13-1: 1/24 - Gi Motor Function

Front 1

Control of the digestive system is structured so that each portion of the GI tract communicates to _______ the more proximal organs and _______ the more distal organs.

Back 1

Each portion of GI tracts inhibits more proximal organs (secretion/motility) and stimulates more distal organs.

Inhibitory input overrides stimulatory input.

Front 2

Enteric NS:
CNS effects on it
Is it dependent on CNS?

Back 2

Can function independently of CNS, but CNS plays role in coordinating fn

Front 3

Myenteric vs Submucous Plexus:
Alternate Name
Location
Funciton

Back 3

Myenteric = Auerbach's Plexus
Lies between circular and longitudinal layers of SM; runs through entire gut

Fn: Motor fn of muscle and secretory function of mucosa

Submucous = Meissner's Plexus

Best developed in small bowerl

Fn: Secretory control; innervates glandular epithelium, intestinal endocrine cells, muscularis mucoase

Front 4

Dorsal Vagal Complex:
Function
Location

Back 4

Fn: Integrates and processes information (CNS interface)

Located in BS

Front 5

Tractus solitarius:
Function

Back 5

Receives sensory information; integrates in nucleus of tractus solitarius

Front 6

Dorsal motor nucleus of vagus:
Function

Back 6

Received input from interneurons in tractus solitarius (which integrates sensory info); projects to all viscera

Front 7

Vagus nerve:
Afferent vs Efferent Fns

Back 7

Afferent (sensory):
Senses stretch/distention, motor activity, chemical/mechanical stimuli

Efferent (motor output) to fore/mid-gut:
Preganglionic fibers, cholinergic fibers, excitatory effects on enteric neurons

Note: in GI, psymp is excitatory and symp is inhibitory!

Front 8

sympathetic neurons are ________ post-ganglionic.

Back 8

Sympathetic mostly post-ganglionic

Front 9

Amine Precursor, Uptake and Decarboxylation Cells (APUD):
Function
Cellular Location

Back 9

Produce gut peptides which later undergo post-translational modification

Produce secretory granules concentrated at basolateral aspect of cells

NOT RELEASED INTO LUMEN

Basolateral release of peptides-->rapid appearance in bloodstream

Front 10

Open vs Closed Endocrine Cell

Back 10

Open cells face lumen and detect luminal environment

Closed endocrine cells cannot monitor luminal environment

Both possess secretory fns

Front 11

Paracrine vs Modified Paracrine

Back 11

Paracrine: release hormones and affect neighboring cells

Modified paracrine: cell possess foot processes which release hormones onto neighboring cells

Front 12

What is an orexigen?

Back 12

Appetite stimulant

Front 13

Ghrelin:
Function
When do levels rise/fall?
Effects

Back 13

Appetite stimulant (orexigen)

Involved in SHORT-TERM control of pre-meal hunger. Levels of ghrelin inc pre-meal and dec within one hour after eating.

Acts on arcuate nucleus in hytpothal to release NPY (neuropeptide Y) and AgRP (agouti-related protein)--both of these are oxrexigenic.

Front 14

Relationship between ghrelin and weight regulation.

Back 14

Ghrelin may be involved in LONG-TERM weight regulation.

Levels rise proportionate to degree of weight loss (makes weight loss via dieting difficult).

Front 15

This hormone is counter-regulatory to leptin.

Back 15

Ghrelin

Front 16

Leptin:
Functions
When do levels rise/fall?
Effects

Back 16

Short and long-term control of food intake/energy expenditure

Levels rise and fall with body fat levels

2 effects:
1) adiposity: inhibits appetite and augments energy expenditure (inversely related with ghrelin level)

2) Hypothalamic effects: inc'd release of alpha-MSH (anorexic neuropeptide); dec'd release of NPY and AgRP (orexigenic)

Front 17

Resistance to this hormone may exist in the obese.

Back 17

Leptin resistance

Front 18

Cephalic vs Luminal Phase:
Hormonal or Neural Mediation?
Events

Back 18

Cephalic (neurally mediated in response to touch, smell, taste):
Oral secretion
Initial gastric secretion
Initial pancreatic secretion

Luminal Phase--neural and hormonal mediation:
Gastric, pancreatic, hepatobiliary secretions
Inhibitory processes

Front 19

Cephalic Phase:
Innervation
Relevant NT/Hormones

Back 19

Cephalic Phase:
vagally mediated
requires gastrin, Ach (cholinergic)

Front 20

Gastric Phase:
Triggering events

Back 20

This is part of luminal phase.

Physical (gastric distention) and chemical (peptides) triggers

Front 21

Intestinal phase:
Triggering events

Back 21

Entry of chyme, peptides into duodenum

Front 22

Sight, smell, taste perceived by _________, and causes the release of ________.

Back 22

Dorsal vagal complex senses sight, smell, taste

Releases ACh, and Gastric Related Peptide (GRP)

Front 23

Effects of ACh release by Dorsal Vagal Complex.

What phase is this?

Back 23

ACh-->
Chief Cells: Release Pepsinogen
Parietal Cells: Release HCl

Pepsinogen + HCl-->Pepsin

CEPHALIC PHASE

Front 24

Effects of GRP release by Dorsal Vagal Complex.

What phase is this?

Back 24

GRP-->G-Cell-->Gastrin

CEPHALIC PHASE

Front 25

What is sham feeding?

Back 25

Taste food, spit it out.

See cephalic responses, but not luminal responses.

The more appetizing the food, the more of a response you'll see.

Front 26

Describe the events that occur once protein enters the stomach.

What phase is this?

Back 26

Protein degraded by pepsin into oligopeptides.

Oligopeptides-->G-Cell-->Gastrin
-->Parietal & Chief Cells
-->HCl and Pepsinogen respectively
(-->Pepsin)

GASTRIC PHASE

Front 27

Somatostatin:
Where and when is it secreted?
When is it inhibited?
Effects?

Back 27

Secreted by D-cells in response to HCl (from parietal cells)

Somatostatin then inhibits G cells, which cease to produce gastrin

Somatostatin inhibited by ACh release from vagus.

This is all via paracrine effects

Front 28

Vasoactive intestinal peptide:
Function

Back 28

Stimulates somatostatin release from D-cells

Front 29

Effects of Dorsal Vagal Complex on gall bladder.

Back 29

1) Gallbladder contraction.
2) Sphincter of oddi relaxation.

Also causes release of pancreatic enzymes.

In short, the DVC is preparing more distal areas for digestion.

Front 30

Enterogastrones:
When are they released?
Effects?
Examples.

Back 30

Enterogastones are inhibitors of gastric mobility and secretion.

Released in response to fatty acids and cause inhibition of G cell and parietal cells.

Examples of enterogastrones:
GIP
PYY
Neurotensin

Front 31

Peptide YY:
What is it?
When is it secreted?
When do levels peak?
Function?

Back 31

Peptide YY = enterogastrone and satiety factor

Secreted in response to ingested nutrients; may also be secondary to neurogenic/endocrine mechanisms (levels increase before nutrients reach L-cells)

Peak within 60 minutes.

Fn: decrease food intake via inhibition of gut motility. Send afferents to inhibit release of hypothalamic oreixgens (NPY, AgRP)

Front 32

Secretin:
Released by what cells?
Under what conditions?
Effects?

Back 32

Secretin:
Released by S-cells in duodenum
in response to duodenal acidification
Stimulates water and bicarb flow from bile/pancreatic ducts
Stimulates pepsinogen secretion
INHIBITS gastric emptying

(forward activation, backward inhibition)

Front 33

Why must the pH of the small intestine be regulated?

Back 33

Duodenal mucosa can't protect itself from stomach acid

AND

Pancreatic enzymes must function at a certain pH

Front 34

Cholecystokinin:
Released by what cells?
Under what conditions?
Effects?

Back 34

Released by I cells of duodenum

Also released by enteric neurons in CNS, and ENS

Stimuli for release:
Fats
AAs
Ca2+
Vagal stimuln

Has secretory and motor effects
Induces satiety

Front 35

What two hormones stimulate biliary and pancreatic secretion?

Back 35

Secretin
CCK (cholecystokinin)

Front 36

What hormone relaxes the sphincter of Oddi?

Back 36

CCK

Front 37

Role of CCK in hunger and satiety.

Back 37

Induces satiety by inhibiting eating/nutrient digestion and by stimulating leptin release

Front 38

Role of H. pylori infection in developing ulcers.

Where are the ulcers?

Back 38

Duodenal ulcers
1) Pt more sensitive and responsive to gastrin than normal pts
2) Gastric acid secretion may be invoked at lower thresholds of gastrin
3) Inhib mechs may be blunted by H Pylori

Front 39

Zollinger-Ellison Syndrome:
Pathophys
Effects
Diagnostics

Back 39

Hyperplasia or malignant tumors of pancreatic G cells (gastrinoma) causing elevation of gastrin-17 and 34 levels

Duodenal wall is another common site

Results in unopposed secretion of gastrin-->unopposed HCl secretion

This causes increase in # of parietal cells-->hypersecretion of acid/pepsin

Results in ulcerations, duodenitis, jejunitis.

Inactvtn of pH dep digestive processes (lipase activity, IF-binding of B12) !!!!!!!!!!!!!!

Dx: Fasting Serum Gastrin, Secretin Stimulation

Front 40

This disease is associated with MEN Type 1.

Back 40

Zollinger-Ellison Syndrome

Front 41

Fasting serum gastrin:
Test
Associated Illness

Back 41

Zollinger-Ellison Syndrome

1) exclude atrophic gastritis, pernicious anemia, Sx causes bc hypo- or achlorhydria reduces neg feedback on gastrin

If fasting gastrin >1000-->Z-E syndrome

Front 42

Secretin Stimulation Test:
Test
Associated Illness

Back 42

Zollinger-Ellison Syndrome

Inject secretin-->marked increase in gastrin (>100 pg/ml over basal level)-->Z-E Syndrome

Won't see increase in gastring level with IV secretin in normal patients

Front 43

Zollinger-Ellison Syndrome:
Treatment

Back 43

Medical:
H+ pump inhibitors
Somatostatin analogues (Sandostatin)

Sx therapy:
Resection (rare)
Cyroblation, embolization

Front 44

Somatostatinoma:
1:31:34

Back 44

xxx

Front 45

Somatostatinoma:
What is it?
Effects?

Back 45

Pancreatic tumor secreting somatostatin (unregulated suppression of GI hormone/peptide release)

Results in:
Diabetes
Gallstones
Steatorrhea (fatty feces)--not releasing panc enzymes to emulsify fats (malabsorption)

Front 46

Octreotide:
Drug Class
Use

Back 46

LA somatostatin analogue

Indications:
Treatment of VIP secreting tumors (VIPomas)
Tx of pts w/metastatic carcinoid tumors

Front 47

VIP:
Roles

Back 47

Swallow-induced lower esophageal relaxation

Internal anal sphincter relaxation

Gut luminal relaxation

Front 48

Achalasia & Hirschsprung's Disease:
What is it?

Back 48

Dec'd [ ] of VIP (at tissue level and at # of VIP neurons)--> failure to relax bowel/sphincters; fnal obstruction

Front 49

WDHA Syndrome:
What is it?
Effects?

Back 49

Watery Diarrhea-Hypokalemia-Achlorhydria Syndrome

Excess VIP produced by islet cell pancreatic tumors (VIPoma)--MEN I

Effects:
Massive intestinal secretion of water and electrolytes:
Profuse diarrhea
Hypokalemia
Dec'd or absent gastric acid secretion (achlorhydria)
Electrolyte depletion with lethargy, muscle weakness, cramping, nausea, vomiting

Front 50

This disorder is associated with neural crest tumors.

Back 50

WDHA
Verner-Morrison
Pancreatic Cholera

Front 51

Verner-Morrison Syndrome:
What is it?

Back 51

Same as:
Watery Diarrhea-Hypokalemia-Achlorhydria Syndrome

Excess VIP produced by islet cell pancreatic tumors (VIPoma)--MEN I

Front 52

Why might someone with WDHA present with hypercalcemia?

Back 52

WDHA associated with MEN I tumors-->hyperparathyroidism-->elevated Ca2+

Front 53

CCK Deficiency:
Effects

Back 53

Poor gall bladder contractility-->gall stones

Reported in pts w/celiac dz, short bowel syndrome, diabetes

Front 54

Poor response to CCK:
Pathophys
Effects

Back 54

Acalculous cholecystitis
Cholesterol gallstones
Impaired gallbladder contraction

Not due to CCK receptor, but in defective signal transduction.

Front 55

Loxiglumide:
Drug Class
Use

Back 55

CCK-A receptor antagonist

Used in those w/chronic constipation (improves colonic transit time)

Front 56

Exenatide:
Drug Clas
Use
Effects

Back 56

amino acid peptide tht mimics Glucagon-like peptide 1 (GLP-1)

used in NIDDM

improves glycemic control, enhances glucose-dependent insulin release, suppresses elevated glucagon secretion, slows gastric emptying

Front 57

GLP-1:
Produced by?
Effects
Inactivation

Back 57

Produced by intestinal L-cell

If hyperglycemic-->insulin secretion to normalize blood glucose

Inhibits glucagon secretion

Delayed gastric emptying

Rapidly inactivated by DPP IV (dipeptidyl peptidase IV)--unlike exenatide!

Front 58

Back 58