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162 Cards in this Set
- Front
- Back
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Organs included in the GI tract
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mouth, pharynx, esophagus, stomach, small and large intestine
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Parts of the Small Intestine
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duodenum, jejunum, illeum
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Parts of the Large Intestine
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cecum, ascending colon, transvere colon, descending colon, sigmoid colon, rectum, anus
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acessory organs to the GI tract
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salivary glands, liver, gall bladder, and pancrease
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Functions of the GI tract
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Protection, Nutrition, Excretion
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3 smooth muscle layers
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Muscularis Externa (longitudinal smooth muscle layer and cicular smooth muscle layer), Muscularis mucosae, mucosal epithelium
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Submuscosa
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between the muscularis mucosae and the circular muscle layer (contains blod, vessels, lymphatics, nerves, submucous glands)
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Parts of the ENS
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myenteric plexus, submucous plexus (interconnectoins between the two)
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Mucosa
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muscularis mucosae, lamina propria, and epithelium
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ENS
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acts as a microcomputer with its own independent software, organized for programmed reflexive operatoins
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CNS
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In a two way traffic manner can modulate the ENS programes, sensory afferents convey information from the gut to the CNS, autonomic nervous system (sympathetic and parasympathetic) input from the CNS to the ENS
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Jobs of the ENS
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motor functions for transport of the luminal content
regulatoin of blood flow regulatoin of secretion and adsorption modulation of the immune response against pathogens |
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Intrinsic primary afferent neurons (IPANS)
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sensory
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Interneurons (ascending and descending)
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process and integrate sensory information, control behavior of efferent neurons
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Muscle motor neurons
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excitatory and inhibitory innervation of smooth muscle
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secretomotor neurons
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innervate the mucosa, control secretion
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vasomotor neurons
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control blood flow
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intestinofugal neurons
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neuronal cell bodies within the ENS, but send axonal projectoins to sympathetic ganglia
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IPANS
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respond to mechanical and/or chemical stimuli to initiate intestinal reflexes.
called IPANS, rather that sensory neurons, because they do not convey sensation from the intestine IPANS trasmit information to other ENS interneurons, secretomotor, and motor neurons, NO nerve endings directly reach the lumen of the gut, activation of an IPAN may require another cell type (entero-endocrine cell) |
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How do IPANS responds to stimuli
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IPANS may respond directly to intramuralstimuli (distention or stretch)
IPANS may respond indirectly to inraluminalstimuli (changes in pH, mechanical distortion of the mucosa by shear force, pressure or volume, changes in soluble concentratoin, protein digestoin products, D-glucose, chemical irritants, invading enteropathogenic microorganisms) |
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secretomotor neurons
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innervate the mucosa, control secretion
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vasomotor neurons
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control blood flow
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intestinofugal neurons
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neuronal cell bodies within the ENS, but send axonal projectoins to sympathetic ganglia
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IPANS
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respond to mechanical and/or chemical stimuli to initiate intestinal reflexes.
called IPANS, rather that sensory neurons, because they do not convey sensation from the intestine IPANS trasmit information to other ENS interneurons, secretomotor, and motor neurons, NO nerve endings directly reach the lumen of the gut, activation of an IPAN may require another cell type (entero-endocrine cell) |
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How do IPANS responds to stimuli
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IPANS may respond directly to intramuralstimuli (distention or stretch)
IPANS may respond indirectly to inraluminalstimuli (changes in pH, mechanical distortion of the mucosa by shear force, pressure or volume, changes in soluble concentratoin, protein digestoin products, D-glucose, chemical irritants, invading enteropathogenic microorganisms) |
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The ENS and Entero-Endocrine Cells
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Specific Stimuli arising from the lumen first activate Entero-Endocrine cells
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In the Stomach,
G-cells secrete D-Cells secrete |
gastrin
somatostatin |
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In the small intestines,
S-Cells secrete I-cells secrete Enterochromafin cells secrete |
secretin
cholecystokinin serotonin (5HT) |
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Enterochromfin cells (EC)
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synthesize and store serotonin (5HT)
"Taste" luminal contents and release 5HT into the lamina propria in response to many different luminal stimuli (nutrients, hyperosmolality, change in pH, mechanical forces, luminal irritants, invading enteropathogenic microorganisms) 5HT bind to receptors on IPANs in the lamina propria to initiate a neural reflex within the ENS that result in changes in secretion and motility |
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Removal of 5HT from the lamina propria
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5HT is a base, at physiological pH, 5HT is positively charged and cannot freely enter cells to be metabolized by intracellular enzymes (MAO)
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How does inactivatoin of 5HT occur
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it occurs mainly by transportermediated uptake intoenterocytes
the serotonic reuptake inhibitot (SERT or HTT) is the primary molecule responsible for inactivating 5HTT in the gut |
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Whats are SERTs used for
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transcription SERT is decreased in patients with IBS
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GI Afferent (sensory) pathways
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vagal afferent neurons
pelvic nerve afferent neurons spinal visceral afferent neurons |
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Where does SNS stimulate in the GI
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esophagus through entire colon, liver, gall bladder and panxreas
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Where is the SNS preganglionic neurons
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neuronal cell bodies in the spinal cord intermediolateral cell column (T1 - L2)
preganglionic nerve fibers pass thorugh paravertebral chain ganglia and porjecto to outlying prevertebral ganglia where they snapse on postganglionic neuronal cell bodies |
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Where are postganglionic neurons in SNS
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neuronal cell bodies in outlying prevertebral ganglia,
superior mesenteric, inferior mesenteric, and celiac ganglia |
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Where do postganglionic nerve fibers project to
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ENS interneurons
Alter neuronal activity within the ENS, can alter secretion, motility, and absorption |
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SNS - Salivary Glands
where are the preganglionic symp neurons |
neuronal cell bodues in spinal cord intermediolateral cell column (T1-L2)
preganglionic nerve fibers enter paravertebral chain ganglia to synapse on postganglionic neurons |
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SNS - Salivary Glands
where are the postganglionic symp neurons |
neuronal cell bodies in paravertebral chain ganglia, postganglionic fibers ascend to superior cervical ganglia and exit the symp chain to innervate the salivary glands, alter salivary gland secretion and blood flow
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PNS - esophogus through transverse colon, liver, gallbladder, and pancrease
Where are the preganglionic parasymp neurons |
neuronal cell bodies in dorsal motor nucleus and nucleus ambiguus of the medulla, preganglionic nerve fibers in cranial nerve X(vagus nervs) project to postganglionic neurons within the ENS
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PNS - esophogus through transverse colon, liver, gallbladder, and pancrease
Where are the postganglionic parasymp neurons |
postganglionic cell bodies within the ENS, their nerve fibers project to ENS interneurons
alter activity within ENS, secretion, motitlity, and absorption |
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PNS - descending colon to Anus
Where are the preganglionic parasymp neurons |
neuron cell bodies in intermediolateral cell column of spinal cord segments S2 to S4
preganglionic nerce fibers in pelvic nerves project to postganglionic neurons in ENS |
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PNS - descending colon to Anus
Where are the postganglionic parasymp neurons |
neuronal cell bodies within the ENS
nerve fibers project to ENS interneurons alter activity within the ENS, alter secretion, motility, and absorption |
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Somatic Nervous System
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Somatic Motor Neurons (contained in cranial nerves or spinal nerves)
skeletal muscle innervation of: (mouth, jaws, tongue, pharynx, upper esophogus, external anal sphincter) |
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Autonomic Nervous System
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PNS and SNS neural innervations of:
secretory salivary glands and pancreas, liver, ENS(lower esophagus through colon and internal anal sphincter) |
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Somatic Nervous System innervation
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cranial nerves innervating skeletal muscle of the jaws, tongue, oral cavity, and upper esophogus,
pudendal nerves innervating the skeletal muscle of the external anal sphincter |
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PNS - Salivary Glands
Where are the preganglionic neurons |
neuronal cell bodies in superior and inferior salivary nuclei of the medulla,
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PNS - Salivary Glands
Where are the preganglionic nerve fibers |
in cranial nerves (V, VII, IX) project to submandibullar and otic ganglia near salivary glands
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PNS - Salivary Glands
Where are the postganglionic neurons |
neuronal cell bodies are in submandibular and otic ganglia
postganglionic nerve fibers project to salivary glands |
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3 neural input to the prevertebral sympathetic ganglia
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1. sympathtic preganglionic fiber from the spinal cord
2. collateral fiber from spinal visceral afferent neuron 3. collateral fiber from ENS sensory afferent neuron |
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"Short-loop" (intrinsic reflex)
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all elements within the ENS
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"Long-loop" (extrinsic reflex)
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Afferent: spinal visceral, vagal, and pelvic nerves
convergence of sensory input, processing, integration, spinal cord, brainstem, midbrain, hypothalamis Efferent: SNS or PNS |
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"Intermediate Loop" (prevertebral ganglionic) reflex
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collateral sensory fibers from sensory ENS and spinal visceral afferents to prevertebral ganglia modify efferent sympathetic nerual traffic
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GI tract is the largest endocrine organ and it secretes
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mucosal endocrine cells (peptide hormones)
mucosal paracrine cells (paracrine peptids) ENS neurons (neurocrine peptides) |
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GI tract is the largest immune organ and it secretes
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immune cells (paracrine peptides, histamine, prostoglandins, etc.)
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GI endocrine cells
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GI hormones are secreted into blood in response to appropriate stimulus
GI hormones act at distant target cells (absorptive, other endocrine, ENS, secretory, paracreine, immune cells) |
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Secretin as a GI hormone example
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secretin, a hormone released into the blood by the small intestine, stimulates gastric D cells to release the paracrine peptide somatastaine
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GI paracrine cells
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are similar to endocrine cells
paracrine substances are secreted into interstitial space in response to appropriate stimuli, diffuse to local target cells |
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Gastric D cells as an example of paracrine cells
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Gastric D cells release somatostatin, a paracrine peptidem that inhibits acid secretion by nearby gastric parietal cells
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GI immune cells
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release paracrine substances into interstitial space in response to appropriate stimuli (cytokines, histamines, peptides, prostoglandins)
paracrine substances relesed from immune cells diffuse to local target cells |
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Neurocrine substances
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ENS neurons release many "neurocrine" substances from "non-classical" synapses
substances may be released in a paracrine-like manner from nerve vericosities (ATP, ACh, NE, GABA) neuroncrine substances diffuse to local target cells |
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Intestinal Epithelium
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participates in digestion and absorption of nutrients
surface epithelial cells are short-lived and undergo continual cell turnover (any injury to the stem cells by infectious microbes could lead to a breach of the epithelial barrier) constantly exposed to intestinal microflora (500 bacterial species, totaling 10^14 microbial cells) |
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The intestinal epithelial barrier
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the intestine is an extremely complex organ
the body's largest surface area (vulnerable to infection by luminal microbes) the lumen is nutrient rick and would seem to provide an ideal medium for microbial proliferation |
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Conflicting needs of the host
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effective absorption of essential nutrients across a intestinal epithelial barrier
exclusion of bacteria, viruses, toxic materials, and immunogenic matherials from the internal millieu |
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Intestinal tissue defense
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exhibit highly efficient host mechanisms that ensure tolerance to commensal bacteria and recognition and elimination of pathogens
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Types of host defense mechanisms
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non-immunological defenses and immunological defenses (innate immune and adaptive immune)
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Types of non-immunological mucosal defenses
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tight junctions between epithelial celss
capacity of the epithelium to rapidly regenerate mucus gastric acid digestive enzymes bile peristalsis enteric microflora |
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What do non-immunological mucosal defenses do
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acid, bile, digestive enzymes, and peristalsis hinder the colonization of the stomach and proximal small intestine by most bacteria
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Bacterial Density
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relatively low in the stomach
increases in the distal small intestines rises to 10^11-10^12 bacteria per gram of colonic content (60% of the fecal mass) |
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How do the small and large intestine differ in their bacterial load
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Each section represents a dynamic ecosystem for several hundreds of bacterial species (commensals and potential pathogens)
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Where are commensal bacteria usually found
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usually found only in the intestinal lumen
the lumen fluid in contact with the apical membranes of mucosal surface cells and intestinal stem cells in the crypts of Lieberkuhn is a rather sterile environment commensal intestinal flora are mainly associated with mucus components (mucins) direct binding to epithelial cells is inhibited |
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The Mucosal Immune System (MIS)
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is functionally and operationally distinct from the systematic immune system
the two sstems may display the opposite immune responses |
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What are the predominant immunoglobins produced b the MIS
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IgA and IgE
(IgG is the predominant antibody in the systemic immune system) |
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True of False
MIS lymphocytes are normally in an "activated" state |
True
(systemic immune system lymphocites are not normally activated until an antigen is encountered) |
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Innate Immune System
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possesses an inborn capacity to recognize microbes and mount antimicrobial defense before encounters with any specific microbe
coding for the molecules involved are included in the germ line molecules may be produced in functional form by many host cells (facilitates rapid(within hours) innate immune responses to microbial infection NO immunologicial "memory"develops |
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Adaptive Immune System (a.k.a aquired immunity)
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has the capacity to develop exquisite specificity against a wide range of antigens
production of antigen-specific immunoglobins IgA and IgE by B lymphocytes and expansion of cytotoxic and helper T lymphocytes requires several days to mount a response immunological memmory may be established |
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Innate immune system recognition by the gut
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the gut epithelium first directly senses the presence of commensal and pathogenenic bacteria through the innate immune system
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Pattern Recognition Molecules (PRMs)
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the gut sensing bacteria is mediated by a variety of germ line-encoded PRMs
PRM's are receptors that specifically recognize essential invariant molecular constituents of microbes knowns as pathogen associated molecular patterns (PAMPs) or microbe associated molecular patterns (MAMPs) PRMs distinguish foreign organisms from host components |
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What does the presence of pathogenic antigens do
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Their presence induces NF - kappaB as well as other signally pathwyas (casapase - 1, IL - 1betaa, type 1 interferons)
trigger innate immune responses alters the MIS alters the activity of the ENS |
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What are the epithelial cell-derived factors involved in mucosal barrier functions
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Goblet cells and surface mucous cells
enterocytes paneth cells |
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Goblet cells and surface mucous cells
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secrete large quantities of mucins that form a protective laer of gel-like mucus over the surface epithelium
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Enterocytes
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Plasma membranes and tight junctions between adjacent cells form a barrier to microbial penetration
secretion of antimicrobial proteins most abundant epithelial cell in both the small and large intestine |
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Paneth Celss
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unique to the small intestine
secrete a large quantity of antimicrobial proteins |
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Mucin glycoproteins
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provides attachment site for commensal and pathogenic microbes (coated in mucus, the microbes may be propelled aborally and eliminated by GI peristalis)
Highly hydrophilic molecules that bind to complex carbs attached to the surface of absorptive epithelial cells to form the glycoalyx |
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Glycocalyx
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forms an effective barrier to bacterial attachment to epithelial cell membranes
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The function of the tight junctions between adjacent enterocytes is
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provide for direct exclusion of bateria and bacterial products
permeability may be modulated by cytokines from immune cells |
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What do proinflammatory cytokines do to tight junction permeability
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increase it
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What do anti-inflammatory cytokines do to tight junction permeability
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decrease it
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Enterocytes
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play a crucial role in innate immunity
contrinual production of antimicrobial peptides and polypeptides |
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B-defensins
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produced by enterocytes
membrane insertion and disruption, pore formation |
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cathelicidins (and cathelin-related antimicrobial peptide or CRAMP)
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produced by enterocytes
membrane insertion and disruption, pore formation proinflammatory (chemotactic for leukocytes) |
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What happens if enterocytes come in direct contact with invading microbes or microbial molecules
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their is a production of higher amounts of antimicrobial factors is quickly introduced
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alpha - defensins
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produced by paneth cells
disrupt bacterial membranes; pore formation |
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lysozyme
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produced by paneth cells
degrades bacterial peptidoglycans in bacterial cell walls |
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secretory phospholipase A
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produced by paneth cells
hydrolyzes bacterial membrane phospholipids |
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What happens when paneth cells come into direct contact with invading microbes or microbial molecules
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production of higher amounts of antimicrobial factors is quickly induced
also release proinflammatory cytokines that "warn" the adaptive immune syste, of severe or persistant infections |
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Second level of immune control at the level of the lamina propria if bacteria breach the epithelial cell barrier
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both innate and adaptive immune responses are involved in the clearance of bacteria from the lamina propria
innate - activation of microphages and neutrophils that directly attack and kill bacteria adaptive - generation of secretory IgA antibodies (sIgAs) directed against bacterial antigens |
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Peyer's Patch (PPs) and Isolated lymphoid follicles (ILFs)
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consist of: A large B cell population, an intrafollicular T cell region, numerous interveing macrophages, and dendritic cells
they are the major sites for induction of the adaptive immuno response, development of sIgA-producing B cells |
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Where are Peyer's Patch (PPs) and Isolated lymphoid follicles (ILFs)found
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under a signle lay of columnar cells - the follicle-associated epithelium (FAE)
which have specialized M cells throughout |
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M Cells
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no microvilli or membrane-associated hydrolytic enzymes, reduced glycocalyx
basalateral membrane forms on invaginated subdomain or intraepithelial "pocket" where it interacts with T cells and B cells The main function of T cells is transepithelial vesicular transport of antigenic proteins and bacteria (both commensal and pathogenic) from the lumen to the subepithelial lymphoid tissues Transported antigenic proteins and bacteria are taken up by dendridic cells (antigen-presenting cells) |
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Dendritic Cells
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underly the FAE M cells
some dendritic cells send long extensions (dendrites) between the tight junctions of the adjacent enterocytes to directly sample for antigenic proteins and bacteria dendritic cells take up antigenic proteins and bacteria from the M cell or the lumen and present them to T and B lymphocytes within a PP or ILF (or upon exiting the lamina propria via the lymph and lodging in a mesenteric lymph node) this leads to activation of B and T cells |
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Lamina propria T cells
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activated T cells
leave the lamina propria in the lymph, traveling to the mesenteric lymphnodes (MLNs) clonally expand in MLNs Return "home" to the lamina propria from the MLNs, these T cells express integrin alpha4beta7 that interacts with mucosal addressin cell adhesion molecule - 1 on endothelial venules in the lamina propria these activated T cells localize in the lamina propria and carry a memory phenotype effetory memory cells and regulatory T cells provide help for B-cell production of sIgAs participate in maintaining tolerance to commensal bacteria |
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Intraepithelial Lymphocytes (IELs)
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some of the returning activated T cells come to reside in the intestinal epithelium, above the basement membrane and between adjacent epithelial cells
they recognized common microbiologen antigens (exert antigen-specific cytotoxicity) Intimate association with epithelial cells allows for a diaglogue between epithelial and IELS Epithelial cells produce various messengers that regulate proligeration and immune function of IELs Conversely, IELs release cytokines that: modulate the expression of adhesion molecules on epithelia modulate epithelial cell growth and accelerate migration of other inflammatory cells to the site |
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Production and secretion of IgA antibodies
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B cells mature into Plasma Cells
B lymphocytes (B Cells) upon being presented with antigenic protein by the dendritic cells are transformed into activated plasma cells that gain the ability to secrete immunoglobin A (IgA) dimers activated plasma cells returen "home" to the lamina propria from the general circulation (B cells and plasma cells also express integrin alpha4beta7 that interacts with MADCAM-1 on endothelial venules in the lamina propria) activated plasma cells secrete large amounts of antigen specific IgA dimers into the lamina propria (IgA monomers joined by a polypeptide, J chain)(dimers bind to polymeric immunoglobin receptor (pIgR) on the basolateral membranes of intestinal epithelial cells |
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Secretion of IgA antibodues into Intestinal Epithelial Celss (or Enterocytes)
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sIgA dimers in the lamina propria bind to the polymeric immunoglobin receptor (pIgR) on the basolateral membrane
the resulting complex is actively transported across the epithelial cell by vesicular transport to the apical surface the dimeric sIgA is released into the intestinal lumer |
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sIgA in the Lumen
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blocks interactions between microbial adhesions and their receptors on epithelial cells (hamper microbial colonization)
binds to and reduces absorption of solube antigens (dampen penetrations of soluble macromolecules through the mucosal surface epithelium) Lumenal sIgA against commensal bacteria limits contact with epithemlium and contributes to "tolerance" |
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sIgA within the enterocyte
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neutralization of viruses and their products
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sIgA in the lamina propria
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may also interact with soluble antigens, then shuttle the immune complexes across the epithelial cells back into the lumen
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Commensal bacteria
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constitue a heterogenous microbial ecosystem contain approx. 10^15 bacteria
reside mainly in the lumen outside the mucus layer modulate expression of host genes that participate in diverse and fundamental physiological functions (capacity to metabolize xenobiotics and endogenous toxins, metabolism of dietary components, perform an instructive role in postnata intenstinal maturation, affect components of the ENS) commensal bacterial PRMs are recognized by the host, they have a symbiotic relationship, steady state induction of protective factors, via constitutive detection of lumen derived microbial products from commensals |
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Bacterial Pathogens
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PMRs activate a rapid strong innate immune response aimed at clearing the intruder (burst of inflammation at the site of infection, tissue destruction and recruitment of immune cell populations (phagocytosis, antigen presentation))
Adaptive response develops more slowly some pathogenic bacteria possess specific virulence factors that allow them to enter epithelial cells, invade and colonize the tissue, damage the host intestine, and create a local or a systemic infect |
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Mast cells
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specific IgE antibodies bind to receptors on surface "sensitizing" the mast cell to a specific antigen, this results in the release of chemical mediators: Histamine, serotonine, prostaglanding, proteoglycans, proteases, and cytoknie
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T or F
immune cells have receptors for neurocrine, endocrine, and paracrine factors that affect their function |
true
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cytokines released by immune cells act on both the ENS and CNS causing
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power propulsion, diarrhea, vomiting, discomfort, nausea
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GI Smooth Muscle
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force producing element through most of the GI tract
alone, these cells are incapable of producing coordinated movements of GI motility Unitary type smooth muscle contirnous sheet coordinated activity results in mixing and propulsion of luminal contents |
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Unitary-type smooth muscle
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contract spontaneously in the absence of nerual or endocrine influences
contract in response to stretch |
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For GI smooth muscles, coordination requires
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electrical activity imposed on smooth muscle cells by "pacemaker" interstitial cells of Cajal (ICC)
rhythmic variations in the membrane potential are known as "slow waves" electrical activity imposed on smooth muscle cells by ENS neurons (hyper- or depolarization of the membrane potential) |
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GI smooth muscle characteristics
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uninucleated
spindle-shaped small high surface to volume ration densely packed arranged in parallel in bundles separated by connective tissue gap junctions b/w adjacent smooth muscle cells (electrical and metabolic coupling) allow smoth muscle cells to a form a "limited" electrical syncytium (electrical events may pass between cells through these low resistance pathways of the gap junctions) |
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Contractions of GI smooth muscle
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increase in intracellular [Ca2+] sufficient for muscle contractions MAY occur during:
slow wave depolarization alone or smooth muscle action potentials (strikes) |
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GI smooth Muscle
slow wave depolarization alone |
few voltage gated calcium channels opened
only a small influx of extracellular calcium and limited mobilization of intracellular calcium occurs usually little or no contraction occurs |
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smooth muscle action potentials ("spikes_
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are elicited if the slow wave depolarization reaches the threshold potential
many voltage-gated calcium channels are opened (greatly increased influx and mobilization of calcium for contractile machinery) duration and strength of contractions is dependent upon the duration of a string of action potentials or spikes (the number of APs in a string is limited bu the duration of the slow wave depolarization) |
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Interstitial Cells of Cajal (ICC)
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derived from the same undifferentiatied mesenchymal cells as smooth muscle cells
2 types Pacemaker and Neurotransmission |
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Pacemaker ICC
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generally found in the reigion of the myenteric plexus in the space between hte circular and longitudinal muscle layers
fine processes and gap junctions interconnect pacemaker ICC also make gap junctions with neighboring smooth muscle celss (variations in the membrane potential of Pacemaker ICC provide the pacemaker activity that drives the "slow waves" typical of phasic GI muscles of the stomach, small and large intestine slower wave activity in GI smooth muscles arises from defined pacemaker regions in each organ unlike the heart, GI muscles do not have point sources or nodes for pacemaker activity phasic regions of the GI tract have a contrinous network of electrically coupled pacemaker cells every region of phasic muscle has intrinisic pacemaker activity |
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Roles of the pacemaker ICC network
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1. propagation of slow waves through the length and circumfrence of the smooth muscle laers and the pacemaker ICC network
2. depolarization of the smooth muscle syncytium |
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T or F
slow wave depolarization of the smooth muscle synctium increases the "open" probabiltity of voltage dependent ion channels |
true
in some cases, smooth muscles responds to slow waves with generalized increase in the "open" probability of Calcium channels during most of the duration of the slow wave (a small mag. inward calcium current during the slow wave may be sufficient to accomplish excitation-extraction coupling In other cases, membrane threshold potential is reached and regenerative fast calcium spike potentials result (a large magnitude inward calcium current accomplishes excitation coupling) In some cases, voltage-dependent K+ channels also "open" and prevent the membrane potential from reaching threshold but also result in a prolonged quasi-stable "plateau potential" (If the duration of the "plateau" is sufficiently long, then enough calcium may enter to accomplish excitation-contraction coupling. |
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How do pacemakers function in vivo
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as a unit
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How do the pacemakers function in the stomach
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there is a proximal to distal pacemaker ICC frequency gradient, and the intrinsic frequencies of pacemaker ICC at more distal sites is slower than that of the corpus
pacemaker ICC along the greater curvature of the corpus usually provide the dominant frequency (~3 cycles per min) because these cells pace at the most rapid frequency (thus there is time for an event generated in the corpus to propogate around the stomach and along the stomach to the pylorus before a distal pacemaker event occurs. This feature forms the basis for gastric peristaltic contractions, which being in the corpus and spread at the rate of slow wave propgation to the pylorus) slows waves do not propagate from the stomach to the small intestine due to a discontinuity of the pacemaker ICC network in the region between the pyloric sphincter and the duodenum |
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Hyperaldosteronism
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decrease salivary Na+ concentration
increase salivary K+ concentration |
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Adrenocortical insufficiency
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increase salivary Na+ concentration
decrease salivary K+ concentration |
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Mastication Functions
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ESSENTIAL for digestion of raw fruits and vegetables
stimulate reflexive increase in saliva flow Reduces size of food particles |
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CNS sensory areas for taste, smell, ect.
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hindbrain
hypothalamus amygdala cerebral cortex |
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Swallowing involves
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oral cavity (CNS)
Pharynx (CNS) Esophogus (CNS and ENS) Orad Stomach - top 1/2 (ENS) |
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Where is the "swallowing center"
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in the medulla and lower pons
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Storage and release of ingested food to the small intestine
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gastric contents released at a rate optimal for function of the small intestine
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digest
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HCl
pepsin; gastic lipase mechanical |
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secretion into the gastric lumen
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mucus; HCO3
HCl; intrinsic factor pepsinogen; gastric lipase |
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secretion into the blood
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gastrin
HCO3 (during HCl seceretion into the lumen) H+ (during HCO# secretion into the lumen) |
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secretion paracrine
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somatostatin
histamine prostaglandins |
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Absorption
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no transport proteins
passive absorption of small, lipophilic molecules |
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protection
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MIS
low pH alkaline mucus Peristalsis interdigestive periodmotility (migrating motility complex (MMC)) |
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fundus
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above the entry of the esophogus
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surface mucous cell
Functions of mucus |
lubrication
cytoprotection |
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cytoprotection
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high [HCO3-] content acts as a buffer against actions of HCl
physical barrier |
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physical barrier
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prevents HCl and/or pepsin from digesting epithelial cells
binds inert particles, non-digested food products, bacteria, viruses, parasites, sloughed cells, etc. acts as a diffusion barrier to nutrients, drugs, uions, toxins, and macromolecules |
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Agents that stimulate gastric mucus secretion
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ACh
released from ENS neurons via "short-" or "long-" loop neural reflexes PGE2 from mucous, cheif and parietal cells Secretin hormone released from the small intestine Local Inflammation cytokines, histamines, prostoglandins, etc. from MIS acting on ENS |
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Agents that INHIBIT gastric mucis secretion
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NSAIDs
inhibit PGE2 production and secretion |
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damaged surface mucous cells can be rapidly replaced by other surface mucous cells that move up along the basement membrane
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covers the damaged surface
does not require immediate cell division |
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Mucous Neck/Undifferentiated Cells
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Secrete mucus
contain relatively few mucous granules Rapidly proliferate and differentiate into other cell types some differentiating cells move up the basement membrane onto the surface to become surface mucous cells other differentiating cells migrate down the basement membrane deeper into the gastric glands to become pariet, cheif or G cells |
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Parietal Cells
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secrete an isotonic solution containing:
HCl intrinsic factor H2O and electrolytes |
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Parietal Cells under non-stimulated, basal conditions
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apical membrane contains collapsed canaliculi
within the cell, near the apical membrane are located tubulovesicles that contain: proton pump - inactive K+ channel - inactive Cl- channel -- inactive |
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Parietal Cells under stimulated conditions
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a cytoskeleton rearrangement causes the tubulovesicular membrane to fuse with the canicular membrane
increase S.A. of the apical membrane; appearance of microvilli insertion of proton pump, K+ channel, and Cl- channel into the canalicular membrane |
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Parietal Cells
AT REST |
HCl production requires:
production of H+ relocation of the proton pump to the canaicular membreane activation of K+ and Cl- efflux pathways |
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Parietal Cells
STIMULATED |
High [H+]
High volume HCl production requires: production of H+ relocation of the proton pump to the canaicular membreane activation of K+ and Cl- efflux pathways` |
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Parietal Cells
HCl secretion can be stimulated by neuroncrine, endocrine, and paracrine substances |
ACh - ENS neurons
acting at three types of muscarinic receptors Gastrin - gastric G cells acting at 2 types of cholecytokinin receptors Ca2+ acts as the 2nd messenger for for ACh and Gastrin Histamine "potentiates" with the stimulatory actions of ACh and gastrin Histamine - gastric ECL - cells acting at the type 2 histamine receptors H2 receptor blocking drugs cAMP acts as the 2nd messenger for histamine |
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Parietal Cells
HCl secretion can also be INHIBITED by neuroncrine, endocrine, and paracrine substances |
Somatostatin (SS) - paractine substance from gastric D-cells that directly inhibits parietal cell secretion
acting at the type 2 somatostatin receptor the following substances inhibit HCl secretion indirectly by stimulating SS secretion VIP - from ENS neurons Cohlecystokinin (CCK) - hormone from l-cells of the small intestine Secretin - horme from S-Cells of the small intestine GLP - 1 and GLP - 2 (enteroglucagons) - hormones from L0cells of the small intestine Gastric Inhibitory Peptide (GIP) - hotmone from K-cells of the small intestinw |
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Fucntions of Gastric HCL
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denatures protein
activates pepsinogen to pepsin solubilizes calcium salts kills bacteria in food keeps the gastric lumen relatively free of microorganisms |
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Functoin of Intrinsic factor
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intrinsic factor forms a complex with cobalamin (sic, vit B12)
the cobalamin-intrinsic factor complex is absorbed in the terminal ilelum |
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functions of pepsin
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initiation of protein digestion to yield small peptides (incomplete)
pH optimum 1-3 contribution to overall coordination of digestive processes (stim release of CCK and gastrin hormones) |
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functions of gastric lipase
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hydrolysis of triglycerides
pH optimun = 3 - 7 yields two free fatty acids and a 2-monoacylglyercide contribution to overall digestive processes |
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Stimulators of Cheif cell secretion
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ACH - from ENS neurons (via muscarinic receptors)
Gastrin - from gastric D-Cells (via B- receptors) CCK - from intestinal l - cells (via CCK - A receptprs) THESE ABOVE use Ca2+ as a second messenger THESE BELOW use cAMP as a 2nd messanger Secretin - form intestinal S-cells VIP - from ENS neurons GLP-1 and GLP-2 (enteroglucagons) - from intestinal L cells GIP - from intestinal K-cells |
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No inhibitors of Cheif Cell secretion except for:
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direct effect of somatostatin
all things that stimulation somatostatin also stimulate cheif cells NET EFFECT: direct effect is stronger than the indirect effect of SS |
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G cells stimulation
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stimulated by:
foodstuffs in the gastric lumen peptides, amino acids, and amines, ethanol, etc, within lumen exert a direct effect ENS stimulation GRP (Gastrin - releasing peptide) from ENS Short and long loop reflexes in response to: luminal peptides, amino acids, Ca2+ distension |
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G cells secretion is inhibited by:
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SS from gastric D cells
released in response to: acidification of the gastric lumen CCK Secretin Etc. |
