Gin6 - Regulation Of Gastrointestinal Motility

GIN 15 September 19. 2007 Dr. Sushil Sarna

Proscribe: Sarah Stafford Reviewer: Rick Chapa Chief Reviewer: Ramona Ataya

Regulation of Gastrointestinal Motility I. Main components of general pain: A. Stimulus B. Autonomic neurons that carry signal generated by the stimulus 1. In the gut, there are several types of afferent neurons: We discussed low threshold enteric mechanoreceptive neurons and high threshold, along with silent gastrointestinal afferents. a. Low threshold neurons send signals to the CNS at distensions of less than 5 mmHg, while high threshold neurons send signals at distensions greater than 20 mmHg. b. Inflammation can cause silent GI afferent nerve sensitization that leads to unusual firing in nerves that are normally quiescent (only signal in a disease state). C. CNS cells that recognize the signal as pain II. Abdominal Pain/ Cramping A. Symptom of multiple disorders including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). 1. IBS- 2:1 women: men; unknown pathophysiology, but three types a. Diarrhea predominant (mouth to cecum transit time decreased- moves faster) b. Constipation predominant (mouth to cecum transit time increasedmoves slower) c. Mixture of both of above d. No satisfactory medication for any type. 2. In both IBS and IBD, abdominal cramping can become debilitating. 3. Main difference is that constipation is not a part of IBD. B. Components of visceral pain of the gut: 1. Stimulus: Strong compression or distention of a segment of the gut a. A strong contraction is usually accompanied by relaxation of the segments of gut distal to the contraction. b. When the neurological signals that induce this response are lost, the distal segments distend, which is perceived as pain. c. Therefore, it is a combination of compression and distention that causes pain, not one or the other. 2. Pain can also be caused by sensitization of afferent neurons (which can occur idiopathically, as a result of post-childhood stressors, or as a result of pathological conditions) that results in visceral hypersensitivity. a. In a normal subject, not even giant migrating contractions reach the nociceptive threshold, so they do not normally cause pain.

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GIN 15 September 19. 2007 Dr. Sushil Sarna

Proscribe: Sarah Stafford Reviewer: Rick Chapa Chief Reviewer: Ramona Ataya

b. When a subject has visceral hypersensitivity the nociceptive threshold is decreased, GMCs can cause pain, but rhythmic phasic contractions still do not. c. Some IBS patients demonstrate this visceral hypersensitivity with abdominal cramping (meaning they feel cramping whenever there is a GMC) while others do not. 3. Impaired inhibition of descending signals from the CNS. a. Descending signals involved in the relaxation of gut distal to contraction sites. b. As described above, without the descending signals, distention leads to pain. III. Esophageal pain A. May be provoked by large amplitude esophageal contractions. IV. Normal Bowel Habits A. Frequency 1. Normally less than 21 and more than 3 a week 2. Less than three is considered constipation 3. More than 21 is considered diarrhea B. Weight 1. Men: 35 to 450 g/stool 2. Women: 5 to 335 g/stool C. Consistency 1. 70-75% water 2. Hard stool considered 40-50% water 3. Loose stools >80% water V. Abnormal Bowel Habits A. Diarrhea 1. Two types: a. Secretory- increased secretions b. Motor- increased speed of transit 2. Symptom of both IBD and IBS 3. Involves increased number of GMCs and a decreased tone (this may seem confusing because we think of tone as something that propels stool forward, but actually, tone propels stool at a slow rate and prevents it from moving at a fast rate; therefore, tone is decreased in diarrhea allowing the increased number of GMCs to propel stool at a much faster rate. B. Constipation 1. Two types: a. Slow transit- contents move from ascending to descending colon at slower speed than normal (normal considered 36 hrs in men, and 48 hrs women); the longer the stool spends in the colon, the more water that is absorbed, compounding the problem by hardening the stool.

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GIN 15 September 19. 2007 Dr. Sushil Sarna

Proscribe: Sarah Stafford Reviewer: Rick Chapa Chief Reviewer: Ramona Ataya

b. Outlet obstruction- normal transit time but contraction of the anal canal results from stimuli that would normally cause relaxation. 2. The picture to the right demonstrates normal defecation and obstructive (biofeedback refers to training of central control which is the accepted treatment). VI. Neuroregulation A. Stimulus (food or sensing food) B. Sensors in gut lumen (chemical and mechanical) C. Signal ENS/ smooth muscle D. ENS signals then create the desired effect (motility, secretion, and/or blood flow) E. Normally the gut is an autonomous organ, but under stress can involve more. Sensors can also send signals to the CNS which send sympathetic and parasympathetic neuronal signals to achieve the same effects 1. Parasympathetic innervation is supplied primarily by the vagal nerves, pelvic nerves, and the pudendal nerve. The vagus nerve innervates the esophagus, stomach, pancreas, small intestine, and the proximal 2/3 of the colon. The pelvic nerves innervate the distal colon, the rectum, and the anus. The pudendal nerve innervates the sphincter. 2. The sympathetic nervous system includes the nerves that run from the spinal chord to the prevertebral ganglia (superior and inferior mesenteric and celiac ganglion) and between the ganglion and the organs of the GI system. 3. The parasympathetic nervous system generally excites the function of the GI tract, while the sympathetic system generally indirect inhibits the function of the GI system by inhibiting the ENS (which excites smooth muscle to contract) with norepinephrine. 4. Signals sent though dorsal motor nucleus. F. Review of anatomy, and locations of important neural structures as demonstrated by the pictures below (Dr. Sarna just went through and pointed out the neural structures)

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GIN 15 September 19. 2007 Dr. Sushil Sarna

Proscribe: Sarah Stafford Reviewer: Rick Chapa Chief Reviewer: Ramona Ataya

1. The above figure demonstrates that unlike in the heart, the parasympathetics and sympathetics do not directly innervate the smooth muscle. They innervate the myenteric plexus and the submucosal plexus. G. Chemical control of smooth muscle contractions (think about the gut like it’s a car: there is an accelerator and a brake) 1. Excitatory a. Acetylcholine b. Choleystokinin c. Gastrin d. Motilin e. Opioids f. Serotonin g. Histamine h. Angiotensin i. Substance P 2. Inhibitory a. Norepinephrine b. Vasoactive intestinal c. polypeptide (VIP) d. Nitric Oxide (NO) e. Adenosine f. Triphosphate(ATP) g. Glucagon h. Secretin i. Opioids H. Regulation of smooth muscle contraction (I took the last bit of this scribe from the 2009 scribe as she covered it in more detail than we did in lecture). 1. Because smooth muscle cells have a negative resting potential, their depolarization can be recorded in much the came way as an EKG. 2. There is a rhythmic depolarization present in smooth muscle cells. These potential changes are known as slow waves, and do not alone cause contractions. Depolarization during each slow wave brings the membrane potential of smooth muscle cells closer to threshold which increases the probability of an action potential. 3. Slow waves set the timing for when potential spikes (spike potentials are what cause contractions) occur because spikes are seen only during the peak of depolarization of the slow wave in conjunction with ACh release - this is how the gut regulates contraction propagation. 4. Slow waves originate in the complex interaction among smooth muscle cells and specialized cells called interstitial cells of Cajal and determine the maximum number of contractions that can occur. 5. Frequency of slow waves along the GI tract a. Stomach: 3 contractions a minute b. Duodenum: 12-15 contractions a minute c. Ileum: 5 contractions a minute d. Colon: Variable (3-9)

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GIN 15 September 19. 2007 Dr. Sushil Sarna

Proscribe: Sarah Stafford Reviewer: Rick Chapa Chief Reviewer: Ramona Ataya

I. Propagation 1. If there is a strong cell to cell coupling between the proximal, middle, and distal gut, slow waves can be propagated down the gut by release of ACh. 2. The sequential slow waves allow for sequential contraction, achieving the desired effect of propulsion. 3. If cell-cell coupling is weak, contraction is disorganized (which is not necessarily bad). 4. Again note: the slow waves determine the sequence of the propagation of contraction because in the gut you do not need constant contraction like in the heart. J. Gut communication 1. Enteric neurons communicate with each other along the length of the gut but smooth muscle cells can only be excited by neurons in close proximity.

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GIN 15 September 19. 2007 Dr. Sushil Sarna

Proscribe: Sarah Stafford Reviewer: Rick Chapa Chief Reviewer: Ramona Ataya

2. The more distal you get, the less coupled the system, leading to decreased propulsion and more mixing (as in the ileum and the colon). K. Overall control of motor activity under myo-neuro-chemical control as depicted in the diagram below.

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