairn terrier
    • Progressive vacuolar hepatopathy: Scottish Terrier

    Physical Examination

    • Clinical icterus when the bilirubin is above 3
    • Icteric plasma can be noted with bilirubin 0.5-1.0
    • Hepatocutaneous syndrome: form of superficial necrolytic dermatitis with hyperkeratosis and crusting of pawpads and mucocutaneous junctions
    • Ascites: accumulation of free fluid in the abdomen, often due to portal hypertension or hypoalbuminemia

    Portal Hypertension

    • Classified based on anatomic location: prehepatic, intrahepatic, posthepatic
    • Causes of portal hypertension: increased vascular resistance, obstruction, chronic hepatitis with fibrosis
    • Portal hypertension can lead to development of multiple acquired portosystemic shunts (MAPSS)
    • Prehepatic and presinusoidal PH result in low protein effusion (< 2.5g/dl), while sinusoidal, postsinusoidal or posthepatic PH have high protein values (> 2.5 g/dl)

    Hepatic Encephalopathy

    • Multifactorial pathogenesis, occurs when toxins derived from the GI tract accumulate
    • Toxins include ammonia, aromatic amino acids, bile acids, endogenous benzodiazepines, gamma aminobutyric acid, glutamine, phenol, short chain fatty acids, tryptophan, and false neurotransmitters
    • Acute HE is caused by fulminant liver failure
    • Chronic HE is usually caused by MAPSS or congenital portosystemic shunt, less severe in cats
    • Cats can develop chronic HE from hepatic lipidosis due to arginine depletion and ammonia accumulation

    Laboratory Evaluation

    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): leakage enzymes that can become elevated with damage to hepatocyte membrane
    • ALT: specific to liver, half-life 48-60 hours in dogs, 6 hours in cats
    • AST: less specific, half-life 22 hours in dogs, 77 minutes in cats
    • Alkaline phosphatase (ALP): cholestatic enzyme, attached to membranes by phosphatidylinositol linkages, low specificity for hepatobiliary disease
    • Gamma-glutamyl transpeptidase (GGT): cholestatic enzyme, also bound to hepatocyte membrane, largely derived from the liver
    • Liver function tests:
      • Hypoglycemia: loss of 75% of liver function, impaired glycogen stores and gluconeogenesis
      • Low blood urea nitrogen: shunting of blood around the liver, or liver failure and acquired shunts
      • Hypoalbuminemia: loss of 70% of liver function
      • Cholestatic disease: hypercholesterolemia
      • Bilirubin:
        • Hyperbilirubinemia: prehepatic (hemolysis), hepatic or posthepatic
        • Hyperbilirubinemia: cholestasis of sepsis, cytokines inhibit expression of hepatocyte transporters necessary for bilirubin transport
        • With bile duct obstruction, conjugated bilirubin in plasma binds irreversibly with albumin (delta bilirubin)
      • Bile acids:
        • Synthesized in the liver from cholesterol, excreted into the biliary tract and stored in the gallbladder
        • Reabsorbed in the ileum and transported back to the liver via the portal vein
        • Efficacy of enterohepatic circulation (EHC) can be estimated by measuring bile acids
      • Ammonia:
        • Accumulates due to action of colonic bacteria on ingested protein
        • Removed by the liver and converted to urea for excretion
        • Increases in ammonia only seen with portosystemic shunting or defects in the urea cycle
      • Coagulation proteins:
        • Liver produces all clotting factors except von Willebrand factor
        • Vitamin K dependent factors: II, VII, IX, X, protein C
        • Cholestasis can lead to impaired vitamin K absorption
        • Splanchnic pooling of blood can lead to thrombocytopenia
        • Diffuse liver disease can lead to hypofibrinogenemia
        • Some liver disease can lead to DIC

    Imaging

    • Radiography:
      • Liver enlargement if caudal margins extend beyond the ribs
      • Microhepatica if the gastric axis is displaced cranially
    • Ultrasound:
      • Hyperechoic hepatomegaly: chronic hepatitis, corticosteroid hepatopathy, fat, vacuolar hepatopathy, toxic insult, lymphoma, phenobarbital
      • Hypoechoic hepatomegaly: acute hepatitis, lymphoma, cholangitis/cholangiohepatitis
      • Useful for assessment of extrahepatic biliary obstruction (EHBDO)
      • Portal vein:Ao ratio less than 0.65, urolithiasis, renomegaly, hepatofugal flow

    Sampling

    • Fine needle aspiration (FNA):
      • Minimally invasive, low risk of bleeding
      • High frequency of inaccurate results due to low cellularity
      • Useful for diagnosis of hepatic lipidosis
    • Biopsy:
      • Can be obtained via needle biopsy, laparoscopically, or surgically
      • Left medial or lateral lobes usually accessible for ultrasound guided Tru Cut
      • Discordant results in 53% of dogs and 50% of cats when comparing ultrasound guided Tru Cut with surgical wedge biopsies

    Cytoprotective Agents

    • Liver is susceptible to oxidative damage
    • Glutathione is an essential antioxidant stored in hepatocytes, synthesized from L-glutamate, L-cysteine, and glycine
    • S-adenosyl methionine (SAMe) increases hepatic glutathione, has anti-oxidant and anti-inflammatory properties, and may be antiapoptotic and anti-carcinogenic
    • N-acetylcysteine (NAC) helps replenish hepatic cysteine and glutathione levels, used for treatment of acetaminophen toxicity
    • Silymarin scavenges free radicals, reduces lipid peroxidation, and may suppress TNFa, IL-1, and NFKB
    • Vitamin E protects phospholipids from injury
    • Ursodeoxycholic acid (ursodiol) has choleretic, cytoprotective, and immunomodulatory effects, including the suppression of IL-2

    Anti-inflammatory and Immunosuppressive Drugs

    • Prednisolone is used to treat dogs with severe liver disease, especially in cases of chronic hepatitis
    • Autoimmunity may be a common cause of chronic hepatitis in certain breeds (e.g., Doberman, English Springer Spaniel)
    • Prednisolone is often used to treat cats with lymphocytic cholangitis and chronic neutrophilic cholangitis
    • Azathioprine is a purine analog that can be used in dogs with chronic hepatitis
    • Cyclosporine is a T-cell inhibitor that has been used with some success in chronic hepatitis

    Medications for Treating Hepatic Copper Accumulation

    • D-penicillamine is a chelating agent that combines with copper, allowing it to be mobilized from the liver and excreted in the urine
    • Trientine is a chelating agent that causes increased urinary excretion of copper
    • Zinc decreases absorption of copper from the GI tract and induces increased synthesis of metallothionein
    • Copper accumulation is an important cause of chronic hepatitis in dogs, and sections of liver should be routinely stained for copper

    Hepatic Encephalopathy

    • Consider a commercial, lower protein diet
    • Protein restriction is contraindicated in cats due to high requirement
    • Lactulose is an osmotic laxative used to treat hepatic encephalopathy
    • Neomycin is a poorly absorbed aminoglycoside antibiotic used to treat hepatic encephalopathy
    • Metronidazole is used to treat hepatic encephalopathy

    Hepatic Fibrosis

    • There are no proven treatments for hepatic fibrosis
    • Chronic inflammation leads to activation of myofibroblasts, including hepatic stellate cells and portal fibroblasts
    • Treat underlying inflammation to prevent additional fibrosis
    • ARB losartan has shown promising antifibrotic effects in rats

    Ascites

    • Spironolactone is the diuretic of choice, as furosemide can lead to hypovolemia, hypokalemia, and hypochloremic alkalosis, which can precipitate HE

    Cytoprotective Agents

    • Liver is susceptible to oxidative damage
    • Glutathione is an essential antioxidant stored in hepatocytes, synthesized from L-glutamate, L-cysteine, and glycine
    • S-adenosyl methionine (SAMe) increases hepatic glutathione, has anti-oxidant and anti-inflammatory properties, and may be antiapoptotic and anti-carcinogenic
    • N-acetylcysteine (NAC) helps replenish hepatic cysteine and glutathione levels, used for treatment of acetaminophen toxicity
    • Silymarin scavenges free radicals, reduces lipid peroxidation, and may suppress TNFa, IL-1, and NFKB
    • Vitamin E protects phospholipids from injury
    • Ursodeoxycholic acid (ursodiol) has choleretic, cytoprotective, and immunomodulatory effects, including the suppression of IL-2

    Anti-inflammatory and Immunosuppressive Drugs

    • Prednisolone is used to treat dogs with severe liver disease, especially in cases of chronic hepatitis
    • Autoimmunity may be a common cause of chronic hepatitis in certain breeds (e.g., Doberman, English Springer Spaniel)
    • Prednisolone is often used to treat cats with lymphocytic cholangitis and chronic neutrophilic cholangitis
    • Azathioprine is a purine analog that can be used in dogs with chronic hepatitis
    • Cyclosporine is a T-cell inhibitor that has been used with some success in chronic hepatitis

    Medications for Treating Hepatic Copper Accumulation

    • D-penicillamine is a chelating agent that combines with copper, allowing it to be mobilized from the liver and excreted in the urine
    • Trientine is a chelating agent that causes increased urinary excretion of copper
    • Zinc decreases absorption of copper from the GI tract and induces increased synthesis of metallothionein
    • Copper accumulation is an important cause of chronic hepatitis in dogs, and sections of liver should be routinely stained for copper

    Hepatic Encephalopathy

    • Consider a commercial, lower protein diet
    • Protein restriction is contraindicated in cats due to high requirement
    • Lactulose is an osmotic laxative used to treat hepatic encephalopathy
    • Neomycin is a poorly absorbed aminoglycoside antibiotic used to treat hepatic encephalopathy
    • Metronidazole is used to treat hepatic encephalopathy

    Hepatic Fibrosis

    • There are no proven treatments for hepatic fibrosis
    • Chronic inflammation leads to activation of myofibroblasts, including hepatic stellate cells and portal fibroblasts
    • Treat underlying inflammation to prevent additional fibrosis
    • ARB losartan has shown promising antifibrotic effects in rats

    Ascites

    • Spironolactone is the diuretic of choice, as furosemide can lead to hypovolemia, hypokalemia, and hypochloremic alkalosis, which can precipitate HE

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    Description

    This quiz covers the diagnostic evaluation of the liver, including the roles of the liver and breed predispositions to certain liver diseases. It is a crucial topic for veterinarians and animal health professionals.

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