Chemical Pathology of

Stomach and Pancreas

Dr Donovan McGrowder
Department of Pathology
University of the West Indies
 Overview

❑ Zollinger – Ellison Syndrome

❑ Acute pancreatitis

❑ Chronic pancreatitis

❑ Pancreatic cancer

❑ Fluorescein dilaurate test

 Introduction

❑ The digestion and absorption of food is a complex process which

depends upon the integrated activity of organs in the alimentary
tract.

❑ Food is mixed with various digestive fluids, which contain

enzymes and cofactors, and is broken down into small molecules
which are absorbed by the intestinal epithelium.
 Introduction

❑ Complex carbohydrates such as starch are converted

to mono- and disaccharides.

❑ The disaccharides undergoes further hydrolysis by

intestinal brush border disaccharidases (e.g. lactase)
to allow absorption of the constituent
monosaccharides.
 Disorders of Gastric
Function

❑ Biochemical test are of limited use in the diagnosis of gastric

disorders.

❑ Biochemical tests can be used to investigate conditions in

which gastric acid secretion is either excessive or inadequate.

❑ The stomach can be directly inspected by endoscopy and

contrast radiography can provide valuable information.
 Gastrin
❑ Gastrin is a major physiological regulator of gastric acid
secretion.

❑ Gastrin is a hormone produced by the antral cells (G-

cells) in the stomach mucosa.

❑ Other sources of production are G cell of duodenum and

delta cells of the pancreas.
 Gastrin
❑ Gastrin is produced from the preprogastrin which has 101
amino acids and it cleaves into gastrin.

❑ Gastrin exists in different forms like:

◼ Small gastrin has 17 amino acids polypeptide.

◼ Large gastrin has 34 amino acids polypeptides.
◼ Mini gastrin has 14 amino acids.
 Gastrin
❑ Gastrin from the three sources goes into circulation
and then to the liver.

◼ From liver stimulates parietal cells to produce

hydrochloric acid (HCl).

❑ Gastrin secretion has diurnal variation.

◼ It's the lowest value is 3 a.m to 7 a.m.

 Serum gastrin –
Laboratory findings
❑ In fasting subjects, serum gastrin normally circulates at levels
less than 100 pg/mL (0 – 100 pg/mL).

❑ A pH less than 5.0 and a serum gastrin greater than 1000

pg/mL are virtually diagnostic of ZES.

❑ Fasting gastrin levels greater than 500 pg/mL are consistent

with patients with Zollinger-Ellison syndrome (ZES), but 40%
of patients with ZES have values between 100-500 pg/mL and
require a stimulation test for further assessment.

❑ Most patients with Zollinger-Ellison syndrome have serum

gastrin concentrations between 150-1000 pg/mL.
 Pentagastrin Test –
Laboratory findings
❑ Maximal gastric acid secretion can be measured by the
pentagatrin test.

❑ Protocols for the test vary but in essence involve measurement

of the acid in fluid aspirated through a nasogastric tube in the
testing state and after the administration of pentagastrin, a
synthetic analogue of gastrin.

❑ Basal acid output is normally < 10 mmol/h in males and < 5.5
mmol/h in females.
 Pentagastrin Test

❑ Maximal acid output is normally 7 - 45 mmol/h in males and 5

- 30 mmol/h in females.

❑ A ratio of basal acid output/maximal acid output > 0.65 is

diagnostic for Zollinger Ellison Syndrome.
 Review Questions

❑ What is Zollinger-Ellison Syndrome?

❑ What are the laboratory findings in a patient

with Zollinger-Ellison Syndrome?
 The Pancreas

❑ The pancreas is an organ of the digestive system and endocrine

system. In humans, it is located in the abdominal cavity behind
the stomach.

❑ The pancreas is a mixed gland, having both an endocrine and

an exocrine function.
 The Pancreas

❑ As an endocrine gland, it secretes into the blood several

important hormones, including insulin, glucagon, somatostatin,
and pancreatic polypeptide.

❑ As an exocrine gland, it secretes pancreatic juice into the

duodenum through the pancreatic duct.
 The Pancreas

❑ The pancreatic juice contains bicarbonate, which

neutralizes acid entering the duodenum from the stomach;
and digestive enzymes, which break
down carbohydrates, proteins, and lipids in ingested food
entering the duodenum from the stomach.
 The pancreas

❑ The secretion of pancreatic juice is primarily under the control

of two hormones secreted by the small intestine.

❑ Secretin is a 27 amino acid polypeptide, which stimulates the

secretion of an alkaline fluid and cholecystokinin (CCK), which
stimulates the secretion of pancreatic enzymes.
 The pancreas

❑ Cholecystokinin is a heterogeneous hormone, the predominant

form in the gut is a 33 amino acid polypeptide.

❑ Both secretin and cholecystokinin are secreted in response to

the presence of acid in the duodenum.
 Pancreatic disorders and
their investigation
❑ The major disorders of the exocrine pancreas are acute
pancreatitis, chronic pancreatitis, pancreatic cancer and cystic
fibrosis.

❑ Biochemical investigations are essential in the diagnosis and

management of acute pancreatitis, of limited use in chronic
pancreatitis and of little use in pancreatic cancer.
 Acute Pancreatitis – Laboratory
investigation

❑ The pancreas becomes acutely inflamed and, in severe cases

haemorrhagic.

❑ This condition presents as an acute abdomen with severe pain

and variable degree of shock.

❑ The most frequent known causes are excessive alcohol

ingestion and gallstones; many cases are idiopathic.

❑ Less common causes include infection, elevated triglycerides in

the blood and hypercalcaemia.
 Acute Pancreatitis – Laboratory
investigation

❑ However, the increase may not be so great, and elevated levels

may be seen in other conditions presenting with acute
abdominal pain, particularly perforated duodenal ulcer.

❑ Amylase is a relatively small molecule, and is rapidly excreted

by the kidneys. In mild pancreatitis, rapid clearance may be
reflected by a normal serum level but increased urinary
amylase.
 Acute Pancreatitis – Laboratory
findings

❑ The clinical diagnosis is supported by finding a high serum

amylase activity. The enzyme is secreted by salivary glands
and the exocrine pancreas.

❑ Its activity is usually (though not invariably) raised in acute

pancreatitis, levels > 10 (upper limit of normal) being virtually
diagnostic.

❑ Normal reference interval for serum amylase is 18 – 98 U/L.

 Causes of an increased plasma
amylase

❑ 10 x ULN

◼ Acute pancreatitis

❑ 5 X ULN

◼ Perforated duodenal ulcer

◼ Intestinal obstruction
◼ Other acute abdominal disorders
◼ Acute oliguric renal failure
◼ Diabetic ketoacidosis.
 Acute Pancreatitis – Laboratory
findings
❑ Measurement of pancreas-specific amylase can improve the
diagnostic specificity of serum amylase determinations.

❑ The reference range for serum lipase is 13 – 60 U/L

❑ Measurement of serum lipase is a more specific test for acute

pancreatitis.

❑ If the lipase level is 2 – 3 times that of amylase it is an

indication of acute pancreatitis due to alcohol or gallstones.

❑ A combination of serum lipase and amylase measurements

have been reported to have specificity and sensitivity of
approximately 90%
 Acute Pancreatitis – Laboratory
findings

❑ Serum lipase offers a higher specificity than serum amylase in

diagnosing acute pancreatitis.

❑ Lipase also offers a larger diagnostic window than amylase

since it is elevated for a longer time, thus allowing it to be a
useful diagnostic biomarker in early and late stages of acute
pancreatitis.
 Acute Pancreatitis – Laboratory
findings

❑ The serum of patients with pancreatitis may be lipaemic (due to

hypertriglyceridaemia).

❑ There may be mild increase in bilirubin concentration (direct and

total) and ALP (and GGT) activity in acute pancreatitis due to alcohol
use.

❑ Hypocalcemia is a frequent finding in acute pancreatitis. Exact

mechanism of hypocalcemia in acute pancreatitis is unknown. The
hypocalcemia observed in early phase are autodigestion of mesenteric
fat by pancreatic enzymes and release of free fatty acids, which form
calcium salts.

❑ Hyperglycaemia – elevated fasting plasma glucose (hydrolysis of

carbohydrates by amylase).
 Review Questions

❑ What is acute pancreatitis?

❑ What are the laboratory findings in a patient

with acute pancreatitis?
 Chronic Pancreatitis

❑ The malabsorption is due to impaired digestion of food, but

there is considerable functional reserve and pancreatic lipase
output must be reduced to only 10% of normal before
steatorrhoea is present. Such reduction only occurs in
extensive disease or if the main pancreatic duct is obstructed.

❑ Alcohol is an important aetiological factor and there may be a

history of recurrent acute pancreatitis.
 Chronic Pancreatitis – Laboratory
investigation

❑ Test of exocrine function are unhelpful in the investigation of

pain thought to be of pancreatic origin. However, they are used
to establish pancreatic insufficiency in patients who present
with malabsorption.

❑ Measurement of plasma amylase and lipase activities are of no

value; they are normal or low in patients with chronic
hepatitis, except in acute exacerbations.
 Chronic Pancreatitis – Laboratory
findings

❑ Test of exocrine function are unhelpful in the investigation of

pain thought to be of pancreatic origin. However, they are used
to establish pancreatic insufficiency in patients who present
with malabsorption.

❑ Measurement of plasma amylase and lipase activities are of no

value; they may be normal levels or mildly increase.
 Chronic Pancreatitis – Laboratory
investigation

❑ Measurement of faecal elastase is a good diagnostic test for

chronic panceatitis.
 Chronic Pancreatitis – Laboratory
investigation

❑ Faecal elastase is reduced in pancreatic exocrine failure.

❑ Elastase 1 is a protease (enzyme which breaks down proteins

and peptides) synthesised by pancreatic acinar cells and
secreted into the duodenum. It is not degraded during transit
and is concentrated in the faeces.
 Chronic Pancreatitis – Laboratory
investigation

❑ Measurement of stool Elastase 1 allows the diagnosis or

exclusion of pancreatic exocrine insufficiency, which can be
caused by chronic pancreatitis, cystic fibrosis, pancreatic
tumour, cholelithiasis or diabetes mellitus.

❑ Specimen:
5 g faeces (random) frozen immediately after collection.

❑ Method:
Immunoassay or Monoclonal ELISA.
 Chronic Pancreatitis – Laboratory
investigation

❑ Reference Ranges:

◼ Normal exocrine pancreatic sufficiency: 200 to >500 ug E1/g

stool

◼ Moderate to mild exocrine pancreatic insufficiency: 100 – 200

ug E1/g stool

◼ Severe exocrine pancreatic insufficiency: < 100 ug E1/g stool

 Review Questions

❑ What is chronic pancreatitis?

❑ What are the laboratory findings in a patient

with chronic pancreatitis?
 Carcinoma of the pancreas

❑ Pancreatic carcinoma may be difficult to diagnose and

presentation often occurs as a result of metastases rather than
as a direct effect of the primary tumour.

❑ Other presentations include obstructive jaundice, when a

tumour in the head of the pancreas obstructs the common bile
duct, and malabsorption.
 Carcinoma of the pancreas

❑ Biochemical tests of pancreatic function are rarely of any use in

diagnosis, and other techniques, particularly imaging are far
more diagnostic tools.

❑ The tumour marker CA 19-9 is relative sensitive for pancreatic

disease, but by the time it is detectable, curative surgery is
rarely possible.

❑ Pancreatic carcinoma is usually diagnosed late, by which time

metastases are often present and only palliative surgical
procedures are feasible.

❑ The reference range of serum CA 19-9 is 0 - 37 U/mL

 Carcinoma of the pancreas –
Laboratory findings

❑ Tumours in the head of the pancreas typically also cause

jaundice, pain, loss of appetite, dark urine, and light-colored
stools. Tumors in the body and tail typically also cause pain.

❑ Liver metastasis from advanced pancreatic adenocarcinoma

may result in increase in AST & ALT, ALP & GGT as well as
direct and total bilirubin.
 Review Questions

❑ What are the laboratory findings in a patient

with pancreatic cancer?
 Tests of pancreatic function

❑ These fall into two groups: direct tests, involving the analysis
of fluid aspirated from the duodenum, and indirect tests in
which intubation of the patient is not required.

❑ Examples include the measurement of bicarbonate

concentration and amylase or trypsin activity in duodenal fluid
either following a test meal (Lundh test) or the administration
of secretin and cholecystokinin.

❑ Bicarbonate concentration and enzyme activities are decreased

in chronic pancreatic insufficiency.
 Tests of pancreatic function

❑ Examples of the more widely used indirect test include the

fluorescein dilaurate and p—aminobenzoic acid (PABA) test.

❑ Both utilize the same principle, measuring the absorption of an

orally administered substance in a form dependent on
pancreatic enzyme activity for its absorption.
 Tests of pancreatic function

❑ Fluorescein Dilaurate Test

◼ This is a non-invasive test of pancreatic exocrine function.

◼ In the fluorescein dilaurate test, the substance is fluorescein

dilaurate.

◼ Fluorescein dilaurate is hydrolysed in the gut by pancreatic

cholesterol ester hydrolase to yield fluorescein, which is
absorbed from the gut, conjugated in the liver to fluorescein
glucoronide and excreted in the urine, where it can be
measured (it's fluorescence is measured).
 Tests of pancreatic function

❑ Fluorescein Dilaurate Test (Pancreolauryl test)

◼ On day one, a tablet containing fluorescein dilaurate is taken

and urine collected for 10 hours.

◼ On day two, the same procedure is repeated but this time

using a tablet containing the equivalent dose of free
fluorescein. This allows for correction in individual variations in
intestinal, hepatic and renal function.

◼ Results are expressed as the ratio of fluorescein excreted after

fluorescein dilaurate and after free fluorescein. A ratio of less
than 20% is considered abnormal.
 Tests of pancreatic function

❑ Fluorescein Dilaurate Test

◼ Fluorescein excreted on day 1/fluorescein excreted on day 2

(x 100)

◼ Normal pancreatic function > 30%

◼ Pancreatic insufficiency < 20%.

 Review Questions

❑ How useful is the fluorescein dilaurate test in

evaluating pancreatic function?
Thank you