UNIVERSITY OF NIS

MEDICAL FACULTY NIŠ

BIOCHEMICAL DIAGNOSIS OF PANCREAS AND

GASTROINTESTINAL TRACT DISEASES
Department of biochemistry, Medical Faculty of Niš

Prof. dr Tatjana Jevtovic

Stoimenov
tanja@medfak.ni.ac.rs
tjevtovic@yahoo.com
The pancreas is a gland with double secretion: endocrine
and exocrine.

- The endocrine role is reflected in the regulation of carbohydrate metabolism

and glycemia. Alpha cells of the islets of Langerhans secrete glucagon, beta
cells secrete insulin, delta cells somatostatin, and PP cells secrete pancreatic
polypeptide.

- The Exocrina role is reflected in: formation and secretion of enzymes:

amylase, lipase, trypsin, DNA, RNA and other ingredients, including
bicarbonates and electrolytes.
- Pancreatic enzymes participate in the digestion of proteins, lipids and
carbohydrates. Activation of proteolytic enzymes of the pancreas is
performed in the duodenum.
 Acute pancreatitis
AP is a group of reversible lesions characteized by inflammation of the
pancreas.
Non-bacterial inflammation...

The degree of pancreas damage ranges from mild to severe

hemorrhagic pancreatitis associated with necrosis and gangrene.
 Etiologic factors in
acute pancreatitis
Gallstones and alcohol cause 80% of all acute pancreatitis,

20% of cases are attributed to infections, drugs, abdominal injuries, pancreatic

and biliary tract surgery.

It is more often caused by stones in women and by alcohol in men.

 Clinical Features
abdominal pain dominates, first in the epigastrium and then spreads to other
areas of the abdomen
 nausea, vomiting
 temperature
 tachycardia
 severe form of pancreatitis - hemorrhage in the retroperitoneal space
 jaundice - the initial sign of calculus-induced pancreatitis
 hypotension
 hypovolemia

- Bluish discoloration of the skin around the umbilicus (Cullen's sign) may occur
as a result of hemoperitoneum
Blue-red-purple or green-brown discoloration (Turner's sign) - indicate
tissue catabolism of hemoglobin.
- Erythematous nodules on the skin and subcutaneous fat necrosis.
 Diagnosis of acute pancreatitis
 Increase in serum amylase over 500 IU / dL

 Increase in urinary amylase that remains even when serum amylase

normalizes

 Increased activity of lipase (produced in the pancreas) in serum

 A more specific and sensitive test than amylase in acute pancreatitis is

serum lipase activity.

 Other parameters:

 moderate leukocytosis
 moderate increase in bilirubin (<2mg / dL)
 increase in hematocrit
 hypocalcaemia (calcium complexes with fatty acids)
Laboratory findings include:
Elevated serum amylase activity...
 During the first 24 hours, followed by rising serum lipase level
 amylase levels return to normal rapidly
 persistent hyperamylasemia indicates the development of complications
 the degree of amylase increase does not follow the severity of the
disease
Other laboratory tests:
 serum lipase increase - indicator of acute pancreatitis (of pancreatic origin)
 serum glucose levels are elevated
 liver function tests (LFT) are abnormal
 hypocalcaemia
Modern markers of acute pancreatitis are inflammatory
markers: IL-6, IL-8, CRP and procalcitonin.
Polymorphonuclear elastase, IL-6, phospholipase-A2 and
trypsin activating peptide are determined as predictors of
the severity of acute pancreatitis.

Modified Glasgow criteria for the prognosis of acute pancreatitis :

• glucose> 10 mmol / L
• leukocytes (WBC)> 15 x 10 / L
• LDH> 600 IU / L
• AST> 200 IU / L
• urea (in serum)> 16 mmol / L
• calcium (serum) <2 mmol / L
• albumin <32g / L
• PaO2 <8 kPa
Chronic pancreatitis is an irreversible process of destruction of exocrine and
endocrine tissue of the pancreas.

The disorder is accompanied by persistent recurrent episodes: severe pain, nausea, constipation,
gas, steatorrhea, diabetes.
The most common causes are: alcoholism (90%), cystic fibrosis of the pancreas, hypercalcemia,
hyperlipidemia, calculosis and hyperparathyroidism.

The "gold standard" for the diagnosis of chronic pancreatitis is postendoscopic

retrograde cholangiopancreatography.

It is useful to determine the activity of serum lipase and urine amylase, and tests
of stimulation of pancreatic juice secretion (Lund's, PABA test or secretin test)
are used to examine pancreatic function.
 Cystic fibrosis of the pancreas
•is an autosomal recessive inherited disease that affects the
secretory cells of the digestive system, disrupting the transport of
ions through the membrane of epithelial cells.

Laboratory findings:
 increase in chloride concentration in sweat (2 to 3 times)
 increase in serum amylase and lipase and amylase activity in urine
 leukocytosis
 hyperglycaemia
 hypocalcaemia
 albumin decrease
 hypoxemia
 Autoimmune pancreatitis (AIP)

- a form of chronic pancreatitis characterized by 1) diffuse enlargement of the

pancreas, 2) lymphoplasmacytic inflammation of the pancreatic parenchyma and 3)
fibrosis.

The disease can affect the gallbladder, bile ducts, kidneys, lungs and salivary
glands.

Clinical symptoms are: abdominal pain, Diabetes mellitus, obstructive jaundice and
weight loss.

Laboratory findings: IgG4, CA19-9, liver enzymes, CBC, amylase and lipase and non-
specific autoantibodies ALA (antilactoferrin antibody), ACA II (anti-carbonic
anhydrase II antibody), ASMA and ANA.
 Pancreatic cancer
- originates from the exocrine part of the organ.
- Risk factors are: poor socio-economic status, smoking, family history,
exposure to toxins, presence of chronic diseases
(diabetes mellitus, chronic pancreatitis, cholecystectomy)

- Adenocarcinoma is most often present, which in 70-80% of cases is localized on the head of the
pancreas.
- Diagnostic tests: alkaline phosphatase activity, gamma-GT and bilirubin concentration detected.
As the disease progresses, hypoalbuminemia and anemia occur, and the penetration of the tumor
into the duodenum increases bleeding, so blood in the stool can be detected.

- The level of tumor markers increases: CEA, AFP, CA 19-9, CA 242 and CA 50, and decreases
trypsin activity. The marker of choice is CA 19-9 which has a diagnostic specificity of 90% and a
sensitivity of 85-95% for a 3 cm tumor.

- Pancreatic oncofetal antigen (POA) can also be detected in pancreatic cancer, and MUC-1
(mucin-1) antigen is also considered a potential marker.

- Marker CA 19-9, tissue plasminogen activator (TPA) and carbohydrate antigen 50 (CA-50) are
usually determined in the differentiation between pancreatic cancer and chronic pancreatitis.
 Malnutrition
- Malnutrition is caused by diseases of the
pancreas, biliary tract, digestive mucosa
and bacterial colonization of the small
intestine.
- Investigation Tests are: xylose absorption
test, disaccharide tolerance tests,
presence of fat in stool, tests for exocrine
pancreatic insufficiency, determination of
iron, albumin, lymphocytes folate and serum
vitamin B12, as well as testing of gastric
and pancreatic juice ingredients using
appropriate tests.
 Gastritis
- Acute - stress or autoimmune gastritis
- Chronic - long-term irritations with the use of non-steroidal anti-inflammatory
drugs, infections caused by Helicobacter pylori, pernicious anemia or
autoimmune disorders.
Laboratory findings: shows sideropenic anemia, and in patients with
atrophic gastritis, pernicious anemia may be demonstrated.
Serum Iron concentration is decreased.
It is possible to prove blood in the stool.
Detection of Helicobacter pylori is based on the presence of the enzyme
urease, which breaks down labeled urea into ammonia and carbon dioxide
(measured by exhalation test), by detecting specific antibodies in serum and
saliva, and by detecting Helicobacter pylori antigen in stool.
- Urea exhalation test: The patient drinks a urea solution containing radioactive carbon atom
13C. Urea is broken down, carbon is released which is delivered to the lungs by the blood and
is exhaled from them. The accuracy of this test is 96-98%
Gastrinoma - a disease in which large amounts of gastrin are
secreted due to tumors, gastrinoma of the pancreas, stomach and
duodenum.
Diagnosis is made by determining serum gastrin.
Peptic ulcer - a common disease caused by a bacterial infection, long-term
use of nonsteroidal anti-inflammatory drugs, although it is most often caused
by Helicobacter pylori.
The main symptom of peptic ulcer is: pain that occurs and disappears at
intervals of several days to several weeks. There is weight loss, loss of
appetite, bloating, belching, nausea and vomiting.
Laboratory tests: complete blood count, glucose, urea, creatinine, bilirubin,
calcium and prothrombin time. In case of bleeding, blood in the stool is proven.

Gastric cancer does not initially differ in symptoms from ulcer disease. Tumor
markers, most commonly CEA and CA 19-9, should be used for differentiation.
Inflammatory bowel disease: ulcerative colitis, Crohn's disease.

Ulcerative colitis is an inflammatory disease of the colon with

ulceration within the intestinal wall. It is manifested by chronic
diarrhea, abdominal pain, loss of appetite and body weight.

Crohn's disease is a consequence of a genetic predisposition. It is an

inflammatory disease of the small and large intestine, which is accompanied by
pain, tension, gas, fever, nausea and diarrhea. In some cases, bleeding occurs.
Biomarkers: increased concentration of non-specific markers of inflammation
(CRP, leukocytosis, sedimentation), then anemia, thrombocytosis. Macrocytic
anemia is a consequence of a lack of vitamin B12 and folic acid.
Colorectal cancer usually occurs around the age of 50 and is more common in
men. Risk factors are a diet rich in animal fats, in patients with metabolic
syndrome and hereditary conditions, familial adenomatous polyposis (FAP). The
disease is accompanied by bleeding that leads to anemia, pain, loss of appetite.
The diagnosis is confirmed by the finding of tumor markers (CEA and CA 19-
9).

Celiac disease is an autoimmune enteropathy in which intolerance occurs

to gluten and gliadin (in wheat, barley and rye). Antigliadin antibodies of
immunoglobulin class IgA (IgA-AGA) and class IgG (IgG-AGA) can be detected in
the serum of patients, the former of which are more specific.
By detecting antiendomysial antibodies (EMA) of immunoglobulin class IgA
(IgAEMA) that are highly specific, in the patient's serum, it can be confirmed
with high probability that it is celiac disease.