Organization of the GI system, Motility and Dysmotility
From Iusmphysiology
Revision as of 20:12, 7 March 2011 by 149.166.25.212 (Talk)
- started here on 02/09/11 at 11AM.
Contents
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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
- Lamina propria
- Inner circular muscle
- Outer longitudinal muscle
- Serosal
- CArries blood vessels
- Mucosa cells
- 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.
- Cecum:
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
- Payer's patches:
- 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 (motor) and submucosal / meissner (sensory) 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
- ...
- Gastrin:
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.
- myopathic: reduced amnplitude of contraction
- 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.
Irritable Bowel Syndrome (IBS)
- 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
Inflammatory Bowel Disease
- 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.