Clinical Pathology of the Liver Flashcards Preview

Semester II Pathology > Clinical Pathology of the Liver > Flashcards

Flashcards in Clinical Pathology of the Liver Deck (29):
1

FUNCTIONS OF THE LIVER

-Carbohydrate dynamics
-Lipid metabolism
-Protein metabolism
-Management of endogenous waste
-Iron transfer
-Bile production and storage
-Synthesis of coagulation factors for blood clotting
-Metabolism of xenobiotics, including many veterinary drugs.

2

BIOCHEMICAL ASSESSMENT OF LIVER DAMAGE AND FUNCTION

Serum chemistry can measure liver DAMAGE- HEPATIC ENZYMES, and/or liver FUNCTION- Substances produced by the liver and substances excreted by the liver.

The liver is very 'hardy'- it can often still function if damaged, and has a huge capacity to regenerate.

Many parameters measured to assess liver function/damage may not be specific for hepatic diseases (eg. hyperbilirubinaemia)- consider underlying diseases/problems.

3

HEPATOCELLULAR ENZYMES

Used to assess liver function.
-ALANINE AMINOTRANSFERASE (ALT)
-ASPARTATE AMINOTRANSFERASE (AST)
-SORBITOL DEHYDROGENASE (SDH)
-GLUTAMATE DEHYDROGENASE (GLDH)
These enzymes are made in hepatocytes. Measuring them gives an indication of hepatocyte damage.

Hepatocellular enzymes are released from damaged hepatocytes.
REVERSIBLE damage- membrane blebbing, enzymes released to sinusoidal blood or lymph.
IRREVERSIBLE damage- blebbing, membrane damage can result in cell breakdown, or necrosis.

Liver damage results in INCREASED hepatocellular enzyme levels.

4

ALANINE AMINOTRANSFERASE (ALT)

Leaks out of cytosol of damaged hepatocytes.
Mostly liver specific (ie. increased ALT= liver damage)
Hepatocytes are very sensitive to degenerative change, leading to increased ALT.
ONLY USED IN SMALL ANIMALS- large animals have very low ALT levels in their hepatocytes.
Magnitude of increase roughly parallels hepatic mass affected.
There is no differentiation between sublethal injury and necrosis- enzyme is released either way.
Poor correlation between serum levels and hepatic dysfunction.

5

ASPARTATE AMINOTRANSFERASE (AST)

Cytosoloc and mitochondrial isoenzymes.
Also found in skeletal muscle, cardiac muscle and erythrocytes- not as specific to the liver as ALT- may be elevated in nonhepatic disease eg. haemolysis, muscle injury.

6

SORBITOL DEHYDROGENASE (SD)

Found in cytosol of hepatocytes
USEFUL IN HORSES AND CATTLE (can't use ALT)
Few labs offer this test, as the enzyme is unstable in vitro.

7

GLUTAMATE DEHYDROGENASE (GLDH)

Found in cytosol of hepatocytes
USEFUL IN HORSES AND CATTLE
Sensitive marker for hepatic injury.

8

INDUCED ENZYMES

Used to assess liver function.
aka. Biliary enzymes- from the biliary tree.
-ALKALINE PHOSPHATASE (ALP)
-GAMMA GLUTAMYL TRANSFERASE (GGT)

9

ALKALINE PHOSPHATASE (ALP)

Found in hepatocytes and in biliary epithelial cells.
Impaired bile flow (cholestasis) increases ALP markedly (in some species; dog)
Isoenzymes are seen- hepatic, intestinal, bone, placental, corticosteroid induced (DOG ONLY).
Most labs just measure total ALP, which mostly comprises hepatic, bone and corticosteroid induced (in dogs) isoenzymes.

10

AKLALINE PHOSPATASE INDUCTION

Seen in the sick animal (normally, very little ALP is seen in the blood because very little is being produced by hepatocytes)
Also seen with certain drugs and metabolites.
Transcription of ALP is induced
More enzyme is seen on the membranes, including vessel endothelium (ie. in blood)

11

INCREASED ALKALINE PHOSPHATASE

Increased ALP can indicate:
-Cholestasis
-Drug induction eg. corticosteroids, phenobarbitone
-Bone remodelling- most relevant in young, growing animals- slightly raised levels are normal.
-CAT- hepatic ALP production is much less, and there is a much shorter half life.
No evidence of corticosteroid induced isoenzyme in cats.
RAISED ALP IS MUCH MORE SIGNIFICANT IN CATS

12

SPECIES SPECIFIC CONSIDERATIONS

-Steroid induced ALP (SIALP) is unique to dogs.
-Cats have less capacity for hepatic ALP production and it has a shorter half life
-Increased ALP is therefore more significant in the cat
-Feline hyperthyroidism increases ALP- hepatic and bone isoenzymes
-Large animals have wide reference ranges- species variation
-Young, rapidly growing animals normally show slightly elevated levels.

13

GAMMA GLUTAMYL TRANSFERASE (GGT)

Membrane bound enzyme
Found in hepatobiliary system and renal tubules
Useful in CATTLE, HORSES, CATS
Elevated serum levels can indicate cholestasis
GGT may rise in dogs receiving corticosteroids
GGT can be found in urine in renal disease (as it is produced in the renal tubules, increased production in disease)

14

PARAMETERS USED TO ASSESS HEPATIC FUNCTION

Substances produced by the liver eg. bile acids
Substances excreted by the liver eg. bilirubin

15

BILIRUBIN

A pigment produced by degradation of the haem portion of haemoglobin
Mostly produced in mononuclear phagocytes
Must be bound to albumin, transported to the liver and conjugated to make it water soluble, before it can be excreted in bile to the GI tract.

16

HYPERBILIRUBINAEMIA

Elevated bilirubin levels, can cause icterus/jaundice.
Can be pre-hepatic, hepatic, or post-hepatic.

17

PRE-HEPATIC HYPERBILIRUBINAEMIA

The liver is normal.
Caused by increased haemolysis.
Much bilirubin is freed (haemoglobin breakdown following erythrocyte lysis)
This overwhelms the liver's uptake and conjugation capacities.
(and/or secretion capacities)
eg. Immune Mediated Haemolytic Anaemia.

18

HEPATIC HYPERBILIRUBINAEMIA

Problem is with hepatocytes.
eg. anorexia/fasting in horses may decrease uptake of bilirubin by hepatocytes- causes hepatic jaundice. In horses, bilirubin is transported to the liver bound to glucose- fasting/anorexia = less glucose so less bilirubin uptake.

eg. Decreased functional liver mass- pathological.

19

POST-HEPATIC HYPERBILIRUBINAEMIA

Bile has already formed, but excretion is decreased.
eg. Obstructive cholestasis- intra or extrahepatic obstruction of bile flow.
eg. Functional cholestasis- peristalsis of ducts is affected- sepsis associated.

20

INTRAHEPATIC CHOLESTASIS

Hepatocyte swelling impedes bile canaliculi and thus bile flow.
Obstructive.
Can cause post-hepatic hyperbilirubinaemia.

21

EXTRAHEPATIC

Compression/blockage of a major bile duct.
Obstructive.
Can cause post-hepatic hyperbilirubinaemia.

22

BILE ACIDS

Synthesised in liver from cholesterol
Conjugated (made water soluble) in liver and secreted into bile (-> small intestine following post-prandial CCK release)
Solubilise lipid, aiding fat digestion
Most are reabsorbed from the small intestine in the portal vein and undergo enterohepatic recirculation- recycling.

23

BILE ACID TESTING

Normal healthy patients should have very low levels of bile acid in the blood.
-DOGS AND CATS- fasting and 2 hours post-prandial serum bile acids are measured.
-Feeding induces a bolus of bile acids to be released in to small intestine
-Levels should be low when tested both in fasting and 2 hours post-prandially, due to efficient reuptake and recycling.
-HORSES- single measurement is used, as horses have no gallbladder so no bile storage.

24

INCREASED BILE ACIDS

1. PORTOSYSTEMIC SHUNTS- portal blood byspasses the liver, hepatic atrophy due to shunt reduces functional hepatic mass. High serum bile acids post-prandially.
2. LIVER FAILURE- loss of functional mass results in decreased bile acid recycling.
3. CHOLESTASIS- causes reflux of bile acids in to blood.

25

PORTOSYSTEMIC SHUNTS

Increases serum bile acids.
Hepatic portal vein portosystemic shunt bypasses liver, delivering bile acids directly to the systemic circulation.

26

REDUCED HEPATIC FUNCTIONAL MASS

Increases serum bile acids.
Liver has reduced functional mass- fewer healthy hepatocytes- so cannot cope with recycling.
More bile acids are delivered to the systemic circulation via the hepatic vein.

27

CHOLESTASIS

Increases serum bile acids.
Bile acid reflux in to liver and hepatic vein causes increased levels of bile acids in systemic circulation.
Gut levels are lower.

28

OTHER USEFUL PARAMETERS

-UREA- produced in liver in urea cycle
-AMMONIA- increase indicates hepatic problem. Not often used, as it breaks down rapidly.
-ALBUMIN, GLOBULIN- blood proteins, decreased in liver dysfunction (hypoalbuminaemia)
-CLOTTING FACTORS- failing liver will produce less clotting factors; liver failure patients can have clotting disorders.
-GLUCOSE
-URINALYSIS- crystals.
-CHOLESTEROL- produced in liver; low in liver dysfunction

29

CLOTTING PROFILES

Used to further investigate possible liver damage (after clinical exam, complete blood count, biochemistry etc)
PT- PROTHROMBIN
KccT- KAOLIN CEPHALIN CLOTTING TIME (activated partial thromboplastin time, PTT)
FIBRINOGEN