GI: Physiology

fundus - up top
body - middle part
antrum - end (near duodenum)

comes from G cells in the antrum of the stomach
Gastrin: increases gastric H+ secretion, increases growth of gastric mucosa, and increases gastric motility
Stimulated by: distention of the stomach, peptides, amino acids, vagal stimulation (from gastrin releasing peptide)
inhibited by pH<1.5

Phenylalaine and tryptophan

Zollinger-Ellison (gastrinoma)
occurs when gastrin is secreted by the non-B cells of the pancreas

CCK comes from I cells in the duodenum and jejunum
CCK: increases pancreatic enzyme secretion, increases contraction of the gallbladdder (relaxes sphincter of Oddi), inhibits gastric emptying
stimulated by increased fatty acids, and amino acids

because of release of CCK - which causes contraction of the gall bladder

From S cells which are located in the duodenum
secretin: increases pancreatic HCO3- secretion, decreases gastric acid secretion, increases bile secretion
stimulated by increase in acid, fatty acids in lumen of duodenum

*the HCO3- neutralizes gastric acid in the duodenum, allowing pancreatic enzymes to function

it neutralizes gastric acid in the duodenum - allowing the pancreatic enzymes to work
released by secretin - from S cells in the duodenum

Somatostatin is from D cells (in pancreatic islets, and GI mucosa)
it decreases gastric acid and pepsinogen secretion, decreases pancreatic and small intestine fluid secretion, decreases gallbladder contraction, and decreases insulin and glucagon release
stimulated by increased acid
decrease production by vagal stimulation

somatostatin- antigrowth hormone effects (digestion and absorption of substances needed for growth)

somatostatin

from K cells in the duodenum and jejunum
GIP - exocrine: decrease gastric H+ secretion
endocrine: increase insulin release
stimulated by increase in fatty acids, amino acids and oral glucose

non-a, non-B islet cell pancreatic tumor that secretes VIP. Copious diarrhea

From parasympathetic ganglia in sphincters, gallbladder and small intestine
it increases water and electrolyte absorption, increased relaxation of intestinal smooth muscle sphincters
stimulated by increased distention and vagal stimulation
inhibited by adrenergic input

it increases smooth muscle relaxation, including lower esophageal sphincter
*If you loose NO - cannot relax lower esophageal sphincter - get achlasia (bird beak sign)

From the small intestine
it produeces migrating motor complexes (MMCs)
it is increased in fasting state

released from P/D1 cells in the stomach
causes increase growth hormone, ACTH, cortisol and prolactin secretion
increased before meals
decreased after meals

ghrelin - lost following gastric bypass surgery
associated with hyperphagia in prader-willi syndrome

made in mucosal cells (stomach, duodenum, salivary glands, pancreas) and brunner's glands (duodenum)
it neutralizes acid
it stimulated with increased pancreatic and biliary secretion with secretin
HCO3- is trapped in mucus that covers the gastric epithelium

made in parietal cells in the stomach - needed for the absorption of vitamin B12 in the terminal ileum
*autoimmune disease against parietal cells = pernicious anemia and chronic gastritis

made by parietal cells in the stomach - causes a decreased pH in the stomach
it is increased by histamine, Ach and gastrin
decreased by somatostatin, GIP, prostaglandin and secretin secretion

made by chief cells in the stomach
it digests proteins
it is increased by vagal stimulation, local acid

inactive pepsinogen - pepsin by H+

HCl and intrinsic factor

inhibits Ach - thus inhibiting the production of HCl from the parietal cells

it does not block the production of gastrin from G cells - b/c that is stimulated by GRP (not Ach)

pepsinogen - converted to pepsin in the presence of H+ (low pH)

vagus nerve - Ach - blocked by atropine

release histamine which activates parietal cells
the ECL cells are stimulated by gastrin

stimulates the release of histamine - which stimulates parietal cells (cause release of intrinsic factor and HCl)

gastrin secreting tumor that causes continuous high levels of acid secretion and ulcers

G cells produce gastrin - which directly stimulates parietal cells to make HCl - also gastrin stimulates ECL cells to make histamine which stimulates parietal cells to make HCl

Parotid, sublingual, submandibular, submaxillary glands.
Parotid is most serous (sides are serous)
Sublingual is most mucinous (mucinous in the middle)

- a-amylase (ptyalin) begins starch digestion; inactivated by low pH on reaching stomach
- HCO3- neutralizes oral bacterial acids, maintains dental health
- mucins (glycoproteins) lubricate food
- antibacterial secretory products
- growth factors that promote epithelail renewal

sympathetic (T1-T3 superior cervical ganglion) and parasympathetic (facial (VII) and glossopharyngeal (IX) nerve activity

low flow rate - hypotonic (more time to reabsorb Na and Cl)
high flow rate - closer to isotonic (less time to reabsorb Na and Cl)

facial nerve (CN VII) - it runs through the parotid gland

M3 receptor - Gq - IP3/Ca2+ = stimulates H+/K+ ATPase - secretes H+ into the gastric lumen (K+ goes into the parietal cell) - causes HCO3 - release into the lumen - alkaline tide

The Vagus nerve - stimulates the G cell via GRP which stimulates a parietal cell - via CCKb receptor - stimulates Gq - IP3/Ca2+ - stimulates K+/H+ ATPase - H goes into the gastric lumen - while K+ goes into parietal cell (HCO3- goes into gastric lumen too - alkaline tide)

inhibits the action of the H+/K+ ATPase on the gastric lumen side of parietal cells - prevents the release of acid into the gastric lumen

converts H2CO3 into H2O + CO2 and vice versa - works in kidneys (proximal tubules) and gastric parietal cells (causes alkaline tide)

they stimulate parietal cells to make HCl and intrinisc factor - they also stimulate ECL cells to release histamine that acts on parietal cells to make HCl and intrinsic factor (works on H2 receptor - stimulates cAMP - which stimulates H+/K+ ATPase - releasing H+ into the gastric lumen - and K+ goes into parietal cell

Cimetidine - reversibly blocks the interaction between histamine and H2 receptor (so can't signal parietal cell to to release HCl and intrinsic factor)

inhibits cAMP (inhibiting - H+/K+ ATPase - inhibiting release of H+)

inhibits cAMP - thus inhibiting H+/K+ ATPase activity (preventing H+ release into gastric lumen)

end in -dine
cimetidine, ranitidine, famotidine, nizatidine
they reversibly inhibit histamine from binding to H2 receptors on parietal cells (thus inhibiting cAMP - and H+/K+ ATPase activity - inhibiting H+ release into the gastric lumen)
used: peptic ulcers, gastritis, mild esophageal reflux

potent inhibitor of P-450; has antiandrogenic effects (prolactin release, gynecomastia, impotentence, decrease libido in men); can cross blood brain barrier (confusion, dizziness, headaches) and placenta.

Both cimetidine and ranitidine decrease renal excretion of creatinine

Other H2 blockers don't have this effect.

end in -prazole
omeprazole, lansoprazole
they irreversibly inhibit the H+/K+ ATPase on the gastric lumen side of parietal cells - inhibit the release of H+ into the gastric lumen

used for: peptic ulcer disease, gastritis, esophageal reflux, Zollinger-Ellison syndrome

secrete alkaline mucus to neutralize acid contents entering the duodenum from the stomach. Located in duodenal submucosa (only GI submucosal glands). Hypertrophy of brunner's glands seen in peptic ulcer disease

brunner's glands - release alkaline mucus - to neutralize the acid released from the stomach - hypertrophy of the glands seen in peptic ulcer disease

peptic ulcer disease

a-amylase, lipase, phospholipase A, colipase, proteases (trypsin, chymotrypsin, elastase, carboxypeptidases)

starch digestion - hydrolyzes 1,4 glycosidic bonds

fat digestion
lipids to fatty acids

trypsin, chymotrypsin, elastase, carboxypeptidases

peptide digestion secreted as proenzymes "zymogens" that are inactive

activated into trypsin via enterokinase/enteropeptidase an enzyme from the duodenal mucosa (brush border) - then trypsin activates the other proteases and activates more trypsin production

starts digestion, hydrolyzes a-1,4 linkages to yield disaccharides (maltose, maltotriose, and a-limit dextrans)

salivary amylase

highest concentration in duodenal lumen, hydrolyzes starch to oligosaccharides and disaccharides

at brush border of intestine - rate limiting step in carbohydrate digestion, produce monosaccharides from oligo- and disaccharides

duodenal lumen

only MONOSACCHARIDES can be absorbed (fructose, glucose, galactose)
glucose and galactose are absorbed by sodium dependent SGLT-1 transporter
fructose - absorbed via facilitated diffusion via GLUT-5 transporter
all of the monosaccharides go from the enterocyte to the blood via GLUT-2 transporter

transports monosacchardies (fructose, glucose, galactose) from enterocyte into the blood

facilitated diffusion of fructose from the lumen of the intestine into the enterocyte

reabsorbtion of glucose and galactose into the enterocyte
it is Na+ dependent!

Iron - absorbed as Fe2+ in the duodenum
Folate - absorbed in the jejunum
vit B12 - absorbed in the ileum with bile acids

unencapsulated lymphoid tissue found in lamina propria and submucosa of small intestine - contain specalized M cells that take up antigen

B cells that are stimulated in germinal centers of peyers patches differentiate into IgA-secreting plasma cells, which ultimately reside in lamina propria. IgA recieves protective secretory component and is then transported across epithelium to gut to deal with intraluminal antigen

IgA - made from peyers patches in the lamina propria and submucosa of the small intestint

M cells - specalized cells of peyers patches - role is to take up antigen

bile salts (bile acids conjugated to glycine or taurine, making them water soluable), cholestrol, phospholipids, water, bilirubin and ions

through bile!

bile
products of lipid digestion are solubilized into micelles by bile salts - the micelles allow fatty acids, monosaccharides, cholesterol to diffuse across the lumenal membrane - on the outside of micelles - there is bile salts

in the terminal ileum - if have resection of the terminal ileum - cannot reabsorb fat and will get steatorrhea

breakdown product of heme metabolism (from hemoglobin in RBC's)

heme (from hemoglobin in RBC) break down produces unconjugated bilirubin (indirect - non water soluble)- in the blood pairs with albumin - and have a albumin-unconjugated bilirubin complex - goes to the liver - UGT pairs unconjugated bilirubin with glucuronyic acid - forms conjugated bilirubin (direct - water soluble) - is excreted from the liver in bile - dumps into duodneum - bacteria in the gut change it to urobilinogen - 80% is excreted in feces as sterocobilin - gives feces its color
20% of urobilinogen is reabsorbed (10% excreted in kidneys as urobillin - gives urine its color, 90% is reabsorbed into enterohepatic circulation

bilirubin excreted in the feces - gives feces its color

bilirubin in the urine - gives urine its color