section

8.2

Serum Markers in the Diagnosis of Tissue Damage

127

FIGURE 8-4

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.

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).

Acute pancreatitis

is

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,

and

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

hyperamylasemia.

Fur-

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

trypsinogen.

It is a 25,000-Da pro-

tein that exists in two isoenzyme forms: trypsinogen

- 1

(cationic) and trypsinogen-2 (anionic). Both forms are

readily filtered through the kidney glomeruli. However,

the tubular reabsorption of trypsinogen

- 2

is less than for

trypsinogen-

1

; a dipstick method has been developed to

detect trypsinogen

- 2

in the urine of patients suspected of

having acute pancreatitis. The test strip contains mono-

clonal antibodies specific for trypsinogen-

2

.

Liver

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