18 Questions
What is the function of S-adenosyl methionine (SAMe) in the treatment of liver disease?
Increases hepatic glutathione and has anti-oxidant and anti-inflammatory properties
What is the effect of ursodeoxycholic acid (ursodiol) on the immune system?
Suppresses IL-2
What is the function of vitamin E in the treatment of liver disease?
Antioxidant that protects phospholipids from injury
What is the effect of silymarin on cytochrome P450 activity in people?
Decreases it
What is the function of glutathione in hepatocytes?
Antioxidant that reduces oxidative damage
What is the effect of N-acetylcysteine (NAC) on hepatic cysteine and glutathione levels?
Replenishes them
What breeds of dogs are commonly associated with chronic hepatitis?
Doberman and English Springer Spaniel
Why is prednisolone preferred over prednisone in the treatment of severe liver disease in dogs?
Prednisone has to be converted to prednisolone in the liver
What is the primary consideration for giving prednisolone in dogs with chronic hepatitis?
Moderate to severe hepatic inflammation on histological examination
What is the typical dosage of prednisolone for dogs with chronic hepatitis?
1-2 mg/kg PO q 24 h
What is the purpose of repeating liver biopsy 6 weeks after starting prednisolone treatment?
To assess the patient's response to treatment
What is the mechanism of action of zinc in reducing copper absorption in dogs?
Zinc increases the synthesis of metallothionein by enterocytes
What is the typical reference interval for hepatic copper concentration in healthy dogs?
1000 mcg/g
What is the recommended duration of treatment for dogs with hepatic copper concentrations >1500 mcg/g?
At least 10 months
What is the purpose of giving lactulose to patients with hepatic encephalopathy?
To reduce ammonia production in the gut
What is a contraindication for protein restriction in cats?
High requirement for protein
What is the recommended timing for measuring the copper concentration of a liver biopsy specimen after starting chelation therapy?
6 months after starting treatment
What is the recommended dietary approach for dogs with hepatic copper accumulation?
Copper-restricted diet
Study Notes
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
Learn about the agents that protect liver cells from damage, including glutathione, S-adenosyl methionine, N-acetylcysteine, and silymarin, and their properties in antioxidant and anti-inflammatory activities.
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