GI Regulatory Systems and Structures for Motility Flashcards
3 GI Sensory Systems:
- Neural
- Sensory Neurons
- Extrinsic primary afferent neurons
- Intrinsic primary afferent neurons
- Sensory Neurons
- Endocrine
- Hormones and paracrines
- Nutrient receptors on enteroendocrine cells
- Sample luminal conditions
- Hormones and paracrines
- Immune
- Gastrointestinal Mucosal Cells
- Detection of microbes
- Macrophages and Intestinal Epithelial cells
- Gastrointestinal Mucosal Cells
4 GI Effector Systems:
- Endocrine
- Secretion
- Digestion
- Absorption
- Motility
- Food Intake
- Nervous System
- Motility
- Secretion
- Digestion
- Food Intake
- Immune System
- Immune Defense
- Immune Tolerance
- Nonimmune System
- Vomitting and Diarrhea
- Detoxifying chemicals
- Sterilizing food by digestive secretion
- Physical Barrier
Known Functions of Gut Microbiota:
- Support digestion and absorption
- Maintain intestinal mucosal barrier
- Promote intestinal epithelial cell differentiation and proliferation
- Shape the host immune system
- 2nd genome of the body
- Prevent colonization by pathogens
- Compete for nutrients and space with beneficial microbiota
Barriers in the GI Tract:
Physical Barrier
- Mucus Layer
- Prevents direct contact with intestinal epithelial cells
- Provides a matrix to trap bacteria
- Tight Junctions
- Prevent penetration
Antimicrobial Products
- Intestinal Epithelial Cells
Digestive Secretions:
- Acid, saliva, bile
- Peptides to kill bacteria and microbes
Paneth cells in the crypt region:
- Can also produce antimicrobial peptides
Colon:
- 2 mucus layers
- due to large numebers of bacteria
The Immune System in the GI Tract
Innate Immune System:
- Broad specificity to antigens
- Macrophages
- Dendritic cells
- Intestinal epithelial cells
Innate immune system induces antigen presenting cells and stimulates the adaptive immune system
- Prep, prepare and prime lymphocytes
Adaptive Immune System:
- Specific to each antigen
- Gut-Associated Lymphoid Tissue (GALT)
- Intraepithelial lymphocytes
- Lymphocytes in the lamina proprina
- Peyer’s Patches
Composition of GALT
(Gut-Associated Lymphoid Tissue)
- Intraepithelial lymphocytes
- lymphocytes in the lamina proprina
- Lymphoid nodules: Peyer’s Patches
Composition of FAE
(Follicle-Associated Epithelium)
- Few goblet cells
- No enteroendocrine cells
- numerous intraepithelial lymphocytes
- Drainage
- M-cells
- Microfold cells
Immune Induction in the GI Tract through Peyer’s Patches
- M-cell uptakes the luminal antigen
- Dendritic cells and macrophages process and present the antigens to B & T cells
- T and B cells are stimulated and activated
- T and B cells enter into circulation via mesenteric lymph nodes,
- In circulation, they mature into antigen specific lymphocytes and differentiate
- Mature T and B cells travel back to the mucosa for protection and to initiate an immune response (host defense)
Intestinal Dysbiosis:
- Disruption to the balance of normal microbiota
- Associated with GI disease
- Local and Distant organs
- NEC (Necrotizing Enterocolitis)
In Animals:
- Animal Health
- Production
- Food Safety
** Interaction with intestinal microbes with their host**
** Vital interaction for the improvement of host health**
Immune System Modulates Neural Control of GI Function
Normal Conditions = Sympathetic Nervous System Active and GI inhibited
- Antigen binds the mast cell
- Mast cells release signals
- Histamine
- Prostaglandins
- Leukotrines
- Signals suppress the release of NE
- Histamines and prostaglandins bind receptors on sympathetic nerve fibers
- Activates intrinsic motor and secretory reflexes
- Promotes secretion of intestinal crypt
- Flushes the bowel & increases secretion and vasodilation
- Dispose of antigens causing problems
- Self Cure
Integration of Neural and Endocrine Regulation
Cephalic Phase:
- Refers to the time before entry into the stomach
- Food in mouth
- Anticipation of food
- Chewing
The Cephalic Phase Triggers:
- Release of GRP in the stomach
- GRP binds receptor on endocrine cell
- G-cell
- G-cell Releases Gastrin
- Hormone that promotes acid secretion
Structures Required for GI Motility
Intestinal Epithelial Cell:
- Most internal towards lumen
- Single layer lining
Lamina Proprina:
- Connective tissue lining IEC
- Arteries, Veins, Lymphatic Vessels
Muscularis Mucosa:
- Single layer of muscle surrounding the lamina proprina
Submucosal Layer:
- Submucosal Plexus
Muscularis Externa Layer:
- Longitudinal Muscle Layer (more external)
- Myenteric Plexus (motility)
- Circular Muscle Layer (more internal)
Unitary Smooth Muscle Cells:
- Coupled with Gap Junctions
- Electric potential generation for synchronous contraction
- Paired with Enteric Motor Neurons
- Paired with the Interstitial Cells of Cajal (ICC)
Enteric Motor Neurons:
- Lack typical synapses at NMJ’s
- Instead present as varocosities (swellings) with many granules
- Varocosities store NT’s
- Granules are the NT’s
Interstitial Cells of Cajal (ICC):
Presence required to initiate a contraction
- Specialized smooth muscle cells
- In close contact with nerve endings
- Connect to neighboring ICC and SMC’s via gap junctions
- Express:
- NT receptors
- Components of pacemaker unit
- Ion Channels
- Transporters
- Energy Production Capacity
- Pacemaker and Mediator of Neurotransmission
Close proximity to enteric motor neurons –> receive signal and spread it over smooth muscle cells rapidly via gap junctions
What are the ICC?
- Specialized pacemaker cells that connect via gap junctions
- They cause a partial depolarization via fluctuations in intracellular Ca2+
Intracellular Membrane potential is more (-) compared to the extracellular membrane
Under resting conditions:
- Depolarization is only partial
- Propagates through muscle layers of GI wall
Slow waves are constantly passing over muscles whether they are actively contracting or not
Slow Waves (Basic Electric Rhythm)
- Oscillating depolarization and repolarization of the membrane of smooth muscle cells
- Unique to GI smooth muscle cell activity
Depolarization: Associated with Ca2+ entry into cell
Repolarization: Associated with K+ exit from cell
Relationship of Slow Waves, Action Potentials & Contractions
- Slow Wave is always present in the GI tract
Depolarization Phase:
- Membrane potential of SMC’s becomes less negative
- Movement towards threshold
- Overlap of Slow wave and AP causes a smooth muscle contraction
Strong contraction with periodic relaxation
What are the contractile parameters determined by slow waves?
- Maximal frequency
- Propagation velocity
- Direction of propagation
Slow waves are myogenic
- Generate themselves
- Don’t require external input
How do neuronal and hormonal inputs effect contrations?
Modulate production of AP’s
Modulate the strength of contractions
Excitatory molecules:
- Elevate the baseline membrane potential of SMC’s
- Increase the chance of production of AP’s
Inhibitory molecules:
- Decrease the baseline membrane potential of SMC’s (hyperpolarization)
- Decrease the chance of production of AP’s
