Chapter 1. Gastrointes0nal Disorders
Introduc)on
There is an acidic environment in the stomach (pH 2),
protein diges8on starts there thanks to the secre8on of
pepsinogen and pH helps to denature proteins. In the
small intes-ne, there are three different compartments
(duodenum, jejunum, and ileum). In the duodenum,
almost all diges8on occurs thanks to exopancrea8c
secre8on, leads to a neutral pH, thus pepsin is de-
ac8vated; lipase and amylase are also released. In the
ileum, absorp8on occurs, bile salts help in the
emulsifica8on process of the lipids. The large intes-ne is
composed by the colon, ending with the rectum and the
anus. In the colon, fermenta8on occurs, where almost all
the microbiota is.
The mucosa has an increased surface area to help in absorp8on, there are villi to increase this surface.
Transporter enzymes are aIached to the mucosa to help in diges8on, like endopep8dase, lactase… Below
submucosa, there are 2 muscle layers involved in the contrac8ons, in mixing, in breaking down the food in
smaller par8cles… This 8ssue is highly innervated.
Adverse reac)ons to food
Food poisoning
Food poisoning results from contaminants within the food:
- Microorganisms: Campylobacter, Salmonella, Shigella, E. coli, viruses.
- Chemical contaminants from water, agricultural chemicals.
- Toxins produced by Staphylococcus aureus, Bacillus cereus, Clostridium botulinum.
During slaughter process, meat can become contaminant. Contaminants can be present in eggs, poultry meat,
cold meats, rice, unwashed vegetables, spices… Young, sick or elderly people are more vulnerable to them
because the immune system is not at its best. Examples:
- Natural toxins: uncooked red kidney beans.
- Toxins from fungi or moulds: aflatoxins.
- Heavy metals: mercury from industrial pollu8on accumulate in animals and fish.
Food aversion
Psychological reac8ons and beliefs, which may not be reproduced on covert introduc8on of the food. Food
avoidance due to an aversion that occurred in the past. Believes that certain foods cause 8redness, sleep
problems, palpita8ons, bloatedness and flatulence. Double-blind tes8ng fails to find scien8fic evidence. E.g.
gluten, milk, citrus fruits…
Food intolerance
Reproducible, adverse reac8ons to a specific food or a food ingredient that are not psychologically based.
Double-blind tes8ng is successful. First step is elimina8on of certain food.
- Enzyme deficiencies: lactose intolerance.
- Pseudo-allergies: dose dependent reac8on, no immunological reac8on. Colorants, conserva8on
products, sulfites, histamine…
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,Enzyme deficiency: Alactasia
In most people (except most north Europeans), lactase is gradually
lost through adolescence. Lactose is a substrate for bacterial
fermenta8on to lactate + CO2, methane, hydrogen, leading to watery
diarrhea and abdominal pain. In yoghurt and other fermented milk
products, lactose is converted to lac8c acid.
- Lactose tolerance test: an increase in blood glucose aXer
lactose consump8on will be less due to insufficient
diges8on.
- Hydrogen breath test: an increase in H2 in breath due to
fermenta8on in the colon.
Certain popula8ons in Africa, Asia and La8no America are more likely to have a lactase deficiency, linked in the
gene8cs.
Pseudo-allergy
Dose-dependent of a certain molecule:
- 25-50 mg histamine intake causes headache.
- 100-150 mg histamine intake causes flushing.
- >500 mg histamine/kg or L can be poten8ally dangerous.
The amount of histamine increases during ripening of fruit and vegetables, during decay of meat and fish.
Symptoms: nausea, vomi8ng, diarrhea, itching in mouth, ur8caria, hypotension. Histamine can result from
fermenta8on in alcohol.
Food allergy
Reproducible food intolerance, evidence of an abnormal
immunological reac8on to the food and a plausible mechanism
implica8ng immunological processes. Allergens are proteins or
chemicals bound to protein. sIgA normally prevents absorp8on
(sIgA is present in breast milk). IgE against allergens and mast
cells release histamine and prostaglandins. Symptoms: dila8on,
permeability and contrac8on of smooth muscle.
There has been a general increase of allergies over the last 30
years. There are several factors that can affect allergies. Gene8c
predisposi8on, they are more inherited from mother than
father. Low birth weight increases the risk of allergies (poorer
immunocompetence). It is beIer to have only breast-feeding
for 4 months and delay the introduc8on solid food un8l 6
months. Hygiene-theory means that more and more we live in cleaner environments, the less our immune
system is adapted. w-6/w-3 theory, when w-6 is predominant, more pro-inflammatory prostaglandins are
released and since they both share the same enzymes to produce eicosanoids, they compete for them.
Tes9ng
Can be done by history of diet and symptoms taken to iden8fy possible triggers, double-blind foods tes8ng,
skin prick-test or assay of IgE levels (RAST method), intes8nal biopsy or intes8nal permeability measured, if
appropriate.
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,Adverse reac9ons
Cow’s milk allergy
1-3% of new-born babies develop this allergy during their first months, it usually decreases with age. Cross
reac8vity (IgE) with milk from goat and sheep can occur, also from soya drink (cannot be called milk).
Preven8on can be performed by breaseeeding un8l 6 months. Produc8on of IgE and IgG an8bodies against a-
lactalbumine, b-lactoglobuline and caseine.
Wheat’s allergy
It occurs aXer inges8on by reac8on on globulines (gliadine) or aXer inhaling by reac8on against albumines.
Reac8on against a-amylase can also happen since it is added in wheat flour. It decreases with age. Cross
immunity of IgE with IgE of the pollen of grass can occur.
Celiac disease
It is an autoimmune disorder, autoan8bodies are produced. 1% of general popula8on is affected but may be
underdiagnosed. A disorder caused by intolerance to the protein gluten found in wheat, barley and rye,
inducing small intes8nal inflamma8on. Gluten is quite resistant to enzymic degrada8on (less diges8ble) and
enhances immunogenicity.
Gluten induces an innate immune response in gene8cally suscep8ble pa8ents. Gluten causes villous atrophy
of the jejunum, changes in small intes8nal permeability. Decreased amount of epithelial surface is available
for diges8on and absorp8on. Inflammatory cascade pathways are ac8vated resul8ng in chronic inflamma8on.
The crypts are very deep, villi are very short so there is less absorp8ve area.
Damage of the gastrointes8nal mucosa leads to reduced produc8on of diges8ve enzymes. Reduc8on of
mucosal surface area leads to malabsorp8on of macro- and micronutrients, weight loss, gastrointes8nal
symptoms (bloa8ng, abdominal pain, diarrhea, steatorrhea).
Symptoms
In childhood: weight loss, anemia, diarrhea, abdominal pain, steatorrhea, blood loss dehydra8on.
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, Diagnosis
Made by serological markers (IgA an8-endomysial an8bodies, 8ssue transglutaminase IgA, an8-gliadin IgG and
IgA) or by enteric biopsies (grading of villous architectural distor8on, crypt hyperplasia, intraepithelial
lymphocyte density).
Therapy
Based on gluten-free diet. The exclusion of prolamins in wheat (gliadin), barley (hordein), rye (secalin). Also
present in sauces, complex dishes, in toothpaste, mouthwash, medica8on capsules... Diet lower in fiber,
vitamins B (e.g. niacin, thiamine, folate), calcium, iron... and higher in fat and added sugar. Encouraged to eat
fruits, vegetables and gluten-free grains (millet, buckwheat, amaranth).
Nonceliac gluten sensi9vity (wheat sensi9vity)
Pa8ents with nega8ve blood tests and small bowel mucosal biopsies that nega8vely tested for celiac disease.
No allergic reac8on (no IgE), thus no wheat allergy. No diagnos8c tes8ng exists (only excluding the others). It
may overlap with irritable bowel syndrome because symptoms are cramps, diarrhea, cons8pa8on, abdominal
pain. Pa8ents follow a gluten-free diet and symptoms disappear.
Exocrine pancrea)c insufficiency (EPI)
Exocrine func8on (excre8on to diges8ve tract) is performed by duct cells which release NaHCO3- to reach a
neutral pH and by acinar cells which release zymogens (inac8ve ezymes). Endocrine cells are inside Islets of
Langerhans which produce insulin and glucagon, their secre8on goes to blood circula8on. The importance of
neutral enteric pH is to protect the mucosa, enzymes are more ac8ve at this pH, it inac8vates pepsin, increases
faIy acid and bile acid solubility, op8mizes pancrea8c and brush border enzyme func8on and prevents mucosal
damage. Secre8n release from duodenal mucosa to neutralize pH and CCK release to s8mulate the produc8on
of zymogens.
Consequences are chronic dietary fat malabsorp8on and deficiencies of fat-soluble vitamins and essen8al faIy
acids. Affects absorp8on of all macronutrients.
Causes
Can be caused by cys8c fibrosis which is hereditary, impairments of CF transmembrane regulator (CFTR),
func8ons as both a chloride and bicarbonate transporter leading to inspissated secre8ons and an impaired
fluid transport which affects both respiratory and diges8ve system. Due to pancrea88s provoked by
hypertriglyceridemia, hypercalcemia and due to alcohol and tobacco use. Pancrea8c resec8ons can happen
due to tumors, or congenital hyperinsulinism.
Therapy
Management of chronic pancrea88s-related EPI with the use of Pancrea8c Enzyme Replacement Therapy
(PERT), increasing duodenal pH to increase efficacy of PERT and addi8on of bile salts.
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