GASTROINTESTINAL
FUNCTION
THE STOMACH
• A) Helicobacterpylori infection is one of the major
cause of peptic ulcer, the ulcer results from
weakening of the protective mucous coating of
the stomach and duodenum.
• The organism protects itself from gastric acidity by
secretion of the urease enzyme which convert the
acidic media into more neutral environment.
• Tests for H. pylori infection:
• 1- Urea breath test: is a non-invasive and
reliable test that depends on the urease activity
of the organism to detect active Infection.
• The patient is given by mouth either 13C- or 14ClabeIled urea and urease (produced by H. pylori)
if present, hydrolyses urea into ammonia and
isotopically labeled carbon dioxide.
• Carbon dioxide is absorbed from the gut and
subsequently expired in the breath where it can
be detected and quantified..
• This test is used both for the identification of
patients with active infection and for establishing
the effectiveness of treatment.
• 2- Serological tests: Patients infected with H.
pylori develop antibodies to the organism that
can be detected in the laboratory using enzymelinked immunosorbent assays (ELlSAs).
• These serological tests are less reliable in
confirming the eradication of the organism
because of the slow reduction in antibody titers.
• Faecal antigen testing: Enzyme immunoassays
can be used to detect the presence of H. pylori
in stool specimens.
• B) Gastrin production:
• Gastrin is a polypeptide released by gastric
antrum and duodenum and is a potent stimulator
of gastric acid production.
• Its release is inhibited by low gastric pH , and its
circulating levels are increased in patients with
chronic hypochlorhydria.
• So, plasma gastrin may be elevated in cases of
decreased HCL production in the stomach such
as due to gastritis, treatment with H2
antagonists, proton pump inhibitors, pernicious
anemia or previous vagotomy.
• The most important clinical application for
the measurement of gastrin is in the
investigation of patients with gastric acid
hyper secretion thought to be caused by a
gastrinoma (Zollinger-Ellison syndrome).
• Zollinger-Ellison syndrome
• This syndrome is due to a gastrinoma, that is,
neoplasia may be due to either:
• a) pancreatic gastrin-producing cells (common)
• b) gastric gastrin-producing cells
• About 60% of gastrinomas are malignant and 30%
occur as part of the MEN syndrome type 1.
• Increased gastrin production leads to chronic
hypersecretion of gastric acid, which in turn causes
peptic ulceration and sometimes diarrhea and fat
malabsorption leading to steatorrhoea.
• The steatorrhoea is believed to be due to
inhibition of pancreatic lipase by the high [H+}
concentration in the intestinal lumen.
• In some patients simple duodenal ulcer or
diarrhea only may be the presenting feature.
• The diagnosis of gastrinoma is based on the
detection of elevated fasting plasma gastrin in
association with high gastric acid secretion.
• Patients should not be receiving proton pump
inhibitors or H2 receptor blocker at the time of
measurement.
• Provocative testing may be necessary in about 15%
of patients where the basal plasma gastrin
concentration is normal or only slightly increased
and gastrinoma is suspected.
• In this provocative test secretin is injected IV, which
usually produces a 2-fold increase in plasma gastrin
in patients with gastrinoma. while no change occurs
in patients with G-cell hyperplasia
THE PANCREAS
• Many factors can result in acute pancreatitis but
most commonly gallstones or alcoholism is the
major ones; vascular and Infective causes have
also been recognized.
• Plasma amylase activity measurements is the
test most commonly used for diagnosis of acute
pancreatitis.
• Plasma calcium may fall considerably in severe
cases of acute pancreatitis, but sometimes not
for a few days; it probably falls as a result of the
formation of insoluble calcium salts of fatty acids
in areas of fat necrosis.
• Amylase in plasma arises mainly from the
pancreas and the salivary glands.
• Plasma P-isoamylase activity is a more sensitive
and more specific lest than total amylase for the
detection of acute pancreatitis, but total plasma
amylase activity is most often measured and is
usually, but not always, greatly increased in
acute pancreatitis.
• Plasma amylase activities greater than 10 times
the normal value are virtually diagnostic of acute
pancreatitis.
• Maximum values of more than five times the
upper reference limit are found in about 50% of
cases, but are not diagnostic of acute
pancreatitis, as this high values sometimes may
be encountered in mesenteric infarction and
acute biliary tract disease, as well as in acute
parotitis.
• Smaller and more transient increases may occur
in:
• - perforated peptic ulcer, or after Injection of
morphine and other drugs that cause spasm of
the sphincter of Oddi.
• Plasma amylase activity usually returns to
normal level within 3-5 days.
THE SMALL INTESTINE
• In small intestinal disease, absorptive function
may be diminished, and permeability is often
increased.
• There are biochemical tests that assess
absorptive function and intestinal permeability,
but endoscopy and biopsy has greatly reduced
the need to perform such tests.
• They may be used to monitor the response to
therapy (e.g. the response of patients with celiac
disease to a gluten- free diet)
• A) Tests of carbohydrate absorption:
• 1- Xylose absorption test
• D-Xylose, is rapidly absorbed from the small
intestine and excreted in the urine; little is
metabolized in the liver.
• Its concentration in blood or excretion in urine
following a standard oral dose of xylose has been
used to investigate the intestine's ability to absorb
monosaccharide.
• Impaired absorption and excretion of xylose occurs
in patients with disease of the small intestine but low
values may also be observed in patients who have
bacterial colonization of the small intestine, since
the bacteria may metabolize xylose.
• Also, low urinary values occur in patients with renal
disease, due to impaired excretion of xylose.
• 2- Disacchartdase deficiency:
• Disaccharidase deficiency is most commonly
presented as intolerance to one or more of the
disaccharides - lactose, maltose or sucrose.
• The defect may be congenital or acquired.
• Disaccharidase activity can be measured in small
intestinal mucosa biopsy specimens.
• This is the most reliable way of specifically
diagnosing
deficiency.
small
intestinal
disaccharidase
• B) Tests for amino acid absorption:
• Certain specific disorders of amino acid transport
affect both intestinal and renal epithelial transport.
• In Hartnup disease, there is impaired transport of
neutral amino acids, and deficiency of some
essential amino acids (especially tryptophan) may
occur.
• In cystinuria , the dibasic amino acids (cystine,
ornithine, arginine and lysine) are affected; however,
there is no associated nutritional defect, despite the
fact that lysine is an essential amino acid.
• These disorders are investigated by examining the
pattern of amino acids excreted in the urine by
chromatography.
• C) Tests for fat absorption:
• Efficient digestion and absorption of fat requires
both effective emulsification and solubilization of
fats; this function is done mainly by bile acids.
• Cholic acid and chenodeoxycholic acid are the
primary bile acids formed in the liver from
cholesterol, conjugated with glycine and taurin and
then excreted in bile.
• Most are reabsorbed unchanged in the terminal
ileum back to the liver where they are re-excreted
in bile (enterohepatic circulation).
• Approximately one-quarter of primary bile acids
conjugates
are
deconjugated
by
intestinal
bacteria; but are subsequently reabsorbed and
completely reconjugated in the liver.
• The secondary bile acid deoxycholic acid,
formed by bacterial action on cholic acid in the
gut is also absorbed in the terminal ileum and
conjugated with glycine or taurine in the liver
prior to being excreted in bile.
• Bile acids must be present in the upper small
intestine in high concentrations sufficient to allow
digestion of fat containing meal.
• Fat malabsorbtion results from low intestinal bile
acids and salts.
• Fat-soluble vitamins (A, D, E and K) also are
affected by the presence of bile acids and salts.
• Malabsorption of fat-soluble vitamins, which is
most commonly manifested as vitamin D
deficiency occurs in conditions causing fat
malabsorption.
• Determination of fat absorption:
• Triglyceride (triolein) breath test :
• Following digestion and absorption of an oral dose
of [14C]-triolein (the marker is in the fatty acid
component), part of the fatty acid is metabolized to
14CO
2,
• A high
which is then excreted in expired air.
14CO
2
excretion is associated with normal fat
absorption, whereas
14CO
2
excretion is low in
patients with fat malabsorption.
ILEAL FUNCTION
• Bile acid malabsorption can be detected by the
measurement of the serum 7a-hydroxy-4-cholesten3-one, an intermediate in the bile acid biosynthetic
pathway, which is increased in the presence of
increased bile acid turnover.
• The test is not widely available at present, but it can
replace the expensive 75Se-homotaurocholate
(75Se-HCAT) test in which the percentage retention
of an oral dose of this synthetic gamma-emitting bile
salt is estimated by whole body scanning, 7 days
after its administration.
Carcinoid tumours and the
carcinoid syndrome
• They arise in the gut or in tissues derived from the
embryological foregut (e.g. the bronchus or thyroid).
• Ileum and the ileocaeccal region are the commonest
sites.
• The tumours produce vasoactive amines which,
because of the venous drainage of the tumours, are
usually carried directly to the liver and there
inactivated.
• Symptoms are only likely to occur either when the
tumour has metastasized to the liver, or the tumour
drains into the systemic circulation (e.g. bronchial
adenoma of the carcinoid type).
• Most carcinoid tumours secrete excessive
amount
of
5-hydroxytryptamine
(5-HT;
serotonin), which is metabolized and excreted in
urine as 5-hydroxy indole acetic acid (5-HIAA).
• Atypical carcinoid tumours secrete excessive
amounts of 5-hydroxytryptophan (5-HTP) and
relatively little 5-HT; they may secrete histamine.
• Whereas only about 1% of dietary tryptophan is
normally metabolized to 5-HTP, and 5-HIAA, in
the carcinoid syndrome, as much as 60% of
dietary tryptophan is metabolized along this
hydroxyindole pathway.
• The carcinoid syndrome is usually associated
with tumours of the terminal ileum and extensive
secondary deposits in the liver.
• The main features include flushing attacks,
abdominal colic and diarrhea, and dyspnoea,
sometimes associated with asthmatic attacks.
• Carcinoid tumours can give rise to severe
hypoproteinaemia and edema, even
absence of cardiac complications.
in the
• There may also be signs of niacin deficiency,
due to major diversion of tryptophan metabolism
away from pathway leading to niacin production.
• Some carcinoid tumours produce ACTH or
ACTH like peptides, and may cause Cushing's
syndrome in the absence of the symptoms
commonly
syndrome
associated
with
the
carcinoid
• Biochemical
investigation
of
5-HT
metabolism:
• Measurement of 5-HIAA excretion in a 24 hour
urine sample is the most widely performed
investigation.
• Bananas and tomatoes contain large amounts of
5-HT; they should not be eaten the day before or
during the urine collection.
• Timing of urine collection: if attacks are frequent,
the time of starting the collection is unimportant.
If attacks are less often than daily, the patient
should be instructed to wait and begin the
collection when the next attack occurs.