Lecture 16 11/7/24

Question 1

What are the characteristics of hepatic circulation?

Answer 1

-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

Question 2

What are the components of a portal triad?

Answer 2

-bile duct
-vein
-artery

Question 3

Which functions of the liver contribute to carbohydrate metabolism?

Answer 3

-storage of glycogen
-gluconeogenesis

Question 4

Which functions of the liver contribute to fat metabolism?

Answer 4

-oxidation of fatty acids
-synthesis of cholesterol, lipoproteins, and phospholipids

Question 5

Which functions of the liver contribute to protein metabolism?

Answer 5

-synthesis of plasma proteins
-synthesis of urea
-removal of ammonia

Question 6

Which function of the liver contributes to bilirubin metabolism?

Answer 6

conjugation of bilirubin

Question 7

Which function of the liver contributes to iron storage?

Answer 7

storage of ferritin

Question 8

Which function of the liver contributes to detoxification?

Answer 8

removal of drugs and hormones from the bloodstream

Question 9

How can enzyme activity be determined in biochemical tests?

Answer 9

-substrate consumption
-product formation

Question 10

What are the characteristics of clinical enzymology?

Answer 10

-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

Question 11

Why is it important to look at enzyme trends rather than single values?

Answer 11

single values could be indicative of a worsening condition, an improving condition, or a persistent increase

Question 12

Which biochemical tests detect hepatocellular injury?

Answer 12

-ALT
-AST
-SDH
-GLDH

Question 13

Which biochemical tests detect cholestasis?

Answer 13

-ALP
-GGT
-bilirubin
-cholesterol

Question 14

Which biochemical tests detect hepatic insufficiency?

Answer 14

-albumin
-urea
-glucose
-cholesterol

Question 15

What are the characteristics of hepatocellular injury?

Answer 15

-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

Question 16

What are the characteristics of alanine aminotransferase/ALT?

Answer 16

-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

Question 17

What are the characteristics of aspartate aminotransferase/AST?

Answer 17

-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

Question 18

In addition to hepatocellular injury, what else can lead to increased AST?

Answer 18

-muscle damage
-intravascular hemolysis
-in vitro hemolysis/poor sample handling

Question 19

What are the characteristics of sorbitol dehydrogenase/SDH?

Answer 19

-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

Question 20

What are the characteristics of glutamate dehydrogenase/GLDH?

Answer 20

-mitochondrial enzyme
-most specific biomarker of hepatocellular injury in birds

Question 21

What is cholestasis?

Answer 21

impaired bile flow

Question 22

What are the obstructive causes of cholestasis?

Answer 22

-hepatocellular swelling
-neoplasia
-choleliths

Question 23

What is the functional cause of cholestasis?

Answer 23

altered biochemical pathway/receptors

Question 24

What are the characteristics of cholestatic enzymes?

Answer 24

-expressed on membranes of hepatocytes and biliary epithelium
-“inducible” enzymes

Question 25

What are the characteristics of alkaline phosphatase/ALP?

Answer 25

-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

Question 26

What are the characteristics of L-ALP?

Answer 26

-produced by liver -indicates cholestatic disease

Question 27

What are the characteristics of C-ALP?

Answer 27

-dogs only -produced by liver -indicates corticosteroid excess or phenobarbital use

Question 28

What are the characteristics of B-ALP?

Answer 28

-produced by bone -indicates young/growing animal, osteosarcoma, or hyperthyroidism

Question 29

What are the characteristics of gamma-glutamyl transferase/GGT?

Answer 29

-most common cause of increase is biliary hyperplasia -can see transient increases in neonates

Question 30

What is bilirubin?

Answer 30

end product of hemoglobin degradation

Question 31

What are the three main fractions of bilirubin?

Answer 31

-unconjugated/bound to albumin -conjugated/water soluble -delta-bilirubin/conjugated to proteins

Question 32

What are the potential lab measurements of bilirubin?

Answer 32

-total bilirubin -indirect/unconjugated bilirubin -direct/conjugated bilirubin

Question 33

What are the characteristics of pre-hepatic hyperbilirubinemia?

Answer 33

-hemolysis cause -clinical examples include IMHA and oxidant injury

Question 34

What are the characteristics of hepatic hyperbilirubinemia?

Answer 34

-obstructive cause -clinical examples include hepatocellular swelling and neoplasia

Question 35

What are the characteristics of post-hepatic hyperbilirubinemia?

Answer 35

-obstructive cause -clinical examples include gall bladder mucocele, choleliths, and neoplasia

Question 36

How does hemolysis lead to pre-hepatic hyperbilirubinemia?

Answer 36

abundant unconjugated bilirubin overwhelms the liver's ability to conjugate and excrete bilirubin

Question 37

How does obstruction lead to hepatic hyperbilirubinemia?

Answer 37

hepatocyte swelling or infiltrative neoplasia squeeze the bile canaliculi, leading to backup of conjugated and unconjugated bilirubin

Question 38

How does obstruction lead to post-hepatic hyperbilirubinemia?

Answer 38

obstruction in gall bladder or bile duct results in backup of conjugated or unconjugated bilirubin

Question 39

What are the characteristics of functional cholestasis?

Answer 39

-impaired excretion of conjugated bilirubin -associated with sepsis and inflammation -see a mild hyperbilirubinemia without other indications of cholestasis

Question 40

What are the characteristics of fasting/anorexic cholestasis?

Answer 40

-seen in horses and cattle -impaired conjugation of bilirubin -increased unconjugated/indirect bilirubin

Question 41

What are the characteristics of cholesterol?

Answer 41

-precursor to bile acids -hypercholesterolemia can occur with obstructive cholestasis

Question 42

What are other causes of hypercholesterolemia besides obstructive cholestasis?

Answer 42

-endocrinopathies -nephrotic syndrome -acute pancreatitis -postprandial/after meals -breed-associated