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Gastrointestinal motility (Stomach (Vomiting (E.g. of central regulation…
Gastrointestinal motility
General Patterns of motility
Peristalsis
Reflex response initiated when the gut wall is stretched by contents of the lumen, occurs in all parts of the GIT from esophagus to rectum.
Stretch initiates a circular contraction behind the stimulus (proximal) and relaxation in front of it (distal)
Moves oral-to-caudal at different rates in different parts of the body
activity can increase or decrease by autonomic input to the gut, occurrence is independent of extrinsic innervation.
Progression of contents not blocked by removal and resuture of segment of intestine in its orinal position, only block if segment replaced is reversed before suturing
Local stretch releases serotonin, activating sensory neurons that activate the myenteric plexus
Cholinergic neuron passing retrograde direction in this plexus activate neurons that release substance P and ACh, causing smooth muscle contraction behind bolus
Cholinergic neuron passing anterograde direction activate neurons passing in anterograde direction activate neurons that secrete NO and Vasoactive intestinal polypeptide (VIP), producing relaxation ahead of stimulus
Segmentation and mixing
when meal is present, enteric nervous system promotes a motility pattern designed to retard movement of intestinal contents along length of intestinal tract to provide time for digestion and absorption (ample mixing of intestinal contents with digestive juices
Segmentation
Segment of bowel contracts at both ends, then a second contraction occurs in the center of segment to force the chyme both back and forward
Unlike peristalsis, retrograde movement of chyme occurs routinely, can occur independent of central input, although the latter can modulate it
Basic electrical activity and regulation of motility
Except esophagus and proximal portion of stomach, smooth muscle of the GIT has spontaneous rhythmic fluctuations in membrane potential between -65 and -45 mV.
Basic Electrical Rhythm (BER) is initaited by interstitial cells of Cajal, stellate mesenchymal pacemaker cells with smooth muscle like features that send long multiply branched processes into intestinal smooth muscle
In stomach and small intestine, there is descending gradient in pacemaker frequency, and pacemaker with highest frequency usually dominates
BER itself rarely causes muscle contractions, but spike potentials superimposed on most depolarizing portions of BER waves do increase muscle tension
Depolarizing portion of spike is due to Ca2+ influx and repolarizing portion due to K+ efflux
Many polypeptides and neurotransmitters affect the BER
e.g. ACh increases no. of spikes and tension of smooth mucle, epinephrine decreases the no. of spikes and tension.
Rate of BER:
stomach: 4/min
duodenum: 12/min
Ileum: 8/min
Colon: 2/min at cecum, 6/min at sigmoid
Function of BER is to coordinate peristaltic and other motor activity, setting the rhythm of segmentation
After vagotomy or transection of stomach wall, peristalsis in stomach becomes irregular and chaotic
Migrating Motor Complex
occurs during fasting (between periods of digestion), pattern of electricacl and motor activity in gastrointestinal smooth muscle becomes modified so cycles of motor activity migrate from stomach to distal ileum.
Each cycle (MMC) starts with a quiescent period (phase I), continues with period of irregular electrical and mechanical activity (phase II) and ends with a burst of regular activity (phase III)
Initiated by motilin, circulating levels increase at intervals of approx 100 min in interdigestive state, coordinated with contractile phases of the MMC
Contractions migrate aborally at 5cm/min, intervals of around 100min
Gastric secretion, bile flow and pancreatic secretion increase during each MMC, serving to clear the stomach and small intestine of luminal contents in prep for next meal
when meal is ingested, secretion of motilin surpressed, MMC abolished until digestion and absorption are complete, there is a return to peristalsis and other forms of BER and spike potentials during this time.
Antibody erythromycin binds to motilin receptors, and derivatives of this compound may be of value in treating patients in whom gastrointestinal motility is decreased
Segment-specific patterns of motility
Mouth and Esophagus
In mouth, food mixed with saliva and propelled into esophagus.
Peristaltic waves in esophagus move the food into the stomach
Mastication (chewing)
Breaks up large food particles and mixes the food with the secretions of salivary glands
wetting and homogenizing action aids swallowing and subsequent digestion
Large food particles can be digested, but cause strong and often painful contractions of the esophageal musculature
Particles that are small tend to disperse in absence of saliva and also make swallowing difficult because they do not form a bolus
Optimal no. of chews depend on food, normally around 20-25
Edentulous (lack teeth) generally restricted to soft diet and have difficulty eating dry food
Swallowing
Reflux response triggered by afferent impulses in trigeminal, glossopharyngeal and vagus nerves
Impulses integrated in nucleus of tractus solitarius and nucleus ambiguus
Efferent fibers pass to pharyngeal musculature and tongue via trigeminal, facial and hypoglossal nerves
Swallowing initiated by voluntary action of collecting oral contents on tongue, propelling them backward to the pharynx, starting a wave of involuntary contraction in the pharyngeal muscles that push material into the esophagus
Inhibition of respiration and and glottic closure are part of the reflex response
Peristaltic ring contraction of esophageal muscle forms behind the material, which is then swept down at approx 4cm/s, generally falling by gravity, with a second wave picking up leftovers
Lower esophageal sphnicter
Muscle of gastroesophageal junction is tonically active and only relaxes on swallowing
Tonic activity of LES between meals prevent reflux of gastric contents into esophagus.
LES made up of 3 components:
Fibers of crural portion of the diaphragm (a skeletal muscle) surrounds the esophagus at this point (extrinsic sphincter) and exert a pinchcock-like action on esophagus
esophageal smooth muscle more prominent at the junction with the stomach
Oblique or sling fibers of stomach wall create a flap valve that helps close off the junction and prevent regurgitation when intragastric pressure rises
Tone of LES under neural control
Release of ACh from vagal endings cause intrinsic sphincter to contract, and release of NO and VIP from interneurons innervated by other vagal fibers causes it to relax
Contraction of crural portion is innervated by phrenic nerves, coordinated with respiration and contractions of chest and abdominal miscles
Intrinsic and extrinsic sphincters thus operate together to permit orderly flow of food into the stomach and prevent reflux of gastric content into esophagus
Aerophagia and intestinal gas
Some air unavoidably swallowed in process of drinking and eating (aerophagia)
Some regurgitated through belching (burp), and some gas are absorbed but much of it is passed to the colon.
In colon, some O2 absorbed, and H2, CO2, hydrogen sulfide and methane formed by colonic bacteria from carbs and other substances are added to it, and is then expelled as flatus
smell is largely due to the sulfides
Vol of gas normally found is 200mL, daily production is 500-1500mL.
In some individuals, gas in the intestines cause cramps, borborygmi (rumbling noises) and abdominal discomfort
Stomach
Food is stored here, mixed with acid, mucus and pepsin, and released in a controlled, steady state into the duodenum
Gastric motility and emptying
When food enters the stomach, fundus and upper portion of body relax, and accommodate the food with little increase in Pressure (receptive relaxation)
Peristalsis begins in lower portion of the body, mixing and grinding the food, permitting small, semiliquid portions of it to pass through the pylorus and enter the duodenum
Receptive relaxation is (in part) vagally mediated and triggered by movemnet of pharynx and esophagus
Intrinsic reflexes also lead to relaxation as stomach wall is stretched
Peristaltic waves controlled by the gastric BER begin soon thereafter and sweep toward the pylorus
Contraction of distal stomach caused by each wave sometimes called antral systole and can last up to 10s, waves occur 3-4 per min
In regulation of gastric emptying, antrum, pylorus and upper duodenum function as a unit.
contraction of antrum is followed by sequential contraction of the pyloric region and the duodenum
In antrum, partial contraction ahead of advancing gastric contents prevents solid masses from entering duodenum, and they are mixed and crushed instead.
More liquid gastric contents are squirted a bit at a time into small intestine
Normally, regurg from duodenum does not occur because contraction of pyloric segment tends to persist slightly longer than the duodenum
Prevention of regurg may also be due to stimulating action of CCK and secretin on pyloric sphincter
Regulation of gastric motility and emptying
Rate at which stomach empties into the duodenum depends on type of food ingested.
Food rich in carb leave stomach in a few hours
Protein-rich food leaves more slower, and fats are the slowest
Rate also depends on osmotic pressure of material entering the duodenum
Hyperosmolality of duodenal contents is sensed by "duodenal osmoreceptors' that initiate a decrease in gastric emptying (probably neural in origin)
Fats, carbs and acid in duodenum inhibit gastric acid and pepsin secretion and gastric motility via neural and hormonal mechanisms (most probably petpide YY)
CCK has also been implicated as an inhibitor of gastric emptying
Vomiting
E.g. of central regulation of gut motility
Starts with salivation and the sensation of nausea
Reverse Peristalsis empties material from upper part of small intestine into stomach
Glottis closes, preventing aspiration of vomitus into trachea
Breath is held mid inspiration, muscles of abdominal wall contract and because the chest is held in fixed position, contraction increases intra-abdominal pressure
Lower esophageal sphincter and esophagus relax, and gastric contents are ejected
"vomiting center" in the reticular formation of the medulla consists of various scattered groups of neurons in this region that control the different components of vomiting act
Irritation of mucosa of upper GIT is one trigger, impulses relayed from mucosa to medulla over visceral afferent pathways in symathetic nerves and vagi
other cause can arise centrally, e.g. afferents from vestibular nuclei mediate nausea and vomiting motion sickness
Nauseating smells and sickening sights
Chemoreceptor cells in the medulla (chemoreceptor trigger zone) is in area postrema, a V-shaped band of tissue on lateral walls of 4th ventricle near the obex -> not protected by BBB
Lesions here have little effect on vomiting response to gastrointestinal irritation or motion sickness, but abolish the vomitnig that follows injection of apomorphine and other emetic drugs, also decrease vomiting in uremia and radiation sickness (associated with endogenous production of circulating emetic substances)
Corticosteroids, cannabinoids and benzodiazepines, alone or in combi with 5-HT3 and D2 antagonists are also useful in treating vomiting due to chemotherapy
Small intestine
Intestinal contents mixed with secretions of mucosal cells and with pancreatic juice and bile
Intestinal motility
12 BER cycles/min in proximal jejunum, declining to 8/min in distal ileum.
Three types of smooth muscle contractions
peristaltic waves, segmentation contractions and tonic contractions
segmentation contraction move chyme to and fro and increase its exposure to mucosal surface, initiated by focal increases in Ca2+ influx with waves of increased Ca2+ concentration spreading from each focus
Tonic contractions relatively prolonged contractions that isolate one segment of intestine from another, delaying transit time
Colon
Reservoir for residues of meals that cannot be digested or absorbed
Motility slowed to allow colon to absorb water, Na+ and other minerals
Converts 1000-2000ml of isotonic chyme from ileum to about 200-250mL of semisolid feces
Motility of colon
Ileum linked to colon by ileocecal valve, which restricts reflux of colonic contents, particularly large numbers of commensal bacteria into the relatively sterile ileum
A portion of the ileum containing the ileocecal valve projects slightly into the cecum, so that increase in colonic pressure squeeze it shut, whereas increase in ileal pressure opens it
normally closed, each time peristaltic wave reach it, opens briefly, allowing some ileal chyme to squirt into the cecum
When food leaves the stomach, cecum relaxes and passage through the ileocecal valve increases (gastroileal reflex)
Vasovagal reflex
Movement also includes segmentation contraction and peristaltic waves
Mass action contraction (only in colon) occurs about 10 times a day, in which simultaneous contraction of the smooth muscle over large confluent areas.
This moves material from one portion of colon to another, and also moves into the rectum, where rectal distension initiates defecation
Movements coordinated by BER of colon, 2/min at ileocecal valve, 6/min at sigmoid
Transit time in small intestine and colon
First part of test meal reach cecum in about 4h, all undigested portions entered colon in 8 or 9h
On average, first remnants of meal transverse first third of colon in 6h, second third in 9h and reach the terminal part of colon in 12h
From sigmoid colon to anus, transport much smaller
70% of test colour beads recovered in stool in 72h, total recovery needs more than a week
Transit time, pressure fluctuation and changes in pH of GIT can be observed by monitoring progress of a small pill
Defecation
Distension of rectum with feces initiates reflex contraction of its musculature and desire to defecate
sympathetic nerve supply to internal anal sphinctor is excitory, whereas parasympathetic is inhibitory
Sphincter relaxes when rectum is distended
nerve supply to external anal sphincter, a skeletal muscle, comes from pudendal nerve
The sphincter is maintain in a state of tonic contraction, and moderate distension of rectum increases force of contraction
urge to defecate first occurs when rectal pressure increases to about 18 mm Hg, when pressure reach 55 mm Hg, external as well as internal sphincter relaxes and there is reflex expulsion of contents of the rectum
Before theh pressure is reached, voluntary defecation can be initiated by straining
Normally, angle between anus and rectum is approx 90 degrees, and this plus contraction of the puborectalis muscle inhibits defecation
With straining, abdominal muscles contract, pelvic floor is lowered 1-3cm and the puborectalis muscle relaxes. The anorectal angle is reduced to 15 degrees or less, and combined with relaxation of external sphincter, facilitates defecation
Distension of stomach by food initiates contractions of rectum and frequently, the desire to defecate -> gastrocolic reflex
May be amplified by an action of gastrin on the colon
Defecation after meals is the rule in children
In adults, habit and cultural factors plays a large role in when defecation happens