Pathology: Lab Markers Of Tissue Injury...

Front 1

What is the significance of serum enzymes?

Back 1

Serum enzymes are sensitive markers of cell injury, demonstrating elevation even after slight tissue or organ injury. While some enzymes are specific to certain organs, others are not.

Front 2

What tissue are trypsin and chymotrypsin levels specific to?

Back 2

Acinar cells of the pancreas

Front 3

In what organ does ornithine carbamoyltransferase originate?

Back 3

Liver

Front 4

What are the principal sources of acid phosphatase?

Back 4

Prostate, lysosomes, (erythrocytes)

Front 5

What are the principal sources of aldolase?

Back 5

Skeletal muscle and heart

Front 6

What are the principal sources of alkaline phosphatase?

Back 6

Bone, liver, intestinal mucosa, placenta, kidney

Front 7

What are the principal sources of amylase?

Back 7

Pancreas, salivary glands

Front 8

What are the principal sources of alanine aminotransferase (ALT)?

Back 8

Liver, (skeletal muscle, heart)

Front 9

What are the principal sources of aspartate aminotransferase (AST)?

Back 9

Heart, liver, skeletal muscle, kidney, brain

Front 10

What are the principal sources of creatine kinase?

Back 10

Skeletal muscle, heart, brain

Front 11

What are the principal sources fo glutamyl tanspeptidase (GGT)?

Back 11

Hepatobiliary tract, (pancreas)

Front 12

What is the principal source of isocitrate dehydrogenase?

Back 12

Liver

Front 13

What are the principal sources of lactate dehydrogenase (LD)?

Back 13

Heart, liver, skeletal muscle, kidney, erythrocytes

Front 14

What are the principal sources of leucine aminopeptidase?

Back 14

Liver, intestine, pancreas, kidney, lung

Front 15

What are the principal sources of 5'-nucleotidase?

Back 15

Hepatobiliary tract, pancreas

Front 16

What is the principal source of ornithine carbamoyltransferase?

Back 16

Liver

Front 17

What enzymes could be tested for that would indicate liver damage?

Back 17

Alanine aminotransferase, (aspartate aminotransferase), isocitrate dehydrogenase, (lactate dehydrogenase), ornithine carbamoyltransferase

Front 18

How are enzymes in the serum measured?

Back 18

They are measured indirectly, by measuring their rate of catalyzing a reaction, rather than by direct measurement of the mass of enzyme present.

Front 19

What are isoenzymes?

Back 19

Isoenzymes are forms of enzymes that are physiochemically distinct but have similar catalytic activity.

Front 20

How are isoenzymes useful in laboratory testing?

Back 20

Because isoenzymes often come from different tissues, identification of the specific isoenzyme in serum can indicate the origin of organ damage when an enzyme of multiple organ origin is discovered in serum.

Front 21

Name an enzyme that has its mass directly measured, rather than its activity.

Back 21

CK-MB is measured by mass rather than activity. This measurement is done by EIA (ELISA).

Front 22

What percentage of the pancreas must be destroyed before pancreatic insufficiency occurs?

Back 22

90%

Front 23

How frequently is pancreatitis found during autopsies?

For how many deaths is it responsible each year?

Back 23

0.5%

1 in 100,000 deaths

Front 24

Name four enzymes produced by the pancreas.

How does the pancreas prevent autodigestion by these enzymes?

Back 24

Lipase
Amylase
Trypsin
Chymotrypsin

The pancreas produces the enzymes as inactive precursors to prevent autodigestion.

Front 25

What is the hallmark of acute pancreatitis?

What are some other symptoms and signs?

Back 25

Abdominal pain. It is initially epigastric and becomes diffuse, radiating to the back.

Other symptoms and signs: nausea, vomiting, tachycardia, low-grade fever

Front 26

Name the two most common predisposing factors for acute pancreatitis.

Name as many of the seven less common predisposing factors as you can.

Back 26

Most common: Alcohol abuse and cholelithiasis

Less common:
Abdominal trauma
Infections (mumps, echovirus, Coxsackie virus)
Hypercalcemia
Penetrating duodenal ulcer
Drug use (steroids, thiazide diuretics, furosemide, estrogen)
Hyperlipoproteinemia (types 1, 4, 5)
Hereditary pancreatitis

Front 27

What happens to the pancreas in acute pancreatitis?

Back 27

Regardless of the cause, pancreatic enzymes are activated and digest the pancreas. The enzymes are also spilled into the peritoneal and retroperitoneal spaces, and then absorbed into the blood. Vomiting occurs, resulting in metabolic alkalosis and dehydration. Hemoglobin and hematocrit are elevated as a result of dehydration and sequestration of fluid in the retroperitoneal space. Hyperglycemia occurs, possibly as a result of abnormal glucagon and insulin secretion. Hypocalcemia may occur as a result of enzymatic fat necrosis.

Front 28

What does the presence of methemalbumin the blood indicate?

Back 28

Methemalbumin indicates hemorrhagic pancreatitis. It is the result of extravasation of the blood in acute hemorrhagic pancreatitis.

Front 29

What lab values are the gold standard for acute pancreatitis diagnosis?

What surgical conditions must be ruled out for this diagnosis to be made?

Back 29

Serum and urine amylase are the gold standards for laboratory diagnosis of acute pancreatitis.

Bowel infarction, ruptured viscus, and penetrating duodenal ulcer must be excluded.

Front 30

What is the sensitivity of serum amylase for acute pancreatitis?

What is the sensitivity of serum amylase and lipase values together?

Back 30

80%

94%

Front 31

What is the connection between the degree of change in serum amylase levels and severity of acute pancreatitis?

Back 31

Once acute pancreatitis has been diagnosed, there is no correlation.

Front 32

How long after serum amylase levels peak with acute pancreatitis do they persist?

What does persistance of abdominal pain beyond 14 days suggest?

Back 32

Four to eight days, with more than seven indicating a severe case.

Pseudocyst formation

Front 33

What surgical conditions can cause elevations in serum amylase?

What conditions might cause transient serum amylase elevation?

Back 33

Mesenteric infarction
Perforated peptic ulcer

Transient elevation:
Salivary gland inflammation or injury
Ruptured ectopic pregnancy
Ovarian cyss
Pulmonary disease
Opiate administration
Renal insufficiency
Diabetic ketoacidosis
Many others

Front 34

How can the specificity of serum amylase level for acute pancreatitis be made to approach 100%?

Back 34

By raising the positive test cut-off to three times the upper limit of the reference range.

Front 35

What condition might cause chronic elevations in serum amylase?

Back 35

Renal failure, due to failure to clear the amylase

Front 36

What is the hallmark of acute myocardial infarction?

What other symptoms may be associated?

Back 36

Crushing, deep chest pain that may be precordial to epigastric.

It is associated with nausea, dyspnea, and diaphoresis. Pain often does not subside until analgesics are administered.

15-30% of MIs are painless. This is more likely to occur in diabetics.

Front 37

What is the present definition of an MI?

Back 37

1. Detectable rise and fall of cardiac biomarkers (troponin is preferred)
2. Myocardial ischemia as evidenced by one of the followng:
a. Symptoms of ischemia
b. ECG changes indicative of new ischemia (ST or T changes, LBBB)
c. New Q waves by ECG
d. Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality

Front 38

What cardiac biomarkers have been used to diagnose acute MI over time?

Back 38

AST was the first enzyme used, shortly followed by LD, LD isoenzymes, total CK, and CK isoenzymes (particularly CK-MB). In the early 1990s, testing shifted to cardiac troponins (cTn).

Front 39

What is the physiologic role of cardiac troponins?

What are the three members of the troponin family?

Which are useful in MI diagnosis?

Back 39

Cardiac troponins are part of a complex of protiens that regulate interactions between actin and myosin.

Family members:
1. cTNT- binds tropomyosin
2. cTnI- inhibitory
3. cTnC- binds calcium

cTnI and cTnT are useful for MI diagnosis, but cTnC is too similar to skeletal muscle troponin C and so it is not used.

Front 40

What is the advantage of using cTn to diagnose CK-MB?

Back 40

cTn and CK-MB both peak between 3-8 hours, but cTn levels persist for much longer and are more useful in diagnosing patients that may delay coming to the hospital. cTnI is also more than twice as specific as CK-MB.

Front 41

What is necessary for high specificity and sensitivity of cTn tests?

Back 41

Serial measurements must be made over 12-24 hours in order for cTn levels be highly sensitive and specific. A single value is not useful for excluding MI because of the delayed release and accumulation of this marker.

Front 42

Name five non-MI ischemic conditions that can elevate cTn levels.

Back 42

1. Coronary embolism
2. Coronary spasm
3. Coronary dissection
4. Aortic dissection
5. Transplant vasculopathy

Front 43

Name two infiltrative diseases of the myocardium that can elevate cTn levels.

Back 43

1. Amyloidosis
2. Sarcoidosis

Front 44

Name two non-MI heart incidents that can elevate cTn levels.

Back 44

1. Cardiac surgery
2. Myopericarditis

Front 45

Name five traumas that can elevate cTn levels.

Back 45

1. AV ablation
2. Defibrillation
3. Chest wall trauma
4. Burns (>30% BSA)
5. Extreme exertion

Front 46

Name as many of the twelve miscellaneous conditions that can elevate cTn levels as you can.

Back 46

1. Congestive heart failure
2. Drug toxicity
3. HTN
4. Hypothyroidism
5. Pheochromocytoma
6. Pulmonary embolism w/ RV infarction
7. Rhabdomyolysis w/ myocyte necrosis
8. Renal failure
9. Respiratory failure
10. Sepsis
11. Tachyarrythmia
12. transient ischemic attack, stroke, subarachnoid hemorrhage

Front 47

What is involved in the "acute phase" inflammatory response?

Back 47

Fever, neutrophilia, changes in plasma concentrations of several proteins

Front 48

What is the cause of fever as part of the acute phase inflammatory response?

How can fever be prevented in this case?

Back 48

Fever is caused by reset of the temperature regulation center of the brain by PGE2. PGE2 production in the hypothalamus by IL-1, which is released from damaged tissues.

Fever can be prevented with antipyretics like aspirin and other inhibitors of prostaglandin production.

Front 49

Describe whether each of the acute phase markers experiences marked, moderate, mild, or no elevation with bacterial infection.

Back 49

Body temperature: marked
Neutrophil count: marked
Acute phase proteins: moderate

Front 50

Describe whether each of the acute phase markers experiences marked, moderate, mild, or no elevation with viral infection.

Back 50

Body temperature: marked
Neutrophil count: none
Acute phase proteins: none

Front 51

Describe whether each of the acute phase markers experiences marked, moderate, mild, or no elevation with chronic rheumatologic disease.

Back 51

Body temperature: mild
Neutrophil count: mild
Acute phase proteins: moderate

Front 52

Describe whether each of the acute phase markers experiences marked, moderate, mild, or no elevation with acute sterile infarct.

Back 52

Body temperature: none
Neutrophil count: mild
Acute phase proteins: mild

Front 53

Name the five plasma proteins that are elevated 1.5- to 3-fold in an acute phase response.

Back 53

1. alpha-1-antitrypsin
2. ceruloplasmin
3. haptoglobin
4. fibrinogen
5. alpha-1-acid glycoprotein

Front 54

Name the two plasma proteins that are elevated 1000-fold in an acute phase response.

Back 54

1. C-reactive protein
2. serum amyloid A protein

Front 55

Match each sign with the other that follows a similar rise and fall time course following an MI:

WBC count
C-reactive protein
fever
ESR

Back 55

Fever follows the WBC curve.
CRP follows the ESR curve.