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97 Cards in this Set

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What are 2 enzymes are most useful in evaluating muscle injury?
1) Creatine kinase (CK)
2) Aspartate aminotransferase (AST)
Where is creatine kinase found in the body? (3)
1) Skeletal
2) Cardiac
3) Smooth muscle
What causes increased creatine kinase levels?
Only due to muscle injury and leakage
How sensitive is creatine kinase to muscle injury?
Very sensitive-increases even if very minor muscle damage
When is the peak activity of creatine kinase after acute muscle injury? Half life of CK?
6-12 hours of acute muscle injury
Half life=2-4 hours
Where does aspartate aminotransferase (AST) have high activity?
In both muscle and liver
What causes increased AST? (2)
Muscle injury
Hepatocellular damage
How long does it take AST concentrations peak? Decrease?
Peak: 24-36 hours
-Longer than CK
Decrease: 12-50 hours
When can you get false increases in AST (not related to muscle or hepatic damage)?
With hemolysis
-Some AST in RBCs so can increase w/ massive hemolysis
Where does Alanine aminotransferase have high activity? Low levels of activity?
Primarily a liver enzyme
-Low levels in cardiac & skeletal muscle
-Increases due to muscle injury are usually mild
What 4 enzymes are released in hepatocellular injury?
1) AST
2) ALT
3) SDH
4) GLDH
What is the test of choice for detection of hepatocellular injury in small animals?
Alanine aminotransferase (ALT)
-Very low activity in other species
-Sensitive and relatively liver specific
Where is lactate dehydrogenase present in the body?
Present in most cells in the body-not organ specific
-May increase in muscle damage, but also in damage to lots of other organs-NOT too useful
What does it mean if only creatine kinase is elevated?
Very acute muscle injury
What does it mean if creatine kinase and AST increases?
Recent or active muscle injury
What does it mean if only the AST is increased?
Muscle injury stopped > day days ago (unless there is also liver damage)
What is myoglobin?
Iron-containing protein in muscle
How is myoglobinuria detected?
With a urine dipstick
-Can't reliably differentiate myoglobin from hemoglobin in urine
What type of injury is myoglobin usually associated with?
Severe, acute muscle injury
If serum or plasma appears hemolyzed, is it more likely to be hemoglobin or myoglobin that is resulting in a positive dipstick?
Hemoglobin
What are 3 other possible lab abnormalities of severe muscle injury (not CK or AST or myoglobinuria)?
1) Hyperkalemia
2) Hyperphosphatemia
3) Hypocalcemia
What are 3 additional diagnostic tests for muscle disorders?
1) Serum Vit E and selenium/glutathione peroxidase
2) Acetylcholine receptor antibodies (myasthenia gravis)
3) Dystrophin
What are 4 functions of the liver?
1) Detoxification-exogenous and endogenous products
2) Synthesis-proteins, carbohydrates, fats
3) Metabolism
4) Storage of energy
How much liver function has to lost before clinical signs develop?
80% loss of function
How much of the liver can regenerate after acute injury?
70%
What are the clinical signs of a hepatopathy? (5)
Icterus, anorexia, vomiting, diarrhea, depression
-Very non-specific
How can can laboratory assays of the liver be helpful?
May decide if hepatocellular, biliary, or vascular depending on pattern and magnitude of enzyme elevation
True or false. Laboratory assays of the liver can usually determine if it is a primary or secondary liver disease.
False, can't tell if primary or secondary
True or false. You can have liver disease without liver failure.
True
What is liver disease?
Includes a variety of processes that cause hepatocellular injury and/or cholestasis
-Can be mild to severe, acute or chronic
What is liver failure?
When there are too few functional hepatocytes to maintain normal function
-Irreversible destruction of 70-80% of liver
What are the 4 categories of lab tests used to evaluate the liver?
1) Enzymes that detect hepatocellular damage
2) Enzymes induced by cholestasis or drugs
3) Liver function tests
4) Other tests that support diagnosis of hepatopathy
Enzymes that are released from the cytoplasm when hepatocytes are injured are known as "______"
Leakage enzymes
Increase of leakage enzymes may be proportional to ______.
Number of hepatocytes injured
-Doesn't reflect cause or reversibility
Why isn't ALT used to check for hepatocellular injury in large animals?
Activity is normally too low
When will ALT increase after acute hepatic injury? Peak? Return to normal?
Within 12 hours of acute injury
Peaks in 1-2 days
Returns to normal w/in 2 weeks
What 2 drugs may slightly increase ALT levels?
1) Steroids
2) Phenobarbital
What causes an increase in AST?
Primarily due to liver or muscle damage
Described the sensitivity and specificity of AST for liver damage.
Sensitive, but not specific for hepatopathy
When is AST most often used as a diagnostic test for a hepatopathy?
In large animals since their hepatocytes don't have enough ALT to use as a diagnostic test
Describe the sensitivity and specificity for sorbitol dehydrogenase (SDH) for detecting a hepatopathy?
Sensitive and liver specific
Sorbitol dehydrogenase is sensitive and specific for the liver and is used in large animals for diagnosis of a hepatopathy. Why isn't it used in small animals?
Because we use ALT in small animals
Sorbitol dehydrogenase is sensitive and specific for the liver and is used in large animals for diagnosis of a hepatopathy. Why isn't it used in small animals?
Because we use ALT in small animals
What is different about SDH in equine serum?
Labile
Less so in ruminants and camelids
What are 3 guidelines to performing an SDH assay?
1) Assay within 5 hours at room temp
2) Assay within 48-72 hours if refrigerated
3) Assay within 1 week if frozen
What is glutamate dehydrogenase used for?
Liver specific and sensitive
-Used in Europe
What are the 2 main enzymes induced by cholestasis or drugs?
1) Gamma glutamyltransferase (GGT)
2) Alkaline phosphatase
What is GGT associated with? Where does most serum GGT come from?
Cell membranes
Most serum GGT comes from liver
What are the 2 most common causes of increased GGT?
Cholestasis or biliary hyperplasia
What is more sensitive to cholestasis or drugs in cats, ALP or GGT?
GGT, except in hepatic lipidosis
When does GGT increase in the urine?
Renal tubular damage
How can you assess passive transfer in a calf?
Cow colostrum is high in GGT so measure GGT levels in calf
What can cause biliary hyperplasia?
Neoplasia, toxins
Alkaline phosphatase is an induced enzyme with isoenzymes made in what 5 locations?
1) Liver
2) Bone
3) Placenta
4) Kidney
5) Intetine
Why is the serum activity of alkaline phosphatase primarily from liver in mature dogs, cats and horses?
Because the half-lives of the isoenzymes in intestine, kidney and placenta are very short and don't persist long in the blood
What are the 3 major isoenzymes of alkaline phosphatase?
1) Liver isoenzyme (LAP)
2) Bone isoenzyme (BAP)
3) Corticosteroid-induced isoenzyme (CALP)
What causes the liver isoenzyme (LAP) to increase in DOGS? (3)
1) Cholestasis
2) Corticosteroids
3) Anticonvulsants
What causes increased liver isoenzyme (LAP) in cats?
Cholestasis only
True or false. The increase of LAP usually preceeds the development of hyperbilirubinemia or icterus in the horse, but dogs are often icteric before serum LAP is increased.
False, dogs increase of LAP increases icterus and hyperbilirubinemia, but in horses icterus preceeds the increase in LAP
When does bone isoenzyme (BAP) increase?
With bone growth/proliferation
-Age-related reference ranges
True or false. Increased CiAP can be from either endogenous or exogenous corticosteroids.
True
What do liver function tests measure? What does an abnormal test indicate?
Things taken up, conjugated or excreted by the liver
Abnormal result indicates either too few hepatocytes or dysfunctional hepatocytes
What produces bilirubin?
Breakdown product of hemoglobin-goes to liver unconjugated
What happens to bilirubin in the liver?
Conjugated w/ sugars and excreted in bile
What happens to conjugated bilirubin produced by the liver?
-A little goes into blood
-Some excreted in kidneys
-Some binds to protein (delta bilirubin) stays around longer
What are 2 pre-hepatic causes of increased total bilirubin?
1) Increased destruction of erythrocytes
2) Unconjugated bilirubin overwhelms transport system-accumulates in blood
What is a hepatic cause of increased total bilirubin?
Decreased uptake of bilirubin by hepatocytes
What are 2 post-hepatic causes of increased total bilirubin?`
1) Disruption of bile flow (cholestasis) out of liver
2) Normally increased conjugated bilirubin
What is direct bilirubin?
Conjugated bilirubin
What is indirect bilirubin?
Unconjugated bilirubin
When does bilirubinemia cause icterus?
When > 2-3 mg/dL
True or false. The renal threshold for bilirubin is pretty high.
False, it is low-may see it in urine before you see it in serum
Any bilirubinuria is significant in what animal? Why?
Cats bc they have a higher renal threshold so any bilirubin in urine is significant
What is a cause of bilirubinemia unique to horses?
Anorexia
Checking bilirubin levels is an insensitive test in what animal?
Cattle
What happens to conjugated bilirubin?
Excreted into bile
What is the sensitivity and specificity of bile acids for liver function?
Relatively sensitive and specific test for liver function
When are bile acids most useful?
When hepatopathy is suspected but not confirmed w/ routine biochemical testing
True or false. Increase of bile acids tells you there's decreased hepatic function.
False, increased doesn't tell you cause of decreased hepatic function
What is the function of bile acids?
Help digest fat-secreted into small intestine after eating
What 3 things are needed in order to maintain normal enterohepatic circulation and serum bile acid concentrations?
1) Good portal circulation
2) Functional hepatocytes w/ normal blood flow
3) Unimpaired bile flow
Where are most bile acids reabsorbed?
In ileum and returned to liver via portal circulation
-5% excreted via feces
How long does it normally take bile acid serum levels to decrease to normal after eating?
Within 2 hours
Decreased clearance or decreased excretion of bile acids will cause increase in ______.
Blood concentration
Which is a more sensitive indicator of liver function, bilirubin or bile acids?
Bile acids
Why should you not bother measuring bile acids in an icteric animal?
Because bile acids increase before icterus develops so there's no point in measuring BAs because you know they will be increased
What are 4 steps to increase the sensitivity of bile acids in small animals?
1) Take fasting sample and give a meal
2) Measure again 2 hours post-prandial
3) Submit both
4) If submitting only one-submit post-prandial sample
How many samples are needed for bile acid testing in large animals?
Only one, they're not affected by fasting and is secreted throughout the day because they're always browsing so don't get bolus of bile acids
Where is ammonia produced, absorbed and carried?
Produced in GI tract
Absorbed into blood
Carried to liver
What are 3 causes of increased blood ammonia?
1) Altered liver blood flow
2) Decreased functional liver mass
3) Increased production or intake of ammonia
What tube to you want to put blood collected to test for ammonia levels?
Want heparinized plasma
What do you do with your heparinized plasma to run an ammonia assay?
Separate within 30 min
Assay within 60 min
-Keep on ice
What are 5 other tests that may be affected by a hepatopathy (not bile acids, bilirubin, enzymes)?
1) Cholesterol: produced and eliminated via liver
2) Albumin: produced in liver
3) Urea: produced in liver
4) Glucose: may be low in hepatic failure
5) Coagulation factors: produced in liver
What changes in RBC indices may occur with liver shunts? (2)
Target cells
Microcytosis
What may you see on a UA that indicates a hepatopathy?
Bilirubinuria
Bilirubin crystals
What are the 3 leakage enzymes related to hepatocellular injury?
1) ALT
2) AST
3) SDH
What are 2 enzymes that are consistent with cholestasis, but not specific?
1) AP
2) GGT
-Induced enzymes