Gastrointestinal Physiology

Chelsea Dawn Unruh

The Basics

Functions of the GI System

Ingestion, digestion, absorption, &
defecation
Principle Processes
Motility, secretion, & membrane transport

Stages of Digestion
Mechanical & Chemical
Mechanical: Increasing surface area
Chemical reaction of digestion: hydrolysis
Anatomical Tube
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The Basics

The gastrointestinal tract is

A tube that propels a substance from one end
to the other while attempting to it break
down with various digestive juices, absorb as
much of its digestive products as possible, &
excret what is left

Associated with accessory glands that
produce the majority of digestive juices

Controlled by both nervous and hormonal
systems

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 Anatomy of GI System

The Gut Tube
Accessory Glands

Oral cavity
Salivary glands

Esophagus
Pancreas

Stomach
Liver

Duodenum

Small Intestine

Large Intestine

Rectum

Anus
Which structures of the GI system are retroperitoneal?
• Most of the pancreas (except tail)
• Most of the duodenum (except first segment)
• Ascending & Descending Colon

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GI Bloodflow

Supply

Celiac a.

Superior Mesenteric a.

Inferior Mesenteric a.

Drainage

Portal Vein

Portal vein carries

absorbed substances to
liver

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General GI Wall Structure

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Nervous System of the GI Tract

Enteric Nervous System (ENS)

Consists of about 10−100 million nerve cells located
in the ganglia of the intestinal wall.

Consists of sensory neurons, interneurons, and
motor neurons

Some sensory signals are transmitted to the CNS

ENS is modulated by the ANS

Two internal nerve plexuses

Auerbach’s & Meissner’s

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Nervous System of the GI Tract

Myenteric or Auerbach’s plexus

Between the longitudinal and circular smooth muscle
layers

Coordinates the movements of muscularis externa

Peristalsis, Segmentation, Propulsion, Grinding, etc.

Excitatory motoneurons contract muscle by ACh to
muscarinic receptors;

Inhibitory use VIP and NO

Sensory neurons respond to chemical or mechanical stimuli
– receptors in all layers of GI tract

Interneurons are involved in the many reflex arcs through GI

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Motility

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Nervous System of the GI Tract

Submucosal or Meissner’s plexus

Located in the submucosa, between the muscularis mucosae
and the circular layer of muscularis externa

involved in internal processing – modulates secretion and
blood flow

stimulatory secretomotoneurons stimulate glands and
epithelium (via Ach, et al.)

sensory neurons respond to chemical or mechanical stimuli
to produce secretomotor reflexes

submucosal vasodilator neurons dilate blood vessels in the
submucosa

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Nervous System of the GI Tract

Autonomic Control of GI

Both ANS systems modulate the ENS

Parasympathetic:

Vagus nerve stimulates secretions and motility through distal colon

Pelvic splanchnic nerves innervate distal colon & rectum

Sympathetic:

Innervation through splanchnic & prevertebral ganglia

Reduces motility, increases sphincter tone

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Nervous System of the GI Tract

Neurotransmitters

Norepinephrine – adrenergic post-gang neurons

Ach – pre- and postgang enteric fibers & post gang parasymp

VIP – mediates relaxation of circular & vascular muscles

Enkaphalin – intensifies contraction of sphincters

GRP – mediates release of gastrin

CGRP (calcitonin gene-related peptide) – stimulates release of
somatostatin

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Nervous System & GI Wall

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 Segments

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Segments & Structure

Mouth

Pharynx

Esophagus

Stomach

Small Intestine

Large Intestine

Rectum

Anus

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Mouth

Ingestion & Digestion

Mechanical

Mastication (chewing, cutting &
grinding with teeth), mixing with
tongue

Chemical

Salivary glands: Parotid,
Sublingual, Submandibular

Secretions (1.5L/day)

Mostly salt & water but also
includes amylase, lingual lipase,
lysozyme, peroxidase, R-binder
(important protein for Vit B12
metabolism), IgA, glycoproteins

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Functions of Saliva

Moistens, cleans, & protects enamel

Lubricant aiding in speech, chewing, & swallowing (mucins)

Dissolves food – allows for taste

Acts as a bonding agent to form bolus

Alkaline secretions neutralize regurgitated gastric acid

Enzymes (amylase & lipase) begin digestion

Immunological: Lysozyme, IgA, & lactoferrin

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Salivary secretion

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Salivary Reflexes

Conditioned

Unconditioned

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Pharynx

Circular muscles

Superior, middle ,and inferior
pharyngeal constrictors force
food down esophagus while
swallowing

Other muscles

Close off oral cavity,
nasopharynx, and trachea
during swallowing

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 Esophagus

Straight muscular tube

Propels food bolus
from pharynx to
stomach

1/3 composed of
striated muscle, 2/3
smooth muscle

LES – physiological
sphincter at cardiac
orifice

Clinical: Correlation
Achalasia – inability of the LES to relax
causing dysphagia, regurgitation, and chest
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pain. Causes: cancer, Chagas disease
Deglutition

Coordinated by swallowing center in medulla oblongata &
pons

≥ 22 muscles involved

2 stages

Buccal - voluntary

Pharyngeal/esophageal - involuntary

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Deglutition

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Stomach

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Stomach

J-shaped muscular sack for food storage & digestion
located in upper abdomen, directly below diaphragm

Empty volume 50 mL, may hold up to 4 L

Structures

4 regions: Cardia, fundus, body, and pylorus/antrum

2 sphincters: Lower esophageal/cardiac, pyloric

Rugae

Innervation

ENS, PNS (vagal), SNS

Circulation

Supplied by celiac artery

Drains to hepatic portal circulation

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Stomach Wall

Mucus Only

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Stomach

Secretory Cells
Secretory Products

Surface mucous & mucous
Mucus, HCO3-
neck cells

Oxyntic (Parietal) cells
HCl, intrinsic factor

Chief (Peptic) cells
Pepsinogen, gastric lipase,

rennin/chymosin (infancy?)

Neurendocrine cells
Peptide Hormones

G cells
Gastrin

D cells
Somatostatin

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 Gastric Protection

H. pylori
• Gram negative microaerophilic rod
• Flagella to bury itself in the protective mucus NSAIDs
• Urease breaks down urea toCO2 and ammonia • COX inhibitors
(neutralizes) •↓ PGs  ↑ acid

•Treatment: Triple Therapy

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Regulation of Gastric Function

Cephalic Phase

Stimulated by sight, smell, or thought of food (1/3 of secretion)

Medicated by vagus nerve, secretions begin before food arrives

Gastric Phase

Stimulated by food in the stomach (2/3 of gastric secretion)

Ingested food stretches and raises the pH activating mechanical
and chemical receptors

Gastric secretion stimulated by ACh, histamine, and gastrin

Intestinal Phase

Stimulated by chyme entering the duodenum

Enterogastric reflexes reduce gastric motility and secretions

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Gastric Acid

Basal Acid Output: <10 mmol/hr

Maximum Acid Output: <50 mmol/hr

↑ w/ pepc ulcer, duodenal ulcer, Zollinger-Ellison Syn.

↓ w/ vagotomy, pernicious anemia

Gastric HCl has pH ~1.0,

Activates pepsin, dissolves food, disinfects, & stimulates
duodenum to secrete secretin

Gastric Enzymes

Pepsin – cleaves protein into smaller peptides

Lipase – digests fats, of little importance except with pancreatic
insufficiency
Gastric juices (pH 1.5−2, about 2−3 liters/day)
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Mechanism of HCl secretion by gastric parietal cells.

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 Agents that stimulate and inhibit H+ secretion by
gastric parietal cells.

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Gastric Motility

Migrating Motor Complexes (MMC) – 90 min cycle

Pacemaker cells (Interstitial cells of Cajal) create 3 phases

Phase I – no contractions

Phase II – 6 min, irregular contractions

Phase III – 3 min, regular contractions (gastric 3 per min, duodenal 11
per min)

Receptive reflex:

Relaxes stomach to allow entry of food, modulated by
swallowing center (vagus)

Enterogastric reflexes: (act on motility & secretion)

Hormonal signaling from intestines slows gastric emptying and
reduces motility

Neural reflex: hyperosmolar chyme & mechanical distention

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Gastric Motility

When receptive reflex is
activated, MMC is replaced
with peristaltic actions

Mechanical churning for
digestion

Emptying time usually ~4hrs

Sympathetic System can
prolong emptying

Antrum holds ~30mL of
chyme and releases ~3mL
into duodenum with each
peristaltic wave

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 Small & Large Intestines

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Small Intestine

In the small intestine (duodenum, jejunum, ileum),
contractile activity serves to mix the chyme with the
alkaline exocrine secretions of the intestine, pancreas, and
liver.

These secretions contain a number of digestive enzymes,
including proteases, amylases, and lipases. Protein, lipids,
carbohydrate, vitamins, water, and electrolytes are
absorbed primarily in the small intestine

3 parts

Duodenum (25cm)

Jejunum (2.5 m)

Ileum (3.5m) and ends at ileocecal junction
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Small Intestine

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 Small Intestine: Duodenum

Segment between pylorus of stomach and jejunum

4 segments: only 1st segment (duodenal cap) is intraperitoneal

Submucosal Brunner’s glands

Produce alkaline mucus to neutralize stomach acid (pepsin is
inactivated by the elevated pH and pancreatic enzymes take over
the job of chemical digestion)

Receives pancreatic digestive
juices and bile juices from liver

Ampulla of Vater (major
duodenal papilla), sphincter
of Oddi

Primary site for Fe2+ absorption
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Small Intestine: Jejunum & Ileum

Major site of digestion: brush border contains numerous
digestive enzymes

90% absorption – specialized transporters, simple
diffusion, facilitated diffusion, active/passive transport

Protection against infection – Peyer’s patches, M cells

Hormone secretion – CCK, Secretin, Somatostatin, etc

Intestinal juice secretion – isotonic fluid (w/ enzymes)
secreted by crypts of Lieberkuhn, mucus from goblet cells

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Small Intestine Motility

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Large Intestine

In the large intestine (cecum, colon, rectum, anal canal),
colonic contractile activity transports chyme slowly and
mixes it thoroughly, exposing it to the absorptive surface
where most of the remaining fluid is absorbed.

Anatomy

Colon Parts: Cecum, ascending, transverse, descending, sigmoid

Ileocecal valve, Haustra, teniae coli, epiploic appendages

Retroperitoneal sections:

Ascending & Descending Colon

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Large Intestine

No further chemical digestion occurs

Most nutrients have already been absorbed

Volume of contents is reduced as liquid is absorbed

Dense population of many species of bacteria = bacterial
flora.

Ferment cellulose and other undigested carbohydrates

Synthesize B vitamins and vitamin K

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Large Intestine Motility

Basal Electric Rhythm

9 waves /min @ ileocecal valve

Up to16 waves/min @ sigmoid

Haustral Shuttling – kneading of mass to ↑H2O
absorption

Segmental propulsion – from one haustra to next

Mass movements (systolic multi-haustral propulsion) -
stronger contractions, moving mass towards rectum 2-5
cm/min. Occur infrequently or as gastrocolic reflex.

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Large Intestine

Transit Time

Can take ≥ 12 hours to pass through large intestine

Rectum can hold ≤ 3 days

↑ fiber = ↓ transit time

Reflexes

Defecation – spinal reflex

Distention of rectum causes internal sphincter to relax (pressure of
18-55mmHg manifests the urge to deficate)

Gastrocolic –

Mass contraction of colon caused by distention of stomach.Very
obvious in infants and children.

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 Major Accessory Glands

Liver & Pancreas

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Liver

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 Liver & Bile Secretion

Clinical:
Cholecystitis
Cholelithiasis
Primary biliary cirrhosis
Etc…
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Bile

Constituents:

bile salts (taurocholate & glycocholate), bile pigments (bilirubin
& biliverdin), lipids (cholesterol, lecithin, fatty acids, and
triglycerides), and electrolytes.

Cholesterol usually between 60-170mg/L

High concentrations predispose to gall stones.

Bile juice has ↑ HCO3- content, much higher than plasma

Alkaline (pH = 7,0-7,4)

Bile salts are the only important factor for digestion

Amphipathic molecules – steroid nucleus (hydrophobic) +
polar (hydrophilic) groups—enhance intestinal absorption of
lipids
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 Enterohepatic circulation

The total bile
pool (2–4 g)
recirculates
about 6–10
times a day

20–30 g of
bile salts are
required for
daily fat
absorption

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Enterohepatic
circulation

85% of bilirubin
formed from
breakdown of
hemoglobin in
RBCs

Stercobilin gives
stools brown
color
Jaundice:
Prehepatic – excessive bilirubin formed, i.e.
↑hemolysis. Elevated indirect bilirubin.
Intrahepatic – liver dysfunction
Posthepatic – impairment of flow, i.e. stone or
tumor. Elevated direct bilirubin & grey stools.
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 Secretion, Digestion &
Absorption

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Fluid Balance

Inflow/Secretions:

Saliva 1-2 L/day

Gastric juices 2-3 L/day

Exocrine pancreas 1.2-1.5 L/day

Bile juices 0.5-1 L/day

Small Intestine 1-2 L/day

Total ~ 8.5 L/day secretions

Only 2 L delivered to colon,
and only 0.1-0.2 L/day in feces

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Electrolyte Absorption

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Absorption

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Carbohydrates

Carbohydrates provide ½ - ⅔ of the energy requirement.

≥50% of dietary carbohydrates consist of starch (amylose

and amylopectin), a polysaccharide

Other important dietary carbohydrates are cane sugar
(saccharose = sucrose) and milk sugar (lactose).

Total of about 350 to 450 grams of carbohydrates per

day.

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Carbohydrate
Digestion

Begins in mouth
with salivary
amylase.

Resumes in
duodenum with
pancreatic
enzymes

Finishes at brush
border with
disaccharidases

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 Carbohydrate Digestion & Absorption

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 Carbohydrate Absorption

α-Amylase breaks α-1,4
bonds of non-terminal
sugars (endoenzymes)

Creates maltriose,
maltose, and α-limit
dextrins

α-Amylase cannot cut:

Terminal α-1,4 link

Adjacent α-1,4 link

α-1,6 link (branching)

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 Carbohydrate
Absorption

Brush border
oligosaccharidases continue
Lactase deficiency digestion
Lactose cannot be broken down and absorbed
Lactase = Glc + Gal
unless sufficient lactase is available. Lactase
deficiencies lead to diarrhea 1) because water is
Both taken up by SGLT1
retained in the intestinal lumen due to osmotic
Maltase = Glc + Glc
mechanisms, and 2) because intestinal bacteria

Taken up by SGLT1
convert the lactose into toxic substances.

Surcase-isomaltase

Actually 2 enzymes capalble of
hydrolyzing sucrose, maltose,
maltotriose, and and α-limit
dextrins

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Carbohydrate Absorption

Secondary active
transport – SGLT1
uses Na+ gradient to
drive Glc into cell

SGLT1 & GLUT5 are
found on apical
membrane

GLUT5 & GLUT2
allow for facilitated
diffusion across
membranes

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Fiber

Fiber = Unavailable carbohydrates,

indigestible oligosaccharides (eg, raffinose)

dietary fiber (cellulose and hemicellulose)

These carbohydrates are not digested in the small intestine.

They pass to the colon, where they are fermented by
bacterial enzymes.

Fiber decreases transit time, adds bulk to feces, and

allows for easier defecation

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Lipids

The average intake of fats (butter, oil, margarine, milk,
meat, sausages, eggs, nuts etc.) is roughly 60–100 g/day,
but there is a wide range of individual variation (10–250
g/day).

Most fats in the diet (90%) are neutral fats or
triacylglycerols (triglycerides).The rest are phospholipids,
cholesterol esters, and fatsoluble vitamins (vitamins A, D,
E and K). Over 95% of the lipids are normally absorbed in
the small intestine. •Deficiency:
•Vitamin A - night blindness
•Vitamin D – rickets
•Vitamin K – clotting factor deficiencies
•Excess
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•Toxicity - hypervitaminosis
Lipid
Digestion

Begins in the
mouth with
lingual lipase

Continues
activity in the
stomach

Emulsification in
duodenum by
bile salts,
formation of
micelles

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Lipid Absorption

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 Cholesterol

Cholesterol is an
important constituent
of cell membranes.

Precursor for bile salts,
vitamin D, and steroid
hormones

Clinical:
Familial hypercholesterolemia
Atherosclerosis
Dyslipidemias

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Protein
Digestion

Begins in the
stomach with
pepsins,
continues with
pancreatic
enzymes

Polypeptides
cleaved into
oligopeptides
and amino
acids

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Protein Digestion

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Protein Absorption

Peptidase activity:

brush borders

within the cytoplasm of
intestinal mucosa cells.

Aminopeptides must be
absorbed by specific amino
acid and peptide transport
systems. Intracellular
peptidases hydrolyze
absorbed peptides.

Basolateral transport:

many different AA
transporters.
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 Hartnup disease
affecting the absorption of nonpolar amino acids,
particularly tryptophan that can be, in turn,
converted into serotonin, melatonin and niacin

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Absorption of whole proteins

Normal cells can
endocytose
proteins and
degrade them
(90%)

M cells endocytose
fewer intact
proteins but 50%
emerge for
presentation to
immuno cells

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 Regulation of the GI Tract

Hormonal and neuronal controls

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Gastrin Family of hormones

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Gastrin

Secreted by the G cells

Gastric antrum & duodenum Zollinger Ellison Syndrome
A non–beta islet cell, gastrin-secreting

Gastrin is released by G cells after:
tumor of the pancreas (seen in MEN-1)

vagal stimulation (via GRP) causing over secretion of HCl and resulting

distention of the stomach in peptic ulcers

presence of protein digestion products in the stomach

Release is inhibited by Somatostatin, PGE2, or when
gastric/duodenal lumen pH <3.5

Stimulates acid secretion and gastric mucosal
growth

Gastrin is the only GI hormone known to be released by
direct neural stimulation

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CCK (Cholecystokinin)

Produced throughout small intestinal mucosa (I cells)

Release stimulated by presence of long-chain fatty acids,
AA, and oligopeptides in lumen
Actions:

gall bladder contraction
↑ motility of SI & LI

Secretion of enzyme-rich
Trophic effect on pancreas
pancreatic juice
↑secretion of enterokinase

Potentiates secretin on
Stimulates insulin &
pancreas glucagon release

Inhibits gastric emptying
Produces satiety

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Parietal Cell Control

Neural Control (Vagus)

ACh (+)

Indirect - stimulates ECL to release Histamine which stimulates
Parietal cells

Direct - stimulates Parietal cells

GRP (Gastrin Releasing Peptide) (+)

Hormonal Control

Gastrin (+)

Histamine (+)

Somatostatin (-)

PGE2(-)
Secretin-Glucagon Family

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Secretin

Produced in duodenum (S cells)

Release stimulated by acidic chyme & presence of protein
digestion products
Actions

Stimulates pancreatic
↑ hepatic secretion of bile
bicarbonate secretion
↓gastric acid

Potentiates CCK effect on
↑tone of pyloric sphincter
pancreas
↓glucagon secretion

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GIP (Gastric Inhibitory Peptide)

Part of Incretin family (with GLP-1)

Produced in duodenum & intestinal mucosa (K cells)

Release stimulated by protein, fat & carbohydrate
fragments in lumen

Actions

Inhibits acid secretion & gastric motility

Stimulates insulin release
Incretins

Causes an ↑in insulin secreon.

Mechanism is used by GLP-1 analogues to
increase insulin secretion in diabetic patients
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Others

VIP (Vasoactive Intestinal Peptide)

Dilates blood vessels & relaxes intestinal smooth muscle

↑ watery secretions VIPoma

Inhibits gastric acid Seen in MEN-1, causes secretory

Peptide YY diarrhea leading to metabolic alkalosis

Inhibitor of gastrin-mediated acid secretion

Release from jejunal mucosa stimulated by fats in lumen

Motilin

Released by neurons in the small intestine and regulates digestive
motility

Paracrine transmitters: Histamine, Somatostatin, and
prostaglandin are the main paracrine transmitters in the GI
tract.

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Stomach
Pancreas
Liver
GB
Gut
Brain

Despopoulos, Color Atlas of Physiology © 2003 Thieme