Liver Notes

Unit 12 - The Liver Study Notes

1. The Liver: A Multifunctional Powerhouse

  • General Description: The liver is a vital organ with a wide array of critical functions.

  • Carbohydrate Metabolism:

    • Stores glucose as glycogen.
    • Converts glycogen back to glucose for energy when needed.
    • Controls blood glucose levels.

  • Detoxification & Waste Removal:

    • Removes toxins like ammonia and other waste products.
    • Acts as the primary site for drug metabolism.

  • Bile Production & Function:

    • Bile is produced by the liver and stored in the gall bladder.
    • It aids in the breakdown and absorption of fats and fat-soluble vitamins.
    • Bile serves as a primary route for eliminating bilirubin.

  • Protein and Clotting Factor Synthesis:

    • Produces most of the proteins in the body.
    • Produces various clotting factors essential for blood coagulation.

  • Storage:

    • Stores vitamins, including fat-soluble vitamins A, D, E, K, and B12.

  • Immune Function:

    • Produces immune factors.
    • Involved in the phagocytosis of bacteria in the bloodstream.

2. Remarkable Regenerative Capacity

  • Regeneration Description:
    • The liver is known as "the great regenerator."
    • Notably, it can withstand up to ~70% loss of functional hepatocytes (liver cells) before showing significant changes on a liver function test (like bile acids).
  • Diagnostic Implications:
    • This fact highlights that enzyme tests (which detect cell damage) can be elevated long before function tests (which detect loss of overall capacity) become abnormal.

3. Bilirubin Metabolism and Jaundice

  • Production of Bilirubin:

    • Unconjugated bilirubin is produced from the breakdown of the heme portion of hemoglobin in red blood cells (RBCs).

  • Conjugation of Bilirubin:

    • The liver's hepatocytes convert unconjugated bilirubin into conjugated bilirubin, making it water-soluble.

  • Excretion of Bilirubin:

    • Conjugated bilirubin is excreted in the bile into the intestines.

  • Jaundice (Icterus):

    • A yellow discoloration of tissues caused by the buildup of bilirubin in the blood (hyperbilirubinemia).

4. Common Liver Diseases & Key Terminology

  • Broad Categories of Liver Disease:

    • Inflammatory (hepatitis)
    • Infectious
    • Metabolic (e.g., hepatic lipidosis in cats)
    • Toxic
    • Vascular (e.g., Portosystemic Shunts - PSS)
    • Storage diseases (e.g., Copper storage in Bedlington Terriers)

  • Essential Terminology:

    • Hepatitis: Inflammation of the liver.
    • Cirrhosis: Irreversible replacement of healthy liver tissue with fibrous scar tissue; a sequela to chronic liver disease.
    • Cholangitis: Inflammation of the bile ducts.
    • Cholangiohepatitis: Inflammation of both the bile ducts and liver cells.
    • Cholestasis: Reduction or stoppage of bile flow.
    • Jaundice/Icterus: Yellowing due to high bilirubin.

5. Liver Enzymes: Indicators of Injury

  • Overview of Enzymes:

    • Enzymes are measured to detect liver cell damage or cholestasis.
    • These enzymes indicate what is wrong but not necessarily how well the liver is functioning.

  • Sample Collection Process:

    • Requires fasting the patient for more than 12 hours.
    • Use serum collection with a red top tube.
    • Separate serum immediately and refrigerate, while DO NOT FREEZE (freezing destroys ALT).
    • Ship samples on ice.
A) Alanine Aminotransferase (ALT)

  • Significance:

    • Indicates injury to hepatocytes (liver cells).

  • Species Specificity:

    • Useful in dogs and cats but not in ruminants or horses due to low levels in their liver cells.

  • Causes of False Elevation:

    • Hemolysis (present in RBCs)
    • Lipemia
    • Muscle damage.
B) Aspartate Aminotransferase (AST)

  • Significance:

    • Indicates liver cell damage OR muscle damage (skeletal or cardiac).

  • Species Use:

    • Can be used in both small and large animals for liver damage; however, lack of specificity is a significant limitation.

  • Causes of Elevation:

    • Pathologic reasons: liver disease, muscle damage (myositis, exertional rhabdomyolysis in horses), cardiac damage, hemolysis.
    • Other reasons: lipemia, drugs (anti-seizure medications), exercise (in horses), IM injections.
C) Alkaline Phosphatase (ALP/ALKP)

  • Significance:

    • Often indicates cholestasis (bile flow obstruction).

  • Non-Pathologic Elevations:

    • High levels can be seen in growing puppies (related to bone growth).

  • Species Notes:

    • In dogs, elevations can indicate liver pathology. Elevated levels may also be seen due to steroid administration (e.g., Cushing's disease).
    • In cats, any elevation is significant due to low baseline levels; a classic cause is hepatic lipidosis ("Fatty Liver Disease").

  • Causes of False Elevation:

    • Hemolysis.
D) Gamma Glutamyl Transferase (GGT)

  • Significance:

    • A marker for cholestasis and biliary duct injury.

  • Species Specificity:

    • In small animals, it is used to evaluate cholestasis.
    • In horses and ruminants, it serves as one of the primary tests for liver disease (both hepatocellular and bile duct injury). Can also elevate with GI disorders in horses.
    • In calves, it is a marker for successful passive transfer of antibodies, with elevations measuring 24 hours after nursing. It is not used in horses for this purpose.

6. Liver Function Tests & Other Key Analytes

  • Overview: These tests assess the liver's functional capacity.
A) Bile Acids

  • Gold Standard Liver Function Test:

    • Measures the liver's ability to uptake, process, and excrete bile acids.

  • Procedure:

    • Requires a fasted (12+ hours) sample. A pre-prandial sample is taken, and after feeding the patient a fatty meal, a second sample is taken 2 hours post-prandially.

  • Species Notes:

    • In dogs and cats, this test is very helpful; elevations typically indicate impaired liver function.
    • In horses, only one sample is needed (as horses lack a gall bladder and secrete bile continuously).
    • In cattle, this test is not useful due to a very wide normal range.

  • Interference:

    • Results are inaccurate if the sample is lipemic or hemolyzed.
B) Bilirubin

  • Types:

    • Total Bilirubin is the sum of Conjugated (Direct) and Unconjugated (Indirect) bilirubin.

  • Causes of Hyperbilirubinemia (The 3 H's):

    1. Hemolytic: Pre-hepatic; results from overwhelming RBC destruction.
    2. Hepatocellular: Hepatic; liver disease impairs bilirubin conjugation.
    3. Cholestatic: Post-hepatic; obstruction of bile flow.

  • Artifacts:

    • Hemolysis and lipemia can cause false elevations. Bilirubin degrades in light, so samples must be processed quickly.
C) Albumin

  • Significance:

    • The liver is the primary site of albumin synthesis.

  • Condition:

    • Hypoalbuminemia can occur with significant, chronic liver dysfunction (>70-80% damage).
D) Sorbitol Dehydrogenase (SDH)

  • Significance:

    • A very specific indicator of acute hepatocellular injury.

  • Species Use:

    • Excellent for horses and ruminants; not commonly used in small animals.

  • Handling:

    • Must be run immediately as the enzyme is unstable.

7. Species-Specific Highlights

  • Horses:

    • Use: GGT and SDH are preferred for liver assessment.
    • Avoid: ALT is less useful.
    • Bile Acids: Only a single sample is required due to the lack of a gall bladder.

  • Ruminants (Cattle, Sheep, Goats):

    • Use: GGT and SDH.
    • Avoid: ALT is less useful in these species.
    • Bile Acids: Not useful in cattle.

  • Cats:

    • ALP: Any elevation is significant and can be indicative of hepatic lipidosis.
    • GGT: In cases of hepatic lipidosis, ALP elevation is typically greater than GGT elevation.

8. Clinical Case: Almo the Cat (Hepatic Lipidosis)

  • Presentation:

    • 5-year-old, obese, anorexic cat presenting with jaundice.

  • Key Bloodwork Findings:

    • Markedly elevated ALP (632) & GGT (130): Strong indicators of cholestasis.
    • Elevated ALT (167): Indicates concurrent hepatocellular injury.
    • Hyperbilirubinemia (30): Causes the jaundice.
    • Albumin and other parameters were within normal limits.

  • Pathophysiology:

    • In cases of anorexia, stored fat is mobilized and overwhelms the liver, causing fat accumulation within hepatocytes (steatosis), which subsequently leads to cell dysfunction and cholestasis.

  • Treatment Cornerstones:

    1. Aggressive Nutritional Support: The most critical step, often requiring an esophageal feeding tube to achieve a positive energy balance.
    2. Hospitalization: Includes administering IV fluids and medications.
    3. Goal of Treatment:
    • Provide energy to stop protein catabolism, allow hepatocyte regeneration, and assist the liver in metabolizing the accumulated fat.

9. Liver Disease and Coagulopathies

  • Overview:

    • The liver produces most clotting factors, and impaired liver function can lead to bleeding disorders.

  • Clinical Signs of Coagulopathies:

    • Petechiae (small red or purple spots on the body)
    • Melena (black, tarry feces)
    • Hematemesis (vomiting blood)
    • Epistaxis (nosebleeds).