Gastrointestinal Physiology

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Gastrointestinal Physiology

• Xia Qiang, MD PhD
• Department of Physiology
• Zhejiang University School of Medicine
• Email xiaqiang_at_zju.edu.cn

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Introduction

• Basic processes of digestion and absorption
• Propulsion and mixing of food in the alimentary
  tract
• Secretory functions of the alimentary tract
• Digestion and absorption in the gastrointestinal
  tract

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The four processes carried out by the GI tract
digestion, secretion, absorption, and motility.
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Many functions in the gut are found in specific
locations along its length. Most of the
absorption of nutrients occurs in the small
intestine, so most of digestion is accomplished
there or upstream.
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• Functions of the digestive system
• Movement propels food through the digestive
  system
• Secretion release of digestive juices in
  response to a specific stimulus
• Digestion breakdown of food into molecular
  components small enough to cross the plasma
  membrane
• Absorption passage of the molecules into the
  body's interior and their passage throughout the
  body
• Elimination removal of undigested food and
  wastes

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• Anatomy
• Components of the digestive system

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Structure of the alimentary canal
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General properties of gastrointestinal smooth
muscle

• Low excitability
• High distensibility
• Tonic contraction
• Autorhythmicity
• High sensitivity to temperature, stretch and
  chemical stimulation

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Electrophysiological properties of
gastrointestinal smooth muscle

• Resting membrane potential
• -40-80 mV
• Ionic basis
• Em (selective membrane permeability to K, Na,
  Cl- and Ca2)
• Electrogenic Na-K pump

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• Slow wave (basic electrical rhythm)
• The spontaneous rhythmic, subthreshold
  depolarizations of the cell membrane (slow wave)
  of the gastrointestinal tract that characterizes
  the underlying electrical activity of the bowel
• Initiated in the interstitial cells of Cajal
  (ICC) (pacemaker cell)

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Santiago Ramon Y Cajal

• He and Camillo Golgi received the Nobel Prize in
  1906 for introduction of the silver-chromate stain

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Calcium imaging in ICC-MY from the guinea-pig
antrum. A colocalization procedure was used to
identify the Rhod-2 signal from ACK2-Alexa 488
labelled ICC-MY. Panel A shows a stack of 30
sequential optical sections made in the Z optical
axis of the ACK2-Alexa 488 signal and the Rhod-2
signal panels B and C show each signal
independently. Panel D shows the stack after the
colocalization algorithm was used on each
confocal slice, showing that most ICC-MY were
well labelled with Rhod-2. It was evident from
this experiment that some, but not all, ICC-MY
were well-labelled with Rhod-2 (see text for more
details). The scale bar in panel D is 40 um and
it applies to all images
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Intracellularly recorded electrical activity from
a guinea-pig antral ICC-MY identified with
ACK2-Alexa 488. Panel A shows a network of ICC-MY
labelled with ACK2-Alexa 488 visualized using
fluorescence microscopy, and a single ICC-MY
impaled with a LY-filled microelectrode. Panel B
shows changes in membrane potential recorded
intracellularly from an ICC-MY. One slow wave,
marked with the horizontal line in Panel B, is
shown in Panel C at an expanded time scale. The
scale bar is 15 um.
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Cyclic changes in intracellular calcium in ICC-MY
in the murine jejunum. Panel A shows a single
confocal image with ACK2-Alexa 488
immunore-activity (green) and Rhod-2 labelling
(red) taken from a time series. ICC-MY were
distinctly labelled with Rhod-2 as shown in panel
B. The average fluorescence intensity delineated
by the white circled region was measured from
images recorded every second, shown in panel C
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• Slow wave (basic electrical rhythm)
• Intensity 1015 mV
• Frequency 312 cpm
• Ionic mechanism
• spontaneous rhythmic changes in Na-K pump
  activity

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• Normal BER frequencies in the gastrointestinal
  system

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• Spike potential (Action potential)
• Duration 1020 ms
• Ionic mechanism
• Depolarization Ca2 influx
• Repolarization K efflux

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Neural control of gastrointestinal function

• Enteric nervous system (intrinsic)
• Autonomic nervous system (extrinsic)

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• Enteric (Intrinsic) nervous system
• Myenteric plexus (Auerbachs plexus)
• Submucosal plexus (Meissners plexus)
• Neurotransmitters secreted by enteric neurons
• Ach, NE, ATP, serotonin, dopamine,
  cholecystokinin, substance P, vasoactive
  intestinal polypeptide, somatostatin,
  leu-enkephalin, met-enkephalin, bombesin, etc.

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• Autonomic nervous system

• Parasympathetic nerve
• Mainly ACh
• Stimulatory ()

• Sympathetic nerve
• NE
• Inhibitory (-)

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• Afferent sensory nerve fiber from the gut
• Sensory fibers with their cell bodies in the ENS
  terminate in the ENS
• Sensory fibers with their cell bodies in the ENS
  send axons upward through the ANS to terminate in
  the prevertebral sympathetic ganglia
• Sensory fibers with their cell bodies in the
  dorsal root ganglia or in the cranial nerve
  ganglia send axons to multiple area of the spinal
  cord or brain stem

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• Gastrointestinal reflexes
• Three types
• Reflexes that are integrated entirely within the
  enteric nervous system
• Reflexes from the gut to the prevertebral
  sympathetic ganglia and then back to the
  gastrointestinal tract
• Reflexes from the gut to the spinal cord or brain
  stem and then back to the gastrointestinal tract

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Gastrointestinal hormones

• The hormones synthesized by a large number of
  endocrine cells within the gastrointestinal tract
• Physiological functions
• Control of the digestive function
• Control of the release of other hormones
• Trophic action

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Gastrointestinal hormones

• Four main types
• Gastrin
• Secretin
• Cholecystokinin (CCK)
• Gastric inhibitory peptide (GIP)

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Splanchnic circulation
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Microvasculature of the intestinal villus
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Digestion in the stomach
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The swallowing reflex is coordinated by the
medulla oblongata, which stimulates the
appropriate sequence of contraction and
relaxation in the participating skeletal muscle,
sphincters, and smooth muscle groups.
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The coordinated sequence of contraction and
relaxation in the upper esophageal sphincter, the
esophagus, and the lower esophageal sphincter is
necessary to deliver swallowed food to the
stomach.
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Specialized cells in the stomach synthesize
and secrete mucous fluid, enzyme
precursors, hydrochloric acid, and hormones.
The abundant smooth muscle in the stomach is
responsible for gastric motility.
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Gastric juice

• Properties
• pH 0.91.5
• 1.52.5 L/day
• Major components
• Hydrochloric acid
• Pepsinogen
• Mucus
• Intrinsic factor

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Hydrochloric acid

• Secreted by the parietal cells
• Output
• Basal 05 mmol/h
• Maximal 2025 mmol/h

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• Mechanism of HCl secretion
• Active transport
• Huge H gradient (3 million)

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Acid production by the parietal cells in the
stomach depends on the generation of carbonic
acid subsequent movement of hydrogen ions into
the gastric lumen results from primary active
transport.
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One inhibitory and three stimulatory signals
that alter acid secretion by parietal cells in
the stomach.
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• Role of HCl
• Acid sterilization
• Activation of pepsinogen
• Promotion of secretin secretion
• Assisted effect of iron and calcium absorption

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Pepsinogen

• MW 42,500
• Secreted by the chief cells as an inactive
  precursor of pepsin
• Activated in the stomach, initially by H ions
  and then by active pepsin, autocatalytic
  activation
• Active pepsin (MW 35,000)

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The acidity in the gastric lumen converts the
protease precursor pepsinogen to pepsin
subsequent conversions occur quickly as a result
of pepsins protease activity.
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• Effect of pepsin
• Pepsin is an endopeptidase, which attacks peptide
  bonds in the interior of large protein molecules

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Mucus

• Secreted by the epithelial cells all over the
  mucosa and by the neck mucus cells in the upper
  portion of the gastric glands and pyloric glands
• Role
• Lubrication of the mucosal surface
• Protection of the tissue from mechanical damage
  by food particles

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• Mucus-HCO3- barrier

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Intrinsic factor

• A high molecular weight glycoprotein, synthesized
  and secreted by the parietal cells
• The intrinsic factor binds to Vit B12 and
  facilitates its absorption

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Secretion of other enzymes

• Gastric lipase
• Gastric amylase
• Gelatinase

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Regulation of gastric secretion

• Basic factors that stimulate gastric secretion
• Acetylcholine ( all secretory cells)
• Gastrin ( parietal cells)
• Histamine ( parietal cells)

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Regulation of gastric secretion

• Nervous regulation
• Short reflex pathways
• Short excitatory reflexes mediated by
  cholinergic neurons in the plexuses
• Short inhibitory reflexes mediated by
  non-adrenergic non-cholinergic (NANC) neurons

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Regulation of gastric secretion

• Nervous regulation
• Long autonomic pathways
• Long excitatory reflexes parasympathetic
• Long inhibitory pathways sympathetic

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Regulation of gastric secretion

• Humoral regulation

Excitatory ACh Histamine Gastrin
Inhibitory Somatostatin Secretin 5-hydroxytryp
tamine (5-HT) Prostaglandin
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Phases of gastric secretion

• Cephalic phase
• Gastric phase
• Intestinal phase

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Inhibition of gastric secretion

• The functional purpose of the inhibition of
  gastric secretion by intestinal factors is
  presumably to slow the release of chyme from the
  stomach when the small intestine is already
  filled or overactive

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Inhibition of gastric secretion

• Reverse enterogastric reflex initiated by the
  presence of food in the small intestine
• Secretin secretion stimulated by the presence of
  acid, fat, protein breakdown products,
  hyperosmotic or hypo-osmotic fluids, or any
  irritating factors in the upper small intestine

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Delivery of acid and nutrients into the small
intestine initiates signaling that slows gastric
motility and secretion which allows adequate time
for digestion and absorption in the duodenum.
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Motor function of the stomach
Proximal stomach cardia fundus corpus
(body) Distal stomach antrum pylorus pyloric
sphincter
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Waves of smooth muscle contraction mix and propel
the ingested contents of the gastric lumen, but
only a small amount of the material enters the
small intestine (duodenum) as a result of each
wave cycle.
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Motor function of the stomach

• Receptive relaxation
• Storage function (1.01.5 L)
• Vago-vagal reflex
• Peristalsis
• BER in the stomach

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Contractions in the empty stomach

• Migrating Motor Complex (MMC)
• Periodic waves of contraction, which move along
  the gastrointestinal tract from stomach to colon
• Purpose of this activity to sweep debris out
  of the digestive tract during the interdigestive
  period
• MMCs can lead to hunger contractions, which are
  associated with discomfort, referred to as
  hunger pains

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Emptying of the stomach

• Emptying rate
• Fluid gt viscous
• Small particle gt large particle
• Isosmotic gt hyper- hypo-osmotic
• Carbohydrates gt Protein gt Fat
• Regular meal 46 hrs

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• Regulation of stomach emptying
• Gastric factors that promote emptying
• Gastric food volume
• Gastrin
• Duodenal factors that inhibit stomach emptying
• Enterogastric nervous reflexes
• Fat
• Cholecystokinin

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• Vomiting

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End.