FHB: GI physiology

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GI physiology review
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Function of the GI system 4 basic digestive
processes MOTILITY SECRETION
DIGESTION ABSORPTION
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Delay of 3 seconds
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Sphincters
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Mucosa epithelium lamina propria
muscularis mucosae exocrine cells
endocrine/paracrine cells Submucosa
connective tissue, blood vessels, glands
submucosal nerve plexus (Meissners
plexus) Muscularis externa smooth muscle
cell layer inner circular layer outer
longitudinal layer myenteric nerve plexus
(Auerbachs plexus) Serosa (adventitia)
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Regulation of GI function
Autonomous
Neural regulation
smooth muscle
extrinsic NS (CNS)
function
intrinsic NS
pacemaker activity
electrical coupling
GI hormones
Paracrine
mediators
humoral regulation
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Autonomous smooth muscle function

• Intestinal smooth muscle cells
• effector organ of GI motility
• Pacemaker activity
• Thin layer of interstitial cells (interstitial
  cells of Cajal) between circular and longitudinal
  cell layer. Conduction through gap junctions.

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Excitation-contraction coupling intestinal smooth
muscle

• Contraction requires an increase of cytosolic
  calcium (Ca2i)
• Electro-mechanical coupling Contractions are
  triggered by action potentials (APs) that travel
  from cell
• to cell through gap junctions.
• Pharmaco-mechanical coupling Contraction occur
  in the absence of action potentials e.g. in
  response to neurotransmitter or hormones.

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Pacemaker activity

• Thin layer of interstitial cells (interstitial
  cells of Cajal) between circular and longitudinal
  cell layer. Conduction through gap junctions.

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GI smooth muscle electrophysiology and contraction
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Resting membrane potential -40 to -80 mV.
membrane potential oscillations Na/K-ATPase. S
low waves Pacemaker activity Ionic events during
slow waves Na-, Ca- and K-currents Modulation
by enteric neurons
Action potentials when slow-waves reach
electrical threshold burst of APs (10-20 ms,
rising phase is carried by Na and Ca2 ions)
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Smooth muscle tone and contraction

• Contraction begins when depolarizing phase
  reaches mechanical threshold.
• Development of muscle tone and contraction
  correlate with the degree of depolarization
• can occur in the absence of APs.
• Baseline tension is non-zero (constant basal
  tone).
• Tonic contractions contractile tension that is
  maintained for prolonged periods of time.
• Phasic contraction twitch-like contraction
  evoked by action potentials. Triggering of APs
  increases strength of contraction. Frequency and
  number of APs grade the degree and duration of
  contraction.

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Neurotransmitters of the autonomic nervous system
sympathetic
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parasympathetic
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Integration of sympathetic, parasympathetic and
enteric nervous system
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Sympathetic efferent innervation Primarily
via postganglionic adrenergic fibers with cell
bodies in prevertebral and paravertebral plexuses
(celiac plexus, superior and inferior mesenteric
plexus, superior and inferior hypogastric plexus)
terminate in submucosal and myenteric plexus.
Typically inhibitory effect on synaptic
transmission in the enteric plexuses. Effects
of sympathetic activity - vasoconstriction of
gastrointestinal blood vessels - inhibition of
glandular function - muscularis externa
inhibition of motor activity - contraction of
muscularis mucosae and certain sphincters
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Parasympathetic efferent innervation Vagus
nerve (upper gastrointestinal tract to transverse
colon) and parasympathetic fibers of pelvic
nerves from the hypogastric plexus Predominantly
cholinergic fibers that terminate on ganglion
cells of intramural plexuses. Stimulation of
motor (smooth muscle cells) and secretory
activity.
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Enteric nervous system
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semi-autonomous nervous system in the wall of the
GI tract ("the little brain in the gut") major
network of ganglia and interconnecting neurons
(about 108 neurons!) 2 major plexuses
myenteric plexus (Auerbachs plexus)
submucosal plexus (Meissners plexus)
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Integration of neuronal control of GI function
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Example of enteric reflex The neural circuit
for peristaltic propulsion of GI (thelaw of
intestine).
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Stretching a segment of the GI tract is sensed by
sensory enteric neurons. This signal is
transmitted via excitatory and inhibitory
interneurons to excitatory (proximal) and
inhibitory (distal) motor neurons, causing
ascending excitation and descending inhibition
of smooth muscle cells --gtGI content is
transported in aboral direction
VIP vasoactive intestinal peptide
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Intestinal reflexes Short range reflexes Food
bolus causes aboral relaxation and proximal
contraction --gt food transport in orthograde
direction (law of the intestine). Regulated by
intrinsic nerves.
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Gastro intestinal hormones are released from
distant endocrine cells and transported by blood
streamto activate secretion (e.g. gastrin from G
cells activate HCl secretion) Paracrine
mediators are released into the neighborhood of
secretory cell and reaches target cells by
diffusion (e.g. histamine paracrine agonist for
gastric HCl secretion).
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Important actions of GI hormones (compare with
table 15) Action Gastrin CCK
Secretin GIP Acid secretion S I I Pancreat
ic HCO3- secretion S S Pancreatic enzyme
secretion S Bile HCO3- S Gallbladder
contraction S Gastric emptying I Mucosal
growth S Pancreatic growth S S S
stimulates I inhibits
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Additional GI hormones Hormones are produced by
enteroendocrine cells in the GI tract in stomach,
small and large intestine
Motilin Serotonin Substance P Vasoactive
intestinal peptide (VIP) Neurotensin
increases intestinal motility increases
intestinal motility increases intestinal
motility neurotransmitter for intestinal smooth
muscle stimulates secretion of water and
ions decreases intestinal motility increases
blood flow to ileum
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Additional GI hormones (cont.)
stimulate hepatic glycogenolysis stimulates
hepatic glycogenolysis local inhibition of
other endocrine cells (e.g. G-cells) inhibits
secretion of HCl increases epithelial
growth increases secretion of HCl
Glucagon Entero-glucagon Glicentin
(glucagon-like substance) Somatostatin Urogast
rone (Epidermal Growth Factor) Histamine
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Gastrointestinal paracrine mediators
Paracrine agonists released by - paracrine
cells - GI immune system - antibodies -
inflammaory mediators (prostaglandins,
leukotrienes, cytokines, histamine, others)
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Lymph node
Villus
Epithelium
Lamina propria
Muscularis mucosae
Submucosa
Circular muscle
Longitudinal muscle
Serosa
Myenteric plexus
Submucosal plexus
Gland in submucosa
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Muscularis externa
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GI immune system - half of the mass of immune
cells in the body are in the GI tract - antibody
secretion to specific food antigens - immunologic
defense against pathogenic microorganisms
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Pancreatic Hormones Pancreatic
hormones insulin glucagon somatostatin
produced and secreted (endocrine pancreatic
secretion) by the islets of Langerhans essential
for the regulation of metabolism
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Regulation of GI function
Autonomous
Neural regulation
smooth muscle
extrinsic NS (CNS)
function
intrinsic NS
pacemaker activity
electrical coupling
GI hormones
Paracrine
mediators
humoral regulation
gt high degree of integration gt high degree of
autonomy
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Example acid secretion by gastric parietal
cell....
cholinergic nerve terminals
G-cells
gastric motility enhances mixing of food and
disgestive juices
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MOTILITY
muscular contractions that mix and move the
contents of the gastro-intestinal tract to the
appropriate sites of digestion and absorption
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Patterns of GI motility
Type of contraction Organ/structure Tonic
contractions upper and lower esophageal
sphincters pyloric valve sphincter of
Oddi ileocecal valve internal anal
sphincter Propulsive peristalsis esophagus
lower 2 thirds of stomach small
intestine rectum
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Patterns of GI motility (cont)
Type of contraction Organ/structure Reverse
peristalsis (antipropulsion) proximal
colon Mass movements ascending,
transverse and descending colon Nonpropulsive
segmentation small intestine
Haustration ascending, transverse and descending
colon
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Patterns of GI motility (cont)
Migrating motor complex migrating
myoelectric complex fasting/empty small
intestine
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Esophagus
Tubular conduit (about 20 cm long) for food
transport from mouth to stomach. Structural and
regulatory aspects Upper third of the
esophagus circular and longitudinal muscle
layers are striated innervation via cranial
nerve. Middle third coexistence of skeletal
and smooth muscle. Primary innervation from
vagus nerve nerve input from neurons of
myenteric plexus Lower third smooth muscle,
enteric nerve system (input from vagus nerve to
enteric nerve system).
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Swallowing center
Neuronal control of esophagus
Pharynx
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UES
Innervation afferent sensory feedback to
swallowing center efferent vagal somatic
motor neurons to striated muscle vagal visceral
motoneurons to smooth muscle, terminating at
neurons of myenteric plexus
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Esophageal sphincters Upper esophageal
sphincter (UES) prevents entry of air Lower
esophageal sphincter (LES) LES zone of
elevated resting pressure ( 30 mm Hg) prevents
reflux of corrosive acidic stomach content. LES
tone is regulated by extrinsic and intrinsic
nerves, hormones and neuromodulators.
Contraction vagal cholinergic nerves
(nicotinic, i.e. atropine insensitive) and
sympathetic nerves (?-adrenergic). Relaxatio
n primary peristalsis --gt inhibitory vagal nerve
input to circular muscle of LES
(neurotransmitters (VIP and NO) and reduced
activity of vagal excitatory fibers
(cholinergic, nicotinic).
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Swallowing

• Swallowing can be initiated voluntarily, but then
  it is under reflex control.
• Swallowing reflex sequence of events that
  result in propulsion of food from the mouth to
  the stomach
• 1. Oral/voluntary phase
• 2. Pharyngeal phase
• 3. Esophageal phase

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Control of esophageal motility Local and
central circuits
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Esophageal pressure profile
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Intraluminal esophageal pressure profile
Pressure in the body of esophagus is negative,
reflecting intrathoracic pressure
pressure wave during swallowing
0 mm Hg ambient pressure
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Stomach
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Functions of stomach motility reservoir for
large volumes of food fragmentation of food
and mixing with gastric secretion --gt
digestion controlled emptying of gastric
content into duodenum
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Reservoir
Mixing Transport
Sphincter
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Gastric filling Empty stomach (volume approx.
50 ml) can expand to gt 1 liter volume increase
is n o t paralleled by similar increase of
intragastric tension because of Plasticity
stomach smooth muscle cells can be stretched
(within limits) without a change in tension
(developed force). Receptive relaxation
Filling (gastric distension) causes reflective
relaxation of the fundus and body of the stomach
reflex is mediated by vagus nerve (VIP and NO as
neurotransmitters).
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Gastric mixing
Chyme mixture of gastric secretion and food
content
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Gastric emptying
antral peristaltic contractions pylorus
regulates emptying neural and humoral/hormonal
fine regulation gastric duodenum/jejunum factor
s outside GI system
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Pyloric valve - regulates emptying of gastric
content - prevents regurgitation of duodenal
content
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Pyloric relaxation inhibitory vagal fibers
(mediated by VIP and NO). Pyloric constriction
excitatory cholinergic vagal fibers, sympathetic
fibers and hormones cholecystokinin, gastrin,
gastric inhibitory peptide and secretin.
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Gastric factors Volume of chyme increased
volume (distension) stimulates motility Fluidity
increased fluidity allows more rapid emptying
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Duodenal/jejunal factors
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CNS
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Small intestine motility
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Types of motility of the small intestine
digestive motility pattern segmentation
peristalsis interdigestive motility
pattern migrating myoelectric complex
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Segmentation Most frequent type of motility
Closely spaced contraction of the circular muscle
layer, dividing the small intestine into small
neighboring segments. In rhythmic segmentation
the sites of circular contractions alternate --gt
mixing Frequency of segmentations decreases in
aboral direction (11-12/min duodenum 8-9/min
ileum) --gt slow forward transport of food content
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Peristalsis Progressive contraction of
successive sections (short distances) of circular
smooth muscle in orthograde direction.
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Contractile activity of the muscularis
mucosae Irregular contractions of sections of
the muscularis mucosae (3/min) --gt change in
topography of the internal surface of the gut
--gt enhancement of the contact between mucosa and
content and facilitation of absorption. Increased
emptying of central lacteals and increased
intestinal lymph flow.
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Emptying of the ileum Ileocecal sphincter
normally closed. Short-range peristalsis in
terminal ileum and distension relaxes IC
sphincter --gt small amount of chyme is squirted
into the cecum. Distension of cecum contracts IC
sphincter. Gastro-ileal reflex enhances ileal
emptying after eating. The hormone gastrin
relaxes ileocecal sphincter.
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The migrating myoelectric complex (MMC)
migrating motor complex occurs in fasted
organism bursts (lasting 5-10 minutes) of
intense electrical and contractile activity that
propagate from stomach (origin) to the terminal
ileum. Repeats every 75-90 minutes.
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ligament of Treitz duodenum-jejunum border
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Motility of the colon Haustration (corresponds
to segmentation in small intestine) Segmental
propulsion or systolic multihaustral propulsion
Antipropulsion (reverse peristalsis) Mass
movement
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Defecation Complex behavior involving voluntary
actions and reflexes. Defecation reflex sacral
spinal cord and efferent cholinergic
parasympathetic fibers in pelvic nerves.
Distension of rectum and relaxation of internal
sphincter. Voluntary actions relaxation of
external sphincter (striated muscle, innervated
by somatic fibers via pudendal nerves) and
increase of intraabdominal pressure
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SECRETION
exocrine glands secrete digestive juices,
consisting of water electrolytes
specific organic constituents important for
digestive process (enzymes, bile salts,
mucus) endocrine glands hormones for regulation
of the GI system
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Functions of GI secretion are digestive
protective For example..... provide enzymatic
machinery for degradation of nutrients provide
factors to facilitate absorption (e.g. bile
salts, intrinsic factor) lubricate food
bolus provide the proper ionic and osmotic
milieus (e.g. pH) for enzymatic hydrolysis and
absorption aid in repair, replacement and
barrier functions of the intestinal epithelium
(e.g. epidermal growth factor) contribute to
body fluid homeostasis immunological functions
through secretory immunoglobulins (antibodies)
and antibacterial compounds
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Secretagogue substance that stimulates a
secretory cell to secrete neurocrine
secretagogue neurotransmitters released from
neurons that innervate the secretory cell (e.g.
ACh from vagus nerve) endocrine secretagogue
hormones released from distant cells and
transported by blood streamto activate secretion
(e.g. gastrin from G cells activate HCl
secretion) paracrine secretagogue released
into the neighborhood of secretory cell and
reaches target cells by diffusion (e.g. histamine
paracrine agonist for gastric HCl secretion).
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Mechanism of exocrine gland secretion
Exocrine gland cells extract from the plasma raw
materials necessary for the synthesis of
secretion products. Secretion products are
emptied into the ducts of the secretory gland and
delivered to the GI tract. Secretion-blood flow
coupling secretion is coupled with increased
blood flow to the exocrine gland (functional
hyperemia) to optimize availability of raw
materials.
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Intracellular mechanisms secretagogues bind
to surface membrane receptors and stimulate
secretion intracellular messengers
cAMP IP3 and Ca2 activation of kinases
--gt altered ion channel function --gt secretion
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Salivary glands parotid submandibular
(submaxillary) sublingual (minor glands in
labial, palatine, buccal, lingual and
sublingual mucosa)
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Structure of salivary glands acinus secretory
endpiece with serous acinar cells with
zymogen granules (salivary amylase, salivary
proteins) mucous acinar cells secrete
glycoprotein mucins ducts drainage system
modifications of acinar secretions
intercalated ducts striated (intralobular)
ducts excretory (interlobular) ducts.
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Composition of saliva electrolytes
proteins mucin (glycoproteins --gt
viscosity) digestive enzymes (salivary amylase
stored in zymogen granules, released into
acinar lumen by exocytosis) protective
proteins (secretory IgA) water
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Protective function bicarbonate
(neutralization of acid produced by bacteria
and gastric reflux) antibacterial
(lysozyme) lactoferrin (binds Fe, decreases
bacterial growth) secretory immunoglobulin
(IgA) epidermal growth factor mouth
hygiene facilitates speaking
Digestive function ?-amylase ( ptyalin)
lingual lipase lubrification food for
swallowing dissolving substances for taste
mechanism
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2-stage model of salivary secretion Primary
secretion product (acinus) is nearly isotonic
with plasma. Secondary modification in ducts
extract Na, Cl-, and add K , HCO3-,
resulting in a hypoosmotic (hypotonic)
secretion.
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Composition and osmolarity dependent on
secretion rate
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Mucus Collective term for secretions that
contain glycoprotein mucins which are
characteristically viscous and sticky.
Protects mucosal surfaces from abrasion by food
contents, lubricates the food bolus in the upper
GI tract and alkaline pH counters regional
acidity (e.g. stomach). Mucus is produced by
various cells in the GI tract mucous cells in
salivary glands goblet cells Brunners
gland neck cells of gastric glands pancreatic
acinar cells.
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Regulation of salivary secretion The primary
physiological control of salivary gland function
is by the parasympathetic nervous system! the
sympathetic nervous system and hormones
contribute to regulation
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Regulation of salivary secretion Autonomic
nervous system Parasympathetic (ACh, VIP)
high and sustained output synthesis and
secretion of amylase and mucins transport
activity of ductular epithelium vasodilation
and increased blood flow positive feed back
on blood supply through kallikrein kininogen
system stimulation of glandular metabolism
and growth Sympathetic transient
increase of secretion vasoconstriction leads
to decrease of salivation
VIP vasoactive intestinal peptide
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Gastric mucosa cardiac glandular
region oxyntic glandular region pyloric
glandular region...... .........with a
variety of secretory cells
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Secretory cells Secretion product surface
mucous cells, mucous neck cells mucus,
HCO3- oxyntic ( parietal) cells HCl,
intrinsic factor chief ( peptic) cells
pepsinogen, gastric lipase neuroendocrine
cells G cells gastrin D
cells somatostatin
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Digestive functions digestive enzymes
pepsinogen (endopeptidase) gastric
lipase HCl secretion (parietal cells) acidic
environment for pH optimum (1.8-3.5) of
digestive enzyme pepsin (activated from
pepsinogen) and lingual lipase (pH optimum 4).
HCl softens food Intrinsic factor binds Vit
B12 and protects from gastric and intestinal
digestion Protective functions gastric
acidity antibacterial mucus and HCO3-
protective layer against damage of gastric mucosa
by low pH
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Pepsinogen secretion Pepsin protease
(endopeptidase) Low gastric pH converts
proenzyme pepsinogen into active pepsin pepsin
itself proteolytically cleaves pepsinogen
(positive feedback) Optimum for proteolytic
activity is around pH 3. ACh, gastrin,
secretin, cholecystokinin and acid stimulate
pepsinogen secretion. Pepsinogen is stored
in zymogen granules and released by exocytosis.
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Ionic composition of gastric juice
Rate of secretion of gastric acid basal rate
1-5 mEq/hr maximal stimulation 6-40 mEq/hr
higher in patients with duodenal ulcers
low flow rate hypotonic high flow rate nearly
isotonic, mainly HCl
Plasma
Gastric juice
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Cellular mechanism of HCl production
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omeprazole
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Carbonic anhydrase drives HCO3- production
H/K pump (ATP-dependent) drives H out and Cl-
follows (via electrogenic anion channel)
HCO3-/Cl- exchange maintains Cl- supply
Alkaline tide net HCO3- release into the blood
stream during gastric acid secretion.
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Regulation of acid secretion
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Gastric mucosal barrier (1) unstirred,
bicarbonate rich mucus layer maintains pH 7 at
cell surface and protects gastric mucosa from
gastric juice (pH 2) (2) tight junctions
between gastric mucosal cells prevent penetration
of HCl between cells (3) luminal membrane of
gastric mucosal cells is impermeable for protons
Protection against self-digestion
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Pancreatic secretion
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Secretory functions of the pancreas endocrine
pancreatic secretion (islets of Langerhans)
hormones (insulin, glucagon, somatostatin)
essential for regulation of metabolism exocrine
pancreatic secretion aqueous component
enzyme component
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Digestive function production and secretion of
digestive enzymes neutralization of acidic
chyme (pancreatic enzymes pH optimum near
neutral pH) Protective function
neutralization of acidic chyme --gt protection
from acid damage of intestinal mucosa
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Pancreatic enzymes
Enzyme specific hydrolytic activity
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Enzyme activation
Proteolytic enzymes are secreted in inactive
zymogen form. Enteropeptidase ( enterokinase)
secreted by duodenal mucosa activates trypsinogen
(--gt trypsin). Trypsin activates itself and the
other proteolytic enzymes. Trypsin inhibitor
protein in pancreatic secretion that prevents
premature activation of proteolytic enzymes in
pancreatic ducts ?-amylase is secreted in
active form
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pH, osmolarity and electrolyte composition of
pancreatic secretion
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Cellular mechanism of pancreatic secretion
carbonic anhydrase reaction produces H2CO3
Na/H exchange and H/K-ATPase eliminate H
Cl-/HCO3- exchange secretes bicarbonate into
duct lumen electrogenic Cl- channels recycle
Cl- back into lumen Acid tide net H
release into the blood stream during pancreatic
secretion.
Carbonic anhydrase
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Bile secretionand liver function
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Structure of the liver
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blood flow
bile flow
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PS portal space with portal vein hepatic
artery bile canaliculus lyphatic vessel CV
central vein
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liver lobule
portal lobule (defined by bile flow)
hepatic acinus (defined by blood flow)
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Hepatic acinus
HV hepatic venule
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Functions of the liver Energy metabolism and
substrate interconversion Synthetic function
Transport and storage function Protective and
clearance function
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Bile secretion digestive/absorptive function of
the liver Components of bile bile salts
(conjugates of bile acids) bile pigments (e.g.
bilirubin) cholesterol phospholipids
(lecithins) proteins electrolytes
(similar to plasma, isotonic with
plasma) 600-1200 ml/day
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Function of bile bile salts (conjugates of bile
acids with taurine or glycine) important for
absorption of lipids in small intestine. Bile
acids emulsify lipids and form mixed micelles
necessary for lipid absorption. bile acids
are derived from cholesterol and therefore are
responsible for excretion of cholesterol.
excretion of bilirubin (product of hemoglobin
degradation). bile acids are actively absorbed
and recirculated through enterohepatic
circulation.
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enterohepatic circulation of bile
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Mechanism of uptake and secretion of bile acids
by hepatocytes
ATP
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Intestinal secretion 1500 ml/day. Composition
mucus electrolytes water
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DIGESTION
degradation of structurally complex foodstuffs
by digestive enzymes 3 categories of energy-rich
foodstuffs carbohydrates, proteins and lipids
ABSORPTION
absorbable units as a result of the digestive
process are transported along with water,
vitamins and electrolytes from the lumen of the
GI tract into the blood and lymph
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Digestion chemical degradation of nutrient
macromolecules by digestive enzymes Luminal
disgestion enzymes secreted into the lumen of GI
tract from salivary glands, stomach and
pancreas Membrane or contact digestion
hydrolytic enzymes synthesized by enterocytes
and inserted into the brush border membranes.
Integral part of the microvillar membrane in
close vicinity of specific carrier proteins (
digestion-absorption coupling) cytoplasmic
disgestion digestive enzymes in the cytoplasm
(peptidases)
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Sites of absorption
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Average daily.... intake 2 liters loss
through GI tract 100 ml (only 5 of intake)
through feces GI secretion 7 liters water
absorption by GI tract 9 liters
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Mechanism of water absorption standing osmotic
gradient hypothesis Absorption of water is
passive and is determined by differences in
osmolarity of luminal content and blood,
therefore net transport of water can occur in
both direction.
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Standing gradient osmosis
1. Active Na pumping (Na/K ATPase) into
lateral intercellular space 2. passive entry of
Cl- into lateral intercellular space 3. establish
osmotic gradient in lateral space 4. entry of
water by osmosis into lateral space 5.
hydrostatic flow of water
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Tight junctions transcellular vs. paracellular
transport Tight junctions connect epithelial
cells of the GI tract. Tight junctions are leaky
(the most in the duodenum) for water and ions.
Transmucosal transport of water and ions can
occur through tight junctions and lateral
intercellular space (paracellular transport 2)
or through epithelial cells (transcellular
transport 1)
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Digestion and absorption of carbohydrates
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Diet contains digestible carbohydrates
monosaccharides glucose, fructose, sorbitol,
(galactose in form of milk lactose
galactoseglucose) disaccharides sucrose,
lactose, maltose oligosaccharides/polysaccharid
es starch (made of amylose and amylopectin),
dextrins, glycogen non-digestible
carbohydrates dietary fibers, mainly cellulose
(ß-1,4 linked glucose polymer humans lack
enzyme to hydrolyse ß-1,4 bonds). Fibers are
extremely important for regular bowel movements.
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Digestive enzymes break down oligosaccharides and
polysaccharides into the 3 absorbable
monosaccharides glucose fructose
galactose
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Digestive enzymes for carbohydrate digestion
luminal digestive enzymes brushborder enzymes
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Luminal digestive enzymes for carbohydrate
digestion salivary and pancreatic amylase
cleaves the ?-1,4 glycosidic bond of amylose and
amylopectin (starch and glycogen) to produce
maltose, maltotriose and ?-limit dextrins.
Note ? -amylase cannot hydrolyze ? -1,6 and
terminal ? -1,4 glycosidic bonds.
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Brush border enzymes digest disaccharides and
oligosaccharides
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Digestion-absorption coupling
G2
G3
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Absorption mechanism of monosaccharides Digestion
by brush border enzymes occurs in close vicinity
to monosaccharide transporters. Glucose and
galactose SGLT1 absorption via a secondary
active (uphill), Na-dependent transport
Fructose GLUT5 absorption by facilitated
(carrier mediated), Na-independent mechanism
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Digestion and absorption of lipids
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Lipids in the GI tract exogenous (diet
triglycerides (90), phospholipids, sterols
(e.g. cholesterol), sterol esters)
endogenous (bile, desquamated intestinal
epithelial cells)
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Digestion of lipids Most of the lipids are
digested in the small intestine, but also in
stomach. Enzymes for lipid digestion lingual
lipase (from salivary secretion break down of
mainly medium-chain triglycerides as abundant
in milk optimal pH 4 --gt lipid digestion in
the stomach) gastric lipase (secreted by chief
cells) pancreatic lipase glycerol ester
hydrolase (triglycerides) pancreatic
phospholipase A2 (phospholipids) pancreatic
cholesterol esterase (cholesterol ester).
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Mechanism of lipid absorption The intestinal
villi are coated by an unstirred water layer
which reduces the absorption of the poorly water
soluble lipids.
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Emulsification In the small intestine lipids
are emulsified by bile acids (i.e. formation of
small droplets of lipids coated with bile acids).
Bile salts (bile salts conjugation of bile
acids with taurine or glycine) are polar and
water soluble, and function as detergents.
Emulsion droplets allow access of the
water-soluble lipolytic enzymes by increasing
surface area.
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Micelle formation and lipid absorption - At
a certain concentration (critical micellar
concentration) bile salts aggregate into micelles
that incorporate lipid digestion products. Lipids
become water soluble by micellar solubilization.
- Lipids diffuse across the unstirred water
layer as micelles and are mostly absorbed
passively (diffusion) by enterocytes (mainly in
the jejunum). - Absorption is enhanced by
Na-dependent long-chain fatty acid transport
protein (MVM-FABPmicrovillous membrane fatty
acid-binding protein) and cholesterol transport
protein in the brush border membrane (secondary
active and facilitated transport).
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In the enterocytes lipids are bound by
cytosolic lipid transport proteins and
transported to the smooth endoplasmic reticulum.
There triglycerides are reassembled from fatty
acids and monoglycerides Triglycerides
together with lecithin, cholesterol and
cholesterol ester, are packaged into lipoproteins
to form water-soluble chylomicrons (lipid
aggregates). Transport of lipids to the
lymphatic vessels by exocytosis. Additionally,
mainly medium-chain and short-chain fatty acids
directly reach the blood stream and are
transported bound to serum albumin.
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Lipid digestion absorption
94
127
Absorption of bile acids. Bile acids are
absorbed in the terminal ileum by Na-dependent
secondary active transport (mainly conjugated
bile acids) and by diffusion (mainly unconjugated
bile acids). Bile acids are recirculated to the
liver via portal circulation and extracted from
portal blood for reuse.
93
128
Digestion and absorption of proteins
129
Proteolytic digestive enzymes gastric
secretion (G) pancreatic secretion (P)
brush border enzymes (BB) cytoplasmic (C)
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Endopeptidase hydrolyzes internal peptide
bonds trypsin (P) chymotrypsin (P)
elastase (P) pepsin (G) Exopeptidase
hydrolyzes external peptide bonds
carboxypeptidase A (P) carboxypeptidase B
(P) aminopeptidase (P, BB, C) P pancreas,
BB brush border, C cytoplasm
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Protein digestion gtgt Gastric proteolysis pepsin
is activated by low pH from proenzyme pepsinogen
and acts as endopeptidase. gtgt Small intestine
major site of protein digestion. Luminal
protein digestion Pancreatic proteases are
secreted as inactive proenzymes. Chyme in the
duodenum stimulates the release of enterokinase
( enteropeptidase) which converts trypsinogen
into trypsin (active form). Trypsin itself
converts the other proenzymes to active enzymes.
Luminal protein digestions produces single amino
acids and small peptides (dipeptides, tripeptides
and tetrapeptides) Brush border peptidases are
integral membrane proteins produce single amino
acids and smaller peptides from tetrapeptides and
larger peptides. Intracellular cytoplasmic
peptidases break down dipeptides and tripeptides
into single amino acids.
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Protein absorption Products of protein
digestion are absorbed as amino acids 7 amino
acid transporters in brush border membrane
(BL, table 39-2) - 5 Na-dependent (absorption
occurs via secondary active process by carrier
that are energetically coupled to the Na
concentration gradient across the brush border
membrane of intestinal epithelial cells) - 2
Na-independent (facilitated transport).
peptides di- and tripeptides by peptide
transporters. ( proteins in the newborn of
some animal species absorption of
immunoglobulins provides an important form of
passive immunity).
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Amino acid transport across the basolateral
membrane 5 classes of amino acid transporter
at the basolateral membrane (BL, table
39-3) - 2 Na-dependent - 3 Na-independent
Amino acids are transported in the portal blood
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protein digestion absorption
95
135
Absorption of vitamins
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Vitamins organic substances needed in small
quantities for normal metabolic function, growth
and maintenance of the body. Fat-soluble
vitamins Vitamins A, D, E and K
Water-soluble vitamins Vitamins B1, B2, B6,
B12, niacin, biotin and folic acid
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Water-soluble vitamins (cont.) Absorption of
Vitamin B12 Vitamin B12 (cobalamin) is bound to
a cobalamin binding protein (intrinsic factor)
secreted by the parietal cells of the stomach.
The Vitamin B12-intrinsic factor complex is
absorbed in the terminal ileum. Transport in
the blood of Vitamin B12 by binding to the
protein transcobalamin. Vitamin B12 is stored
in the liver.
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