Gastrointestinal tract disease

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Gastrointestinal tract disease

• Prepared by
• Siti Norhaiza Binti Hadzir

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Scheme demonstrating various stimuli of stomach
and duodenum
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Pathological conditions of GIT

• Ulcers
• Zollinger-Ellison syndrome
• Pernicious anemia
• Malabsorption syndromes
• Diarrhea

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Peptic Ulcer Disease

• Occurring in any part of the gastrointestinal
  tract exposed to the action of acidic gastric
  juice.
• Occur principally in the duodenum (duodenal
  ulcer) and stomach (gastric ulcer).
• Peptic ulcer occur at all ages the most common
  age at onset is 20-40 years.
• Duodenal ulcers are associated with blood group
  O, absence of blood group antigens in saliva
  (non-secretors) and the presence of HLA-B5
  histocompatibility antigen.

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Pathogenesis of Peptic Ulcer

• Hyper-secretion of acid
• - Acid is necessary for peptic ulcers to
  form, and ulcers do not occur in achlorhydric
  states.
• - The cornerstone of treatment of peptic
  ulcer is to decrease secretion of acid histamine
  H2 receptor antagonists and proton pump
  inhibitors are highly effective.
• Decreased Mucosal Resistance to Acid
• - It is believed to be the primary cause of
  most gastric ulcers.
• - Prostaglandin E2 level in gastric juice
  have been shown to be consistently decreased in
  patients with peptic ulcer.

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• Helicobacter pylori Infection
• - In the stomach, the organism grows in the
  surface mucous layer, which may become altered,
  decreasing mucosal resistance.
• - H pylori can cause damage by 1) secreting
  urease, protease and phospholipase, 2) attracting
  neutrophils that release myeloperoxidase and 3)
  promoting thrombotic occlusion of capillaries,
  leading to ischemic damage of the epithelium.

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Diagnosis of peptic ulcer

• Based on morphological grounds (roentgenographic
  photography by the use of x-ray and endoscopic
  examination).
• Serological tests that detect antibodies to H.
  pylori
• Urea breath test- the individual ingests a test
  meal containing carbon-13 or carbon 14 labeled
  urea. Urease releases CO2 and the amount of
  labeled CO2 in breath is directly related to
  urease activity.
• A stool antigen test for detection of H pylori.

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Zollinger-Ellison syndrome

• An extreme form of peptic ulcer disease, caused
  most commonly by a gastrin-secreting tumor of the
  pancreas (gastrinoma) or by antral G-cell
  hyperplasia of the stomach
• The unrelenting gastrin release stimulates
  hypersecretion of HCl by the stomach
• The typical clinical presentation is recurrent
  peptic ulceration often accompanied by diarrhea
  (gastrin inhibits salt and water absorption by
  the intestine)
• The large amount of gastric interferes with fat
  digestion and leads to steatorrhea.

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Gastric analysis

• Measure secretion rate of gastric juice.
• A 1 hour basal specimen is collected (basal acid
  output BAO). Reference value should be
  1-6mEq/hour.
• An acid production stimulant is then injected
  (pentagastrin)
• Four 15 minutes consecutive specimens are
  collected.
• Maximum acid output (MAO) is the sum of all four
  15 min post-stimulation acid collections.
  Reference values for MAO are less than
  40mEq/hour.
• The BAO/MAO should be less than 0.3.

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Diagnosis of Zollinger-Ellison Syndrome

• Typically demonstrate a high basal acid secretion
  with minimal change after stimulation.
• BAO is 15mEq/hour
• BAO.MAO ratio is 0.6 or greater.

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Pernicious anemia (PA)

• PA is a disease that consists of gastric
  achlorhydria, gastric atrophy and failure to
  secrete intrinsic factor.
• Intrinsic factor deficiency prevents absorption
  of Vit B12.
• Vitamin B12 is an essential nutrient that is
  required for normal synthesis of myelin and
  nucleic acids.
• This leads to damage to posterior columns of the
  spinal cord (causing a sensory neuropathy), and
  in many cases, megaloblastic anemia.
• It is caused by autoimmune destruction of gastric
  mucosa (parietal cells) and intrinsic factor
  blocking antibodies.

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Diagnosis of PA

• The Shilling Test of Vit B12 absorption is used
  as the evaluator.
• Patient should fast overnight since food may
  contain vit B12 and also to prevent food
  interference (protein bind to radioactive B12.
• Oral dose of radioactive cobalt-labeled B12.
  Usual dose is 0.5µg. Measures the or orally
  ingested isotope excreted in the urine.
• 2-6 hour later, 1000µg of non-isotopic vitamin
  B12 is given subcutaneously or intramuscularly to
  saturate tissue binding sites to allow a portion
  of any labeled B12 absorbed from the intestine to
  be excreted or flushed out in the urine.
• In PA, there is less than 8 urinary excretion of
  the radioisotope.

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Malabsorption Syndromes

• The syndromes are the result of any interference
  with the process of digestion and absorption of
  food.
• Clinical features- loose stools, containing fat
  that gives a greasy appearance and foul odor to
  the stools (steatorrhea) loss of weight, and
  features secondary to fat soluble vit deficiency
  (bone disease, prolonged clotting times, poor
  night vision, neuropathy).
• Can be divided into 2 true malabsorption,
  maldigestion.
• True malabsorption- GIT is impaired, cannot
  absorb variety of nutrients.
• Maldigestion- digestive process impaired
  (pancreatic insuficiency, inadequate pancreatic
  enzyme activation, excessive acid production,
  inadequate bile acid production or secretion.

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Test of malabsorption

• Since fat absorption is vulnerable to defects in
  either intraluminal digestive enzymes or defects
  at the mucosal absorptive surface, the
  demonstration of steatorrhea by qualitative or
  ultimately quantitative (72 hours) fecal fat
  measurement is the major criterion for
  establishing the presence of fat malabsorption.

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Quantitative Fecal Fat Excretion

• Anything that causes malabsorption will cause
  problems with fat absorption first.
• Sudan staining look for fat globules (neutral
  fat can be seen as bright orange droplets)
• Quantitative Fecal Fat excretion
• Pt placed on 100 gram/day fat diet for 3 total
  days. Normal? excrete 3-5 grams fat/day. gt 15
  grams excretion over the 3 days is () result ? 2
  SD gt normal mean.
• Can easily get false positive/negative Poor food
  intake, constipation, forgot to collect stool.
  Eating nuts that cause fat in stool.

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D-Xylose Absorption-Excretion Test

• Dz that involves epithelium or mucosa itself.
• D-xylose is a water soluble, non-metabolized
  pentose that is absorbed mainly in the duodenum
  and jejunum. No intraluminal handling. No
  pancreatic enzymes needed. Will normally absorb
  across epithelium. Assimilation of this sugar
  does not require the intraluminal pancreatic
  stage of digestion.

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D-Xylose Absorption-Excretion Test
Test procedure

• The standard test dose is 25gm of D-xylose in 250
  ml of water, followed by another 250ml water.
• The pt is fasted overnight, since xylose
  absorption is delayed by food.
• The normal persons peak D-xylose are reached in
  approximately 2 hours and fall to fasting levels
  in approximately 5 hours.
• D-xylose 80-95 is excreted mostly in the urine
  in the first 5 hour and the remainder 24 hour
  later.

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Interpretation

• Normal values for 2 hour blood D-xylose levels
  are more than 25mg/100ml.
• Values less than 20mg/100ml are strongly
  suggestive of malabsorption.
• -Abnormal test Intestinal mucosal disease.
  Also with the small intestinal bacterial
  overgrowth.
• Normal test deficiency of intraluminal
  (pancreatic) digestive enzymes or bile acid
  deficiency

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PABA Test to Evaluate Pancreatic function

• Test is done w/PABA (?-aminobenzoic acid) and an
  attached tripeptide. If have exocrine function
  then will cleave off tripeptide.
• Normal function Ingest PABA-tripeptide ?
  tripeptides cleaved ? liberating PABA which is
  absorbed ? excreted in urine.
• Abnormal no cleavage of tripeptide. Is absorbed,
  but PABA is not excreted in urine.

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Other Tests for Malabsorption

• Pancreatic Function Tests. The secretin test is
  used to measure secretory capacity of the
  exocrine pancreas. After administration of
  secretin, bicarbonate concentration is measured
  in the juice aspirated from the duodenum.
• Measurements of serum iron, calcium, cholesterol,
  folate and vitamin B12 often are used as
  screening tests for malabsorption, but are not
  specific.
• Prothrombin Time. If prolonged, may reflect
  malabsorption or liver disease. These
  possibilities can be distinguished by measuring
  the response to parenterally administered vitamin
  K.
• Serum Carotene. Carotene is a fat-soluble
  substance present in yellow vegetables and
  fruits, eggs, etc. Serum carotene levels tend to
  be depressed in patients with fat malabsorption,
  but can be decreased also if the intake of
  dietary carotene is low.

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Diarrhea

• Excessive production of feces, usually as a
  result of overabundance of water in the stool.
• Severe diarrhea causes sodium and water depletion
  and loss of potassium and bicarbonate.
• There are 2 causes of diarrhea 1) decreased
  absorption of fluid and electrolytes. 2)
  increased secretion of fluid

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Decreased Absorption of Fluid and Electrolytes

• Decreased absorption of fluid and electrolytes in
  intestinal malabsorption.
• Absorption of water in the intestines is
  dependent on adequate absorption of solutes. If
  excessive amounts of solutes are retained in the
  intestinal lumen, water will not be absorbed and
  diarrhea will result (osmotic diarrhea).
• Ingestion of a poorly absorbed substrate The
  offending molecule is usually a carbohydrate or
  divalent ion. Common examples include mannitol or
  sorbitol, epson salt (MgSO4) and some antacids
  (MgOH2).
• Malabsorption lactose intolerance resulting from
  a deficiency in the brush border enzyme lactase.
  Lactose cannot be effectively hydrolyzed into
  glucose and galactose for absorption. The
  osmotically-active lactose is retained in the
  intestinal lumen, where it "holds" water.

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Increased secretion of fluid

• Vibrio cholerae, produces cholera toxin, which
  activates adenylyl cyclase, causing a prolonged
  increase in intracellular concentration of cyclic
  AMP within crypt enterocytes. This change results
  in prolonged opening of the chloride channels
  that are instrumental in secretion of water from
  the crypts, allowing uncontrolled secretion of
  water. Additionally, cholera toxin affects the
  enteric nervous system, resulting in an
  independent stimulus of secretion.
• In addition to bacterial toxins, a large number
  of other agents can induce secretory diarrhea by
  turning on the intestinal secretory machinery,
  including

• some laxatives (foods, compounds, or drugs taken
  to induce bowel movements or to loosen the stool,
  most often taken to treat constipation).
• hormones secreted by certain types of tumors
  (e.g. vasoactive intestinal peptide)
• a broad range of drugs (e.g. some types of
  asthma medications, antidepressants, cardiac
  drugs)
• certain metals, organic toxins, and plant
  products (e.g. arsenic, insecticides, mushroom
  toxins, caffeine)

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Diarrhea Associated with Deranged Motility

• In order for nutrients and water to be
  efficiently absorbed, the intestinal contents
  must be adequately exposed to the mucosal
  epithelium and retained long enough to allow
  absorption.
• Disorders in motility than accelerate transit
  time could decrease absorption, resulting in
  diarrhea

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