PhysiologyandEvaluationofGastricMotility

蘇育正

高雄醫學大學附設醫院

消化系中心

內科部胃腸內科

TMPD measurement

••A electrical potential difference exists between the mucosa and serosal surface of the gastrointestinal tract.

• The magnitude of this potential difference varies along the gastrointestinal tract.

• There is a steep transmucosal potential difference gradient (TMDP) across the pylorus.

•Means of continuous •Non-invasive assembly• Allows continuous monitoring

of position

IIIII I

空腹 飯後

Normalantroduodenal motility

Continuous disorganized motor activity and the normal phases of the MMC cannot be distinguished. This pattern is suggestive of a neuropathic cause

Small Intestinal Regulation of Gastric Emptying

Negativefeedbackpathways(mechenical&Chemical)

Small intestinalnutrients (PH, osmolarity and specific nutrients)

Slowgastricemptying

• Relaxesproximalstomach• Reducesantralcontraction• Stimulatespyloricmotility

IntestinalFeedback-ManometricTracingofAntral.PyloricandDuodenalmotility

Solid

Liquid

IntestinalFeedbackMechanism:CCKpathway

GastricemptyingafteradministrationofplaceboandCCKreceptorantagonist

(Borovicka1996)

Placebo

loxiglumide

Reflex Modulation of Gastric Motility

• 1. Duodenal mechanical receptor-- reduces fundic tone through vagal and splanchnic nonadrenergic, noncholinergic pathways.

• 2. Duodenal chemical rector---duodenal protein or lipid perfusion, mediated by vagal nonadrenergic, noncholinergic pathways possibly involving NO and CCK. Fundic relaxations in response to duodenal acid exposure are mediated by multiple pathways.

• 3. Colonic distention: inhibits gastric accommodation and emptying ,and this contributes to the delayed gastric emptying observed in patients with chronic constipation.

• 4. Ileal brake mechanism: complex carbohydrates, fats and proteins in the distal small bowel reduce fundic tone and gastric emptying. The mechanisms involved in the ileal brake include the incretin hormones (GLP-1, peptide YY, neurotensin) and neural reflexes.

Signaling from the upper gastrointestinal tract (GIT) during and after food intake

A. Gastric distension and gastric accommodation are major determinants of nutrient signaling. Signals are generated from gastric mechanosensitivereceptors, which relay their information via vagal nerves to the brain

B. Signaling-related intestinal exposure to nutrients. Nutrients is mainly sensed by entero-endocrine cells in the mucosa of the small intestine that release a variety of peptides and small molecules. These can act locally, activate vagal nerves that signal to the brain, or enter the blood stream and act as hormones.

A: During and initially after food intake B: After food intake, when the stomach gradually empties

Tests to assess gastric motor and myoelectric function.

Tests to assess gastric motor and myoelectric function.

Gastric Scintigraphy

• radiolabeledmealstillthe“commonstandard”• widelyavailable,welltolerated• allowsolid- andliquid-phasestudies• assessglobalstomachneuromuscularactivity

-----------------------• widenormalrange• radiationexposure• takes2-4hours

Gastric emptying scans: Advantages

• Widely available but not always 4 hrs• Solid phase scans should be performed for 4 hours• Solid phase scans are the most sensitive for detecting gastroparesis• Results are reported as the % of the meal retained (or emptied) after a

specific time period• Gastroparesis defined as mean +/- 2 SD• Consider rapid emptying

Gastric emptying scans: Disadvantages

• Poorcorrelationbetweensymptomsandemptyingtimes• Largevariabilitywithinindividualpatients• Resultsinfluencedbygender,serumglucose,weight,andmenstrualcycle

• Resultsfromshortstudies(90mins)areextrapolatedandareusuallyincorrect

• Poorstandardizationbetweensites• Resultsdonotpredictresponsetotherapy

Wireless Motility Capsule: Measure of Gastric Function

• Capsule that measures pH, pressure, temp• Measures Gut Transit and Motility

• Gastric and small bowel transit time• Antral and prox small bowel contractility

• Ambulatory Test• Capsule swallowed with test meal• Emptying of an Indigestible Object by MMC

• Normal Gastric Emptying Time (

• Gastric emptying time: period of time ranging from abrupt rise in temperature to abrupt rise in pH by at least 3 units.

• Small bowel transit time: period of time ranging from abrupt rise in pH to abrupt drop in pH by 1 unit that is sustained for at least 10 min (at least 30 min after gastric emptying).

• Colon transit time: period of time ranging from abrupt 1-unit drop in pH to abrupt drop in temperature

Concurrent gastric transit measurement with wireless motility capsule and scintigraphy. The sharp rise in gastric pH (at 4 h), corresponding with transit of the capsule to the duodenum, occurs after all of the meal has left the stomach

• The time–13CO2 concentration curve provides information about gastric emptying, as this is the rate-limiting step

• Gastric emptying curves in a healthy subject and in a gastroparetic subject showing percent dose 13C excreted (kPCD) at different time points following ingestion of a standardized 13C-Spirulina platensis gastric emptying breath test meal

• Validation of this test in patients with emphysema, cirrhosis, celiac sprue, and pancreatic insufficiency is needed, because it is not clear whether substrate metabolism in these disorders may also be a rate-limiting step for 13CO2 excretion.

Motility testing, When does it help?

• Unexplained nausea and/or vomiting• "Motilitylike” nonulcer dyspepsia• Diabetes in whom gastroparesis is suspected (particularly those with poor

glycemic control)• Suspected dumping or stasis syndrome following gastric surgery• Refractory gastroesophageal reflux disease• Suspected chronic intestinal pseudo-obstruction• Known gastric emptying disturbance in whom an objective evidence of a response

to motility altering drugs is desired• 2015 up-to-date

1. Delayed gastricemptying(gastroparesis),2. Rapidgastricemptying(asseenindumpingsyndrome),3. Disorderswithmotorandsensoryabnormalities (e.g., functional

dyspepsia).

Evaluationofpatientswithpossiblegastricmotilitydisorders1. Gastricemptyingscintigraphy,2. Wirelessmotilitycapsule,3. Antroduodenal manometry,4. Electrogastrography (EGG),5. Gastricaccommodationorcompliancetest(barostat,singlephoton

emissioncomputedtomography[SPECT]imaging, andliquidnutrientsatietytesting).

GastricMotilityDisorders

Gastroparesis: Definition

delayed gastric emptying in the absence of a fixed mechanical obstruction of the pylorus or small intestine.

Etiology of Gastroparesis(Nonobstructive Delayed Gastric Emptying).

• Endocrine or metabolic:ü Diabetes mellitus, Thyroid disease , Renal insufficiency

• After gastric surgery:ü After resection , After vagotomy

• Central nervous system disorders:ü Brainstem lesions, Parkinson disease

• Peripheral neuromuscular disorders:ü Myotonia dystrophica, Duchenne muscular dystrophy

• Connective tissue disorders:ü Scleroderma, Polymyositis/dermatomyositis

• Infiltrative disorders:ü Lymphoma, Amyloidosis

• Diffuse gastrointestinal motility disorder:ü Chronic intestinal pseudoobstruction

Gastroparesis:Causes• Mechanical: outletobstructionfromcancerorPUD,HPS• Metabolic andendocrine:DKA, diabetic*, hypothyroid,electrolyte imbalance• Post-gastricsurgery*:vagotomy,partialgastrectomy• Acid-peptic disease• Gastritis:atrophic,perniciousanemia,acute viralgastroenteritis• Collagen vascular disease:scleroderma• Medications: anticholinergics, narcotics,levodopa,salbutamol,loperamide• Pseudo-obstruction: idiopathic,secondary (amyloidosis,MD,paraneoplastic)• Electrical dysrhythmia: tachy,brady,orgastroduodenaldysychrony• Centralnervoussystemmediated:tumor,bulbarpoliomyelitis,depression• Idiopathic*

Pathophysiologyofgastroparesis

Adapted from Brian Lacey

Brain

Gastroparesis: suggestive symptoms

• Earlysatiety/anorexia/foodavoidance• Bloating/fullness• Heartburn• Nausea• Abdominalpain• Weightloss• Postprandialvomiting

Gastroparesis vs Functional DyspepsiaReclassifying these patients under the umbrella term of functional dyspepsia with or without disordered gastricemptying will enable clinicians and researchers to focus on the predominantsymptoms expressed by the majority of patients with this disorder.

Am J Gastroenterol 2012;107:1615–1620

(A) Prevalence of Dyspeptic Symptoms

(B)PathophysiologicAbnormalities

Prevalence(%

ofpatients)

ClinicalandPathophysiologicalCharacteristicsofAcute-OnsetFunctionalDyspepsia(TackJ,Gastroenterology2002)

Placebo

L-NMMA4mg/kg/hr

L-NMMA8mg/kg/hr

Intraballoonvolum

e(m

l)Sumatrip

tan-indu

cedrelxation(ml)

Sumatriptan:5-HT1receptoragonist,putativeactivatorofgastricnitrergicneurons.L-NMMA:NOSinhibitor

Control

UnspecifiedDyspepsia

PresumedPost-infectiousDyspepsia

TimeafterAmylNitrate(min)TimeafterSumatriptan(min)

defectiverelaxationoftheproximalstomach,butnotthedistal

stomach

Impairedgastricgastricandenterogastricreflexes

alternationofintragastricmealdistribution

oversensitivity ofhypersensitive antrum

dypeptic symptoms

Aproportion ofFDpatients havesignificantly greaterfastingandpostprandial antralsizedwhen comparedwithhealthysubjects.(Hausken, ScanJGastronterol 1992)

Abnormal Intragastric Distribution of Meal Intake

Fundic Barostat

Antro-Fundic DysfunctioninFunctionalDyspepsia

(Maria2003)

Antro-fundic

Duodeno-fundic

Duodeno-antral

Reflexrelaxatio

n,m

l

FDpatientsshowedsignificantsmallerfundicresponsestobothantral&duodenalstimulibutsomewhatlargerantralresponsetoduodenalnutrientinfusion.

IntraduodenalnutrientinfusionBarostatdistension

GASTROENTEROLOGY 2003;124:1220–1229

Ulcer-likeDyspepsia

Dysmotility-likeDyspepsia

HealthySubjects

HealthySubjects

Dyspepsia Healthy

HypersensitivityandClinical Symptoms

GASTROENTEROLOGY 2003;124:1220–1229

1. the exquisite sensitivity of the antrum to luminal distention, which is further exacerbated by luminal nutrients

2. the proximal– distal gastric dystony due to selectively impaired relaxation of the fundus in response to gastrogastric and enterogastric reflexes.

3. Resultant symptomatic antral overload and may hence contribute to the clinical complaints.

Functional Dyspepsia & Eosinophilia

檔案中找不到關聯聯識別碼 rId2 的圖像部分。

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2007;5:1175–1183

Duodenal mucosa with crypt and lamina propria eosinophils (arrow) in a patient with functional dyspepsia including symptoms of early satiety and normalendoscopy. The eosinophils are clustered around the base of the crypt.

Maximum eosinophil count in the duodenum (combined sites) in cases with non-ulcer dyspepsia and controls. P value from logistic regression analysis including age, sex, and H pylori status as covariates in the model. † Including age and gender as covariates in themodel.