Gastroenterology Introduction
Transcript of Gastroenterology Introduction
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Salivary
Composition and
Regulation
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Intracellular
Mechanisms for
Saliva Production
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Mechanisms and Regulation of Swallowing
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Intra-luminal Esophageal Pressures
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Electrical Activity in the Gastrointestinal Muscularis Externa
smooth muscle in two layers:
inner circular
outer longitudinal
smooth muscle connected by gap junctionseach functions as a syncytium
two types of waves:
slow wavesnot action potentials
do not cause contraction
do not cause Ca2+ influx
slowly changing membrane potential
amplitude: 5- 15mV
frequency: 3- 12 cycles/ min
interstitial cells of Cajal: pacemaker(?)
spike potentialsaction potentials
threshold is -40mVfrequency is directly related to depolarization
duration of spike is 10- 20msec (10- 40X longer than a neuron)
spike frequency regulate muscle tone
spike mediated by slow Ca2+ Na+ channels
allows Ca2+ to enter the SM
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Enteric Nervous System
submucosal (Meissners) plexusexcitatory activity
1) controls local intestinal secretions
2) controls absorption
3) controls muscularis mucosa
myenteric (Auerbachs) plexus)excitatory activity
1) increased tonic contraction
2) increased intensity of rhythmic contractions
3) increased frequency of contraction
4) increased velocity of conduction (peristalsis)
inhibitory activity1) NT is VIP (vasoactive intestinal (inhibitory) peptide)
2) may regulate (lower) sphincter tone
regulatedby the ANSpost ganglionic fibers of the SYM
directly inhibit smooth muscle (minor effect)
inhibit the enteric plexi (major effect)preganglionic fibers of the PS (vagus and pelvic nerves)
increases activity of the enteric plexi
activity of the GI tract (motility and secretion)
regulatedby afferent neurons from the mucosa
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Peristalsis
coordinated contraction of the muscularis externa
which propels food through the GI tract, in the
aboral direction
-inherent property of many syncytial smooth muscle tubes
-stimulation causes inner circular muscle to contract
-usual stimulus is distention, but irritation to the epithelial
cells (chemical or physical) can initiate contraction
-smooth muscle cells downstream will be inhibited
(receptive relaxation)
-mediated by the enteric nervous system (primarily themyenteric plexus). The PS will increase force and
frequency of peristalsis.
(Called the Law of the Gut )
-peristalis can be blocked by atropine and congential
defects of the myenteric plexus
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STOMACH
Mucous (neck and surface) cellsmucus
Oxyntic (parietal) cellsHCl
intrinsic factor
Peptic (chief) cellspepsinogen
gastric lipase
G cellsgastin
(postprandial alkalosis?)
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STOMACH
Mucous (neck and surface) cellsmucus
forms protective barrier against autodigestion
small amount of absorption of H2O, ions, and some drugs
Oxyntic (parietal) cellsHCl
antimicrobial
protein denaturation
converts pepsinogen into pepsin
intrinsic factorrqrd for absorption of vit B12 (erythropoiesis)
Peptic (chief) cellspepsinogen
converted to pepsin
breaks peptide bonds (protein digestion)
gastric lipasesplits short chain triglycerides into fatty acids and monoglycerides
(MINOR effect primarily by pancreatic lipase)
G cellsgastrin
stimulates parietal cells to secrete HCl (paracrine effect)
stimulates chief cells to secrete pepsinogen (paracrine effect)
contracts lower esophageal sphincter
increases gastric motility
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Regulation of H+ Production via Parietal Cells in the Stomach
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Regulation of Gastric Emptying
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Phases of Gastric Digestion
Cephalicmediators:
sight, smell, and taste of food
effects:increased gastric secretion (vagal mediated)
Gasticmediators:
distension of stomach (stretch receptors)
decrease in gastric pH (chemoreceptors)
effects:increased gastric secretions
increased gastric peristalsis/ mixing
Intestinalmediators:
distension of duodenum (stretch receptors)
fatty acids and glucose in duodenum (chemoreceptors)
cause release of CCK and secretin (hormones)
effects:reduces gastric secretions
reduces gastric motility
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Gastric Acid Secretion During:
CEPHALIC PHASE GASTRIC PHASE
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Gastrin (hormone!) Secretion
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Pepsinogen (enzyme!) Secretion
DIGESTIVE HORMONES
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DIGESTIVE HORMONES
Gastrinstimulus:
distension of stomach, partially digested food in stomach, caffeine, high gastric pH
site of secretion:
G (enteroendocrine) cells (in pylorus of stomach)actions:
MAJOR: secretion of gastric juice, increase gastric motility, increases growth of gastric mucosa
MINOR: constricts lower esophageal sphincter, relaxes pyloric and ileocecal sphincter
Secretinstimulus:
acidic chyme in the duodenumsite of secretion:
S (enteroendocrine) cells in the mucosa of the duodenum
actions:MAJOR: secretion of pancreatic juice (high HCO3-)
MINOR: inhibits gastric secretions, increases pancreatic growth,
enhances effect of CCK
Cholecystokinin (CCK)stimulus:
amino acids, triglycerides, and fatty acids in the sm int
site of secretion:CCK cells in the small intestine
actions:MAJOR: increases pancreatic secretions, contraction of gall bladder, relaxation of sphincter of Oddi
MINOR: inhibits gastric emptying, potentiates secretin
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PANCREATIC (ACINAR) SECRETIONsecretion of digestive enzymes
Protein digestion
proteins peptides amino acids
trypsin (trypsinogen)chymotrypsin (chymotrypsinogen)
carboxypeptidase (procarboxypeptidase)
trypsinogen activated by enterokinase
(from intestinal mucosa)
trypsinogen can be autoactivated by trypsin
chymotrypsinogen and procarboxypeptidase also activated by trypsin
to prevent autodigestion of the pancreas, trypsin inhibitor is also released
(overwhelming the inhibitor leads to acute pancreatitis)
Carbohydrate digestion
starches and glycogen disaccharidespancreatic amylase
Fat digestion
neutral fats fatty acids and monoglyceridespancreatic lipase
cholesterol esterase
phopholipase
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PANCREATIC (DUCTAL) SECRETIONsecretion of bicarbonate ions
large quantity of HCO3- in the pancreatic juice to
neutralize the HCl emptied into the duodenum
from the stomach
1) CO2 diffuses into the ductule cell, combines with
H2O and forms carbonic acid
2) carbonic acid dissociates into H+ and HCO3-
3) to maintain electroneutrality, HCO3- and Na+ are
actively transported into the lumen
4) Na+ and H+ are exchanged on the basolateral
surface (source of Na+)5) increased Na+ and HCO3
- in the lumen causes
osmosis of water
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Regulation of Pancreatic Secretions
Neural:acetylcholine- vagally mediated PS response
Humoral:secretin-
stimulus: pH (< 4.5) in the duodenum
produced in inactive form (prosecretin) in S cells
effect: releases NaHCO3 into the duodenum
HCl + NaHCO3 NaCl + H2CO3- raises duodenal pH (protecting mucosa)
- acceptable pH range for pancreatic enzymes
cholecystokinin
stimulus: proteins and fats in the duodenum
produced by the I cells in the duodenum
Pancreatic secretions are regulated by duodenal contents:
1) acid in the duodenum secretin
2) fat (soap) in the duodenum
secretin + CCK
3) peptones in the duodenum
CCK
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Pancreatic Secretion During:
CEPHALIC PHASE INTESTINAL PHASE
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Secretion of Bile by the Liver
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Secretion of Bile by the Liver
0.6- 1.0L/ dayFxns:
emulsify large fat particles for lipase activity
aid in absorption of digested fat end products
aids in excretion of bilirubin and cholesterol
Biliary Secretion1. hepatocytes secrete bile into the canaliculi
large amts of bile acids and cholesterol
fat cholesterol cholic acid/ chenodeoxycholic acid
glyco and tauro- conjugated bile acids
2. terminal bile ducts hepatic ducts
addition of watery NaHCO3 soln
can double total quantity of bile
stimulated by secretin (HCO3 secretion)
Storage and Concentration of Bile in the Gallbladdergallbladder can store 30- 60 mL of bile
can store 450mL of bile secretion (12 hrs)water, Na+, Cl-, and electrolytes removed
concentrates bile constituents (bile salts, cholesterol, lecithin, and bilirubin)
caused by active transport of sodium across gallbladder epithelium
bile can be concentrated 5 fold (up to 20 fold)
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Regulation of Gallbladder EmptyingStimulatory role of Cholecystokinin
fatty foods in the duodenum
vagal and enteric nervous system (minor)
low fat meals result in poor gallbladder emptying fatty meals completely empty the gallbladder in ~ 1hr
Enterohepatic Circulation of Bile Salts 94% of bile salts reabsorbed
diffusion in the jejunum
active transport in the ileum
enter the portal blood and return to the hepatocytes
salts are nearly 100% reabsorbed in hepatocytes
resecreted into the bile
small quantities are lost in the feces
production of de novo bile salts are controlled by the availability
of bile salts in the enterohepatic circulation
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CCK Regulation of Bile Release in the Duodenum
Li S ti f Ch l t l
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Liver Secretion of Cholesterol
and Gallstone Formation
1-2 g of cholesterol removed from blood to form bile salts
cholesterol is INSOLUBLE in water
when combined with bile salts and lecithin, form micelles
micelles form a colloidal soln when the amt of cholesterol exceeds the levels of bile salts and
lecithin to solubilize them, cholesterol stones will precipitate out
excessive water and bile salt reabsorption by the gallbladder
epithelium may also cause cholesterol precipitation
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Secretions in the Small Intestine
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Secretions in the Small Intestinesecretion of mucus by Brunners glands in the duodenum
secrete large amts of alkaline mucus near papilla of Vater
stimulus:
tactile or irritating stimulus in duodenum
vagal stimulation (inhibited by SYM: cause of duodenal ulcers)
secretinfxn: protection from acidic gastric juices
secretion of intestinal digestive juices by crypts of Lieberkuhnlie btwn intestinal villi
similar to villi, contain:
goblet cells- produce mucus
enterocytes- secrete water and electrolytes
(all secretions reabsorbed by the enterocytes of the villi)
two active secretory processes:
Cl- secretion
HCO3- secretion
(Na+ and H2O follow)
secretion of digestive enzymes by villienterocytes have digestive enzymes active during absorption through the epithelium
1) peptidase: small peptides amino acids
2) sucrase, maltase, isomaltase, and lactase: disaccharidesmonosaccharides3) intestinal lipase: neutral fats glycerol and fatty acids
Secretions of the Large Intestinemucus secretion
protects against intestinal excoriation
provides adherent medium for holding fecal matter together
protection against bacterial activity in the feces
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Gastrointestinal Blood Flow
illustrated is the villus in the small intestine
blood flow is directly related to GI activity
during absorption and peristalis, Q may increase 8X
Countercurrent Blood Flownotice that arterial and venous blood flow in opposite directions in the villi
so what?!
Increased blood flow:
1) CCK, VIP, secretin, gastrin
a) secreted from the mucosal cells
2) kallidin and bradykinin
a) secreted from GI glands
b) powerful vasodilators
3) decreased oxygen (adenosine mediated)
a) where does adenosine come from?
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Hepatic Portal System
everything absorbed from the intestines travels to
the liver
nonfat, water soluble nutrients hepatocytes (storage)
reticuloendothelial cells (immunological)
fats into the lacteals and then lymphatic system
Digestion of Carbohydrates
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Digestion of Carbohydrates
sourcessucrose (cane sugar), lactose (milk), and starches (polysaccharides)
amylose, glycogen, alcohol, lactic and pyruvic acid, pectins and dextrins
cellulose: no enzymes exist to hydrolyze cellulose
digestion of carbohydrates in the mouth and stomachptyalin (a amylase)- in saliva in the mouthhydrolyze starches into maltose and glucose polymers
deactivated by stomach acid
digestion of carbohydrates in the small intestinepancreatic amylase- from pancreatic acinar cells; secretin regulated
all carbohydrates hydrolyzed to maltose and/ or sm glucose polymers by upper jejunum
hydrolysis of disaccharides into monosaccharides by intestinal epithelial enzymeslactase: lactose galactose and glucose
sucrase: sucrose fructose and glucose
maltase: maltose and sm glucose polymers glucose
a- dextrinase: maltose and sm glucose polymers glucose
Digestion of Proteins
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gest o o ote s
digestion of proteins in the stomachpepsin: most active btwn 2.0- 3.0, inactive > pH 5.0
only enzyme able to appreciably digest collagen
does NOT fully digest proteins into amino acids
digestion of proteins by pancreatic secretionsproteolytic pancreatic enzymes:trypsin and chymotrypsin: small polypeptides
carboxypeptidase: carboxy-teminal amino acids
proelastase: digests elastin fibers
digestion of peptides by enterocyte peptidaseson the brushborder (microvilli) of the enterocytes
aminopolypeptidase
dipeptidase
proteins absorbed as tri- and di- peptides or single amino acids)
Digestion of Fats
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g
sourcesneutral fats (triglycerides)
composed of glycerol and three fatty acids
sm quantities of phospholipids, cholesterol, and cholesterol esters
digestion of fats in the intestines/emulsification of fat by bile acids and lecithin
agitation in the stomach begins emulsification
most emulsification occurs in the duodenum w/ bile and lecithin
emulsification increases the surface area of the fats by 1000X
digestion of triglycerides by pancreatic lipasepancreatic lipase- from pancreatic acinar cells
enteric lipase- from enterocytes
role of bile salts
accelerates fat digestion
formation of micelles
digestion of cholesterol esters and phospholipids
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ABSORPTIVE PATHWAYS
POSTABSORPTIVE PATHWAYS
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POSTABSORPTIVE PATHWAYS