Contents 1 Learning Objectives 2 Gastric motility 3 Enteric nervous system 4 Vagus nerve 5 Diabetes 6 Oxycodone 7 Differential Diagnosis 8 Cool Site 9 Friday's Notes

[edit] Learning Objectives

1. List the three muscle layers of the stomach and describe how they work together for the digestion of food and gastric emptying.

• Inner oblique, middle circular, outer longitudinal muscle layer
• Food digestion: 3 waves/min produced by pacemaker cells in mid body. Upon stimulation, contraction occurs moving food from body to the pyloric sphincter. The pylorus and terminal antrum contract almost simultaneously so that the pylorus closes as food passes thru. Food particles <1 mm are permitted to pass at this time, none larger. Due to the closing pylorus, food that does not enter the stomach sent back to the fundus in a process known as retropulsion. It is further mixed and digested by the high acidity. Larger particles pass to the small bowel via the migrating myoelectric complex, in which the terminal antrum contracts while the pylorus is relaxed.

2. List the instrinsic (myenteric plexus) and extrinsic (vagal) innervation of the stomach and explain how they regulate normal gastric motility and gastric emptying.

• Instrinsic innervation directly controls these activities, by causing contraction or relaxation. Extrinsic innervation modulates or fine tunes gastric motility and gastric emptying.

3. Define gastroparesis and list the causes of impaired gastric motility.

• Gastroparesis is a collection of disorders in which gastric emptying is impaired or delayed W/O evidence of obstruction.
• Etiology of impaired gastric motililty
  • Systemic disease resulting in neuromuscular f’n abnormalities i.e. DM, scleroderma
  • Vagotomy, other surgical or medical Tx
  • Meds i.e. anticholinergics, opiates
  • Surgical or medical Tx

4. Describe the typical clinical presentation of diabetic gastroparesis, list the risk factors for this condition, and discuss the diagnostic work up.

• Clinical presentation
  • Early satiety: decreased stomach empting, higher fundal tone
  • N/V: late postprandial vomiting of undigested or only partially digested food
  • Bloating
  • Upper ab discomfort
• Risk factors
  • Long standing gastric outlet obstruction
• Diagnostic work up
  • Gastric emptying scintagraphy – 2hrs post-radiolabeled intake
  • Solid-phase gastric emptying study
  • Antroduodenal manometry

5. List and describe the mechanisms that contribute to delayed gastric emptying in patients with diabetes mellitus.

• Mechanisms contributing to delayed gastric emptying
  • Hyperglycemia leading to hyperosmotic lumen???
  • Lack of insulin, complete lack or insufficient amount
  • Neuropathy
    • Promote isolated pyloric contraction, leading to antral dilatation
    • Evoke electrical dysrhythmias
  • Adipokines released by adipocytes recruit inflammatory cells which may damage cells w/i abdomen – think greater omentum, maybe cells i.e. neurons underneath greater omentum are destroyed
  • Induce antral HYPOmotility, reducing incidence of antral comp of MMC

6. List the medications that can be used for the treatment of diabetic gastroparesis and describe the mechanisms of action.

• Metoclopramide (Reglan®)
  • Dopaminergic ANTAgonist, cholinergic stimulant
  • Prokinetic: increase stomach & intestinal contractions; increase LES resting tone
  • Also serves as antimetic
• Erythomycin
  • Mimics motilin, which triggers gastric contraction via MMC

7. Describe the non-medical interventions for this condition (diet, surgical).

• Diet:
  • Take small meals
  • Increase proportion of nutrients supplied by liquids
  • Low fat, decrease fiber
• Jejunosomy when oral intake fails, leading to malabsorption
• Gastrostomy-jejunostomy tube (percutaneous or surgical): decompresses stomach & permits enteral nutrition
• Near-total gastrectomy w/ Roux-en-Y anastomosis
  • Roux-en-Y anastomosis: stomach cut in 2 & the smaller proximal portion is attached to jejunum

Indication for pts w/ long-standing, complicated T1DM

[edit] Gastric motility

• Be able to draw the different layers of the stomach

For those of you who have Netter's, there is an awesome picture of stomach musculature - plate 260 in my edition. It shows that theere is an innermost oblique layer of muscles that is not particularly dense, a middle circular layer, and an outer longitudinal layer that is concentrated chiefly at the lesser and greater curvatures and the pyloric area.

ASR

Anatomically, the stomach can be divided regions: fundus, body, and antrum.

Based on motility, the stomach can be divided into two regions: orad and caudad.

Orad region: proximal; contains fundus and proximal portion of body, and is thin walled. Receives food bolus.

Caudad region: distal; contains antrum and distal portion of body, and is thick walled: generates much stronger contractions than orad region. Contractions of caudad region mix the food and propel it into the small intestine.

Costanzo, Physiology

MDM

• What is the pacemaker of the stomach and how does it work?

The pacemaker zone is located near the middle of the body of the stomach. Cells there initiate peristaltic waves toward the pylorus. These are the cells responsible for the BER or basal electric rhythm. These cells cannot break the threshold of contraction in the surrounding smooth muscle cells and require enteric nerve innervation to increase the electrical impulse amplitude by superimposing on the basal signal.

Lange Physiology, Accessmedicine.com

JT

Pacemaker activity is controlled by slow waves, oscillating depolarization and repolarization of the membrane potential of smooth muscle cells. At the peak of a slow wave oscillation (pacemaker activity + neural/hormonal stimulation), depolarization of the membrane surpasses threshold. This resulting in bursts of six action potentials. Following the electrical response, contraction of smooth muscle occurs. Slow waves originate in the interstitial cells of Cajal, which are abundant in the myenteric plexus.

Costanzo, Physiology

The waves of depolarization that occur in response to the pacemaker activity of the network of interstitial cells of Cajal are not of sufficient magnitude to initiate action potentials in the smooth muscle. Rather, it is only when the release of stimulatory neurotransmitters from enteric nerve endings is superimposed on these waves of depolarization that an action potential may occur, leading in turn to contraction of the smooth muscle

Lange Gastrointestinal Physiology

MDM

• How gastric motility works normally
  • Digestion
    • Where does digestion occur?

Throughout the GI tract, although the breakdown of food occurs primarily in the mouth, stomach and small intestines, while the absorption of nutrients occurs primarily in the duodenum. Sources: Costanzo Physiology, Wikipedia "digestion" ASR

Stomach: Mixing and digesting occur in caudad region. Waves of contraction begin in middle of body and move distally toward pylorus. Contractions increase in strength as they approach the pylorus. The contractions mix gastric contents and periodically propel a portion of it through the pylorus into the duodenum. Much of the chyme is not immediately injected into the duodenum, however, because the wave of contraction also closes the pylorus. Therefore, most of the gastric contents are propelled back into the stomach for further mixing and further reduction of particle size, a process known as retropulsion.

Stomach contractions are influenced by neural and hormonal input:

Increased contractions: parasympathetic stimulation, gastrin, motilin

Decreased contractions: sympathetic stimulation, secretin, GIP

Costanzo, Physiology

MDM

• • • How much occurs in the stomach versus the small intestine?

The stomach physically shears food by its motility. Carbohydrates begin to be digested by alpha-amylase in saliva, however the low pH of the stomach inactivates this enzyme and no further carbohydrate digestion occurs in the stomach. Acid in the stomach denatures proteins and also cleaves the proenzyme pepsinogen to form the active enzyme, pepsin. Pepsins reduce no more than 15% of the proteins in a given meal to amino acids and short peptides. Lipids are hydrolyzed in the stomach to a significant extent by preduodenal lipases, the main component being gastric lipase, secreted by gland cells in the fundus of the stomach. Pancreatic enzymes are thought to be more important than these in triglyceride absorption preparation.

Devlin

JT

• • • Is there some kind of acid-secreting problem in the stomach?
    • What exactly is digestion?

Digestion is the chemical breakdown of ingested food into absorbable molecules. Source: Costanzo Physiology ASR

• What happens in gastroparesis
  • Gastroparesis is a collection of disorders of varied etiologies in which gastric emptying is impaired or delayed, yet without evidence of obstruction
  • What causes gastroparesis?
    • Idiopathic – most common
    • May result from a systemic disease resulting in abnormalities of neuromuscular function, such as DIABETES or scleroderma
    • May occur as a result of either surgical or medical treatments – surgery that injures the vagus will impair gastric emptying since extrinsic input to the stomach is needed to mediate the full expression of this response
    • Several medication (anticholinergics and opiates) are known to impair gastric emptying

• • • Why does he have sensation of filling up quickly?
  • Symptoms
    • Early satiety, nausea, vomiting, bloating, and upper abdominal discomfort
      • Pts typically exhibit late postprandial vomiting of undigested or only partially digested food, liquid diets are tolerated well

Emi Bays, lange gastrointestinal physiology

• • • What causes constipation/diarrhea?
  • Risk factors?

• • Treatment
    • Metoclopramide (mechanism)
      • Antiemetic, prokinetic
      • Enhances GI motility, and is an effective antinauseant, originally developed to treat nausea during pregnancy
      • Mechanism: enhances gastric motility without stimulating gastric secretions
        • Peripherally – augments cholinergic activity either by causing release of Ach from postganglionic nerve endings or by sensitizing muscarinic receptors on smooth muscle; effects on the resting tone of the lower esophageal sphincter combined with gastric emptying reduce gastroesophagela reflux
        • Centrally – blocks dopaminergic receptors; effectively antagonizes the actions of apomorphine, a known central dopamine agonist

Emi Bays, access medicine drug monograph

• • • Other treatments
    • Surgery?
  • Prognosis
  • Vomiting - what is happening?

Vomiting reflex: early events include reverse peristalsis, clearing much of small intestine. Pyloric sphincter/stomach relax to receive material. Retching can occur, with partial relaxation of lower esophageal sphincter (LES) to allow gastric contents into esophagus (but not pharynx). Reflex steps follow: 1) forced inspiration, 2) raising of hyoid bone & larynx to open upper esophageal sphincter, 3) closing of glottis & nasal passage, 4) strong downward contraction of diaphragm & contraction of all abdominal wall muscles. This squeezes stomach, increasing gastric pressure. Finally lower & upper esophageal sphincters relax reflexly while pylorus and antrum contract. Gastric contents exit mouth.

GI Motility 2, Study Guide

MDM

• • • He vomited undigested food - what does this indicate?
    • What does violent vomiting cause?
  • What is a solid-phase gastric emptying study?
    • How do they calculate the half-time?

[edit] Enteric nervous system

• submucosal plexus

This is located bewteen the submucosa and the layer of circular muscle.

• myenteric plexus

This is located between the circular muscle and the longitudinal muscle.

• what innervates the different parts of the stomach

The stomach is regulated by the autonomic nervous system, both the extrinsic and intrinsic components. The extrinsic component consists of the sympathetic and parasympathetic nervous systems and the intrinsic component is the enteric nervous system. The intrinsic/enteric nervous system is found within the submucosal and myenteric plexuses in the wall of the stomach. Ganglia in these plexuses receive input from the parasympathetic and sympathetic nervous systems. But it can control the function of the GI tract in the absence of extrinsic innervation because it also receives information directly from mechanoreceptors and chemoreceptors in the mucosa and can send motor information directly to smooth muscle, secretory, and endocrine cells through interneurons. The neurocrines used to relay signals include ACh, norepinephrine, VIP, and gastrin-releasing peptide (among others). Parasympathetic innervation has long preganglionic fibers that synapse in ganglia in or near target organs; in the stomach the ganglia are within the intrinsic system. the postganglionic neurons of the parasympathtic nervous system release either acetylcholine or one of several peptides (including VIP). The vagus nerve as afferent (sensory) and efferent (motor) fibers. The sympathetic nervous system has short preganglionic fibers that pass through paravertebral ganglia and synapse in ganglia outside the GI tract. Sympathetic nerves that innervate the stomach synapse in the celiac ganglia, from which the postganglionic fibers leave to synapse on ganglia in myenteric and submucosal plexuses or directly innervate smooth muscle, endocrine, or secretory cells. Sympathetic fibers are called adrenergic because they release norepinephrine; they are both efferent and afferent.

Sources: Costanzo Physiology, Netter's Atlas, Dr. Freeman's lecture

ASR

[edit] Vagus nerve

• What is its role in gastric motility?

Parasympathetic innervation stimulates gastric motility.

Devlin

JT

• What happens if it is not functional (i.e., if it is cut)?

Gastric acid secretion is diminished and gastric emptying may be delayed, or at least less well regulated.

BMJ http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1589202

JT

[edit] Diabetes

• Connection between gastroparesis and diabetes
  • Unexplained episodes of postprandial hypoglycemia in insulin-treated diabetics may be due to delayed gastric emptying (Lange endocrinology) consequent to autonomic neuropathy
  • Most challenging form of gastroparesis is that experienced by pts with long-standing diabetes mellitus
  • Reflection of a more generalized neuropathy, but may aggravate their underlying disease
  • Because the delivery of nutrients to the duodenum is unpredictable, this has implications for the ability of the subject to maintain glycemice control
  • Hyperglycemia per se may also exert effects on gastric motility, either directly or via effects on the vagus nerve

Emi Bays, Lange Endocrinology and Gastrointestinal physiology

• Effect of neuropathy?
• How does neuropathy occur?
  • Neuropathy of the autonomic nervous system is common in pts with diabetes of long duration
  • Most of the types of neuropathy are thought to be due to ischemia or infarction of nerves or nerve fascicles, due to a diabetic microvasculopathy
  • The basis of autonomic neuropathy is not well understood – duchen and associates, who studied the sympathetic ganglia in diabetic pts with autonomic symptoms, described vacuoles and granular deposits in sympathetic neurons and little if any neuronal degeneration; there was also a loss of myelinated nerve fibers in the vagus and splanchnic nerves and the rami communicantes, as well as changes in the neurons of the intermediolateral columns of the spinal cord

Emi Bays (Adams and Victors Neurology)

[edit] Oxycodone

• Is it affecting his gastroparesis?
• Could the back pain be related to his problem?

[edit] Differential Diagnosis

• Different pathologies that can cause similar symptoms
• Are there other diseases that cause loss of vibratory sensation?

[edit] Cool Site

http://www.wzw.tum.de/humanbiology/motvid01/movie_09_1mot01.wmv

[edit] Friday's Notes

• Gastric motility
• Be able to draw the different layers of the stomach
  • Mucosa
  • Submucosa
  • Muscularis externa: inner oblique, middle circumferential, outer longitudinal
• What is the pacemaker of the stomach and how does it work?
  • Group of cells (myocytes) that sets the basal electric rhythm to initiate peristalsis but is not strong enough to produce action potentials.
• How gastric motility works normally
• Where does digestion occur?
  • Proximal part of stomach has parietal cells that secrete gastric acid
  • Antrum region has G cells that release gastrin that stimulate parietal cells and vagus nerve release gastrin releasing peptide
  • Sympathetic inhibits the GI tract and the parasympathetic stimulates it.
• What exactly is digestion?
  • Pacemaker cells set a normal rate but not strong enough to produce contraction. Need extrinsic input in order to produce action potentials.
  • Enteric system causes MMC every 60-90 min.
  • Vagotomy prevents relaxation of pyloric sphincter, and consequently draining of the stomach. Can cause atony of the stomach. Also lose vagovagal reflexes.
  • Alpha amylase in mouth break down carbs which are neutralized by acid in stomach. Mouth also has lingual lipase.
  • Stomach: Peptidases break down protein, lipases hydrolyze triglycerides (see Wiki)
  • Nutrients aren’t absorbed until food reaches small intestines
  • Retropulsion in stomach helps break down food. Contractions move from pacemaker to pylorus and back.
• What happens in gastroparesis?
  • Gastric emptying is delayed or impaired without obstruction
  • Symptoms: early satiety, nausea, vomiting, bloating, upper abdominal discomfort
  • Solid phase emptying test: time it takes for stomach to empty
    • Label a meal radioactivity and scan every 5 minutes to see the progression of the food and exactly how long it takes for stomach to empty out
• Treatment –
  • Dietary changes – get glucose levels under control first
  • Metoclopramide (mechanism)
    • Anti-nausea, augments cholinergic activity in peripheral, blocks dopaminergic receptors in central
  • Oxycodone
  • Erythromyocin – mimics effects of motilin (hormone), motalin secreted from duodenum, stimulates contraction of stomach muscles
  • See Wiki
• Connection between gastroparesis and diabetes
• Effect of neuropathy?
  • Ischemia or infarction of nerves
  • Progressive degeneration of myelin
  • Trouble controlling glycemic levels due to hyperglycemia and delayed gastric emptying
  • High glucose levels cause vascular damage (cytokines from smooth muscle induces thickening of blood vessel walls, atherosclerosis)
• Differential diagnosis
• Different pathologies that can cause similar symptoms
  • Stricture of pyloric sphincter
  • Tumor
  • Obstruction