Lecture 16 11/7/24 Flashcards
What are the characteristics of hepatic circulation?
-oxygenated blood arrives at the liver via the hepatic artery
-deoxygenated blood arrives at the liver via the portal vein for filtration
-deoxygenated, filtered blood leaves the liver via the hepatic vein
What are the components of a portal triad?
-bile duct
-vein
-artery
Which functions of the liver contribute to carbohydrate metabolism?
-storage of glycogen
-gluconeogenesis
Which functions of the liver contribute to fat metabolism?
-oxidation of fatty acids
-synthesis of cholesterol, lipoproteins, and phospholipids
Which functions of the liver contribute to protein metabolism?
-synthesis of plasma proteins
-synthesis of urea
-removal of ammonia
Which function of the liver contributes to bilirubin metabolism?
conjugation of bilirubin
Which function of the liver contributes to iron storage?
storage of ferritin
Which function of the liver contributes to detoxification?
removal of drugs and hormones from the bloodstream
How can enzyme activity be determined in biochemical tests?
-substrate consumption
-product formation
What are the characteristics of clinical enzymology?
-enzyme unit of measure is activity (U/L)
-activities less than 3x the upper reference limit are considered mild
-activities less than the lower reference limit are clinically insignificant
-trends are more informative than a single measurement
Why is it important to look at enzyme trends rather than single values?
single values could be indicative of a worsening condition, an improving condition, or a persistent increase
Which biochemical tests detect hepatocellular injury?
-ALT
-AST
-SDH
-GLDH
Which biochemical tests detect cholestasis?
-ALP
-GGT
-bilirubin
-cholesterol
Which biochemical tests detect hepatic insufficiency?
-albumin
-urea
-glucose
-cholesterol
What are the characteristics of hepatocellular injury?
-detect “leakage” enzymes
-magnitude of increase varies with micro-anatomic injury site, specificity of enzyme, and half-life of enzyme
-non-specific tests; does not indicate cause
What are the characteristics of alanine aminotransferase/ALT?
-cytosolic enzyme
-sensitive marker of hepatocellular injury in dogs and cats
-specific for hepatocellular injury unless there is severe musculoskeletal injury
-not as useful in large animal
What are the characteristics of aspartate aminotransferase/AST?
-cytosolic and mitochondrial enzyme
-very sensitive indicator of hepatocellular injury
-less specific than ALT for hepatocellular injury
-found in muscles and erythrocytes in addition to liver
-preferred in large animal
In addition to hepatocellular injury, what else can lead to increased AST?
-muscle damage
-intravascular hemolysis
-in vitro hemolysis/poor sample handling
What are the characteristics of sorbitol dehydrogenase/SDH?
-cytosolic enzyme
-high specific marker of hepatocellular injury
-preferred in horses, cattle, and camelids when available
-labile with a very short half life; difficult to get to lab in time
What are the characteristics of glutamate dehydrogenase/GLDH?
-mitochondrial enzyme
-most specific biomarker of hepatocellular injury in birds
What is cholestasis?
impaired bile flow
What are the obstructive causes of cholestasis?
-hepatocellular swelling
-neoplasia
-choleliths
What is the functional cause of cholestasis?
altered biochemical pathway/receptors
What are the characteristics of cholestatic enzymes?
-expressed on membranes of hepatocytes and biliary epithelium
-“inducible” enzymes
What are the characteristics of alkaline phosphatase/ALP?
-sensitivity for cholestatic disease is variable
-high sensitivity in dogs
-low sensitivity in cats and horses
-specificity for cholestatic disease is low
-should be evaluated in conjunction with other cholestasis indicators
What are the characteristics of L-ALP?
-produced by liver
-indicates cholestatic disease
What are the characteristics of C-ALP?
-dogs only
-produced by liver
-indicates corticosteroid excess or phenobarbital use
What are the characteristics of B-ALP?
-produced by bone
-indicates young/growing animal, osteosarcoma, or hyperthyroidism
What are the characteristics of gamma-glutamyl transferase/GGT?
-most common cause of increase is biliary hyperplasia
-can see transient increases in neonates
What is bilirubin?
end product of hemoglobin degradation
What are the three main fractions of bilirubin?
-unconjugated/bound to albumin
-conjugated/water soluble
-delta-bilirubin/conjugated to proteins
What are the potential lab measurements of bilirubin?
-total bilirubin
-indirect/unconjugated bilirubin
-direct/conjugated bilirubin
What are the characteristics of pre-hepatic hyperbilirubinemia?
-hemolysis cause
-clinical examples include IMHA and oxidant injury
What are the characteristics of hepatic hyperbilirubinemia?
-obstructive cause
-clinical examples include hepatocellular swelling and neoplasia
What are the characteristics of post-hepatic hyperbilirubinemia?
-obstructive cause
-clinical examples include gall bladder mucocele, choleliths, and neoplasia
How does hemolysis lead to pre-hepatic hyperbilirubinemia?
abundant unconjugated bilirubin overwhelms the liver’s ability to conjugate and excrete bilirubin
How does obstruction lead to hepatic hyperbilirubinemia?
hepatocyte swelling or infiltrative neoplasia squeeze the bile canaliculi, leading to backup of conjugated and unconjugated bilirubin
How does obstruction lead to post-hepatic hyperbilirubinemia?
obstruction in gall bladder or bile duct results in backup of conjugated or unconjugated bilirubin
What are the characteristics of functional cholestasis?
-impaired excretion of conjugated bilirubin
-associated with sepsis and inflammation
-see a mild hyperbilirubinemia without other indications of cholestasis
What are the characteristics of fasting/anorexic cholestasis?
-seen in horses and cattle
-impaired conjugation of bilirubin
-increased unconjugated/indirect bilirubin
What are the characteristics of cholesterol?
-precursor to bile acids
-hypercholesterolemia can occur with obstructive cholestasis
What are other causes of hypercholesterolemia besides obstructive cholestasis?
-endocrinopathies
-nephrotic syndrome
-acute pancreatitis
-postprandial/after meals
-breed-associated
