TOPIC 2 - GASTROINTESTINAL SYSTEM

NGUYEN PHAM TUONG VY - BTBTWE22137

INTRODUCTION

Human digest all food mostly as an extracellular process within the gastrointestinal tract (GIT) otherwise known as the alimentary
canal. The GIT is a hollow continuum of several organs extending from the mouth to the anus (Figure 1). In normal human adults,
the GIT is about 7–8 metres long and consists of upper and lower gastrointestinal tracts. The upper tract consists of the mouth,
pharynx, oesophagus, and stomach. The lower intestinal tract consists of the small and large intestine.

Figure 1 - The gastrointestinal tract showing the major organs involved.

The main functions of the GIT are the ingestion, digestion, and absorption of nutrients, conservation of secretions, and
elimination of unabsorbed waste products. This requires the coordinated function of the GIT and other associated organs.
Digestion involves physical and biochemical processes where food is mixed with a series of secretions containing enzymes at
optimal pH, and moved along the gut in a controlled way to allow maximal absorption of digestion products. In addition to the
organs of the GIT, both the liver and exocrine pancreas produce secretions which are essential for digestion.

Complex unconscious neural and humoral processes are involved in the secretory and motility processes and the controlled
movement of the milieu from one alimentary compartment to the next, with entry to each being controlled by circular sphincter
muscle groups (Table 17.2)
GASTROINTESTINAL TRACT (GIT) DISEASES

The gastrointestinal (GI) tract, despite its seemingly straightforward role in digestion, is vulnerable to a surprisingly wide array of
diseases. Disorders of the GIT can affect the stomach, pancreas, gall bladder, and small and large intestine. Some diseases can
affect more than one area of the GIT. Most of the conditions affecting the small intestine will cause malabsorption (Table 17.4 &
Figure 56.1 ).
Some of typical diseases are demonstrated as the follow:

● Peptic ulcers (mainly gastric or duodenal)

The stomach produces hydrochloric acid which is required for activation of digestive enzymes and kills bacteria. However, acid is
corrosive in action and so the cells lining the stomach (and duodenum) produce mucus which has a protective effect. There is a
balance between the amount of acid produced and the mucus defence barrier. An ulcer develops if this balance is disrupted, for
example by excessive production of hydrochloric acid and pepsin in gastric juice or a reduction in the protective mechanisms of
the mucosa.

Clinical features of peptic ulcers include a chronic upper abdominal pain that is relieved by foods or antacids. About eight out of
ten cases of peptic ulcers are due to a Helicobacter pylori infection. This infection weakens the stomach (or duodenal) lining by
causing inflammation which results in disruption of the mucus layer, allowing the hydrochloric acid and pepsin to cause damage
producing ulceration.

● Gastrinomas

Gastrin is synthesized and released from the G cells in the gastric antrum (distal stomach) and duodenum, and stimulates
secretion of gastric acid from parietal cells in the stomach. Where gastric pH is low, gastrin release is inhibited. Conversely, release
is increased in conditions or therapies resulting in low or negligible gastric acid concentration (hypo- or achlorhydria).

The most frequent reason for measurement of plasma gastrin concentration is in the investigation of gastrinoma (as in the
Zollinger Ellison syndrome). This is a rare disorder characterized by severe, multiple, and recurrent peptic ulcers that arise due to
excessive gastric acid secretion. This can be caused by neoplasia (gastrinoma) arising within the pancreas (most frequent) or
within the duodenum. Chronic overproduction of gastric acid can lead to fat malabsorption and steatorrhoea caused by acid
inhibition of the pancreatic lipase.

● Acute pancreatitis

The main causes of acute pancreatitis are gallstones, other gallbladder (biliary) disease, and alcohol use. Viral infection (mumps,
coxsackie B, mycoplasma), traumatic injury, congenital, pancreatic or common bile duct surgical procedures, certain medications
(for example oestrogens, corticosteroids), or idiopathic are other causes. Acute pancreatitis is initiated by auto-digestion of the
pancreatic tissue by activated pancreatic enzymes and can result in haemorrhage. The patient can often experience severe
abdominal pain.

● Bacterial overgrowth

Bacterial colonization of the small bowel can lead to fat maldigestion and steatorrhoea as a result of bile salt de-conjugation, and
the resultant reduction in micelle formation. The most common causes arise from gut surgery, resulting in anatomical changes
which predispose to bacterial growth.

Other causes of colonization include pathological processes such as jejunal diverticulae (outpouch from the main gut lumen) or
internal fistulae (an abnormal connection or passageway between two epithelium-lined organs or vessels that normally do not
connect). This can occur in Crohn’s disease. Neuropathies (nerve damage) which lead to stasis in the gut such as diabetic
neuropathy and systemic sclerosis also predispose to colonization.

● Diarrhea

Diarrhea is defined as passage of stool weight of >200 g/day. Stool frequency or liquidity are also used to describe diarrhea, but
both can increase without stool mass. Patients may have profuse diarrhea in the absence of nutrient malabsorption or mucosal
disease, for example when a bacterial toxin triggers secretory diarrhea. Many patients with diarrhea have a mixture of
mechanisms contributing to their diarrhea. An osmotic component, inhibition of active transport, motility changes, and secretory
processes may all contribute to a different degree in most forms of diarrhea (Table 17.6)
MONITORING AND EVALUATION OF GIT DISEASES

The major GIT tract diseases investigated using biochemical tests are overall listed in Table 17.3 and Table 56.1.
For more clearly explanation, some types of monitoring diseases must be focus as the follow:

● Peptic ulcers (mainly gastric or duodenal)

There are currently three types of Helicobacter pylori tests

- Urea breath test - This test has the advantage in that it can be used both to establish the presence of Helicobacter pylori
where suspected and also monitor eradication of the infection.
- Serological Helicobacter pylori IgG antibody - can be used to establish infection, but cannot be used to monitor
treatment because of residual antibody present after treatment.
- Faecal Helicobacter pylori antigen - a direct measurement of Helicobacter pylori and improved assays have now been
described where predictive values are equivalent to that of the urea breath test.

The metabolism of urea to ammonia and carbon dioxide by microbial urease, protects these mucosal bacteria from gastric acidity.
This reaction forms the basis of the urea breath test (UBT) which detects gastric Helicobacter pylori. Where ulceration has been
shown not to be associated with Helicobacter pylori infection, plasma gastrin concentrations may assist in diagnosis.

In the UBT, patients are given C13 labelled urea with a fruit drink and a breath sample is taken after 30 minutes. This is assayed by
mass spectroscopy for C13 labelled carbon dioxide which diffuses across the gastric mucosa and is transported to and released
from the lungs. High concentrations of labelled breath 13CO2 indicate the presence of Helicobacter pylori in gastric mucosa.

● Gastrinomas
The diagnosis of gastrinoma is based on the detection of a high plasma gastrin concentration in the presence of symptoms of acid
hyper-secretion. Patients should not be receiving acid inhibiting drugs at the time of testing. The basal plasma gastrin
concentration may be normal or only slightly increased in some patients with gastrinoma.

● Acute pancreatitis

Confirmation of the clinical diagnosis usually depends on the plasma amylase activity. In severe cases, plasma calcium
concentration may fall following the formation of insoluble calcium salts of fatty acids in areas of fat necrosis. Increased amylase
concentration in the plasma normally arises from the pancreas (P-isoamylase) and the salivary glands (S-isoamylase).

In the rare condition of macroamylasemia, part of the plasma amylase exists as a high molecular weight form which cannot be
cleared by the kidneys. This can be demonstrated by a persistently high amylase concentration in the plasma in the presence of a
normal amylase concentration in the urine. Serum lipase is a more specific measure of acute pancreatitis than total amylase and
has a diagnostic power similar to p-isoamylase, but is seldom performed.

● Bacterial overgrowth

The most commonly used tests for bacterial overgrowth now are breath tests of which three have been described:

- C14 glycocholate breath test - isotopically labelled glycocholate is given orally. Bacterial metabolism of glycocholate
leads to release of glycine and further metabolism to C14O2 in the liver. This is then measured in expired air between two
and six hours following intake. This test is sensitive but is also positive in patients with ileal disease.
- C14 xylose breath test - this results in small bowel bacterial metabolism of xylose and release of C14 O2 in breath.
- Glucose breath hydrogen test - is the most frequently used test. Patients should be on a low fibre diet for two days prior
to the test to reduce baseline values of hydrogen production from colonic bacteria. They are then given 50 g glucose
solution and breath samples (end alveolar air) measured at 15-minute intervals for two hours. An increase above baseline
of >20 parts per million within the first hour indicates bacterial colonization. Later rises should be interpreted with
caution as these may indicate malabsorption. This can be done as a point of care test.
● Diarrhea - A systematic approach to investigation of chronic diarrhoea is outlined in the Method box below.
REFERENCES

1. Allan Gaw, Michael J Murphy, Rajeev Srivastava, Robert A Cowan, Denis St J O’Reilly. Clinical Biochemistry - An Illustrated
Colour Text.
2. Dr Nessar Ahmed. Clinical Biochemistry. School of Healthcare Science. Manchester Metropolitan University.