Liver & Muscle Clinical Pathology

Front 1

What are 2 enzymes are most useful in evaluating muscle injury?

Back 1

1) Creatine kinase (CK)
2) Aspartate aminotransferase (AST)

Front 2

Where is creatine kinase found in the body? (3)

Back 2

1) Skeletal
2) Cardiac
3) Smooth muscle

Front 3

What causes increased creatine kinase levels?

Back 3

Only due to muscle injury and leakage

Front 4

How sensitive is creatine kinase to muscle injury?

Back 4

Very sensitive-increases even if very minor muscle damage

Front 5

When is the peak activity of creatine kinase after acute muscle injury? Half life of CK?

Back 5

6-12 hours of acute muscle injury
Half life=2-4 hours

Front 6

Where does aspartate aminotransferase (AST) have high activity?

Back 6

In both muscle and liver

Front 7

What causes increased AST? (2)

Back 7

Muscle injury
Hepatocellular damage

Front 8

How long does it take AST concentrations peak? Decrease?

Back 8

Peak: 24-36 hours
-Longer than CK
Decrease: 12-50 hours

Front 9

When can you get false increases in AST (not related to muscle or hepatic damage)?

Back 9

With hemolysis
-Some AST in RBCs so can increase w/ massive hemolysis

Front 10

Where does Alanine aminotransferase have high activity? Low levels of activity?

Back 10

Primarily a liver enzyme
-Low levels in cardiac & skeletal muscle
-Increases due to muscle injury are usually mild

Front 11

What 4 enzymes are released in hepatocellular injury?

Back 11

1) AST
2) ALT
3) SDH
4) GLDH

Front 12

What is the test of choice for detection of hepatocellular injury in small animals?

Back 12

Alanine aminotransferase (ALT)
-Very low activity in other species
-Sensitive and relatively liver specific

Front 13

Where is lactate dehydrogenase present in the body?

Back 13

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

Front 14

What does it mean if only creatine kinase is elevated?

Back 14

Very acute muscle injury

Front 15

What does it mean if creatine kinase and AST increases?

Back 15

Recent or active muscle injury

Front 16

What does it mean if only the AST is increased?

Back 16

Muscle injury stopped > day days ago (unless there is also liver damage)

Front 17

What is myoglobin?

Back 17

Iron-containing protein in muscle

Front 18

How is myoglobinuria detected?

Back 18

With a urine dipstick
-Can't reliably differentiate myoglobin from hemoglobin in urine

Front 19

What type of injury is myoglobin usually associated with?

Back 19

Severe, acute muscle injury

Front 20

If serum or plasma appears hemolyzed, is it more likely to be hemoglobin or myoglobin that is resulting in a positive dipstick?

Back 20

Hemoglobin

Front 21

What are 3 other possible lab abnormalities of severe muscle injury (not CK or AST or myoglobinuria)?

Back 21

1) Hyperkalemia
2) Hyperphosphatemia
3) Hypocalcemia

Front 22

What are 3 additional diagnostic tests for muscle disorders?

Back 22

1) Serum Vit E and selenium/glutathione peroxidase
2) Acetylcholine receptor antibodies (myasthenia gravis)
3) Dystrophin

Front 23

What are 4 functions of the liver?

Back 23

1) Detoxification-exogenous and endogenous products
2) Synthesis-proteins, carbohydrates, fats
3) Metabolism
4) Storage of energy

Front 24

How much liver function has to lost before clinical signs develop?

Back 24

80% loss of function

Front 25

How much of the liver can regenerate after acute injury?

Back 25

70%

Front 26

What are the clinical signs of a hepatopathy? (5)

Back 26

Icterus, anorexia, vomiting, diarrhea, depression
-Very non-specific

Front 27

How can can laboratory assays of the liver be helpful?

Back 27

May decide if hepatocellular, biliary, or vascular depending on pattern and magnitude of enzyme elevation

Front 28

True or false. Laboratory assays of the liver can usually determine if it is a primary or secondary liver disease.

Back 28

False, can't tell if primary or secondary

Front 29

True or false. You can have liver disease without liver failure.

Back 29

True

Front 30

What is liver disease?

Back 30

Includes a variety of processes that cause hepatocellular injury and/or cholestasis
-Can be mild to severe, acute or chronic

Front 31

What is liver failure?

Back 31

When there are too few functional hepatocytes to maintain normal function
-Irreversible destruction of 70-80% of liver

Front 32

What are the 4 categories of lab tests used to evaluate the liver?

Back 32

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

Front 33

Enzymes that are released from the cytoplasm when hepatocytes are injured are known as "______"

Back 33

Leakage enzymes

Front 34

Increase of leakage enzymes may be proportional to ______.

Back 34

Number of hepatocytes injured
-Doesn't reflect cause or reversibility

Front 35

Why isn't ALT used to check for hepatocellular injury in large animals?

Back 35

Activity is normally too low

Front 36

When will ALT increase after acute hepatic injury? Peak? Return to normal?

Back 36

Within 12 hours of acute injury
Peaks in 1-2 days
Returns to normal w/in 2 weeks

Front 37

What 2 drugs may slightly increase ALT levels?

Back 37

1) Steroids
2) Phenobarbital

Front 38

What causes an increase in AST?

Back 38

Primarily due to liver or muscle damage

Front 39

Described the sensitivity and specificity of AST for liver damage.

Back 39

Sensitive, but not specific for hepatopathy

Front 40

When is AST most often used as a diagnostic test for a hepatopathy?

Back 40

In large animals since their hepatocytes don't have enough ALT to use as a diagnostic test

Front 41

Describe the sensitivity and specificity for sorbitol dehydrogenase (SDH) for detecting a hepatopathy?

Back 41

Sensitive and liver specific

Front 42

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?

Back 42

Because we use ALT in small animals

Front 43

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?

Back 43

Because we use ALT in small animals

Front 44

What is different about SDH in equine serum?

Back 44

Labile
Less so in ruminants and camelids

Front 45

What are 3 guidelines to performing an SDH assay?

Back 45

1) Assay within 5 hours at room temp
2) Assay within 48-72 hours if refrigerated
3) Assay within 1 week if frozen

Front 46

What is glutamate dehydrogenase used for?

Back 46

Liver specific and sensitive
-Used in Europe

Front 47

What are the 2 main enzymes induced by cholestasis or drugs?

Back 47

1) Gamma glutamyltransferase (GGT)
2) Alkaline phosphatase

Front 48

What is GGT associated with? Where does most serum GGT come from?

Back 48

Cell membranes
Most serum GGT comes from liver

Front 49

What are the 2 most common causes of increased GGT?

Back 49

Cholestasis or biliary hyperplasia

Front 50

What is more sensitive to cholestasis or drugs in cats, ALP or GGT?

Back 50

GGT, except in hepatic lipidosis

Front 51

When does GGT increase in the urine?

Back 51

Renal tubular damage

Front 52

How can you assess passive transfer in a calf?

Back 52

Cow colostrum is high in GGT so measure GGT levels in calf

Front 53

What can cause biliary hyperplasia?

Back 53

Neoplasia, toxins

Front 54

Alkaline phosphatase is an induced enzyme with isoenzymes made in what 5 locations?

Back 54

1) Liver
2) Bone
3) Placenta
4) Kidney
5) Intetine

Front 55

Why is the serum activity of alkaline phosphatase primarily from liver in mature dogs, cats and horses?

Back 55

Because the half-lives of the isoenzymes in intestine, kidney and placenta are very short and don't persist long in the blood

Front 56

What are the 3 major isoenzymes of alkaline phosphatase?

Back 56

1) Liver isoenzyme (LAP)
2) Bone isoenzyme (BAP)
3) Corticosteroid-induced isoenzyme (CALP)

Front 57

What causes the liver isoenzyme (LAP) to increase in DOGS? (3)

Back 57

1) Cholestasis
2) Corticosteroids
3) Anticonvulsants

Front 58

What causes increased liver isoenzyme (LAP) in cats?

Back 58

Cholestasis only

Front 59

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.

Back 59

False, dogs increase of LAP increases icterus and hyperbilirubinemia, but in horses icterus preceeds the increase in LAP

Front 60

When does bone isoenzyme (BAP) increase?

Back 60

With bone growth/proliferation
-Age-related reference ranges

Front 61

True or false. Increased CiAP can be from either endogenous or exogenous corticosteroids.

Back 61

True

Front 62

What do liver function tests measure? What does an abnormal test indicate?

Back 62

Things taken up, conjugated or excreted by the liver
Abnormal result indicates either too few hepatocytes or dysfunctional hepatocytes

Front 63

What produces bilirubin?

Back 63

Breakdown product of hemoglobin-goes to liver unconjugated

Front 64

What happens to bilirubin in the liver?

Back 64

Conjugated w/ sugars and excreted in bile

Front 65

What happens to conjugated bilirubin produced by the liver?

Back 65

-A little goes into blood
-Some excreted in kidneys
-Some binds to protein (delta bilirubin) stays around longer

Front 66

What are 2 pre-hepatic causes of increased total bilirubin?

Back 66

1) Increased destruction of erythrocytes
2) Unconjugated bilirubin overwhelms transport system-accumulates in blood

Front 67

What is a hepatic cause of increased total bilirubin?

Back 67

Decreased uptake of bilirubin by hepatocytes

Front 68

What are 2 post-hepatic causes of increased total bilirubin?`

Back 68

1) Disruption of bile flow (cholestasis) out of liver
2) Normally increased conjugated bilirubin

Front 69

What is direct bilirubin?

Back 69

Conjugated bilirubin

Front 70

What is indirect bilirubin?

Back 70

Unconjugated bilirubin

Front 71

When does bilirubinemia cause icterus?

Back 71

When > 2-3 mg/dL

Front 72

True or false. The renal threshold for bilirubin is pretty high.

Back 72

False, it is low-may see it in urine before you see it in serum

Front 73

Any bilirubinuria is significant in what animal? Why?

Back 73

Cats bc they have a higher renal threshold so any bilirubin in urine is significant

Front 74

What is a cause of bilirubinemia unique to horses?

Back 74

Anorexia

Front 75

Checking bilirubin levels is an insensitive test in what animal?

Back 75

Cattle

Front 76

What happens to conjugated bilirubin?

Back 76

Excreted into bile

Front 77

What is the sensitivity and specificity of bile acids for liver function?

Back 77

Relatively sensitive and specific test for liver function

Front 78

When are bile acids most useful?

Back 78

When hepatopathy is suspected but not confirmed w/ routine biochemical testing

Front 79

True or false. Increase of bile acids tells you there's decreased hepatic function.

Back 79

False, increased doesn't tell you cause of decreased hepatic function

Front 80

What is the function of bile acids?

Back 80

Help digest fat-secreted into small intestine after eating

Front 81

What 3 things are needed in order to maintain normal enterohepatic circulation and serum bile acid concentrations?

Back 81

1) Good portal circulation
2) Functional hepatocytes w/ normal blood flow
3) Unimpaired bile flow

Front 82

Where are most bile acids reabsorbed?

Back 82

In ileum and returned to liver via portal circulation
-5% excreted via feces

Front 83

How long does it normally take bile acid serum levels to decrease to normal after eating?

Back 83

Within 2 hours

Front 84

Decreased clearance or decreased excretion of bile acids will cause increase in ______.

Back 84

Blood concentration

Front 85

Which is a more sensitive indicator of liver function, bilirubin or bile acids?

Back 85

Bile acids

Front 86

Why should you not bother measuring bile acids in an icteric animal?

Back 86

Because bile acids increase before icterus develops so there's no point in measuring BAs because you know they will be increased

Front 87

What are 4 steps to increase the sensitivity of bile acids in small animals?

Back 87

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

Front 88

How many samples are needed for bile acid testing in large animals?

Back 88

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

Front 89

Where is ammonia produced, absorbed and carried?

Back 89

Produced in GI tract
Absorbed into blood
Carried to liver

Front 90

What are 3 causes of increased blood ammonia?

Back 90

1) Altered liver blood flow
2) Decreased functional liver mass
3) Increased production or intake of ammonia

Front 91

What tube to you want to put blood collected to test for ammonia levels?

Back 91

Want heparinized plasma

Front 92

What do you do with your heparinized plasma to run an ammonia assay?

Back 92

Separate within 30 min
Assay within 60 min
-Keep on ice

Front 93

What are 5 other tests that may be affected by a hepatopathy (not bile acids, bilirubin, enzymes)?

Back 93

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

Front 94

What changes in RBC indices may occur with liver shunts? (2)

Back 94

Target cells
Microcytosis

Front 95

What may you see on a UA that indicates a hepatopathy?

Back 95

Bilirubinuria
Bilirubin crystals

Front 96

What are the 3 leakage enzymes related to hepatocellular injury?

Back 96

1) ALT
2) AST
3) SDH

Front 97

What are 2 enzymes that are consistent with cholestasis, but not specific?

Back 97

1) AP
2) GGT
-Induced enzymes