Motility of the Digestive Tract (DT)
The Digestive Tract (DT) is muscular and contracts rhythmically to conduct
food through its length (peristalsis). The timing, strength, and coordination of
muscular contraction is influenced by the composition of food and by
state-specific body-brain conditions. If the contractions are too vigorous,
crampy pain is experienced. If the contractions are too frequent, diarrhea
results. Constipation occurs when contractions are sluggish and slow, or if
sustained contractions act to obstruct the tube.
Disorders of peristalsis are referred to as "Motility Disorders." Medical
diagnoses sometimes refer to motility disorders as if they were the cause of
symptoms. With a few exceptions, motility problems are not causes but they are
effects of food-DT interaction and DT-brain interactions.
The stomach stores and mixes ingested food, regulating the rate of transfer
into the duodenum. Pacemaker cells of Cajal (ICCs) are located in the
greater curvature that send activation signals in circumferential and
longitudinal directions. Spike waves occur when the slow wave reaches a
threshold and produce contractions. In guinea pig gastric smooth muscle, protein
kinase C modulates the contraction frequency and the intracellular calcium
concentration modulates the amplitude. Calcium is released in response to
increased metabolic activity of the mitochondria.
The stomach and duodenum signal each other via release of neurotransmitters
and hormones. Distension of the gastric antrum causes relaxation of the pylorus
(antro-sphincteric reflex) and duodenum (antro-duodenal reflex).
Distension of the duodenum causes antral relaxation (duodeno-antral reflex).
Distension of the pyloric sphincter causes antral contraction (sphinctero-antral
reflex). These reflexes facilitate the transport of gastric contents into the
Every medical student learns that there is a dense arborization of signal
pathways linking the brain with almost every body cell. This autonomic nervous
system is the main driver and regulator of digestive tract functions. The
sympathetic part of the autonomic system is the fight or flight arousal system
that prepares the body for action. Digestive functions are shut down by
sympathetic nervous system activity. Fight and flight arousal requires increased
blood flow to muscles and decreased flow to the digestive tract. Secretions and
motility are decreased. The fear response may trigger vomiting and defecation to
empty the digestive tract in preparation for fleeing. People exposed often to
threatening circumstances will experience digestive tract malfunctions from
functional dyspepsia and gastroparesis to ulcers and inflammatory disorders in
the small and large intestines.
The parasympathetic part of the autonomic system is concerned with processing
food, resting, and restoration. The parasympathetic system uses
acetylcholine as the transmitter and is found everywhere in the body, sending
signals to muscle cells to contract. In the brain, acetylcholine has arousal
functions in the right amounts but tends to cause depression in overdose.
Many common digestive tract symptoms are generated by over active
acetylcholine mechanisms, especially nausea, vomiting, belching, cramps,
defecation, sweating and runny nose. Nicotine mimics some of the actions of
acetylcholine and even veteran smokers who chew nicotine gums for the first time
may get these effects.
Drugs that block acetylcholine activity are popular in medicine and have many
uses. Atropine is the prototype and along with related compounds has been used
in medicines to treat upset digestive function. Atropinic drugs reduce
secretions and block crampy abdominal pain from vigorous contractions of
intestinal smooth muscle. Too much atropine and you are dry-mouthed, constipated
and have trouble urinating; you may also have trouble thinking and remembering.
Motility disorders are often caused by drugs that block acetylcholine activity
such as antidepressants and antihistamines.
FD, Motility Disorders Management
Here are the basic principles:
Digestive disorders are common diseases that originate in the food supply.
Diet revision should be primary therapy. The solution is to adjust the incoming
food supply until the problem is resolved.
The gastrointestinal tract is a sensing, reactive device which monitors the
material flowing through it. Symptoms arising from this system provide
information about its dysfunction.
Seven basic symptoms alert the patient to gastrointestinal tract displeasure
with food choices - nausea, heartburn, vomiting, bloating, pain, constipation
In the stomach, a surface reaction results in upper-middle abdominal pain and
nausea; sometimes vomiting is triggered. These are defensive responses that
reject the offending food. Vomiting usually relieves pain and other discomforts.
Some people induce vomiting to avoid discomforts after eating.
Recurrent irritation in the upper DT is food-caused until proven otherwise.
Obviously smoking, drinking alcoholic beverages, coffee and teas are the first
problems to eliminate, but surface "allergy" to common, "normal" foods may also
be responsible. Symptoms from the upper digestive tract are often associated
with lower abdominal pain, bloating, constipation and diarrhea. A trial of diet
revision can provide prompt relief. Iffood holiday is unsuccessful,
further investigation is always required.
Stomach Problems & Gastroparesis
Gastroparesis means stomach paralysis. The term refers to a variety of
disorders characterized by delayed gastric emptying in the absence of
obstruction. Problems in the stomach may be part of a more general food
reactive, motility disorder. Recall that pacemaker cells of Cajal (ICCs),
located in the greater curvature of stomach, send activation signals that
produce produce contractions. A complex of interacting signals regulates stomach
contraction and emptying. There is ample opportunity for things to go wrong. The
first and most prevalent cause of motility disorders is eating too much of the
wrong food. The definition of wrong is both general and highly
In addition, many diseases interfere with stomach motility. Sanjeevi
stated: "Abnormal gastrointestinal motility is seen in a third of diabetic
patients as well as in patients with chronic neurological and rheumatological
conditions, renal failure, and cirrhosis. The causes include disturbances in the
functioning of vagal neurons, enteric neurons, ICCs, smooth muscle cells, or
humoral factors. Genetic factors also contribute since gastric dysmotility
occurs predominantly in females. Recently, it was shown that healthy female rats
exhibit increased gastric neural nitric oxide synthase (nNOS) expression whereas
diabetic female, but not male, rats exhibit significantly decreased nNOS
expression as well as impaired relaxation. ICCs express KIT protein or CD117, a
transmembrane receptor with tyrosine kinase activity. Immunostaining of full
thickness antral biopsies obtained from 14 medically refractory gastroparetic
patients undergoing placement of a gastric electrical stimulator showed absence
of ICCs in one-third of the patients. Measurement of the emptying of solids is
more sensitive for detection of gastroparesis than liquids. Solid emptying
exhibits a lag phase followed by a prolonged linear emptying phase.
Unexpectedly, the prime abnormality in patients with dyspepsia and autonomic
dysfunction appears to be rapid gastric emptying. Accelerated early phase
emptying may lead to delayed late phase emptying due to feedback inhibition by
the duodeno-antral reflex."
Drugs for Motility Disorders
Drugs used in the attempt to improve gut motility (without adequate diet
revision!) have a dismal record of doing harm with little or no benefit.
In his review, Sanjeevi summarized the main disappointments:
Metoclopramide may induce anxiety, tremors, dystonia, Parkinson's like symptoms,
and depression. Erythromycin has a narrow therapeutic window, disrupts the
bacterial flora, promotes antimicrobial resistance, and may induce cardiac
arrythmias. Cisapride has been severely restricted due to risk for prolongation
of the cardiac QT interval. Tegaserod has recently been withdrawn from the
United States market due to cardiovascular side effects. A recent trial found
that tegaserod had no significant effects on gastric motor, sensory, or
myoelectric function in healthy volunteers using the SPECT technique. The
earlier developed motilin receptor agonist, ABT-229, failed to show significant
efficacy in relieving symptoms in patients with gastroparesis or functional
dyspepsia. A newer motilin agonist, mitemcinal, produced a better response rate
than placebo in symptomatic diabetic patients with body mass index <35 kg/m2 and
hemoglobin A1c <10%. Subanalysis suggested that the improvement was more
impressive in patients with nondelayed gastric emptying. Itopride, a dopamine
(D2) antagonist, in US studies did not demonstrate asignificant effect on
the symptoms of upper abdominal pain and fullness or the Patient Global
Assessment questionnaire in patients with functional dyspepsia.
Two agents show some promise: Domperidone, a dopamine 2 antagonist improves
gastrointestinal transit. `Domperidone minimally crosses the blood-brain barrier
and has few, if any, central nervous system side effects. Domperidone is
available in 58 countries, but only through an investigation drug program in the
United States for patients with medically refractory gastroparesis.
Ghrelin, a peptide present in gastric mucosa and neurons, enhances gastric
emptying and accelerates fasting motility. In idiopathic gastroparesis,
administration of ghrelin enhanced gastric emptying and improved meal-related
symptoms suggesting a potential for ghrelin receptor agonists in the treatment