What is the most sensitive measure of hepatic function?
Serum bile Acids
Serum bile acids are useful for detecting 2 particular liver related issues, what are they?
portosystemic shunts and detecting liver disease in non-icteric patients
Normal levels of serum bile acids require what?
1. functional hepatocytes with normal blood flow 2. unimpaired bile flow 3. good portal circulation
What are consequences of dysfunction in relation to bile secretion?
1. Hyperbilirubinemia and Icterus 2. malabsorption of fat and fat soluble vitamins (ADEK) 3. Failure to eliminate toxins normally excreted in bile (endotoxins, bilirubin, phylloerythrin, etc)
What is Bilirubin a product of?
It is a catabolic product of hemoglobin (also myoglobin)
Conjugated bilirubin is the pigment of bile, while bile acids are the key component
What is the route of production and excretion for bilirubin?
It is bound by albumin-->carried to liver-->removed from plasma by hepatocytes-->conjugated and excreted in bile
Unconjugated hyperbilirubinemia is rare, except in what species?
HORSES, you can see a mild icterus with anorexia
What deconjugates bilirubin in the gut?
Bacteria degrade it into urobiliogens-->residue of intact pigments that are excreted in the feces (brown poop)
What are 3 general causes of hyperbilirubinemia?
1. Pre-hepatic (hemolytic-autoimmune)=increased production
-decreased PCV & RBC's
2. Primary Hepatic (injury to hepatocytes and/or bile flow IN liver)
-impaired uptake, conjugation, and/or secretion=liver disease
3. Post-Hepatic (obstructive)
-Inhibition of outflow from liver (impaired excretion to SI)=Common bile duct disease
It is the reduction of bile flow
-if long standing, the bile acids in bile will damage cell membranes and there will also be evidence of hepatocyte damage (increased leakage and induced enzymes)
What is Extrahepatic cholestasis? What are some examples?
Extrahepatic cholestasis=Obstructions resulting in decreased bile flow
-Calculi (choleliths=bile stones) most common
-inflammation and/or fibrosis
-parasites (liver flukes)
-pancreatic lesions (notably in dogs and cats)
What are choleliths?
They are concretions formed from constituents of bile (stones)
What are 3 causes of intrahepatic cholestasis?
More common in veterinary medicine
1. Diffuse hepatocellular damage: decreased uptake, conjugation, or secretion
-anything that damages hepatocytes is likely to injure the membrane and enzymes of the secretory apparatus
2. Lesion that causes hepatocellular swelling leading to occulsion of the canaliculi and impede intrahepatic bile flow (hepatic lipidosis=kitty cats)
3. Cholangitis/Cholangiohepatitis: inflammatory processes centered around the biliary tree
-inflamation and fibrosis around the biliary tree can block or impede the flow of bile out of the lobule and from the liver-producing icterus
What are 2 types of Feline Cholangiohepatitis "syndromes"?
1. Lymphocytic cholangitis
- 2nd most common cause of icterus in cats
- lymphocytes and plasma cells centered on portal triads/bile ducts and biliary hyperplasia and fibrosis
2. Suppurative/neutrophilic cholangitis
- less common
- thought to be ascending bacteria
This image is of an inflammed portal triad that is infiltrated with lymphocytes. What disease is this in cats? What type of cholestasis is this?
Feline Lymphocytic Cholangitis
What are Liver functions in energy metabolism and storage?
1] Surveillance of glucose intake (via surveillance of portal blood) 2] Storage of glycogen as a potential source of plasma glucose
(skeletal muscle stores glycogen for its own use)
3] Site of gluconeogenesis - production of energy from protein
4] Synthesis of fatty acids as storage form for excess calories
5] Metabolism of fatty acids to ketones (energy source), triglycerides, etc.
Fill in the box
Trigylcerides + Apoprotein
When does fatty changes in the liver have clinical significance?
The clinical question is, "does the increased hepatic lipid have pathologic significance?
-hepatocyte lipid accumulation may refelct underlying metabolic disese (diabetes mellitus, massive mobilization of peripheral fat stores, etc.)
-Hepatocyte swelling, if severe, may mechanically interfere with blood and bile flow through the liver
-the affected liver may also have diminished metabolic capabilities due to the intracellular accumulation of triglycerides. It may be more susceptible to toxic and nutritional insults
If you saw this liver what would you think?
Fatty liver (fatty lipidosis)
What is the clinical presentation for a cat with hepatic lipidosis?
Fat cat with recent weight loss, anorexia, depression and Icterus
What is the pathogensis for Feline hepatic lipidosis?
Not entirely clear:
Mobilization of fat stores due to anorexia results in hepatic lipidosis: intracellular lipid accumulation "poisons" hepatocyte and decreases metabolic capabilities
-Possbile evidence that deficiency of some essential amino acids (due to anorexia & decreased intake) also contributes by blocking lipoprotein synthesis and impairing fatty acid oxidation--> cats has unique amino acid requirements
What might you see with a Chemistry panel with a cat with hepatic lipidosis?
-Increased Serum ALP
- GGT may be mildly elevated or normal (induced enzymes)
-ALP>GGT- in other diseases it is usually the opposite
What is the prognosis for a cat with Hepatic lipidosis?
What is the resident surveillance cell in the Liver?
Kupffer cells/ Macrophages
What is the purpose of kupffer cells in the liver?
They help filter blood by:
- remove microbes
- remove endotoxins
- remove fibrin degradation products
Liver dysfunction can lead to what consequences relating to the liver's filtering ability?
Diminished ability to remove microbes, and/or endotoxins from portal blood will allow them ot reach the systemic circulation--> bacteremia, endotoxemia
Diminished ability to remove FDP--> contribute to a coagulopathy, DIC
What are 2 consequences of liver disease in response to a disruption in the liver's ability to maintain normal salt and water balance?
1. fluid retention in the form of ASCITES