GASTROINTESTINAL FUNCTION

1
GASTROINTESTINAL FUNCTION
2
THE STOMACH
3

• 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.

4

• 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
  14C-labeIled 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.

5

• 2- Serological tests Patients infected with H.
  pylori develop antibodies to the organism that
  can be detected in the laboratory using
  enzyme-linked 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.

6

• 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.

7

• 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).

8

• 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.

9

• 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.

10

• 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

11
THE PANCREAS
12

• 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.

13

• 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.

14

• 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.

15
THE SMALL INTESTINE
16

• 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)

17

• 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.

18

• 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 small intestinal disaccharidase
  deficiency.

19

• 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.

20

• 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).

21

• 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.

22

• 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.

23

• 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 14CO2, which is then excreted in
  expired air.
• A high 14CO2 excretion is associated with normal
  fat absorption, whereas 14CO2 excretion is low in
  patients with fat malabsorption.

24
ILEAL FUNCTION
25

• Bile acid malabsorption can be detected by the
  measurement of the serum 7a-hydroxy-4-cholesten-3-
  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-homotaurocholat
  e (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.

26
Carcinoid tumours and the carcinoid syndrome
27

• 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).

28

• 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.

29

• 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 in the absence
  of cardiac complications.

30

• 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 associated with
  the carcinoid syndrome

31

• 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.