Organization of the GI system, Motility and Dysmotility

From Iusmphysiology

• started here on 02/09/11 at 11AM.

Contents 1 Organization of the GI system, Motility, and Dysmotility 1.1 Objectives 1.2 Digestive system 1.3 General structure 1.4 Closer look 1.5 Small versus large 1.6 Function and requirements 1.7 Immune functions of GI tract 1.7.1 Peyer's patches 1.7.2 Increased epithelial permeability 1.8 REgulation of the GI function 1.8.1 Illustration 1.8.2 Ganglia 1.8.3 Illustration 1.8.4 Parasymp and brain interaction 1.8.5 Parasymp can affect smooth muscle of arteries 1.8.6 Nueronal-immune singaling 1.8.7 Peptide hormones 2 =Motility 2.1 Peristalsis 2.2 Segmenting contractions 2.3 Rhythmic contractions 2.3.1 Pacemakers of the GI tract 2.3.2 EC-coupling in smooth muscle 2.4 The migrating motor complex 2.4.1 Interlumenal pressure recording 2.5 Disorders affecting GI tract motility 2.5.1 Hirschsprung's disease 2.5.2 Idiopathic motility disorders 2.5.2.1 Contraction scans 2.5.3 IPS 2.5.4 IBD 2.5.5 Diabetes 2.6 Summary

Organization of the GI system, Motility, and Dysmotility

• This will be an overview with some principles.
• Then more on mobility.

Objectives

• Provide an overview of the GI system.
• Understand the general mechanisms regulating GI function - neuronal, hormonal-endocrine, paracrine.
• Understand the general organization of the ENS and the role of long and short reflexes in regulating GI function.
• Describe the functions of the major GI hormones.
• Describe the motile processes in the GI tract.
• Describe motility dysfunction.

Digestive system

• SErioes of hollow organs
• Critical for survival
  • Absorption
  • Excretion
  • Electrolyte balance
  • Immune function
• Think of the lumen as the outside of the body.
  • Thus it makes sense that there are lots of immune cells in there.

General structure

• A series of layers
• Inner to outer
  • Mucosa cells
    • Absorptive, epithelial
  • Muscularis
  • ?
  • Inner circular muscle
  • Outer longitudinal muscle
  • Serosal
    • CArries blood vessels
• Similar thorughout the tract

Closer look

• The overall is same between large and small intestine.
• Epithelial cells are villi and crypts in the small intestine
• Large intestine has no villi, only crypts.
• Villi increase SA for absorption of nutrients.
• There are lots of cell types of epitheila
  • Aborptive cells
  • Goblet cells
    • Lubrication of food
  • Endocrine cells
  • STem / progenitor cells
    • Make all the other cell types
  • Paneth cells
    • Like a neut
    • Part of immune system
• Similar cell pops in large and small intestine.
• Epithelium of the lumen is continally replaced by stem cells
  • Differentiate as they migrate upward.
  • Lifespan is 1-2 days

Small versus large

• Small:
  • Duodenum: gets secretion from pancreas and bile duct, gets food from stomach
  • Jejunum:
    • 40% of small
  • Ileium
• Large:
  • Cecum:
    • Blind sac
  • Colon:
    • Ascending, transverse, and descending
  • Rectum:
    • Short terminal section that is continuous with anal canal.

Function and requirements

• Secretions:
  • needed for lubrication of foood
  • especially mucins from goblet cells
  • needed for absorption, too.
• Motility is needed, too
  • For pushing food through
  • For mixing
  • For expelling
  • For storage

Immune functions of GI tract

• GALT!
• Can be subdivided:
  • Payer's patches:
    • Aggregations of lymphocytes
  • Diffuse immune cells:
    • Migrate from patches and live between epithelial cells and in the lamina propria.
    • Live with mast cells
• Functions:
  • Protection against microbial pathogens
  • Generate tollerance to good, residual bacterial
• Paneth cells:
  • Act like neuts
  • Secrete alpha defensins that form poors in bacterial membranes

Peyer's patches

• Epithelial cells that line the patches have M cells
• M cells pass intact proteins from lumen directly to APCs below the epithelium.
  • A sampling of lumen cells.
• Lymphocytes can get activated, go off to lymphoid tissue, and come back.
• Plasma cells can reside in the peyer's patch and produce Ig that can be put back into the lumen by the M cells.
  • Make more Ig than the rest of the immune system put togheter!

Increased epithelial permeability

• If a pathogen gets in, T cells can be activated, go to lymph node, then come back and attack the pathogen and cause inflammation.
• this releases cytokines which further damage the barrier
  • Can be cyclical like cholitis.

REgulation of the GI function

• Nueronal:
  • Beginning and end are voluntary but most is autonomic.
  • Enteric nervous system: has sensory nuerons, transmission, and response neruons.
  • Has severna NTs: ach, peptides, bioactive amines
  • Regulates absorption and mobility
  • Intrisically regulated becase all happesn wtihin enteric
  • Two major groups of neurons:
    • submucosal: next to epithelail cells; controls absorption
    • myoteric: between muscle layers; controls mobility
  • Higher centers also talk to brain, via autonomic nervous system, hormones, and immune system.
• Hormonal:
  • All three used: autocrine, para, endocrine
• Neuro-hormonal:
  • Neurons synapsing on hormone cells to release hormones

Illustration

• Red = enteric nervous system
  • Uses interneurons to trasfer signal from snesory to motor neurons
• Short reflex is from snesory, through itner, to motor
• Long relfexes go from sensory to brain to inter to motor.
• More neurons in enteric system than the rest of the autonomic system put together.

Ganglia

• Picture of locaiton of myenteric and ? ganglia.

Illustration

• Shows ganglia nd how they can interact with brain, parasymp, symp
• In general, the parasympathetic nerves use ach to increase motility and secretion.
• In general, the sympathetics use NE to decrease motility and secretion.
• This is important for coordinated movement of the tract.
• Other NTs:
  • Probably should remember most of these.
  • Serato: diff depending on receptor; see slide
  • NO, ATP, VIP = relaxation

Parasymp and brain interaction

• Vagovagal reflex:
  • Afferent fibers from rrecepotrs in gi send to medulla,
  • Vagal efferent fibers used to tell the gi tract what to do about signals.
• Parasymp increase motility, decrease contraction of vascular sm and sphincter.

Parasymp can affect smooth muscle of arteries

• Agents that initiate gi tract motility also cause relaxation of arteries to increase blood flow.
• Ach release diffuses to interact with endothelial cells which increase NO production, which goes to the vascular smooth muscle, actvates Guanylate cyclase, reduces cGMP, opens channels....etc.

Nueronal-immune singaling

• Some mast cells in the lamini propria can sense NTs and react
  • Signal can come from brain or ENS
• Histamine:
  • Can affect smooth muscle and peithelial cells.
  • Can increase acid secretion.

Peptide hormones

• Yes, you need to know all these.
• Two for tomorrow:
  • Gastrin:
    • Targets parietal cells of stomach (acid producing cells, increases activity)
  • Somatostatin
    • From D cells in the stomach and duod
    • ...

=Motility

• Three general patterns:
  • peristalsis: for movement, occurs throughout tract
  • rhythmic segmentation: mixes, small and large
  • tonic contractions: controlling movement between compartments, sphincters

Peristalsis

• Squeezing toothpaste out of the tube.
• Contract circular muscle layer behind and relax in front of the food.
• The stretch of the wall detects the bolus of food.
  • CAuses NT release behind (ach or substance P) behind the bolus to cause contraction.
  • Causes NT release in front of the bolus to cause relaxation.

Segmenting contractions

• Squeeze in the middle of the tube of toothpaste.
• Some forward some backward.
• Impt for mixing with digestive enzymes.

Rhythmic contractions

• Electrical properties of muscle is important for this contraction.
• Slow waves are imnportant.
• When resting, slow waves donm't fire APs.
• When stimualted, (stretch, etc), the likelihood that slow waves cause AP is increased.
• Stimuli does not change frequency of the slow wayves, just the chance that it will cause an AP.
• Pacemaker cells generate these slow wayves.
  • Found in the stomach.
• Smooth muscle cells are connected with gap junctions.

Pacemakers of the GI tract

• ICC = interstitial cells of cahal = pacemaker cell.
  • Interstitial cell
• Gap jxns are

EC-coupling in smooth muscle

• VGCC open, ca flows in,
  • directly activates contraction
  • acts on ryanidine receptor to release Ca
• Can also cause contraction without an AP:
  • Binding to protein that activates PKC (PIP2-> DAG, IP3), Ca increases, contraction
  • SR can release Ca b/c of ryanidine OR IP3 receptor.

The migrating motor complex

• This occurs when not digesting.
• Has a housekeeping role.
• Tends to correlate with increased motilin.
• four phases:
• 1, quiescence
• 2, 30 minutes of peristalsis that originates in the stomach, moves through LI, and gets larger and larger.
• 3, rapid, large peristalis contractions
  • pyloric sphinctor is open, which is important for cleaning out the stomach.
• 4, short transition back to the inactive period.

• Erythromycin mimics motilin and will increase GI motility.
  • Can be used to increase motility as well as it's original antibiolitc purpose.

Interlumenal pressure recording

• Pressure goes up in phase 2, especially in the stomach.
• Can see that pressure moves food forward.

Disorders affecting GI tract motility

• We'll talk about the later end first.

Hirschsprung's disease

• Lack fo nerves in the colon.
• That means the food doesn't get released.
• Pseudoobstruction occurs; moves out instead of along the tract; megacolon.
• Caused by mutations in receptor tyrosine kinase (RET) or EDNRB.
• These affect precursors of the enteric neurons; they are imnportant for migration to the colon of the neuron.

Idiopathic motility disorders

• Many motility disorders have no explanation.
• CAtegories:
  • myopathic: reduced amnplitude of contraction
    • can be seen in muscular dystrophies
  • neuropathic: nerves aren't organized correctly
    • Poor pattern.
• Traces on right:
  • Too little contraction.

Contraction scans

• Uncoordinated contractions won't carry food forward as it should.
• Can be seen in diabetes where nerves of the gut are damaged.

IPS

• Irritable bowel syndrome
• Intestinal contractions can be stronger and laster longer.
  • Too quick
  • Gas, bloating, diarrhea
• Or the opposite!
• Cuases:
  • Unknown
  • Changes in nerves?
  • Increased senstiivity to stretching?
  • Hormonal influence? (women twice as likely to have IBS than men).
    • Women's IBS symptoms worse during period
• Treatment:
  • Changes in diet; avoid caffeine and -oh which make motility worse; add fiber
  • Exercise; reduces stress, helps increase motility
  • Drugs; anticholimines and anti-depressants

IBD

• Two classes: Crohn's disease, ulcerative cholitis
• Crohn's diease:
  • Anywhere in the gi tract
• Colitis
  • Mostly colon and rectum
• Symptoms
  • Same between the two
• Cause:
  • Seems to be over active immune system
  • Macrophages and cytokines and bears, oh my!
• Treatment:
  • Steroids, immunosuppresants

Diabetes

• Can damage enteric nerves through high glucose that hurts blood supply to nerves.
• Decreased release of stem cell factors, then lack of pacemaker cells.
• Cyclic because then glucose absorption gets worse.

Summary

• GI is regulated by complex pathways: neuro, hormonal, immune.
• ENS is a "mini brain" because it can receive, pass, and transmit signals.
• ENS is modified by CNS, espeically vagal nerve.
• Neuronal pathways can act on endocrine cells, too.
• Motility is imnporant for mixing, moving, ejecting, and storing.
• Peristalsisi is most important motility.
  • Slow waves
• Diseases affect motility:
  • Hirschprung, no ganglia, no motility
• IBS, IBD
  • Lots of idiopathic-ness, immune system.

• stopped here on 02/09/11 at 12PM.