Gastro Physiology Flashcards
Gastric mucosa 3 layers
Mucuosal consists of epithelial cells (absorptive & secretory functions), lamina propia (conncetive tissue, blood/ lymph vessels), muscalaris mucosae (smooth muscles)
Gastric Submucosa
collagen, elastin, most of the blood vessels & the submucosal plexus (Meissner’s
Gastric hormones (4)
released from endocrine cells (free cells or clusters spread over large areas but not concentrated in glands) of GI into portal circulation, pass thru liver to systemic circulation & target cells in the GI (gastrin, CCK, secretin, GIP)
Gastric paracrine
peptides that act a short distance from where they are released; only paracrine is somatostatin which inhibits actions throughout GI (histamine acts locally but it is not a peptide)
from cholinergic neurons: contract smooth muscle in wall & relax sphincters, increase salivary, gastric, pancreatic secretion
Ach
from adrenergic neurons: relax smooth msucle in wall and contract sphincter, increases salivary secretion
NE
NT that increases gastric secretion
GRP
from neurons of mucosa & smooth muscle: contraction of smooth muscle, decreases intestinal secretion
Enkephalin (opiates)
neurons of mucosa and smooth muscle, relaxes smooth muscle, decreases intestinal secretion
Neuropeptide Y
cosecreted with Ach, contracts smooth muscle increasing salivary secretion
Substance P
Gastrin - 2 types
little gastrin (G-17 secreted by G cells in atrum in response to food & G34 between meals – both come from different biosynthetic pathways); the C-terminal tetrapeptide is minimal fragment necessary for activity (1/6 as active as the entire gastrin molecule); functions to increase H+ secretion and growth of gastric mucosa (small peptides and amino acids in stomach (esp. aromatics like tryptophan and phenylalanine), distention of stomach, vagal stimulation through GRP causes release; inhibited by low gastric acid pH
CCK
promotes fat digestion & absorption; has the same C-terminal as gastrin & therefore some gastrin activity (but you need the C-terminal heptapeptide); secreted by the I cells of the duodenal and jejunal mucosa; response to presence of monoglycerides/ FFAs but NOT TAGS, and to small peptides (fat & protein stimuli) 5 actions: increases secretion of pancreatic enzymes, bicarb, inhibits gastric emptying, stimulates gall bladder contraction & also relaxation of the sphincter fo Oddi, stimualtes growth of exocrine gall bladder and pancreas
Secretin
needs the entire molecule to be active; from the S cells of the duodenum in reponse to H+ and DDAs in the lumen; pancreatic lipases function optimally at pH of 6-8 and are inactivated at pH < 3; secretin inhibits the effect of gastrin
Gastrin Inhibitory Peptide (GIP)
from cells of duodenal and jejunal mucosa in response to all 3 nutrients (carbs, peptides, fats), stimulates insulin secretion
motilin
from upper duodenum during fasting states; initiates the gastrointestinal motility- the interdigestive myoelectric complexes at 90 minute intervals
pancreatic polypeptide
response to nutrients fat, protein, carbs to inhibit pancreatic secretion of bicarb and enzymes
Frequency of slow waves along GI tract
stomach with the lowest rate, duodenum with the highest rate; frequency of waves is not influenced by hormones (but the APs/ contractions are influenced)
Origin of slow waves (pacemaker?)
interstitial cells of Cajal in the myenteric plexus
Phases of swallowing
oral (tongue pushes food to pharynx w/ high density of somatosensory receptors to initiate involuntary swallowing reflex in medulla)
pharyngeal (pharynx upper esophageal sphincter opens by swallowing reflex and inhibit breathing), esophageal by reflexes)
esophageal phase (primary peristaltic wave coordinated by swallowing reflex, but if food not cleared, a secondary peristaltic wave is initiated by distention of the esophagus (mediated by the enteric NS)
Lower esophageal sphincter opens by
by vagal N, which is petidergic and releases VIP to relax LES
Receptive Relaxation
VIP also relaxes the orad region of the stomach
Esophagus intrathoracic location (only the LES is in the abdomen), intraesophageal pressure is loess than atm P & lower than abdominal pressure problem of keeping air out and no GERD resolved w/ …?
upper and lower esophageal sphincters
The thickness of the stomach muscle wall increases …
distally
fundus, proximal body of stomach; receptive relaxation (vagovagal reflex - VIP) increases the volume to accommodate up to 1.5L food
Orad region
distal body & antrum (caudad has a much thicker wall & more forceful contractions); retropulsion propels gastric contents back into stomach for further mixing
Caudal region
Migrating myoelectric complexes
at 90 minute intervals function to clear the stomach (3-4 min interval frequency), PNS (gastrin & motilin as well) increases APs and SNS (secretin, GIP) decrease APs
Neurocrins from PNS - name 3
VIP, enkephalins, motilin
2 kinds of contractions in small intestine
segmentation: mixing chyme w/o forward movement & peristaltic – forward movement
Orad contraction involves 2 compounds?
ACh and Substance P
Caudal relaxation involves 2 compounds?
VIP and NO
gastrocolic reflex
distention of the stomach increases frequency of mass movement sin the large intestine
parotid glands
serous cells – aqueous fluid
Kallikrein
involved in synthesis of bradykinin, a potent vasodilator; during periods of high saliva flow, increase in bradykinin increases bloodflow
4 components of gastric juices
Pepsinogen - pepsin by low pH to digest proteins
HCl - lowers pH to activate pepsin
IF - B12 absorption
Mucus protects against corrosive effects of HCl
oxyntic glands
Body of the stomach contains oxyntic glands, which empty their secretory products into the lumen of the stomach
oxyntic cells
parietal cells, secrete IF and HCl
3 phases of gastric HCl secretion
cephalic (anticipation) - 30%
gastric - 60%
intestinal - 10%
inhibited by a low pH
Prostaglandins in stomach?
increase secretion of both mucus and bicarb, thereby enhancing the protective barrier
chief cells
peptic cells, secrete pepsinogen
G cells
secrete gastrin into bloodstream
Mucus neck cells secrete
mucus, bicarb, pepsinogen
Acinar cells of pancreatic exocrine tissue?
secrete enzymes (amylase and lipase are secreted as active enzymes); pancreatic proteases are inactive & made active in the duodenum; the stimulus for the enzyme secretion is the presence of peptides in the duodenum
Centroacinar cells & ductal cells
secrete aqueous HCO3 initially isotonic (stimulus for the aqueous secretions is the presence of H+ ions)
CCK secretion by?
Note:
Intestinal phase of pancreatic secretion: CCK receptors on acinar cells, most important stimulus for the enzymatic secretions
I cells secrete CCK due to presence of small peptides (tryptophan, phenylalanine, methionine) & fatty acids / Ach stimulates enzyme secretion by vagovagal reflexes
Major stimulus for aqueous secretion?
Secretin from the S cells of the duodenum in response to low pH in the duodenum
Aqueous secretions contain bicarb
Primary Bile Acids
(made by hepatocytes): Cholic Acid & Chenodeoxycholic Acid
Secondary Bile Acids
(dehydroxylated by intestinal bacteria) Deoxycholic Acid & Lithocholic Acid
Conjugation of Bile Acids to bile salts (makes them more water soluble)?? how?
the liver conjugates bile acids with amino acids, glycine & taurine to form bile salts, this changes the pKs of bile acids more water soluble (lower pKas allow them to be ionized at a pH of 3-5)
major bile pigment?
Bilirubin – byproduct of hemoglobin metabolism, the major bile pigment; cells of the reticuloendothelial system degrade hemoglobin, yielding bilirubin, which is carried in the blood bound to hemoglobin
-The liver extracts bilirubin from blood & conjugates it to glucoronic acid to form bilirubin glucuronide, which is secreted into bile & excreted in feces
Formation of urobilinogen
Some bilirubin glucoronide is decongugated & reduced to urobilinogen by intestinal bacteria, some excreted, some reabsorbed
Rate limiting step in bile acid synthesis
cholesterol 7-alpha hydroxylase
-alpha-amylase role? formation of 3 dissaccharides?
digests the 1,4 glycosidic binds in starch leading to formation of 3 dissacharides =
alpha-limit dextrins
maltose
maltotriose
intestinal brushborder enzymes
alpha-dextrinase, maltase, sucrase
3 monosaccharides
glucose, galactose, fructose
Trehalose
2 glucose
Lactose
glucose, galactose
Sucrose
Fructose
Glucose
glucose & galactose transport
Glucose & galactose are cotransported w/ sodium into epithelial cells (secondary active transport – uses the electrical gradient created by the Na-K ATPase on the basolateral surface
Fructose transport
facilitated diffusion
Exopeptidases
hydrolyze one amino acid at a time from the C-terminal
Endopeptidases
interior peptide bond of proteins, includes in the stomach, pepsin, and in the small intestine: tryptin, chymotrypsin, elastase, carboxypeptidase A, carboxypeptidase B (all of these proteases are activated by trypsin (which is activated by enterokinase in the brush border)
Pancreatic Lipase
triglyceride > Monoglyceride + 2 FAs
Pancreatic lipase is inactivated by bile acids, but to solve this problem it is secreted w/ colipase, activated in intestinal luman by trypsin, displaces the bile acids from interphase so lipase can function
Choleserol ester hydrolase
cholesterol ester cholesterol + FA
Phospholipase A2
Phospholipid Lysolecithin & FA
Water Soluble Vitamins
B1, B2, B12, C, biotin, nicotinic acid, pantothenic acid – sodium dependent transport in small intestine w/ exception of B12 (cobalamin) – requires intrinsic factor
Fat Soluble Vitamins
diffuse across apical membrane & are incorporated into chylomicrons
B12 absorption
Free salivary B12 binds R protein, IF is secreted by gastric parietal cells, pancreatic proteases degrade the R protein, absorbed by specific transporters in the ilium
Calcium absorption
depends on 1,25 dihydroxycholecalciferol, which induces synthesis of Vit D-dependent Ca2+ binding protein (calbindin D-28K) in intestinal epithelial cells
Iron absorption
Iron is absorbed across the apical surface by intestinal epithelial surface as free iron or as heme iron; inside the cells, heme iron is digested by lysosomal enzymes to release free iron, which binds apoferritin & is transported across to blood bound to beta-globulin called transferrin (takes from SI to liver to bone marrow)
Jejunum electrolyte absorption
Jejunum – major site for sodium reabsorption; ~ early proximal tubule of the kidney (sodium enters cell, coupled w/ glucose / galactose; H+ secreted into the lumen & bicarb into blood net absorption of NaHCO3
Ilium electrolyte absorption
also contains a Cl-HCO3 exchange on apical surface (secretes bicarb into the lumen) net absorption of NaCl
Colon electrolyte absorption
similar to principle cells of the collecting duct of the kidneys; sodium channels (and chloride channels) – increased by aldosterone, secretes potassium into the lumen; increased flow rate in colon increases channel activity (can lead to potassium wasting)
Sucrose
Fructose (needs fructokinase, aldo B)
glucose
lactose
galactose, glucose
maltose
2 glucose
