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Flashcards in GI Function and Regulation Deck (62):

What are the four main functions of the GI tract?






Where does the bulk of absorption occur?

small intestine


T or F. Practically the entire GI tract is colonized by bacteria

T. 99% in the large intestine and rectum, and none usually in the stomach due to the acidic nature 


The epithelium is polarized both functional and structural with the basal membrane being attached to the BM and the apical membrane being formed into many microvilli (aka brush border)


What are the main cells of the epithelium?

the absorptive, endocrine, goblet, and M cells


Describe the anatomy of GI epithelium

it is folded heavily into finger-like villi with intermittent, depression-like crypts which house the stem-cells of the epithelium. The epithelium sloughs and is renewed about every 3-4 days


How does blood flow to the GI change after a meal?

increases up to 8x

NOTE: This effect can be so pronounced as to decrease peripheral BP after/during a meal/heavy stomach activity


What mediates the increase in GI blood flow during/after a meal?

secretion of mucosal vasodilators, such as CCK, VIP, gastrin, and secretin

Kallidin is secreted and activiates bradykinin, a potent vasodilator

And the reduced O2 concentration to the heavy metabolic activity might result in increased blood flow


How might villi respond to chronic levels of low oxygen?

Because there is a continuous arterial-to-venous blood shunt that occurs along the vertical path of the villi that even under normal circumstances shunts 80% of oxygenated blood into venous circulation without perfusing the villi, a. hypoxia would exacerbate this shunt and lead to villi necrosis 


How is the GI blood flow regulated?

Parasympathetic increased blood flow and sympathetic decreases


Describe the parasympathetic innervation of the GI

this mostly consists of the efferent and affarent fibers of the vagus and pelvic nerves from the brain and sacral regions of the spinal cord.


Describe the sympathetic innervation of the GI

Neurons in the spinal cord synapse in the celiac, SM, and IM ganglia, which then use another set of ANS fibers to synapse into the GI organs


Where is the myenteric plexus located?

between the circular and longitudinal layers of smooth muscle in the muscularis externa 


The enteric system can allow the GI to function even in the absence of central neural input


What neurotransmitters function in the extrnsic nervous system of the GI? Intrinsic?

Extrinsic- Ach and NE

Intrinsic- Substance P and VIP


What are the main functions of substance P and VIP?

Substance P is activating to the GI smooth muscle, and VIP is inhibitory


What are the main types of neurotransmitter systems in the GI?

Endocrine (e.g. gastrin)

Paracrine (e.g. histamine)



What are the 5 major GI hormones?







What are the candidate (i.e. the physiologic function is not completely established yet) GI hormones?

Pancreatic polypeptides


Substance P




What are the main criteria for GI hormones?

-stimulation and activity seen in different parts of the GI

-Effective in the absence of nerves (ie not neurocrine)

-Can be isolated from the site of stimulation

-Substance and structure confirmed


What are the major groups of GI hormones?

-based on structure homology

gastrin-family (gastrin, CCK)

secretin family (secretin, VIP, GIP, and Glucagon)


Describe the structure of Gastrin

It is a 17 AA peptide that is aminated at the C-terminal and cyclized at the N-terminal, which both make the peptide VERY stable (cant be broken down by carboxypeptides, aminopeptidases, etc.)

NOTE: Gastrin is originally synthesized as a 34-AA pro-gastrin structure in the G-cells in the stomach, which produce a protease to produce a glycine-exteded gastrin, which does NOT act on CCK-2 receptors (may have other receptors). Amination of the C-terminal removes the glycine to produce active G-17 


What is the minimum sequence required for biologic activity of Gastrin?

Trp-Met-Asp-Phe (NH2) at the C-terminal.



What is the main function of gastrin?

to stimulate perietal cells to secrete gastric acid via binding to the gastrin/CCK-2 receptors (not CCK-1 receptors)


What is the difference between Gastrin 1 and 2?

Gastrin 1 is not sulfated at the 12-AA tyrosine, while Gastrin 2 is, which has a MUCH higher affinity for the gastrin receptor and thus is much more active


What is the half-life of G17?

7 minutes 

NOTE: There is also a G-34 produced by G cells in the duodenum that is not the same as the pro-gastrin produced in the stomach and has a half-life of about 38 minutes. We dont know its function yet


Notice that since the 5-AA on the C-terminal are identical to gastrin, it can also stimulate acid secretion

Notice here the tyrosine moves to the 7AA from the C-terminal and is ALWAYS sulfated unlike gastrin


What receptor does CCK work through?

CCK-1 only when sulfated and CCK-2 when desulfated

NOTE: sulfated gastrin II cannot bind to CCK-1 receptors, so it seems that having the tyrosine on the 7AA position is important for acting through CCK-1



T or F. If the 7-AA tyrosine from the C-terminal is desulfated, it cannot work on the CCK-1 receptors

T. When this happens, it can bind to CCK-2 receptors and act like gastrin to stimulate acid secretion


One of the main functions of CCK is gallbladder contraction via CCK-1 receptor binding


T or F. For the hormones of the secretin family, i.e. secretin, VIP, GIP, and glucagon, there is no minimum sequence needed for activity, but instead the ENTIRE sequence is needed



The apical membrane may have receptors that stimulate release of hormones into the circulation


Blue is where these hormones are made normally and the black is where they can be made under pathological conditions


What are the criteria for physiologic roles of GI hormones?

-responds to endogenous normal stimuli

-active dose (D50) matches endogenous concentration

-Response to continuous administration, not just bolus


What are the main functions of gastrin? What stimulates it to be released?

acid secretion and mucosal growth

It is stimulated to be released from protein, stomach distension, and nerve input after/during a meal because protein digestion requires acid and proteases (acid inhibits its release)


What are the main functions of CCK? What stimulates it to be released?

pancreatic HCO3- and enzyme secretion

gallbladder contraction (to stimulate more HCO3- release from bile)

pancreatic growth

inhibited gastric emptying

Stimulators: protein, fat, and acid (some) because fat digestion and absorption requires lipases and bile salts


What are the main functions of Secretin?

-pancreatic HCO3- secretion

Bile HCO3- secretion

pancreatic growth


What stimulates secretin release?

acid and fat (some)


What are the main functions of GIP?

stimulates insulin release from oral glucose 

inhibits acid secretion


What are the main functions of Motilin?

stimulates gstric and intestinal motility


What are the main neurocrines of the GI?


-Bombesin or GRP



What is the site of release of VIP?

mucosa and smooth muscle of GI tract


What are the actions of VIP?

relaxes sphincters and gut circular muscle

stimulates intestinal and pancreatic secretions

relax vascular smooth muscle to increase blood supply to the intestine


What is the function of Bombesin/GRP?

This is released from gastric mucosa neve endings that stimulates gastrin release from G cells in the stomach antrum


Where are Emkephalins released?

mucosa and smooth muscle of GI tract


What are the functions of Enkephalins?

stimulate smooth muscle contraction and inhibit intestinal secretions


What are the main paracrine molecules?

somatostain and histamine


What are the actions of somatostatin?

inhibits gastrin release and basically all other hormone release (glucagon, insulin, growth hormone, etc.)


Where is somatostatin released from?

GI mucosa and pancreatic D cells


What are some releasers of somatostatin?


NOTE: Vagus nerve inhibits release


What are the main functions of histamine in the GI?

stimulates acid secretion (gastrin can directly act on parietal cells to some extent but mainly promote acid release by stimulating histamine)


Where is histamine released in the GI?

oxyntic gland mucosa ECL-cell


What are the main releasers of histamine in the GI?

gastrin and Ach


What are the main releasers of GIP?

protein, fat, and carbs


What are the main releasers of Motilin?

nerve primarily, and

some fat and acid


What is Zollinger-Ellison Syndrome?

A syndrome marked by a gastrinoma, a gastrin-secreting tumor that can occur in the pancreas, although it is most commonly found in the duodenum


Where do most gastrinomas occur?

More than 80% of gastrinomas arise within the triangle defined as the confluence of the cystic and common bile duct superiorly, the second and third portions of the duodenum inferiorly, and the neck and body of the pancreas medially.

Those occurring in the pancreas have a greater potential for malignancy


What is the clinical triad of Zollinger-Ellison syndrome?

Duodenal ulcers, diarrhea, and steatorrhea


What causes the diarrhea seen in ZES?

The acidic content of the small intestine causes the release of secretin, which is responsible for the diarrhea, in part, caused by the outpouring of water and bicarbonate from the pancreas and small intestine.

Excessive HCl acid production also causes hyperperistalsis


What causes of steatorrhea seen in ZES?

the high amounts of acid cause inactivation of pancreatic lipase causing decreased absorption of fat, leading to increased fat in feces


What is Werner-Morrison Syndrome?

Aka VIPoma, this is a rare endocrine tumor, usually (about 90%) originating from non-β islet cell of the pancreas, that produce vasoactive intestinal peptide (VIP). It may be associated with multiple endocrine neoplasia type 1.


How does a VIPoma present?

The massive amounts of VIP in turn cause profound and chronic watery diarrhea and resultant dehydration, hypokalemia, achlorhydria (hence WDHA-syndrome, or pancreatic cholera syndrome), metabolic acidosis, vasodilation (flushing and hypotension), hypercalcemia and hyperglycemia.