Transcript GI Physiology IV: Early Intestinal Phase of Digestion

GI Physiology IV:
Early Intestinal Phase
of Digestion
IDP/DPT GI Course, Fall 2011
Jerome W. Breslin, Ph.D.
LSUHSC-NO Department of Physiology
MEB 7208 (1901 Perdido St.)
568-2669
[email protected]
Required Reading
• Kim Barrett, Gastrointestinal Physiology
• Chapter 5 - section on cellular basis
of transport
• Chapter 9
• Chapter 15
• Chapter 16
Outline - Lecture 4
• Quick review of some things from lecture 3
• The Small Intestine & Early Intestinal Phase of
Digestion
• Regulation: Secretin and Cholecystokinin
• Motility of the Small Intestine
• Intestinal Digestion and Absorption
• Proteins, Carbohydrates, Lipids
• Water Soluble Vitamins
• Water and Electrolytes
Figure 15-34
Video endoscopy has
greatly enhanced our
understanding of
normal processes
in the gut,
and reveals
complications
resulting from
disease.
Intestinal Phase
•Initiated by entry of chyme from the stomach
into the duodenum.
• Reflex response to distention, low pH, osmolarity, and
various digestive products.
•Responses:
•Modification of osmolarity of chyme.
•Modification of luminal pH.
•Secretion of enzymes.
•Secretion of emulsifying agents.
•Regulated patterns of motility.
Figure 15-24
(CCK, Secretin)
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.
The Small Intestine
•GI section between pyloric sphincter
and ileal-cecal valve.
•3 sections – duodenum, jejunum &
ileum.
•Digestion, secretion and absorption
all occur here.
•Final site of digestion.
•Neuro-hormonal regulation of both
secretion and motility.
Figure 15-7
nutrients
By projecting
into the lumen,
the villi increases
the surface area
for absorption of
nutrients.
Microvilli [aka brush
border] fringe the
villi to further increase
surface area.
Figure 15-27
Secretin’s receptors are
found in the pancreas, which
responds with additional
bicarbonate delivery: gastric
motility and secretion are
inhibited.
Secretin is secreted by
the S Cells in the
Crypts of Lieberkühn.
Figure 15-31
Cholecystokinin (CCK)
stimulates the
gallbladder, which
responds by
contracting and
delivering more
bile to the duodenum
through the sphincter
of Oddi, which relaxes
(opens) in response to
CCK.
CCK is secreted by the
intestinal mucosa.
Figure 15-28
Cholecystokinin’s receptors
are located:
• in the pancreas, which
responds with additional
enzyme delivery
• in the gallbladder, which
contracts to deliver more
bile
• in the sphincter
of Oddi, which relaxes to
facilitate delivery of the
enzymes and bile salts
Intestinal Motility
•Intestinal motility is coordinated by the
enteric nervous system and modified by
long and short reflexes and hormones.
•During and shortly after a meal, intestinal
contents are mixed by segmenting
movements of the intestinal wall.
•After food is digested and absorbed,
segmentation is replaced by peristalsis
moving undigested material from small
intestine into large intestine.
Fig 9-4
Barrett
Small Intestinal Motility
• SEGMENTATION/MIXING
• stationary contraction/relaxation cycles
• subdivision and mixing of chyme
• pacemaker cells generate basic electrical
rhythm
• BER decreases along length of intestine
•duodenum 10-12/min
•Ileum 7-9/min
• slow migration toward large intestine
Small Intestinal Motility
(continued)
• MIGRATING MYOELECTRIC COMPLEX
• Peristaltic activity that replaces segmentation at
completion of absorption
• Repeated waves traveling about 2 feet
• Migrates down small intestine taking about 2 hr to
reach large intestine
• Process repeated from beginning
• candidate hormone: motilin
Fasting Motor Pattern:
“Migrating Myoelectric Complex” (MMC)
From Stomach to the Ileum
~100 minute cycle: Phase I (~50 min) = quiescent
Phase II (~40 min) = irregular contractions
Phase III (5-10 min) = forward contractions
Regulation of MMCs is poorly understood:
1. Independent of vagus and splanchnic innervation
2. Phase III of the MMC is related to elevated plasma
Motilin (secreted by M cells).
Just before vomiting, BER is suspended.
Then, rapid burst of electrical activity moving in the oral direction.
Laxatives (Cathartics) cause increased spike potentials, and more forward contractions.
In the above example, castor oil can act as a laxative vs. a control oil (triolein).
Intestinal Digestion
•Chyme mixed with secretions from
pancreas, liver & duodenum.
•Secretions modify the pH, osmolarity,
and continue the digestive process to
make the digested material ready for
absorption into the intestinal blood or
lymphatic system.
•Type and volume of secretions
depend on the constitution of the
chyme.
Digestion
in
the
Gut
3 SUB-PHASES OF INTESTINAL
• LUMINAL
• Mixing of chyme with enzymes
• BRUSH BORDER
• Specific enzymes present on the
DIGESTION
luminal surface of the enterocytes
• CYTOSOLIC/INTRACELLULAR
• Intracellular digestion in the
enterocytes
Digestion in the Gut
• Proteins:
• All 3 phases, luminal, brush border and
cytosolic digestion may be involved
• Carbohydrates:
• Only luminal and brush border digestion –
no intracellular digestion by the enterocyte
• Lipids:
• All digestion is luminal; triglyceride is reformed in the enterocyte!
Figure 15-26
Were digestive enzymes synthesized in their active form, they would
digest the very cells that make them. Hence, inactive precursors (e.g.,
trypsinogen) become activated (trypsin).
Absorption in the Gut
• Proteins:
• Active transport of amino acids and small
peptides (< 5 amino acids).
• Carbohydrates:
• Uptake of monomers only
• Active transport of glucose; facilitated diffusion
for other sugars.
• Lipids:
• Uptake of free fatty acids and glycerol.
• Mechanism of uptake by the enterocytes
probably diffusion.
is
Three sites of protein
digestion:
1. Lumen
2. Brush
Border
3. Cytoplasm
PepT1
Short peptide uptake
coupled to proton transport
Barrett
Fig. 15-8
Activation of Proteases in the Small Intestine
Fig. 15-6
Protein Digestion
•Proteases stored in inactive form in pancreas
& secreted in response to neurohormonal
stimulation.
•Pancreatic trypsinogen converted to active
form by duodenal brush-border enterokinase.
•Trypsin activates all other luminal peptidases.
•Digestion of oligopeptides in lumen and small
peptides at brush border.
•Uptake of free amino acids, di- and tripeptides by active transport mechanisms.
•Cytosolic degradation of di- and tri-peptides.
Amino Acids, Dipeptides, and Tripeptides are
Absorbed by Specific Transporters.
Cytoplasmic
Peptidases
Barrett,
Fig. 15-8
There are also many brush border transporters for individual
amino acids.
Carbohydrate
•Polysaccharides digested in duodenal
lumen by pancreatic amylase to produce
oligosaccharides and disaccharides.
•Brush border digestion of polymers by
specific amylases and disaccharidases
forms monosaccharides.
•Simple sugars taken up by active transport
processes into enterocytes.
•NO uptake of disaccharides or
oligosaccharides!
Carbohydrate Digestion &
Absorption (continued)
•Sugars enter blood stream by facilitated
diffusion or active transport mechanisms.
•Glucose in the intestinal lumen stimulates the
release of GIP (Glucose dependent
insulinotropic peptide or gastrointestinal
inhibitory peptide).
•GIP stimulates the release of insulin from the
pancreas in anticipation of glucose in the
portal blood.
•GIP inhibits gastric motility to facilitate
Digestion of Carbohydrates Occurs in
the Intestinal Lumen & at the Brush
Border
Berne & Levy Fig. 33-2
Monosaccharides are absorbed by
specific transporters on the brush border
membrane.
Berne & Levy Fig. 33-2
1. Sodium gradient for SGLT1 driven by Na+/K+ ATPase.
2. Basolateral GLUT2 transports monosaccharides to the blood.
Berne & Levy Fig. 33-4
Lipid
Digestion
&
Absorption
•Lipid digestion in luminal phase
only.
•Digestion requires bile salts,
pancreatic lipase, co-lipase and
phospholipids.
•Lipids emulsified by bile salts and
phospholipids.
•Triglyceride digested to form free
fatty acids and a monoglyceride.
•Digestion productions taken up by
Figure 15-9
A molecular model
of a bile salt, with the
cholesterol-derived
“core” in yellow.
A space-filling model
of a bile salt. The
non-polar surface
helps emulsify fats, and
the polar surface
promotes water solubility.
Figure 15-10
Bile salts and
phospholipids convert
large fat globules into
smaller pieces with
polar surfaces that
inhibit reaggregation.
Figure 15-12
Big Droplets of Fat
Small Droplets of Fat
Micelles
Fatty Acids and
Monoglycerides
Chylomicron Assembly
Distribution and Processing
Figure 15-11
Emulsified fat globules are
small enough that lipase
enzymes gain access to
degrade triglycerides
to monoglycerides and
fatty acids, which enter
the absorptive cells by
simple diffusion or aggregate
to form loosely held micelles,
which readily break down.
Lipid Absorption
•Free fatty acids and monoglycerides reformed into
triglycerides inside the enterocytes.
•Triglycerides packaged together with cholesterol
and apo-lipoprotein molecules to form very large
lipoproteins – CHYLOMICRONS.
•Chylomicrons secreted into lacteals – terminal of
lymphatic system - enters systemic circulation in
neck.
Water Soluble
Vitamins
• Each has specific transporters (too many to
mention)
• Vitamin B
12:
Requires Intrinsic Factor
secreted by parietal cells in stomach.
• Pernicious Anemia: Caused by Vitamin B
12
deficiency secondary to Atrophic gastritis
(chronic inflammation of stomach mucosa),
or more specifically loss of parietal cells.
Intrinsic Factor is
required for vitamin
B12 (cobalamin)
uptake.
Absorption is in
terminal ileum.
Fig. 15-9, Barrett
•
Water and Electrolyte
Absorption in the Small
Sodium absorption
generally coupled to
Intestine
nutrient absorption (e.g. SGLT1,
PEPT1).
• Electrogenic: forces anions (mainly
chloride) to passively follow the
sodium transport by paracellular
route.
• Water transported passively, following
osmotic gradients (favoring absorption).
Water balance
in the GI tract.
Barrett, Fig. 5-1
Chloride secretion in small
intestine and colon.
Barrett,
Fig. 5-8
Fig. 5-4: Balance between absorption andCholera
secretion in health and secretory diarrhea.
toxin binds and activates the Gs Gprotein, causing elevated cAMP and
increased Cl- secretion. Leads to secretory
diarrhea.
Fig. 5-9: cAMP regulates CFTR
Immature cells in Crypts of Lieberkuhn
Bicarbonate secretion in the
duodenum
Neutralization of HCl
from the stomach.
Fig. 5-10 in
Barrett
GUT LUMEN
H2CO3
Cl
-
H2O
H+
H2O + CO2
HCO3-
Na+
Cl-
CFTR
Na+
IMMATURE CELLS IN
CRYPTS OF LIEBERKUHN
ClMATURE ENTEROCYTES
2ClK+
Na+
Na+
K+
Na+
CO2
Na+
K+
K+
ATP
K+
Na+
ATP
K+
2Cl-
BASOLATERAL AREA
CO2