Serum Markers in the Diagnosis of Tissue Damage
Pancreatic duct obstruction by a gallstone at the ampulla of Vater. Obstruction can lead to pancreatitis, from induction
of bile reflux, which eventually damages acinar cells of the pancreas.
The pancreas is both an exocrine and an endocrine
gland. The exocrine function is digestion of food sub-
stances (Chapter 12); the endocrine function involves
glucose homeostasis (Chapter 22).
characterized by epigastric pain; it is an inflammatory
process and potentially fatal. Obstruction of the pancreatic
duct (Figure 8-4), which delivers pancreatic juice to the
small intestine, by gallstones (Chapter 12) or alcohol
abuse is the most common cause of acute pancreatitis,
representing 80% of all causes. The pathophysiology
is due to inappropriate release of pancreatic enzymes
and their premature activation. The principal pancreatic
enzyme is trypsinogen, which after activation to trypsin
converts many other enzymes to their active forms.
Some of these are kallikrein, phospholipase A2, elastase,
enzymes of blood coagulation and fibrinolysis,
complement. Effects of these abnormal processes are
autodigestion of the pancreas, vasodilation, increased
capillary permeability, and disseminated intravascular
coagulation. These can result in circulatory collapse,
renal insufficiency, and respiratory failure.
Laboratory diagnosis of acute pancreatitis involves the
measurement of the pancreatic digestive enzymes: amy-
lase and lipase (Chapter 12). Elevated serum amylase level
is a sensitive diagnostic indicator in the assessment of
acute pancreatitis, but it has low specificity because there
are many nonpancreatic causes of
thermore, amylase (M.W. 55,000) is rapidly cleared by the
kidneys and returns to normal levels by the third or fourth
day after onset of the abdominal pain. Amylase activity
in the serum appears within
2 - 1 2
hours after the onset of
pain. Serum lipase also is used to assess pancreatic dis-
orders and has a higher specificity than serum amylase.
It appears in the plasma within 4-8 hours, peaks at about
24 hours and remains elevated for 8-14 days. Measure-
ments of amylase and lipase provide 90-95% accuracy in
the diagnosis of acute pancreatitis with abdominal pain.
Pancreatic isoamylase level has not proven useful in com-
parison with measurements of both amylase and lipase.
The catalytic activity of lipase requires the presence of
both bile salts and colipase (Chapter 12) and must be in-
corporated in assays of serum lipase activity.
Since exocrine cells of the pancreas contain many en-
zymes, attempts have been made to use markers other
than amylase and lipase to diagnose acute pancreatitis.
One such enzyme is
It is a 25,000-Da pro-
tein that exists in two isoenzyme forms: trypsinogen
(cationic) and trypsinogen-2 (anionic). Both forms are
readily filtered through the kidney glomeruli. However,
the tubular reabsorption of trypsinogen
is less than for
; a dipstick method has been developed to
in the urine of patients suspected of
having acute pancreatitis. The test strip contains mono-
clonal antibodies specific for trypsinogen-
The liver is the largest glandular organ and its parenchymal
cells are called hepatocytes. Liver has numerous func-
tions, including metabolism, detoxification, formation and
excretion of bile, storage, and synthesis. Liver diseases
include alcohol abuse, medication, chronic hepatitis B and
C infections, steatosis and steatohepatitis, autoimmune