CLS 382 - Lecture 8

Clinical Enzymology – Pancreas

 Pancreatic tissue
• The pancreas consists of two kinds
of tissues that perform different
functions:
➢ The exocrine pancreas:
- makes, stores and releases powerful
enzymes (in an inactive form to the
small intestine) to digest fats, proteins,
and carbohydrates.
- makes and releases bicarbonate to
neutralize stomach acids and allow for
the activation of pancreatic enzymes
once needed.
➢ The endocrine pancreas:
- produces hormones that help
maintain normal blood sugar levels by
regulating glucose transport into the
body's cells, where it is used for energy
(e.g. insulin and glucagon)
• Pancreatitis may occur when digestive
enzymes become activated while still
inside the pancreas, causing irritation
and injury to pancreatic tissue and
leading to inflammation.
• In acute pancreatitis, inflammation develops quickly and then goes away after a few
days to weeks.
• The main causes are gallstones (block the pancreatic duct) and long-term alcohol
abuse.
• Moderate to severe attacks may require a long hospital stay to monitor for and treat
serious complications.
• With treatment, mild attacks may get better after a few days. In mild cases, your
pancreas may return to normal once it has healed.
• Recurrent attacks of acute pancreatitis can lead to chronic pancreatitis.

• Chronic pancreatitis is long-lasting inflammation in the pancreas.

• Long-term alcohol abuse is the main cause. Smoking cigarettes also increases risk.
• It can lead to the formation of scar tissue in the pancreas that keeps it from working
properly.
• A pancreas that does not work properly can lead to digestive problems and diabetes.
• Pancreatitis occurs more often in men than in women. It is becoming more common,
though the reasons for this aren't clear.
• For instance, in the US, nearly 275,000 people are hospitalized with acute
pancreatitis each year. Chronic pancreatitis is less common, with about 86,000
people hospitalized.
 Causes of pancreatitis
• Gallstones and long-term alcohol abuse are the main causes of pancreatitis. Others include:
➢ Medications (e.g.) valproic acid (for seizure or bipolar disorders)
estrogen (menopause or osteoporosis)
➢ Viral infections such as mumps and Epstein-Barr virus
➢ Very high blood triglyceride level (hypertriglyceridemia)
➢ high blood calcium level (hypercalcemia)
➢ Cystic fibrosis (or being a carrier of a gene that causes cystic fibrosis)
➢ Inherited defects that result in early activation of digestive enzymes
➢ Pancreatic cancer
➢ Certain autoimmune conditions
➢ Injury (trauma) to the pancreas
• Some cases of acute and chronic pancreatitis have no clear cause
• Pancreatitis can cluster in some families, and there are several known genes that contribute
to increased risk for pancreatitis.
• In children, cystic fibrosis is a major cause of chronic pancreatic failure.
• It is usually suspected clinically in infancy as the children present with chronic refractory foul
stools, recurrent chest infections and failure to thrive.
• It is diagnosed by confirming an increased concentration of chloride in the sweat.
• Genetic confirmation is usually made, but the condition can be caused by a large number of
mutations in the CFTR gene.
 Diagnosis
• Pancreatitis is diagnosed with physical exam/medical history, blood tests, and imaging
• At least 2 of the 3 following criteria must be present to diagnose acute pancreatitis:
i. Abdominal pain that is "consistent with the disease"
ii. Levels of lipase or amylase (pancreatic enzymes) that are 3x higher than the ULN
iii. "Characteristic" abdominal imaging results
Laboratory Tests
1- Lipase (preferred); as it is more specific than amylase for diseases of the pancreas,
particularly for acute pancreatitis and for acute alcoholic pancreatitis.
• Levels start to rise within (4-8) hrs of the onset of pancreatitis symptoms and typically return
to normal within a week.
• Acute pancreatitis is diagnosed if the lipase level reaches 3 times above the upper limit of
normal. As chronic pancreatitis gets worse, lipase levels may return to normal or decrease.
2- Amylase; while the amylase test is sensitive for pancreatic diseases, it is not specific.
• An elevated amylase level may indicate a problem, but the cause may not be related to the
pancreas.
• Levels start to rise (2-12) hrs after the onset of acute pancreatitis symptoms and typically
return to normal within a week.
• Acute pancreatitis is likely if the level reaches 3 times above the upper limit of normal.
• Amylase also may be monitored in people with chronic pancreatitis. It will often be
moderately elevated until the cells that make it become damaged, at which point blood
levels of amylase may be decreased.
• The pancreas is the major source of digestive enzymes. Deficiency of these enzymes causes
profound maldigestion, and subsequently malabsorption.
• In suspected enzyme deficiency, a therapeutic trial of oral enzyme replacement with food
will usually confirm the diagnosis.
• Fecal elastase or chymotrypsin are occasionally measured to confirm the presence of
residual pancreatic function.
• Quantitative measurements of pancreatic enzymes in intestinal secretions are no longer
performed in routine clinical practice.
 Other tests
• To help diagnose or detect complications of • To help diagnose and evaluate chronic
acute pancreatitis pancreatitis
➢ Complete blood count –CBC- ➢ Pancreatic enzymes elastase (reduced) and
(WBC count could point to infection) chymotrypsin (absent) in stool in pancreatic
➢ Triglycerides insufficiency (which could be caused by chronic
pancreatitis). Both are occasionally measured to
➢ Liver panel (including bilirubin and confirm the presence of residual pancreatic
liver enzymes) function
➢ Glucose ➢ Fecal fat (fat in the stool) as excess fat in stool is
often the first sign of pancreatic insufficiency
➢ Calcium (largely replaced now by fecal elastase).
➢ Magnesium ➢ Immunoreactive trypsinogen (IRT):
trypsinogen, an inactive precursor produced by
➢ C-reactive protein (CRP is a measure of the pancreas that is converted to the enzyme
inflammation) trypsin; the pancreatic enzyme that digests
proteins. IRT may be elevated with pancreatitis
➢ Sweat (chloride) test for diagnosis of CF
➢ Tests for genetic mutations such as those
associated with CF (CFTR Gene Mutation
Testing) or other causes of hereditary
pancreatitis