gastroenterology introduction

7/31/2019 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

gastroenterology introduction

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