45: Introduction to GI Flashcards
Describe the principal areas, organs and their general functions in the gastrointestinal system. Given a cross section of the bowel wall, identify the primary layers, including the epithelial layer, muscle layers, myenteric and submucosal plexuses.
Stomach anatomy from proximal to distal: fundus, body, antrum.
- The mucosal surface faces the lumen and consists of a layer of epithelial cells (secretory & absorptive functions), lamina propria (connective tissue, blood & lymph vessels), and the muscularis mucosae (smooth muscle which influences local infolding to promote absorption).
- The submucosal layer consists of collagen, elastin, glands, and blood vessels. The two primary smooth muscle layers controlling motility are the circular and longitudinal muscles. The two nerve networks that make up the ENS are the myenteric and submucosal plexuses.
- The serosal surface faces the blood.
Describe how afferent and efferent extrinsic nerves (sensory, sympathetic and parasympathetic) interact with the enteric intrinsic nervous system to regulate the motility and secretory functions of the GI tract.
ENS can function independently of nervous system & can be modulated extrinsically by sympa & parasymp nervous systems.
In ENS, sensory or afferent neurons monitor changes in luminal activity by activating internourons that activate efferent secretomotor neurons.
Efferent motor neurons stimulate or inhibit a effector cells: blood vessels, smooth muscle, epithelial cells, enteric endocrine cells.
Receptors in the GI mucosa relay afferent info to CNS via vagus triggering efferent vagal reflexes called vagovagal reflexes.
Mechanoreceptors sense stretch of the smooth muscle, and signal is transduced through the myenteric plexus, stimulating contractions.
Chemoreceptors sense the chemical composition of the chyme and regulate motility and secretion of buffers to control luminal pH during the influx of acidic chyme into the duodenum.
Osmoreceptors sense the osmolarity of the chyme in the small intestine. Thus, the osmoreceptors control the amount of chyme entering the small intestine, as well as the amount of secretions necessary to buffer the chyme.
Parasympathetic preganglionic fibers (vagus and pelvic nerves) terminate on postganglionic cholinergic or peptidergic neurons located in the plexuses. PNS activation leads to increased motility in the wall of the gut, relaxation of sphincters, and enhanced secretions (e.g. mucus, hormones, acid, buffers). Vagovagal reflexes are prominent in coordinating GI function. These are long reflexes in which both afferent and efferent impulses are carried by neurons in the ‘mixed’ vagus nerve. Acetylcholine (ACh) is the major neurotransmitter for pre- and post-ganglionic fibers of PNS, but some postganlionic fibers release peptides (e.g. substance P, VIP).
SNS innervates ENS via postganglionic fibers from the celiac plexus, hypogastric, and the superior & inferior mesenteric ganglia. Norepi has inhibitory effects on excitatory cholinergic neurons through the process of presynaptic inhibition.
In general, stimulation from the parasympathetic nerves enhances motility and secretions through the ENS, whereas sympathetic stimulation reduces motility and secretions.
Describe the functional properties of GI motility in the digestive and interdigestive states, and how they are regulated, including the roles of interstitial cells of Cajal, ENS, ANS.
The interstitial cells of Cajal are the pacemakers located in the GI tract. They are abundant in the myenteric plexus. Their purpose is to generate slow electrical waves. Contractions of GI muscle occurs when AP’s are generated @ the peaks of the slow waves that are continuously occurring, generated by the ICC pacemaker cells.
Neural and hormonal input modulate the production of action potentials and thus the strength of muscle contractions.
- slow waves - These are slow undulating changes in the resting membrane potential (no action potentials/no muscle contractions). They typically vary in intensity between 5 – 15 mV.
- spike potentials – These action potentials are produced when threshold is reached(~ -40mV) during the plateau phase of the slow wave, triggering phasic contractions. Depolarization of the slow waves above -40 mV stimulates action potentials, which causes contraction of the smooth muscle. In GI muscle, the action potentials last 10-40 times longer than the nerve action potential, and are produced largely by Ca2+ entry through L-type VSCCs (plus some Na+ influx). Thus, disordered GI motility may be a side effect of treating cardiovascular disease with L-type VSCC blockers.
Peristalsis is intensified after a meal by stretch of duodenum by chyme. The gastroenteric reflex enhances peristaltic motility & secretions. The gastroileal reflex triggers opening of ileocegal valve to allow chyme from large to small intestine–distention of ileum leads to relaxation of sphincter. The enterogastric reflex decreases gastric motility & secretions & stimulates contraction of pyloric sphincter to stop chyme form entering duodenum–with the prupose of optimizing digestion/ absorption.
Peristalsis and Segmentation Motility in the small intestine is primarily under local control of the myenteric plexus and consists of both peristalsis and segmentation. Segmentation forms pockets of chyme and serves to mix and propel the chyme, although normally peristalsis creates aboral movement (away from mouth). Peristaltic rushes can occur when the intestines are irritated, moving chyme rapidly through the intestines. Irritation of the intestinal mucosa by infectious agents, for example, causes a peristaltic rush/diarrhea that serves to clear the intestine of the irritant.
Peristaltic propulsion involves formation of a propulsive and a receiving segment, mediated by reflex control of the intestinal musculature. Proximally, the circular muscle contracts & longitudinal muscle relaxes. Distally (past bolus), the circular muscle relaxes & the longitudinal muscle contracts. Mnemonic: C before L.
The myenteric reflex promotes peristaltic movement of chyme from stomach to small intestine to large intestine.
Peristalsis involves the coordinated activity of excitatory neurons: Ach & substance P & inhibitory motor neurons: VIP in response to intestinal distention.
Fasting is an interdigestive state that is characterized by long periods of quiescence in conjunction with short rhythmic waves of strong propulsive contractions that pass down the distal stomach and small intestine. The contractions are known as the Migrating Motor Complex (MMC) and can be divided into phases characterized by quiescence (I), little activity (II), and strong activity (III). The MMC:
1) Functions to ‘sweep’ the stomach and small intestine of residue including undigested food/fiber, bacteria (may prevent overgrowth), desquamated cells. Note during this phase, the pyloric sphincter is inhibited and particles larger than 2 mm can pass into the duodenum.
2) Is observed ~3 hours after last meal and occurs at cyclic intervals of ~90 min (with ingestion of food, normal segmental and propulsive patterns resume).
3) Begins in the distal ⅓ of the stomach and continues to the terminal ileum, emptying material into the colon.
4) Motilin, synthesized in the duodenal Mo cells, is released into the circulation and stimulates the contractions (5-10 min) seen during the active phase. Motilin acts through the ENS and ANS to stimulate contractions.
Vagotomy reduces MMC contractile activity.
Know the general pathophysiology of diseases or states associated with disordered motility and ileus.
Physiological ileus is the absence of motility in the small & large intestine. It is a normal state and remains in effect for varying periods of time in different intestinal regions. A subset of inhibitory neurons are active and suppress the response of the circular muscle to the electrical slow waves.
Pathological ileus (paralytic ileus) is a state when the normal periods of quiescence are much longer. In this case, the inhibitory neurons are abnormally active and continuously suppress myogenic activity. Passage of stool and gas are impaired, and individuals experience cramping pain, nausea and vomiting. As examples, altered motility and delayed transit is common after abdominal surgery (postoperative ileus), anticholinergic or opiate drug treatment.
Describe the sequence of events associated with swallowing a bolus of food, including voluntary and involuntary responses.
Swallowing (Deglutition) carries food from the pharynx to the esophagus.
The voluntary stage of swallowing involves:
1) Shaping of food into a bolus
2) Collection on the tongue
3) Raising of the tongue against the hard palate to create a pressure gradient that pushes the bolus
into the pharynx.
The involuntary events of the swallowing reflex are initiated when food enters the pharynx:
1) Food in the pharynx activates sensory neurons that project via the vagus and glossopharyngeal
nerves to the swallowing center in the medulla.
2) Efferent impulses are sent back to the pharynx, esophagus, esophageal sphincters and stomach
causing: the soft palate to pull upward preventing food reflux into the nasopharynx, movement of epiglottis and pharynx to prevent food from entering trachea, and relaxation of the UES. Steps 1 and 2 are referred to as the pharyngeal phase of swallowing.
3) The swallowing reflex also initiates a primary peristaltic wave that propels food through the open UES, followed by closure of the UES, and continued peristalsis that traverses the length of the esophagus, terminating in opening of the LES, and receptive relaxation of the stomach. This is referred to as the esophageal phase of swallowing. If the primary wave fails to move all food into the stomach, a secondary peristaltic wave results from distension of the esophagus.
During the pharyngeal phase, tactile areas near the pharyngeal opening (especially the tonsillar pillars) transmit impulses through the sensory portions of CN V and IX to the swallowing center in the medulla oblongata. This initiates an orderly sequence of motor impulses from medulla and lower pons via sequential activation of CN V, IX, X, and XII. The process takes ~ 6 sec. The swallowing center inhibits the respiratory center during this time.
Note that the pharynx and upper ⅓ of the esophagus are striated muscle, which are controlled by skeletal nerve impulses from CN IX and X. The remainder of the esophagus is smooth muscle.
Esophageal pressures during swallowing. The swallowing center in the medulla that initiates deglutition includes the nucleus ambiguus (CN IX and X), the dorsal motor nucleus of the vagus (CN X).
Ingestion of a meal requires transient relaxation of the proximal stomach with each bolus of food, called receptive relaxation in the lower esophageal sphincter & fundus.
Receptive relaxation in the lower esophageal sphincter and fundus is primarily regulated by a vagovagal reflex after swallowing. The transmitter released by the postganglionic vagal fibers is vasoactive intestinal polypeptide (VIP). If the primary peristaltic wave does not clear the bolus of food from the esophagus, a secondary peristaltic wave is triggered by the enteric nervous system. The secondary wave begins at the point of distension and travels downward.
In the stomach, receptive relaxation results in an increase in intragastric volume but not intragastric pressure.
As food accumulates in the stomach there is a gradual relaxation of the entire stomach, called accommodation, which allows storage of food without an increase in intragastric pressure. This process is also mediated by a vagovagal reflex.
Gastric emptying is affected by contents of meal. High fat meal = slow emptying & liquid saline meal = rapid emptying. Receptors in the small intestine sense the contents of the chyme & regulate emptying to optimize absorption.
Explain why voluntary and involuntary responses associated with swallowing a bolus of food are disrupted in achalasia and GERD?
Lower Esophageal Sphincter. The resting tone of the lower esophageal sphincter (LES) is usually high, preventing reflux of stomach contents. When food is swallowed, esophageal peristalsis is initiated by the vagus nerve and is propagated by the enteric nerves. As the bolus of food reaches the LES, local vasoactive intestinal peptide (VIP, and probably NO as well) is released, and the sphincter tone relaxes, allowing the bolus to enter the stomach.
Achlasia = lower esophageal sphincter does not relax & stays toned. Over months and years, the esophagus becomes enlarged, holding as much as a liter of food. It can become infected, causing ulcerations, and may rupture leading to death.
GERD = LES is too relaxed. In GERD, refluxed contents from the stomach can damage the esophageal epithelium.
