Hepatic Diseases I/II + Liver Refresher

T/F: Hepatic Dysfunction normally presents as unique and easily identifiable clinical signs

False, it often presents with non-specific signs (Anorexia, V+/D+, lethargy)

T/F: PU/PD is only seen in cases of renal issues, not hepatic dysfunction

False, PU/PD is commonly seen with hepatic dysfunction

Why is PU/PD seen with hepatic dysfunction?

• When the liver is not functioning properly, it produces less urea

  • Urea is produced by the liver metabolizing ammonia (important for hepatic encephalopathy)

• While urea is excreted by the kidneys in urine as waste, some of it is also reabsorbed to aid the kidney in properly concentrating the urine, this happens in the medulla

How does hepatic dysfunction cause Stranguria via the formation of urate stones in the bladder?

• When the liver doesn’t function normally it results in a decrease in the production of urea, however, the building blocks that make up urea continue to accrue

• These building blocks are ammonia and Uric Acid

• When these reach high enough concentrations in the urine they interact to form ammonia biurate crystals, which gradually precipitate and coalesce into solid stones known as ammonium urate uroliths

A key sign of hepatic dysfunction is _______ ________ (caused by a buildup of ammonia in the blood)

Hepatic Encephalopathy

The most well known clinical sign of hepatic dysfunction is ______, what causes this discoloration?

• Icterus

  • Buildup of bilirubin as a result of the liver not being able to process it

What are the main diagnostic tools that can be used to assess the health of a patient’s liver? (use hint for #)

1. CBC

2. Chemistry

3. UA

4. Pre/Post Prandial bile acids

5. Coagulation tests PT/PTT

6. Radiographs

7. Ultrasound

8. CT

9. FNA/Biopsy

What abnormalities would you expect to see on a CBC for a patient that has hepatic dysfunction? Are these findings specific for Liver dysfunction?

• Inflammatory Leukogram for infectious causes of hepatic dysfunction

  • Left Shift

  • Neutrophilia

  • Monocytosis

• Anemia for chronic hepatic disease

• Lymphopenia

Non-specific

What are the hepatocellular leakage enzymes? If elevated what do they indicate?

• AST/ALT

• They indicate irritation to or death of hepatocytes

What are the Cholestatic liver enzymes? If elevated what do they indicate?

• Alk Phos and GGT

• Inflammation in the bile duct, obstruction, cholestasis

What 4 liver products would you expect to be decreased on the chem profile of a patient with a failing liver?

1. Glucose

2. Urea

3. Albumin

4. Cholesterol

GUAC

What does elevated bilirubin indicate?

Indicates an imbalance between the production of bilirubin and the liver's ability to conjugate and excrete it, which clinically manifests as icterus (jaundice)

What are the 3 potential causes of elevated bilirubin? Provide at least one disease for each option

1. Pre-Hepatic

   1. Increased breakdown of RBCs, so much so that the liver can’t keep up

   2. Ex: IMHA, oxidative damage (e.g., zinc or allium toxicity), infectious hemoparasites (e.g., Babesia)

   3. Key indicators:

      1. Characterized by a marked decrease in packed cell volume (PCV), regenerative anemia, hemoglobinemia, and hemoglobinuria.

      2. Liver enzymes are often initially normal unless secondary hypoxic injury occurs.

2. Hepatic

   1. Caused by primary liver dysfunction that impairs the hepatocytes' ability to uptake, conjugate, or excrete bilirubin into the biliary canaliculi.

      • Common causes:

        • Chronic hepatitis, copper-associated hepatopathy, infectious diseases (e.g., Leptospirosis, Canine Adenovirus-1), severe hepatotoxicity, or hepatic neoplasia.

      • Key indicators:

        • Typically accompanied by marked elevations in hepatocellular leakage enzymes (ALT, AST).

        • If hepatic failure is severe (>70% loss of functional mass), synthetic products like albumin, BUN, glucose, and cholesterol will also be decreased.

3. Post-Hepatic

   1. A blockage of the gall bladder/bile duct is preventing the excretion of bile, causing a backup

   2. Common causes: Gallbladder mucocele, cholelithiasis (gallstones), severe acute pancreatitis (causing common bile duct compression), biliary neoplasia, or biliary tract rupture.

   3. Key indicators:

      1. Accompanied by marked elevations in inducible cholestatic enzymes (ALP, GGT) and hypercholesterolemia.

      2. Diagnostic imaging (ultrasound) is required to identify the obstructive lesion or dilated bile ducts.

T/F: In causes of liver failure the USG in a UA should be normal

False, it should be decreased (bc less urea to help concentrate the urine)

Are urate crystals indicative of only liver dysfunction?

• Yes and no

  • Certain breeds can be predisposed to forming urate crystals

  • Otherwise, they are strongly indicative of liver dysfunction

What is the purpose of the Pre/Post-prandial bile acid test?

It tests the liver's ability to efficiently extract and clear bile acids from the bloodstream after they have been released for digestion

In patients with hepatic dysfunction, what is the expected results with a Pre/Post prandial bile acids test?

• You would expect to see elevated bile acids

  • The pre-prandial bile acids serves as a baseline

  • During the postprandial blood work, A healthy liver will efficiently extract >95% of these returning bile acids from the portal blood on the first pass, keeping systemic blood concentrations low.

T/F: Elevated bile acids are indicative of hepatic dysfunction alone

False, it could also be caused by a bile duct obstruction or rupture

T/F: There is no need to measure bile acids in cases of elevated bilirubin, as they you know that they will be low

False, while it is true you don’t need to measure them, it is because they will be ELEVATED

What is another product of the liver that in instances of hepatic dysfunction would affect normal hemostasis?

• PT/PTT (Clotting factors)

  • Hepatic dysfunction increases clotting time

  • Usually only noticeable during liver failure

T/F: A mild increase in clotting time for PT/PTT is suggestive of liver failure

False, it is considered to be a mild artifact or patient variation

What is wrong with this radiograph? What condition could be causing it?

• Microhepatica

  • Cirrhosis

What is wrong with this radiograph? What condition could be causing it?

• Hepatomegaly

  • Cushings

  • Infections

  • Neoplasia

  • Heart Failure

What is the best diagnostic tool for visualizing the liver (that is widely available)?

Ultrasound

What is the best diagnostic tool for diagnosing anomalous vessels in regards to hepatic dysfunction?

CT

T/F: Full anesthesia is normally required for US guided FNA

False, only sedation is required

Describe the pros and cons of a punch biopsy of the liver vs a FNA

• Biopsy

  • Pros:

    • More information

  • Cons:

    • More expensive

    • Requires full anesthesia

    • Laparoscopic or exploratory procedure

• FNA (Best suited for diagnosing masses, lymphoma or lipidosis)

  • Pros:

    • Less invasive

    • Only requires sedation

    • Cheaper

  • Cons:

    • Tiny sample with no architecture

When trying to diagnose hepatic dysfunction, what is the diagnostic approach you would take, in order

1. Signalment, history, physical exam

2. CBC, Chem, UA

3. Bile acids or PT/PTT

4. Diagnostic imaging

   1. Ultrasound first, provides the most information

5. FNA/Biopsy

What role do antibiotics play in treating cases of hepatic dysfunction?

• They are only required when we have confirmed that the dysfunction is due to bacterial causes

  • This is determined via liver/bile culture

Say you have a patient who has hepatic dysfunction due to Immune-mediated chronic hepatitis, you are deciding between giving them prednisone and prednisolone, which should you give and why?

Prednisolone, it is the active form and doesn’t need to be activated by the liver

Which of these is not an immunosuppressive medication that could be used to treat hepatic dysfunction?

Ursodial

What is the function of Ursodial?

• It is a synthetic bile acid

• It promotes more watery bile, and less inflammation

**What is the clinical use of ursodial?**

Helps with cholestasis

What is cholestasis?

It is when normal flow of bile from the liver slows down or stops

How does Milk Thistle/Silymarin work? When is it best utilized

It is a strong free radical scavenger that can help treat cases of toxicity

T/F: Milk Thistle/Silymarin can be used empirically for patients with hepatic dysfunction to see if it helps

True

What is SAMe? How does it help the liver?

• S-adenosyl-L-methionine

• It is a building block of glutathione (a free radical scavenger)

  • Essentially it provides the liver with subtrate that helps it do its job

Why does lactulose, a medication that helps treat constipation, used in some cases of hepatic dysfunction?

1. Promotes the growth of beneficial bacteria

2. Speeds food through the gut

3. Acidifies the stool to trap ammonia

What very serious side effect of hepatic dysfunction/liver failure is lactulose used to treat?

• Hepatic encephalopathy

  • Since it traps ammonia it can decrease the levels that is causing the altered mentation

In hepatic encephalopathy in dogs, why is the gut bacteria so important to the condition?

• Gut bacteria are critical in the pathogenesis of hepatic encephalopathy (HE) because they are the primary producers of ammonia and other enteric neurotoxins that the compromised liver is unable to clear from circulation.

• When the liver isn’t functioning normally (dysfunction/failure) it can no longer keep up and that results in accumulating levels of ammonia in the blood

Which of these drugs can’t shouldn’t be used to treat hepatic encephalopathy in dogs?

Sodium bicarbonate

Describe the clinical progression/cause of Steroid Hepatopathy

Hyperadrenocorticism or prednisone therapy → High levels of circulating glucocorticoids → Hepatocytes to become engorged with lipid and glycogen → Liver to be unable to do its job

What CBC/Chem/UA changes and radiograph results would you expect to see in a patient experiencing steroid hepatopathy?

• Elevated liver enzymes (especially alk phos)

• Hepatomegaly

How do you treat steroid hepatopathy?

• Treat the underlying cause (hyperadrenocorticism or prednisone therpay)

A dog presents with lethargy, vomiting, PU/PD, and icterus. Serum biochemistry reveals marked increases in ALT and AST. Which of the following best describes what these enzymes primarily indicate?

Hepatocellular leakage associated with hepatocyte injury

A dog with severe liver disease has decreased glucose, urea, albumin, and cholesterol concentrations. Which important concept does this pattern demonstrate?

Decreased production of hepatic products associated with liver failure

A dog has an increased total bilirubin concentration. Which finding would be most useful in distinguishing post-hepatic icterus from hepatic icterus?

Evidence of bile duct or gall bladder obstruction

A dog with hepatic encephalopathy is being treated medically. What is the primary rationale for using lactulose?

It acidifies intestinal contents and helps trap ammonia while altering intestinal bacterial activity

A dog is diagnosed with copper storage disease. Which diagnostic test is most appropriate for confirming the diagnosis?

Liver biopsy with measurement of hepatic copper concentration

What causes Non-specific Reactive Hepatopathy (Hint: It’s in the name)?

• It’s caused by sepsis from endotoxemia

• Any disease of the guyt can affect the liver since it receives part of its blood supply (portal vein) from the GIT

An immunocompromised patient presents with the following

• Mildly Increased ALT and Alk Phos

• Increased bilirubin

• Fever

• Diarrhea

What disease process of the liver are you suspecting?

• Non-specific Reactive Hepatopathy

  • The patient has GI inflammation and endotoxemia which are both affecting the liver and causing elevated values

T/F: Periodontal disease can cause Non-specific reactive hepatopathy

True!

A cat presents to your clinic that hasn’t been eating well for the past week. They moved into a new house and the cat was too stressed to eat, now they are not themselves, and have been very lethargic. They used to be tempted by treats but now won’t eat anything. The BCS of the cat is 7/9. What is your main differential?

Hepatic Lipidosis

Describe the disease process of hepatic lipidosis

• Obese cats suddenly go anorexic

• They mobilize fat too rapidly, resulting in it being deposited into the hepatocytes

• The hepatocytes become filled with lipid and can no longer function

How do you correct cases of hepatic lipidosis?

Feeding tube and correct any underlying diseases

Which of these images has the liver abnormality?

The right has an intra-hepatic PSS

What is a Portosystemic shunt? Why are they so dangerous?

• An abnormal vessel from the hepatic portal vein that bypasses the liver and enters system circulation

• They let blood from the GIT enter systemic circulation without being filtered by the liver first

A patient with a PSS most often presents with ________ __________

Hepatic Encephalopathy, typically seen after meals

What is the difference between a PSS and Portal Vein Hypoplasia? Is the treatment different?

• PSS

  • A large shunt that bypasses the liver

  • Tx

    • Surgical ligation or coil embolization

• PVH

  • Abnormal hepatic vasculature on a microscopic level

  • Essentially a bunch of tiny shunts through the liver

  • Tx

    • Supportive care if needed

    • Condition is often not life threatening

T/F: A CT angiogram can be used to diagnose both PSS and PVH

False, only PSS

Name 3 different causes of Acute Hepatic Diseases

1. Hepatotoxins

2. Bacterial infections

3. Viral

One of the most important things to do if a patient has liver dysfunction as a result of hepatotoxins is to give IV fluids, describe why this is so beneficial

• They increase liver perfusion

• Cause diuresis

• Aid with excretion of toxin

T/F: In cases of toxin ingestion → hepatic damage SAMe or milk thistle could be beneficial drugs to give

True, they are or help make antioxidants!

T/F: Lepto can only affect the kidney

False, it can affect the liver too

What is bacterial cholangiohepatitis?

It is when GI bacteria enter the liver via the bile duct or blood and cause inflammation that affects the bile ducts, gallbladder, and surrounding liver tissue

What is the most common etiology of Viral hepatitis in dogs?

• Canine Adenovirus type 1 (CAV-1) aka Infectious canine hepatitis

  • However, it is incredibly rare since the vaccine is so effective

What is immune-mediated cholangiohepatitis, and how is it diagnosed/treated?

• An inflammatory liver condition where the body’s immune system mistakenly attacks its own bile ducts, gallbladder, and surrounding liver tissue → Fibrosis/Cirrhosis

• Dx

  • Biopsy

• Tx

  • Immunosuppressant meds (Pred, cyclosporin)

T/F: Immune-mediated cholangiohepatitis presents acutely and severely

False, it often is asymptomatic for years because the liver compensates for it until it can’t

Copper storage disease is a congenital disease in what dog breed?

Bedlington Terriers

How does Copper storage disease cause liver dysfunction?

Copper accumulates in the liver resulting in oxidative damage

T/F: When submitting a liver biopsy for a suspected case of Copper Storage Disease you should place the whole sample in a formalin jar ASAP to preserve the copper

False, save part of the sample outside of the fixative, otherwise it cannot be tested

What are the 2 main types of 1° Hepatic Neoplasia?

1. Hepatocellular carcinoma

2. Cholangiocellular carcinoma

What is a Gall Bladder Mucocele?

Abnormal formation of bile-laden mucus in the gall bladder → Causes the gall bladder to slowly grow in size → Pressure necrosis of the wall → Rupture of the gall bladder → Peritonitis

What is the primary treatment of gall bladder mucocele?

Surgical excision

What is Cholelithiasis?

Gall bladder stones