Hepato (liver assays)

Hepatocyte function tests primarily run in vet settings

Bilirubin (TBIL) and Bile Acids

What is the largest internal organ?

The liver

What are all functions of the liver run by?

Enzymatic reactions

Functions of the liver

Metabolizing and synthesizing molecules, digestion and absorption, secretion of bilirubin and bile. Elimination of toxins.

What all end with “ASE”

Enzymes

What small organ is closely associated with the liver?

The gall bladder

Some malfunctions in liver or gallbladder

Icterus, hypoalbuminemia, hemostasis problems, hypoglycemia, hyperlipoproteinemia, hepatoencephalopathy.

What do liver cells do to avoid damage to the whole liver?

They compartmentalize so the damage in one zone does not affect all the liver functions.

What are the 3 main kinds of major hepatobiliary assays?

Enzymes released from damaged hepatocytes, enzymes associated with cholestasis, and hepatocyte function tests.

Enzyme Released From Damaged Hepatocytes (Hepatobiliary Assays)

Alanine transaminase, aspartate transaminase, iditol dehydrogenase, glutamate dehydrogenase

Enzymes Associated With Cholestasis

Alkaline Phosphatase, Gamma glutamyltransferase.

What are the two hepatocyte function tests.

Bilirubin, and Bile acids.

What is the problem with Albumin and Cholesterol tests for hepatocyte tests?

These tests are less sensitive and may not indicate a problem until 2/3 to ¾ of tissue is damaged.

Bilirubin

Insoluble molecule derived from the breakdown of hemoglobin by macrophages in the spleen.

How does bilirubin get to the liver?

Bilirubin binds to albumin for transport to the liver.

Hepatic cells metabolize and conjugate bilirubin into what?

they metabolize and conjugate the bilirubin to the molecule bilirubin glucuronide.

What is a major component of bile?

Bilirubin glucuronide (Metabolized and conjugated by the hepatic cells

How is bilirubin glucoronide transported from the liver to the GI tract?

It is made as a major part of bile and then secreted into the GI tract.

What happens with Billirubin glucuronide in the GI tract

Bacteria in the GI acts on bilirubing glucuornide and produces urobilinogens

What form of bilirubin is broken down and excreted in the feces or absorbed in blood and excreted in kidney?

Urobilinogen

What happens to urobilinogens after they have been made from the bacteria and the bilirubin glucoronide?

they are broken down and excreted in feces or may be absorbed in the blood end excreted through the kidneys.

Measurement of what can help pinpoint cause of icterus

Bilirubin

Free floating Bilirubin can cause what?

Icterus

If there is unconjugated bilirubin that can indicate problems with what?

Unconjugated bilirubin indicates a problem with the uptake by the liver, or hemolytic anemia that overtakes the liver’s ability to conjugate.

What is unconjugated bilirubin

Pre-hepatic(before being in the liver). Bound to Albumin.

How much of the total bilirubin in serum is unconjugated?

2/3rds

Conjugated bilirubin indicates what

bile duct obstruction

What are bile acids

Synthesized in the hepatic cells from cholesterol and are conjugated with glycine and taurine.

What animals do not have a gallbladder?

Horses and rats

Bile acids function

Aid in fat absorption and modulate cholesterol levels

Bile secretion

They are secreted across the canalicular membrane and reach the duodenum via the biliary system

Bile storage

They are stored in the gallbladder until contraction associated with feeding.

What happens with bile after reaches ileum?

It is transported back to the portal circulation and back to the liver.

What % of bile acids are actively resorbed in ileum? What happens to the rest?

90%-95%. Rest is secreted in feces

Postprandial def

After eating

BA concentrations are higher or lower after eating?

Higher

When are the two samples for bile acid tests taken

One after 12 hours of fasting and one two hours after eating

What animal only gets one bile acid sample taken?

Horses

What does Bile acid test tell us?

About portal circulation and hepatic function.

What are we comparing between 2 bile acid samples

in the bile concentration

Factors that effect bile acid test results

Inadequate fasting, food aromas, prolonged fasting, diarrhea.

Bile acid test procedure

12 hour fast, collect the pre-prandial sample, let the pet eat, wait 2 hours, take the post-prandial sample, send out serum.

Elevated Bile acids indicate what and can mean

Liver diseases like: congenital portosystemic shunts, chronic hepatitis, hepatic cirrhosis, cholestasis, neoplasms.

Unspecific for type of liver problem bile acids test?

a screening test.

What is cholesterol

Plasma lipoprotein produced primarily in the liver but also ingested in food

Cholestasis casues increased what in some animals

Cholesterol

What is cholesterol sometimes used to screen for?

Hypothyroidism.

Enzymes released from damaged hepatocytes

As hepatocytes are damaged, enzymes leak into blood. ALT, AST, Dehydrogenase enzymes.

What does ALT (enzyme stand for?)

Alanine Transaminase

What does AST stand for?

Aspartate Transaminase

What are the dehydrogenase enzymes?

Iditol (Sorbitol) dehydogenase (ID/SD), Glutamate dehydrogenase (GLDH)

What are the only readily available enzyme tests for enzymes released from damaged hepatocytes.

ALT and AST

What is the major source of ALT?

Hepatocyte, where it is found free in the cytoplasm.

How quick do we see elevations of ALT with liver damage?

Within 12 hours

Who is ALT considered a liver specific test in?

Dogs, Cats, and Primates. Others do not have enough for it to be considered a liver specific test.

What can ALT be elevated due to?

Damage to renal cells, cardiac muscle, skeletal muscle, and the pancreas.

Is ALT a screening test?

Yes because it is not specific eno0ugh to identify specific liver disease.

Aspartate Transaminas (AST)

Present in hepatocytes in both cytoplasm and bound to the mitochondrial membrane.

What is required to release the membrane-bound AST?

More severe liver damage.

How fast do AST levels rise?

Slower than ALT but return to normal faster.

What other tissues is AST found in?

RBCs, cardiac muscles, skeletal muscles, kidneys, and pancreas.

What are some common causes for elevation of AST?

Liver disease, muscle inflammation, necrosis, hemolysis

What is the primary source of Iditol Dehydrogenase?

Hepatocyte

where else is Iditol Dehydrogenase found?

Kidney, small intestine, skeletal muscles, and RBCs.

Who is Iditol Dehydrogenase especially useful in evaluating liver diseases in?

It is especially useful in large animals. Large animals do not have diagnostic levels of ALT so ID/SD is the diagnostic test. *****

Glutamate Dehydrogenase (GLDH)

Mitochondrial bound enzyme - High concentrations in cattle, sheep, and goats

What are the enzymes associated with Cholestasis

AP/ALK Phos, GGT

What is cholestasis?

Bile duct obstruction

What does AP/ALK Phos stand for?

Alkaline phosphatase.

Where is AP/ALK Phos found in?

Osteoblasts, chrondroblasts, intestines, and placenta and liver cells. There are higher levels in young, growing animals.

What is AP/ALK Phos used to detect?

Used to detect Cholestasis in small animals.

What does GGT stand for?

Gamma Glutamyltransferase

Where is Gamma Glutamyltransferase found?

Many tissues but mainly the liver

Who has higher GGT

Cattle, Horses, Sheep, Goats, and Birds, have higher than dogs and cats.

What is GGT elevated with?

Liver disease, especially obstructive liver disease.