Pancreatic Disorders For The Pathologist

Front 1

What is macroamylasemia?

Back 1

It is caused by an amylase-macromolecule complex that cannot be excreted due to its large size and therefore has a longer half-life.

Front 2

How is macroamylasemia characterized?

Back 2

Characterized by persistently elevated serum amylase in the face of no pancreatic disorder and low urine amylase.

Front 3

Who is more likely to have macroamylasemia?

Back 3

Men in their 5th-7th decades.

Front 4

How is the diagnosis of macroamylasemia made?

Back 4

Demonstration of macroamylase molecules by ultracentrifugation or chromatography.

Front 5

What characterizes acute pancreatitis?

Back 5

New-onset sharp epigastric pain radiating to the back and flank with nausea and vomiting.

Front 6

What are some causes of acute pancreatitis?

Back 6

Bile stones, alcohol, triglycerides, mumps, cytomegalovirus, varicella zoster, herpes simplex, coxsackievirus, hepatitis B, and HIV.

Front 7

What is amylase?

Back 7

It is an enzyme that consists of primarily salivary and pancreatic isoenzymes. 6 bands are seen on electrophoresis with the first 3 being salivary and the slowest 3 being pancreatic.

Front 8

What are the kinetics of amylase?

Back 8

Rises over first 2-12 hours, peaks at 48 hours, and returns to normal in 3-5 days.

Front 9

What are the limitations of amylase testing?

Back 9

Limited sensitivity in patients with hypertriglyceridemia and alcoholism (have lower amylase).
Specificity is limited by elevations in amylase from inflammatory intra-abdominal processes and parotid and submandibular gland inflammation.

Front 10

What affect does triticum vulgaris have?

Back 10

It is a wheat germ lectin that inhibits salivary amylase.

Front 11

Does the level of amylase correlate with severity of disease?

Back 11

No, but higher levels are more specific for acute pancreatitis.

Front 12

How stable is a specimen for amylase testing?

Back 12

The specimen is stable for 1 week at room temperature or 6 months if refrigerated.

Front 13

What type of specimen for amylase testing should be avoided?

Back 13

Plasma specimens anticoagulated with citrate or oxalate because amylase is a calcium-containing enzyme so falsely low activities can result.

Front 14

Does hemolysis present a problem in specimens for amylase testing?

Back 14

No.

Front 15

What do values of amylase persisting for more than 5 days possibly represent?

Back 15

Necrosis or pseudocyst formation.

Front 16

What conditions are associated with lower than normal levels of amylase?

Back 16

Chronic pancreatitis, congestive heart failure, bone fractures, 2nd and 3rd trimester of pregnancy, GI cancer, and pleurisy.

Front 17

What is the clearance ratio of amylase?

Back 17

Clearance ratio (%)= (Urine amylase/Serum amylase) x (Serum creatinine concentration/Urine creatinine concentration) x 100.
Normal ratio is 1-4%, and pancreatitis is 7-15%.

Front 18

What is the fractional excretion of amylase?

Back 18

FE = clearance of amylase/clearance of creatinine.

Front 19

In which patients with acute pancreatitis are the levels of amylase normal?

Back 19

Those patients with hypertriglyceridemia-associated acute pancreatitis because triglycerides competitively interfere with the amylase assay.

Front 20

What non-pancreatic conditions are associated with hyperamylasemia?

Back 20

Diabetic ketoacidosis, peptic ulcer disease, acute cholecystitis, salpingitis, ectopic pregnancy, intestinal obstruction, bowel ischemia, macroamylasemia, renal insufficiency.

Front 21

What substances activate amylase?

Back 21

Chloride, bromide, and iodide.

Front 22

What conditions cause elevations of pancreatic-type (P-type) amylase?

Back 22

Acute pancreatitis, chronic relapsing pancreatitis, glomerulonephritis, and hypoparathyroidism.

Front 23

What conditions cause elevations of salivary-type (S-type) amylase?

Back 23

Alcohol ingestion, mumps, chronic pancreatitis, pancreatic insufficiency, acute gastroenteritis, cholelithiasis, ARDS, chronic renal failure, lung cancer, and Sjögren’s syndrome.

Front 24

What is the most common P-type amylase?

Back 24

P1.

Front 25

What change in P2/P1 amylase or P3/P1 amylase ratio suggests a pancreatic pseudocyst?

Back 25

These ratios are increased in 90% of patients with a pseudocyst.

Front 26

What is the ratio of P2/P1 and P3/P1 in pancreatitis and pancreatic cancer.

Back 26

Ratio of P2/P1 is <0.25 whereas the ratio of P3/P1 is <0.04.

Front 27

What is lipase?

Back 27

It is an enzyme made by pancreatic acinar cells that is essentially specific for the pancreas.

Front 28

What are the kinetics of lipase?

Back 28

Rises 4-8 hours after onset, peaks at 24 hours, and remains for 8-14 days.

Front 29

What patients should be tested for lipase levels?

Back 29

Patients with clinical symptoms but with amylase that is low (alcoholics, hypertriglyceridemia, late-presenters).

Front 30

What substances inhibit serum lipase?

Back 30

Proteins, bile acids, and phospholipids.

Front 31

What substance reverses the inhibition of lipase?

Back 31

Colipase. It is essential to add colipase to the reagent to measure lipase activity.

Front 32

How stable is a specimen for lipase testing?

Back 32

Stable for 1 week at room temperature with an ideal pH of 8.8.

Front 33

What is the relationship between lipase and the kidneys?

Back 33

Filtered by the glomeruli and completely reabsorbed by the proximal tubules. Lipase is found in the urine of patients with renal disorders.

Front 34

What does the lipase/amylase ratio predict?

Back 34

It predicts alcohol-induced pancreatitis (>3 is predictive while >5 is diagnostic).

Front 35

What values have a 95% predictive value for gallstones as the underlying cause of acute pancreatitis?

Back 35

ALT and AST >150 IU/dL.

Front 36

What is trypsinogen?

Back 36

Trypsinogen 1 and trypsinogen 2 are produced in the pancreas and are activated to trypsin in the duodenum.

Front 37

What substance inactivates trypsin?

Back 37

Trypsin is inactivated by complexing with alpha-1-antitrypsin (AAT) or alpha-2-macroglobulin.

Front 38

What values are elevated in biliary acute pancreatitis?

Back 38

Trypsinogen 1, amylase, and lipase

Front 39

What values are more likely to be elevated in alcohol-associated pancreatitis?

Back 39

Trypsinogen 2 and trypsin-2-AAT.

Front 40

What value can best distinguish between biliary and alcoholic causes of acute pancreatitis?

Back 40

Ratio of trypsin-2-AAT to trypsinogen 1.

Front 41

Do trypsinogen levels correlate to severity of pancreatitis?

Back 41

Yes.

Front 42

What value is associated with biliary tract cancer?

Back 42

Elevated trypsin-1-ATT.

Front 43

What is the significance of measuring carbohydrate deficient transferrin (CDT)?

Back 43

It is an ideal marker in a patient suspected of being an alcoholic that has not had alcohol in a while (CDT remains elevated for weeks after binge drinking).

Front 44

What is the significance of measuring trypsinogen activation peptide (TAP)?

Back 44

>30 mmol/L is associated with severe disease.
Negative predictive value of 100%.

Front 45

What hematocrit value is associated with pancreatic necrosis?

Back 45

>44 on admission or rising over the first 24 hours.

Front 46

What C-reactive protein value is associated with pancreatic necrosis?

Back 46

>200 IU/L.
Useful after first 36-48 hours.

Front 47

For what is the Ranson criteria used?

Back 47

Identifies patients at risk of fulminant pancreatitis.
Cannot be assigned until 48 hours after admission.
90% specific.

Front 48

What characterizes chronic pancreatitis?

Back 48

Marked by progressive destruction of acinar tissue and islet cells.
Presents as mild glucose intolerance to frank diabetes mellitus, maldigestion/malabsorption, and chronic abdominal pain.

Front 49

What laboratory value is suggestive of chronic pancreatitis?

Back 49

Low pancreatic elastase in the stool.

Front 50

Which pancreatic enzyme gives greater sensitivity in a patient with delayed presentation?

Back 50

Lipase because it remains elevated longer than amylase.

Front 51

What mutations have been found in patients with familial recurrent acute pancreatitis?

Back 51

Cationic trypsinogen (PRSS-1), pancreatic secretory trypsin inhibitor (PSTI), and cystic fibrosis transmembrane conductance regulator (CFTR).

Front 52

What are the tests of pancreatic exocrine function?

Back 52

Secretin-cholecystokinin (secretin-CCK) test, fecal elastase-1, and fecal fat.

Front 53

How is the secretin-CCK test performed?

Back 53

An endoscope is introduced and the duodenal concentrations of pancreatic exocrine products (bicarbonate, amylase, lipase, trypsin) are measured after IV administration of secretin and CCK.

Front 54

What is fecal elastase-1?

Back 54

A proteolytic enzyme produced by the pancreas that is concentrated in the feces.

Front 55

What is the significance of the fecal elastase-1 test?

Back 55

It is increased in acute and relapsing chronic pancreatitis more so than amylase and persists longer.

Front 56

How much stool is needed to form a fecal elastase-1 test?

Back 56

Requires 100 mg of FORMED stool.

Front 57

What is the significance of the values obtained from the fecal elastase-1 test?

Back 57

Normal: >200 μg/g.
Mild/moderate pancreatic insufficiency: 100-200 μg/g.
Severe insufficiency: <100 μg/g.

Front 58

What are the pitfalls of the fecal elastase-1 test?

Back 58

Lacks sensitivity for detecting mild to moderate disease, cannot diagnose chronic pancreatitis, and is unable to differentiate between pancreatic and nonpancreatic steatorrhea.

Front 59

What is serine protease inhibitor (SPINK1)?

Back 59

It is a protein that stabilizes trypsin in the pancreas.
Mutations in SPINK1 have been found in pancreatitis and pancreatic cancer cases.

Front 60

What is cystic fibrosis?

Back 60

Characterized by chronic lung disease and malabsorption due to pancreatic involvement. Also have meconium ileus at birth.
1 in 20 whites is a carrier.

Front 61

How is the diagnosis of cystic fibrosis made?

Back 61

Diagnosis is made on increased sodium and chloride in sweat.
Children with CF have chloride concentrations >60 mmol/L on at least two occasions.

Front 62

What must be done in a patient with indeterminate results on a sweat chloride test?

Back 62

Can undergo a repeat sweat chloride test following mineralocorticoid administration (e.g., fludrocortisone). In patients with CF, the electrolyte values remain unchanged whereas they decrease in normal individuals.

Front 63

What are the limitations of the sweat chloride test?

Back 63

People with malnutrition, renal insufficiency, nephrogenic diabetes insipidus, glucose-6-phosphatase deficiency, hypothyroidism, and other conditions can have sweat chloride levels >60 mmol/L.
Sweat electrolytes in premenopausal women undergo cyclic fluctuation, reaching a peak chloride concentration 5-10 days prior to the onset of menses.
Men also show fluctuations in sweat electrolytes.

Front 64

How is the sweat chloride test performed?

Back 64

Pilocarpine is introduced into the skin to stimulate sweat gland secretion.
The sweat is collected using filter paper or gauze, weighed, diluted with water, and analyzed.
Chloride is measured directly using 20 µL of a chloride analyzer.

Front 65

What is the genetic mutation in cystic fibrosis?

Back 65

Autosomal recessive mutation in CFTR gene on chromosome 7.
Classic mutation is delta F508.

Front 66

What laboratory findings are associated with a pancreatic pseudocyst?

Back 66

Increased amylase.
Decreased CEA.
Increased CA 19-9.

Front 67

What laboratory findings are associated with serous cystadenoma of the pancreas?

Back 67

Decreased amylase.
Decreased CEA.
Decreased CA 19-9.

Front 68

What laboratory findings are associated with mucinous cystadenoma of the pancreas?

Back 68

Decreased amylase.
Increased CEA.
Normal to increased CA 19-9.

Front 69

What laboratory findings are associated with intradctal papillary mucinous tumor of the pancreas?

Back 69

Increased amylase.
Increased CEA.
Normal to increased CA 19-9.

Front 70

What laboratory findings are associated with solid-cistic (solid-pseudopapillary tumor) of the pancreas?

Back 70

Decreased amylase.
Decreased CEA.
Decreased CA 19-9.

Front 71

What clinical sequelae are associated with glucagonoma?

Back 71

Necrolytic migratory erythema, weight loss, diabetes, depression, deep venous thromboses.

Front 72

What clinical sequelae are associated with insulinoma?

Back 72

Hypoglycemia.

Front 73

What clinical sequelae are associated with somatostatinoma?

Back 73

Gallstones, diabetes, diarrhea, hypochlorhydria.

Front 74

What clinical sequelae are associated with VIPoma?

Back 74

Diarrhea, hypokalemia, acidosis, hypochlorhydria.

Front 75

What is vasoactive intestinal peptide (VIP)?

Back 75

a neuropeptide member of the secretin-glucagon family that is released in response to gut distention that results in relaxation of vascular and nonvascular smooth muscle (vasodilator effect) and stimulates water and electrolyte secretion by activating cyclic AMP (cAMP).

Front 76

What are the characteristics of VIPoma?

Back 76

60% are malignant and 6% associated with MEN I.
Characterized by pancreatic cholera (watery diarrhea >700 mL/day), hypokalemia, and achlorhydria (WDHA).
Diarrhea does not improve with fasting and has 300 mmol of potassium secreted per day.
Patients have hypokalemic, hyperchloremic metabolic acidosis.

Front 77

How is the diagnosis of VIPoma made?

Back 77

Diagnosis confirmed by raised fasting VIP levels associated with secretory diarrhea and presence of a lesion (usually in the pancreas).

Front 78

How is measurement of VIP performed?

Back 78

Serum being tested must be added immediately to aprotinin, a protease inhibitor.
Sample must then be separated within 10 minutes of collection and frozen to -20ºC.
False-positive elevated VIP are seen in small bowel ischemia or severe dehydrating diarrhea.
Serum pancreatic polypeptide level should be done at the same time because it will be elevated if the VIPoma is located in the pancreas.