Control of acid secretion
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•Gastrin released from antral G cells in
response to food (protein) binds to
cholecystokinin receptors (CCK-2R) on
the surface of enterochromafin-like (ECL)
cells, which in turn release histamine.
•The histamine binds to H2 receptors on
parietal cells and this leads to secretion
of hydrogen ions in exchange for
potassium ions at the apical membrane.
•Parietal cells also express CCK-2R and it is
thought that activation of these
receptors by gastrin is involved in
regulatory proliferation of parietal cells.
•Cholinergic (vagal) activity and gastric
distension also stimulate acid secretion;
somatostatin, vasoactive intestinal
polypeptide (VIP) and gastric inhibitory
polypeptide (GIP) may inhibit it.
•(ACh-R = acetylcholine receptor; ATPase
= adenosine triphosphatase)
•Gastrin, somatostatin and ghrelin:
•The hormone gastrin is produced by G cells mainly in the
gastric antrum, with somatostatin being secreted from D
cells throughout the gastrointestinal tract.
•Gastrin stimulates acid secretion and mucosal growth while
somatostatin suppresses it.
•Ghrelin, secreted from oxyntic glands, stimulate acid
secretion, as well as appetite and gastric emptying.
•Protective factors:
•Bicarbonate ions, stimulated by prostaglandins, mucins and
trefoil factor family (TFF) peptides, together protect the
gastroduodenal mucosa from the ulcerative properties of
acid and pepsin.
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Small intestine
•During fasting, a wave of peristaltic activity passes
down the small bowel every 1–2 hours.
•Entry of food into the gastrointestinal tract
stimulates small bowel peristaltic activity.
•Functions of the small intestine are:
1.digestion (mechanical, enzymatic and peristaltic)
2.absorption –the products of digestion, water,
electrolytes and vitamins
3.protection against ingested toxins
4.immune regulation.
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Digestion and absorption
•Fat:
•Dietary lipids comprise long-chain triglycerides,
cholesterol esters and lecithin.
•Lipids are insoluble in water and undergo lipolysis
and incorporation into mixed micelles before they
can be absorbed into enterocytesalongwith the
fat-soluble vitamins A, D, E and K.
•The lipids are processed within enterocytes and
pass via lymphatics into the systemic circulation.
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Digestion and absorption
•Carbohydrates:
•Starch is hydrolysedby salivary and pancreatic
amylases to:
•α-limitdextrinscontaining4–8 glucose molecules
•the disaccharide maltose
•the trisaccharidemaltotriose.
•Disaccharides are digested by enzymes Fixed to the
microvillousmembrane to form the monosaccharides
glucose, galactose and fructose.
•Glucose and galactose enter the cell by an energy-
requiring process involving a carrier protein, and
fructose enters by simple diffusion.
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Protective function of the small intestine
1.Physical defencemechanisms:
•There are several levels of defencein the small bowel.
•Firstly, the gut lumen contains host bacteria, mucins and secreted
antibacterial products, including defensinsand immunoglobulins that help
combat pathogenic infections.
•Secondly, epithelial cells have relatively impermeable brush border
membranes and passage between cells is prevented by tight and adherens
junctions.
•These cells can react to foreign peptides (‘innate immunity’) using pattern
recognition receptors found on cell surfaces (Toll receptors) or
intracellularly.
•Lastly, in the subepitheliallayer, immune responses occur under control of
the adaptive immune system in response to pathogenic compounds.
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2.Immunological defencemechanisms:
•Gastrointestinal mucosa-associated lymphoid tissue (MALT) constitutes
25% of the total lymphatic tissue of the body and is at the heart of
adaptive immunity.
•Within Peyer’s patches, B lymphocytes differentiate to plasma cells
following exposure to antigens and these migrate to mesenteric lymph
nodes to enter the blood stream via the thoracic duct.
•The plasma cells return to the lamina propriaof the gut through the
circulation and release immunoglobulin A (IgA), which is transported into
the lumen of the intestine.
•Intestinal T lymphocytes help localiseplasma cells to the site of antigen
exposure, as well as producing inflammatory mediators.
•Macrophages in the gut phagocytose foreign materials and secrete a range
of cytokines, which mediate inflammation.
•Similarly, activation of mast-cell surface IgEreceptors leads to
degranulation and release of other molecules involved in inflammation
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Pancreas
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Colon
•The colon absorbs water and electrolytes.
•It also acts as a storage organ and has contractile activity.
•Two types of contraction occur:
•The First of these is segmentation (ring contraction), which leads
to mixing but not propulsion; this promotes absorption of water and
electrolytes.
•Propulsive (peristaltic contraction) waves occur several times a day and
propel faecesto the rectum.
•All activity is stimulated after meals through the gastrocolicreflex in
response to release of hormones such as 5-hydroxytryptamine (5-HT,
serotonin), motilin and CCK.
•Faecalcontinence depends on maintenance of the anorectal angle and
tonic contraction of the external anal sphincters.
•On defecation, there is relaxation of the anorectal muscles, increased
intra-abdominal pressure from the Valsalva manoeuvreand contraction of
abdominal muscles, and relaxation of the anal sphincters.
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Intestinal microbiota
•The human microbiota comprises 1014 microbial residents in the human
body, vastly outnumbering host cells.
•Indeed, the number of bacterial genes in the microbiota genome exceeds
that of the host by 100-fold or more.
•There is a degree of heritability of this microbiota, but it is clear that there
are many environmental factors that can affect it, including diet, drugs,
physical activity, smoking, stress and natural ageing.
•Generally, the adult intestinal microbiota is acquired by the age of 2 years.
•A dysbiosisor imbalance between the different components of the
intestinal microbiota has been associated with diseases of the
gastrointestinal tract, such as inflammatory bowel disease and colorectal
cancer; liver disease, including hepatocellular carcinoma; and
pathologies outside the gastrointestinal tract, such as diabetes, obesity,
cardiovascular disorders, cerebrovascular disorders, asthma and
psychiatric disorders, such as depression.
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Control of gastrointestinal function
•The nervous system and gastrointestinal function:
The central nervous system (CNS), the autonomic
system (ANS) and the enteric nervous system (ENS)
interact to regulate gut function.
•parasympathetic pathways (vagal and sacral efferent),
which are cholinergic, and increase smooth muscle
tone and promote sphincter relaxation
•sympathetic pathways, which release noradrenaline
(norepinephrine), reduce smooth muscle tone and
stimulate sphincter contraction.
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The enteric nervous system
•It comprises two major networks intrinsic to the gut wall:
•The myenteric (Auerbach’s) plexus in the smooth muscle
layer regulates motor control
•the submucosal (Meissner’s) plexus exerts secretory control over the
epithelium, entero-endocrine cells and submucosal vessels.
•Together, these plexuses form a two-layered neuronal mesh along the
length of the gut.
•Although connected centrally via the ANS, the ENS can function
autonomously using a variety of transmitters, including acetylcholine,
noradrenaline (norepinephrine), 5-HT, nitric oxide, substance P and
calcitonin gene-related peptide (CGRP).
•There are local reflex loops within the ENS but also loops involving the
coeliac and mesenteric ganglia and the paravertebral ganglia.
•The parasympathetic system generally stimulates motility and secretion,
while the sympathetic system generally acts in an inhibitory manner.
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Peristalsis
•Peristalsis is a reflex triggered by gut wall distension, which
consists of a wave of circular muscle contraction to propel
contents from the oesophagusto the rectum.
•It can be influenced by innervation but functions
independently.
•It results from a basic electrical rhythm originating from the
interstitial cells of Cajalin the circular layer of intestinal
smooth muscle.
•These are stellate cells of mesenchymal origin with smooth
muscle features, which act as the ‘pacemaker’ of the gut.
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Migrating motor complexes (MMCs)
•are waves of contraction spreading from the
stomach to the ileum, occurring at a frequency of
about 5 per minute every 90minutes or so,
between meals and during fasting.
•They may serve to sweep intestinal contents
distally in preparation for the next meal and are
inhibited by eating.
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PART 2
INVESTIGATION OF GASTROINTESTINAL DISEASE
Plain X-rays
•Plain X-rays of the abdomen are useful in:
1.Diagnosis of intestinal obstruction or paralytic ileus,
where dilated loops of bowel and (in the erect
position) Fluid levels may be seen.
2.Calcified lymph nodes,
3.Gallstones
4.Renal stones can also be detected.
•Chest X-ray(performed with the patient in erect
position) is useful in the diagnosis of suspected
perforation, as it shows subdiaphragmaticfree air.
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Plain X-rays
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Contrast studies
•X-rays with contrast medium are usually
performed to assess not only anatomical
abnormalities but also motility.
•Barium sulphate
•Water-soluble contrast
•The double contrast technique
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Ultrasound, computed tomography (CT) and
magnetic resonance imaging (MRI)
•Are key tests in the evaluation of intra-abdominal
disease.
•They are non-invasive and offer detailed images of
the abdominal contents
•Fluorodeoxyglucose-positron emission tomography
(FDG-PET) is used in the staging of malignancies
and images may be fused with CT to enhance
localisation.
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Endoscopy
•Videoendoscopesprovide high-definition imaging
and accessories can be passed down the
endoscope to allow both diagnostic and
therapeutic procedures
•Endoscopes with magnifying lenses allow almost
microscopic detail to be observed, and imaging
modalities, such as confocal endomicroscopy,
autofluorescenceand ‘narrow-band imaging’, are
increasingly used to detect subtle abnormalities
not visible by standard ‘white light’ endoscopy.
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Endoscopic ultrasound
•Endoscopic ultrasound (EUS) combines endoscopy with intraluminal ultrasonography using
a high-frequency transducer to produce high-resolution ultrasound images.
•This allows visualisationthrough the wall of the gastrointestinal tract and into surrounding
tissues, e.g. the pancreas or lymph nodes. With Perform fine needle aspiration or biopsy of
mass lesions.
•It can therefore be used to:
1.The diagnosis of pancreatic tumours,
2.Chronic pancreatitis
3.Pancreatic cysts
4.Cholangiocarcinoma
5.Common bile duct stones, ampullarylesions and submucosal tumours.
6.It also plays an important role in the staging of certain cancers, e.g. those of oesophagus
and pancreas.
7.Can be used in the drainage of pancreatic fluid collections
8.Coeliac plexus block for pain management.
•Possible complications of EUS include bleeding, infection, cardiopulmonary events and
perforation.
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Sigmoidoscopy and colonoscopy
•Sigmoidoscopy can be carried
out either in the outpatient
clinic using a rigid plastic
sigmoidoscopeor in the
endoscopy suite using a
colonoscopefollowing bowel
preparation.
•When sigmoidoscopy is
combined with proctoscopy,
accurate detection of
haemorrhoids, ulcerative colitis
and distal colorectal neoplasia is
possible.
•After full bowel cleansing, it is
possible to examine the entire
colon and the terminal ileum
using a colonoscope.
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Histology
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Tests of infection
1.Bacterial cultures Stool cultures are essential in the
investigation of diarrhoea, especially when it is acute
or bloody, in order to identify pathogenic organisms.
2.SerologyDetection of antibodies plays a limited role
in the diagnosis of gastrointestinal infection caused
by organisms such as Helicobacter pylori, Salmonella
species and Entamoeba histolytica.
3.Breath tests Non-invasive breath tests for H. pylori
infection and breath tests for suspected small
intestinal bacterial overgrowth.
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