1. duodenum

2. pancreas

3. ascending colon

4. descending colon

5. rectum

6. kidney

7. adrenal

8. bladder

1. mucosa

2. submucosa

3. muscularis externa

4. serosa or adventitia

1. mucosal epithelium: single layer of cells (absorption, protection, secretions)

2. lamina propria: mucus glands, lymph nodules (MALT), capillaries (nourishment, receives nutrients)

3. muscularis mucosa: smooth muscle (weak contractions to wiggle mucus)

connective tissue (collagen, elastin)

nerves

blood vessels

glands in some regions

lymphatic vessels

ENS: submucosal or meissner's plexus: regulates glands and muscles in mucosa and submucosa

smooth muscle for mix, propel, segmentation, peristalsis

1. inner circular

ENS: myenteric or auerbach's plexus: controls GI motility

2. outer longitudinal

last tunic is either:

serosa: protective visceral peritoneum

adventitia: derived from adjacent connective tissue > fibrous sheath in areas of high mechanical stress

oral cavity

pharynx

esophagus

rectum

stomach

small intestine

most of large intestine

mouth

oropharynx

esophagus

anal canal

1. nasopharynx

2. oropharynx

3. laryngopharynx

-oro and laryngo are stratified squamous with mucus glands

-2 skeletal layers: inner longitudinal and outer pharyngeal constrictors

all glands of stomach

mucin, bicarb

all glands in the stomach

mucins

fundus

HCl, intrinsic factor

fundus

pepsinogen and gastric lipase

antrum

G: gastrin

D: somatostatin

fundus

histamine (paracrine)

1. intrinisic activity of the pacemaker cells (ICC)

2. conditioned stimuli (extrinsic) to the salivary centers and vagal nuclei of the medulla

3. NT (neurocrines) from CNS or ENS

4. endocrine hormones (endocrines) from endocrine cells

5. local factors (paracrines)

6. other stimuli detected by sensory receptors (intrinsic): mechano, osmo and chemoreceptors

1. voluntary/buccal > upper 1/3 and 2/3 of the esophagus is skeletal muscle so its voluntary control, everything else is muscularis externa > not voluntary control

2. pharyngeal

3. esophageal

upper part of the fundus

can hold 4L or 1 gal

location: G cells of the antrum

stimulus: stomach distension, amino acids

action: 1) increase frequency and velocity of gastric slow wave

2) stimulates antrum motility (contraction)

3) raise LESP

4) stimulate gastric acid secretion (histamine from enterochromaffin-like cells and HCl from parietal cells) 

5) increases gastric emptying

location: endocrine cells in the duodenal mucosa

stimulus: fatty chyme, partially digested proteins

action:

1) inhibit gastric emptying by increasing pyloric sphincter tone

2) stimulates gallbladder secretions: increase gallbladder contraction and relax sphincter of oddi

3) stimulate pancreas secretions: acinar cell secretion of pancreatic enzymes

location: endocrine cells in the duodenal mucosa

stimulus: pH less than 4.5 in the duodenum

action:

1) stimulates pancreatic bicarb secretion: from ductal cells

2) stimulates liver water and bicarbonate secretion into bile > bile ducts

2) inhibits gastric acid secretion

3) inhibits gastric emptying

location: endocrine cells in the duodenum and jejunum

stimulus: fatty acids, amino acids, glucose

action: 1) stimulates secretion of insulin, 2) inhibits gastric emptying, 3) inhibits gastric secretion of HCl

location: endocrine cells in the duodenum and jejunum

stimulus: fasting

action: stimulates motility of stomach and small intestine

gastrin

motilin

substance P

protein

high fat

alcohol

caffeine (cola, tea, coffee)

peppermint

spearmint

chocolate

cigarette smoking

citrus juice

CCK

secretin

GIP

higher pH

isotonic osmolality

smaller particle size

lower caloric load of the contents

stimulus: presence of food in the stomach

action: sends signals to the colon through ENS to start mass movement

stimulus: presence of chyme in the duodenum

action: duodenum sends signal to colon through ENS to start mass movement

stimulation: distension in the rectum

action: PNS stimulation (from the sacral region) of the internal anal sphincter to relax, urge to defecate because contractions of colon and rectum are stimulated

-can control using external anal sphincter > voluntary control

99.5% water

.5%: electrolytes (Na, K, Cl, HCO3, PO4), digestive enzymes (salivary amylase, lingual amylase), proteins (mucins, lactoferrin, lysozyme, muramidase, defensins, IgA Ab), bicarbonate buffers

moisten air

solvent for food chemicals

moistens food for swallowing and bolus formation

primary saliva! > isotonic with plasma

1. secretions mediated by second messenger systems, receptors located on the basal membrane (Ca, cAMP)

2. secrete proteins in zymogen granules through exocytosis

3. secrete ions (Cl- is main ion excreted, but also Na, K, HCO3) > Cl/HCO3 symporter

4. secrete all water in saliva

1) modify saliva using ion transporters (Cl-HCO3 antiporter, sodium-H antiporter, H/K antiporter)

2) pH and HCO3 increase with flow rate

1) simple unconditioned salivary reflex: ingested food activates chemo and pressoreceptors

2) acquired conditioned (learned) salivary reflex: 1) thought, sight, smell, sound of food, 2) nausea increases salivation, 3) fatigue, sleep, fear, dehydration decreases salivation

extrinisic salivary glands excrete saliva

intrinisic salivary glands keep the mouth moist

bile salts

ethanol

tobacco

caffeine

corticosteroids

NSAIDS

surface mucus

neck mucus

parietal

chief

endocrine (G and D)

ECL

absorptive (enterocytes)

goblet cells

enteroendocrine

grandular/paneth cells

stem cells of the crypts

1. H+ leaks into mucosa > kills epithelia

2. less epithelia > less mucin and bicarb secretion > less protection leads to further damage

3. capillaries damaged > bleeding

4. COX inhibited (COX needed to synthesize gastroprotective PGE2 prostaglandin)

1. ach from vagal PNS or ENS which binds to M3 muscarinic receptors

2. gastrin from G cells in the antrum which binds to CCK-B receptors

3. histamine from enterochromaffin-like mast cells in the gastric mucosa which binds to H2 receptors

1. prostaglandin which binds to PGE2

2. EGF

3. SST/somatostatin fro the D cells

1. stimulate HCl release

2. stimulate pepsinogen release

3. stimulate stomach mucosal growth

4. stimulate gastric contractions

5. stimulate histamine release

1. inhibit gastrin release

2. inhibit histamine release

3. inhibit HCl secretion

stimulus: thought, smell, sight, taste of food

chewing

swallowing

action: vagus nerve CNX sends afferent to the ENS submucosal plexus to start HCl and pepsinogen secretion

stimulus: stretch receptors (distension)

increased pH (chemoreceptors)

protein

caffeine

alcohol

partially digested peptides

action: intrinsic nerves, vagus nerves, gastrin > promote HCl and pepsinogen release

1. excitatory component: duodenum wants more food > short

2. inhibitory component: inhibitory stimuli:

distension

lipids

acids

hyperosmotic chyme at duodenum

action: 

neural response: enterogastric reflex

hormonal response: CCK, secretin, GIP 

result: inhibit gastric secretion and emptying

mucosa > oblique muscle layer > submucosa > muscularis externa > serosa

-located in the stomach

muscularis externa: inner oblique, middle circular, outer longitudinal

a type of specialized epithelial cell covering the small intestine > absorptive cell

-absorptive cell is covered by brush border = microvilli

-contains integral membrane proteins > food needs to be touched to be digested

type of specialized epithelial cell

-protect intestinal epithelium from bacteria

1. smell, sight taste or thought of food > CNS > vagal efferents > ENS > effectors 

2. stimulus in GI tract > chemo/osmo/mechanoreceptors activated > vagal afferents > CNS > vagal efferents > ENS > effectors > response

-called the vagovagal reflex

1. volume of chyme in the stomach > extrinisic and intrinsic

2. fluidity of chyme

3. volume and chemical composition of chyme in the duodenum: stimulates the mechano/osmo/chemoreceptors

-can be either the neural response (intrinsic enterogastric reflex) or the hormonal response (enterogastrone release)

1. H.pylori sits on mucus barrier

2. urea > urease > bicarb + ammonia

3. ammonia kills mucus cells and damages mucus layer

4. bicarb protects the H.pylori against stomach acids

5. H.pylori burrows deeper into the mucus and stomach acids destroy the cells even more

ACINAR CELLS: luminal transporters 1. Cl/HCO3 symporter 2. Na flows through tight junctions

-Cl, HCO3, K secreted

-Cl is main ion secreted

DUCTAL CELLS: luminal transporters: 1. Na/H antiporter 2. HCO3/Cl antiporter, 3. H/K antiporter

-Na, Cl reabsorbed

-HCO3 and K secreted

NET: BICARB AND K SECRETED

1. antibiotics (tetracycline AND metranidazole)

2. bismuth containing compounds: (pepto-bismol)

-soothes the stomach and magnesium is toxic to h.pylori

3. H2 receptor blockers (cimetidine, ranitidine)

4. PPI's

1. activates pepsinogen

2. kills most bacteria/microorganisms

3. denatures proteins

4. destroys plant cell walls

5. break down animal connective tissue

6. inactivates salivary amylase

1. CO2 from blood diffuses into the parietal cell

2. CO2 converted to HCO3 and H+ using carbonic anhydrase

3. Cl/HCO3 antiporter on basal membrane brings Cl into the cell and HCO3 out into the blood

4. Cl diffuses out into the stomach lumen

5. H/K ATPase = proton pump > H+ transported into the stomach lumen and K+ brought into the parietal cell

6. HCl formed in the lumen of the stomach

1. H2 receptor antagonists: cimetidine/tagamet, ranitidine/zantac, famotidine/pepcid

2. PPI's: omeprazole/prilosec, lansoprazole/prevacid, pantoprazole/protonix

3. anticholinergics: dicyclomine/bentyl, belladona/donnatel

1. lifestyle changes: elevate the head of the bed, dietary changes to increase LSEP, stop things that decrease LSEP (smoking, alcohol)

2. antacids

3. H2 receptor antagonists: nizatidine/axid

4. PPI: rabeprazole/aciphex

5. prokinetic agents: bethanechol, metoclopramide

1. provide essential enzymes required for digestion

2. neutralizes acidic chyme

1. pancreatic amylase

-starch and disaccs > oligo and disaccs

2. trypsin

3. chymotrypsin

4. carboxypeptidase

-large poplypeptides > small polypeptides and small peptides

5. pancreatic lipase

-emulsified fats

-stored in zymogen granules and released by the acinar cells

acinar cells: release the 5 enzymes by zymogen granules

ductal cells: site of H20 and electrolyte secretion, also secretes bicarb

27% of CO 

1350 mL/min

-300 mL to the hepatic artery > nutrient rich, oxygen rich blood from the descending aorta

-1050 mL to the hepatic portal vein > nutrient rich, oxygen poor blood from the small intestine

4 lobes: 2 major (large R and small L), 2 minor (caudate and quadrate)

-liver is made up by lobules = functional units

-hepatocytes organized into octagonal plates > central vein in center and sinusoids (lined by endothelial cells and have kupffer cells) empty into the central vein

-portal triad: edge of the plates

1. hepatic duct: removes bile > joins with the cystic duct to form the bile duct that leads to the small intestine

2. hepatic portal vein: absorbed and secreted materials

3. hepatic artery: oxygenated blood for the hepatocytes

central vein > hepatic vein > inf vena cava > R atrium

1. Regulatory:

A) blood resevoir

B) filtration of blood from microorganisms by the Kupffer cells

C) synthesis of IGF's (somatomedians)

D) storage of vitamins (A, D, B12) and ions (iron in the form of ferrin)

E) forms coagulation factors (II, VII, IX, X)

F) excretion of drugs, bilirubin and liver metabolized hormones (thyroid hormones and steroids) into the bile

produces bile to be exported to duodenum

1. bile salt: amphiphatic

2. bile pigment: bilirubin from hemoglobin breakdown

3. cholesterol

4. neutral fat

5. phospholipid

6. variety of electrolytes

1. bile storage: when sphincter of oddi is closed bile backs up into the bile duct into the cystic duct > based on pressure flow gradient and heister's values

2. bile concentration: reabsorbs water so it is 20x more concentrated

1. CCK (enterendocrine cells in duodenum): stimulate gallbladder contraction and oddi sphincter relaxation

2. secretin (enteroendocrine cells in the duodenum): stimulate bile ducts to produce more water and bicarb into the bile

3. vagus nerve efferents from PNS: stimulate minor gallbladder contractions

4. recycled bile acid: get reabsorbed into the hepatocytes and cause increased bile secretion and decreased bile acid production

site of final digestion of starch and protein and absorption into the capillary system

enzymes = integral membrane proteins

1. starch and disacc enzymes: dextrinase, glucoamylase, lactase, maltase, sucrase

2. small polypeptides and small peptides enzymes: aminopeptidase, carboxypeptidase, dipeptidase

mainly mucus from goblet cells

-lubricates walls of the colon

-helps fecal matter to stay together (compaction)

STARCH AND DISACC

1. salivary amylase in the mouth

2. pancreatic amylase in the duodenum

OLIGO AND DISACC (lactose, maltose, sucrose)

3. brush border enzymes (dextrinase, glucoamylase, lactase, maltase, sucrase)

-lactase: lactose > galactose + glucose

MONOSAC (glucose, galactose, fructose)

4. glucose and galactose > SGLT1 Na+ cotransport on the luminal membrane

5. fructose > GLUT5 facilitated transport on luminal membrane

6. GLUT2 on basolateral membrane

PROTEIN

1. pepsin (activated pepsinogen in the stomach) > minor role

LARGE POLYPEPTIDES

2. pancreatic enzymes (trypsin, carboxypeptidase, chymotrypsin) in the duodenum

SMALL POLYPEPTIDES AND SMALL PEPTIDES

3. brush border enzymes (aminpeptidases, carboxypeptidase, dipeptidase)

AA, SOME DI/TRIPEPTIDES

4. Na cotransport on luminal membrane

5. other transporters on basolateral membrane

UNEMULSIFIED FATS

1. lingual lipase: minor role in the mouth

2. gastric lipase in the stomach (from chief cells)

3. emulsified by detergent action of bile salts

4. pancreatic lipolytic enzymes (3) > most important is pancreatic lipase

MONOGLYCERIDES, FATTY ACIDS, GLYCEROL

5. diffusion on the luminal membrane 

6. reesterified to triglycerides in the absorptive cell

7. protein coat added to form chylomicrons in the absorptive cell

8. chylomicrons are exocytosed on the basolateral membrane

9. lacteal system

-cholesterol converted to cholic acid (bile acid) then conjugated with glycine > bile salt

-amphiphatic

-increases solubility of lipids in the intestine and increases rate of absorption (must be bile salt+fatty acid to be absorbed into the absorptive cells)

required for absorption of fat soluble vitamins and cholesterol

1. chylomicron: exogenous triglyceride from dietary fat

-mostly triglyceride

2. very low density lipoprotein: endogenous triglyceride produced in liver

-mostly triglyceride

3. LDL: bad cholesterol, should have less than 100 mg/dL

-mostly cholesterol

4. HDL: good cholesterol, should have more than 40 mg/dL

-mostly protein and phospholipid

bile produced by the liver (stored in the gallbladder) > hepatic duct + cystic duct = bile duct > bile duct + main pancreatic duct > hepatopancreatic ampulla and sphincter to the small intestine

bile salts emulsifies fats in the small intestine > bile salts get reabsorbed at the ileum back into the liver through the hepatic portal vein

absorption rate depends on gastric emptying for poorly absorbed substances

-ethyl alcohol: water soluble, rapidly absorbed

-fasting: 30 min to reach peak alcohol

-food in gut: delays absorption by slowing down gastric emptying

-aspirin: rapidly absorbed in stomach and upper small intestine

-disrupts mucus layer and damages epithelia

-functional unit of absorption = villus

-transcellular: through the cell using sodium cotransport

-paracellular: between cells (vitamins)

absorption of most nutrients

remaining AA and peptides absorbed

site for water absorption: 1.5 L of fluid passes the ileocecal valve everday > 150 mL is lost in the stools

-max absorptive capacity is 4.5 L > too much water will cause diarrhea

-water moves by transcellular and paracellular

2L ingested, 7L from digestive secretions

92% reabsorbed in small intestine

6-7% reabsorbed in large intestine

1% lost in feces

water movement is passive > depends on solutes

keeps the luminal contents isoosmotic with plasma

mostly absorbed along small intestine through active transport

-absorption of Ca requires ACTIVATED VIT D CALCITRIOL

fat soluble vitamins (ADEK) > solubilized with micelles > absorptive cell > lacteals > lymphatic system > R thoracic duct > systemic circulation > hepatic artery > liver

water soluble vitamins (BC) > absorbed by diffusion in the small intestine 

-B12 must be complexed with intrinsic factor to be ACTIVELY ABSORBED absorbed at the ileum