This document discusses the physiology, pathophysiology, diagnosis, and treatment of gastroparesis. It begins by defining gastroparesis and describing the main causes. Deranged mechanisms that can cause gastroparesis involve abnormalities in smooth muscle, enteric nerves, or interstitial cells of Cajal. Diagnosis involves gastric emptying tests. Dietary recommendations focus on small, low-fat, low-fiber meals. Standard medications include metoclopramide and domperidone, which act on dopamine receptors. Novel potential treatments discussed include new prokinetic drugs, botulinum toxin injections, gastric electrical stimulation, and endoscopic procedures.

1. Kurdistan Board GEH/GIT Surgery J Club
Supervised by:
Professor Dr.Mohamed Alshekhani.
MBChB-CABM-FRCP-EBGH.

2. MAIN FUNCTIONS OF STOMACH
I. PROXIMAL
Functions: Accommodation
Storage of ingested food
Regulation of intragastric
pressure
Tonic movement of chyme
Motor Pattern: Tonic activity
II. DISTAL
Functions: Grinding of food
Emptying to duodenum
Motor Pattern: Phasic activity

3. B3
Pacemaker
region
Corpus
Fundus
Antrum
Pylorus
Pacemaker potentials
determine contractile
parameters
Contractile parameters
•Max frequency
(3/min)
•Propagation velocity
•Propagation
direction
Motility of the Antral Pump Is Initiated by
a Dominant Pacemaker in the Mid-
corpus
The antral pump is formed by the mid and distal corpus, antrum, and
pylorus
Pacemaker
potential
B87

4. B4
% Meal
remaining
in stomach
Lag phase
Emptying
phase
Onset and Rate of Gastric Emptying
Varies With the Composition of the Meal
Time after meal (min)
Solid meal
Liquid
meal
100
75
50
25
0
200 6040 10080
Semisolid
meal

8. Gastric emptying – evolving
concepts
• Relationship with symptoms unclear
– NOT nausea, vomiting or pain
– Accelerating gastric emptying does not
necessarily improve symptoms
– Symptomatic improvement including
weight gain is possible without improving
gastric emptying
Gastroparesis is frequently overdiagnosed
on the basis of outdated emptying tests

9. Causes of Gastroparesis
• Idiopathic 36%
• Diabetic 29%
• Upper GI surgery 13%
• Parkinson’s 8%
• Collagen tissue disorder 5%
• Intestinal pseudo-obstruction 4%
• Miscellaneous (Incl eating disorders) 6%
Soykan et al, DDS 1998; 43:2398-2404

10. Drugs that delay gastric emptying
(Partial listing)
β Agonists
Anticholinergics
Tricyclic agents
Phenothiazines
Dopamine agonists
Opiates
Proton pump inhibitors
Miscellaneous
Dexfenfluramine Antihistamines
Lithium
Tetrahydrocannabinol
Tobacco

11. Workup for suspected
gastroparesis
UGI Series: Excludes mechanical
obstruction
Retention of barium w/o
obstruction is diagnostic
Endoscopy: Bezoar without obstruction
highly suggestive
Gastric Emptying: Solids more sensitive
than liquids

12. Normal values for low fat, egg white
GES
Lower normal limit Upper normal limit
Time for gastric retention* for gastric retention**
0.5 hr. 70%
1.0 hr. 30% 90%
2.0 hr. 60%
4.0 hr. 10%
* Lower value suggests rapid emptying
** Higher values suggest delayed emptying
Am J Gastroenterol 2008

13. 2. A 30 y.o. woman with a one year history of type II
diabetes mellitus presents with nausea and early
satiety. Her blood sugars have been erratic and
her last HBAIC was 9.2. Endoscopy was normal
and a gastric emptying test showed 20%
retention of the meal at 4 hours (normal < 10%).
Which of the following would you recommend:
• a) Metoclopramide
• b) Rigorous control of blood sugars
• c) Erythromycin
• d) Botulinum toxin injection of the pylorus

14. Slow gastric emptying was frequent in women
with type 2 diabetes with hyperglycemia and
normalized after diabetic control
J Diabetes & Complications, 2013

15. 2. A 23 y.o. woman developed a viral illness associated with
fever, myalgias, nausea, vomiting and diarrhea. Although
most of her symptoms resolved over 2 weeks, she
continued to have nausea, occasional retentive vomiting,
early satiety and a 10 lb. weight loss. Endoscopy showed a
modest amount of retained food in the stomach and a
gastric retention of a test meal consisting of egg whites,
toast and jam at 4 hours was 35% (normal <10%).
Which of the following would you recommend first?
a) Metoclopramide
b) Botulinum toxin injection (pylorus)
c) Erythromycin
d) Gastric stimulator

16. Management of Gastroparesis
Dietary Modifications
Small frequent (6/day) meals
Reduced fat (<40 gm/day)
Soup, crackers, noodles, pasta,
potatoes, rice, cheese
Reduced fiber → helps avoid
bezoar
Liquid caloric supplementation

17. Prokinetic Agents
• ACh-esterase inhibitors: pyridostigmine
• Motilides: erythromycin
• Antidopamine agents: domperidone*
• Antidopamine/serotonin agents:
• metoclopramide
• Serotonin agents: tegaserod*, prucalopride*
*Not available in USA

18. ERYTHROMYCIN
• Motilin agonist
• No antiemetic effect
• Stimulates antral contractions
(IV >> PO)
• Stimulates MMC
• Dose: 125-250 mg bid/tid (PO)
3 mg/kg q 8 hours (IV)

19. Metoclopramide
• Central/peripheral D2 antagonist and
5 HT agonist
• Increases antral contractions
• Decreases fundal relaxation
• Improves antroduodenal
coordination
• Dose: 5-20 mg qid (PO, IV, SQ, SL)

20. Metoclopramide
• 30% of patients experience side
effects
• 10% have neurologic side effects
Parkinson-type syndrome
Tardive dyskinesia
• Hyperprolactinemia
* Boxed Warning for chronic
use issued by FDA*

21. Domperidone
• Peripheral D2 antagonist
• Increases antral contractions
• Decreases fundal relaxation
• Improves antroduodenal
coordination
• Dose: 10-30 mg qid (PO)
Limited availability in USA

22. Efficacy of Domperidone in Diabetic
Gastroparesis
□ Improved symptoms in 64%
□ Improved gastric emptying in 60%
□ Reduced hospital admission in 67%
□ 28 trials (19 double arm); 1016 patients
Sugumar A et al, CGH 2008

23. Effects of Botulinum Toxin on GE and
GI Symptoms
Within Group Between
Group P
Botox P Placebo P
Improved % 37.5 56.3 0.29
GCSI score -6.8 + 9.2 0.01 -10.1 + 12.7 0.01 0.42
GVAS score -190 + 228 0.01 -176 + 256 0.02 0.88
% Gastric
retention 2 hr
-16.3 + 22.9 0.02 -10.8 + 20.6 0.08 0.52
% Gastric
retention 4 hr
-13.3 + 18.0 0.01 -3.6 + 25.5 0.62 0.27
Friedenberg FK, et al. Am J Gastro 2008

24. 3. A 28 y.o. man with IDDM is referred for chronic and
recurrent nausea and vomiting. He reports 3-4 episodes
yearly for the past 5 years with frequent ED visits or
hospitalizations lasting 3-4 days. Between episodes, he
feels well and has lost no weight. During these episodes,
he finds great relief when taking hot showers.
The most appropriate intervention for this patient is:
• a) Domperidone 20 mg AC meals
• b) Nortriptyline in doses up to 100mg hs
• c) Discontinue smoking marijuana
• d) Strict control of blood sugars; metoclopramide
10 mg SQ during episodes

25. DD:Cyclic Vomiting Syndrome
Recurrent and stereotypical episodes of
severe nausea and vomiting separated
by symptom free intervals
- Gastric emptying rapid or normal
- Maintenance of weight

26. DD:Cannabinoid Hyperemesis
- Cyclic vomiting syndrome
- Compulsive hot water bathing
- Poor response to TCAs

27. Cyclic Vomiting in Adults
(Non-Cannabinoid)DD”
• Association with migraine headaches
• Psychological disorders
(anxiety/depression)
• Absence of compulsive hot water
bathing
• Often responds to TCAs

28. Physiology of gastric emptying:
• Different meals are emptied at different rates, based on physical
consistency, fat content& total caloric load.
• Liquids of low caloric density empty under the pressure gradient
between fundic tone & pylorus with little motor action of the
distal stomach& liquids empty exponentially from the stomach.
• Higher caloric liquids or homogenized solids empty almost
linearly under the pressure gradient from the fundus&
coordinated antropyloroduodenal motility.
• Digestible food of more solid consistency requires antral
trituration until the particle size is reduced to < 2 mm; after
which , food empties linearly from the stomach at a rate similar to
that of a homogenized solid meal.
• Trituration involves establishing liquid shearing forces where
solids & liquids are repeatedly propelled against a closed pylorus
at the maximum frequency of 3 / minute in humans.

29. Definition of gastric emptying:
• Gastroparesis is a syndrome of significantly delayed gastric
emptying in the absence of mechanical obstruction&cardinal
symptoms of early satiety, postprandial fullness, nausea,
vomiting, bloating&upper abdominal pain.
• Diabetes, postsurgical, post-viral or idiopathic are the most
common associated conditions
• Extrinsic neurologic disorders as parkinsonism, paraneoplastic.
• Scleroderma

30. Deranged mechanisms:
• In gastroparesis, there is an abnormal function of smooth muscle,
enteric & extrinsic autonomic nerves, or the interstitial cells of
Cajal (pacemakers in the stomach wall).
• The pathophysiological disturbances from diverse pathologic
mechanisms seem to be uniform.
• Myopathic disorders are typically infiltrative diseases, such as
scleroderma or amyloidosis; degenerative disorders, such as
hollow visceral myopathy; or mitochondrial cytopathy.
• When these disorders cause gastroparesis, they invariably present
as a more generalized motility disorder affecting other regions,
such as the small bowel, esophagus, LES.
• Gastric emptying delay in gastroparesis is associated with distal
antral hypomotility, pylorospasm, or intestinal dysmotility.

31. Deranged mechanisms:
• Measurement of gastric emptying does not differentiate
neuropathic from myopathic disorders but requires appraisal for
systemic, serologic, or biopsy of the underlying diseases (eg,
scleroderma or mitochondrial cytopathy, Urine or SPE, fat or
duodenal biopsy for amyloidosis) or, rarely, documentation of
low-amplitude eso (typically < 30 mm Hg), LES resting pressure
(typically < 20 mm Hg),15,16 antral (typically < 40 mm Hg), or
duodenal (typically < 10 mm Hg) contr amplitude by manometry.
• Antral hypomoility is usually present when there is pylorospasm
• Decreased PP antral motility index prolongs gastric emptying for
solids by prolonging the lag time & lowering post-lag emptying.
• Intestinal dysmotility retards the gastric emptying, typically
without prolonging lag phase of gastric emptying.
• Finding residual food in the stomach at the time of endoscopy
after a period of fasting may occur in patients with gastroparesis.

32. Diagnosis:
• Gastric emptying by scintigraphy is still widely used.
• Measurement Gastric emptying of low 2% fat Egg Beaters
(chicken egg white) or 30% fat, 320-kcal meal is gold standard.
• Significant delay is documented by at least 10% retention at 4
hours with the EggBeaters meal&> 25% retention at 4 hours with
the 320-kcal, 30% fat meal.
• FDA approved:
• A.Wireless motility capsule, which detects gastric emptying time
at the point of care by identifying the sudden change in pH from
entry into the duodenum.
• B. C13 isotope with solid meal &after emptied from stomach,
digested & absorbed in the proximal SI, liver metabolized &
excreted by lungs, resulting in rise in expired 13 CO2 over
baseline, inaccurate in malabsorption, liver, or lung diseases; 80%
specificity, 89% sensitivity compared with simultaneous
scintigraphy&agreed with it 73%– 97% of the time.

33. Dietary recommendations:
• Foods provoking symptoms;orange juice,fried chicken, cabbage,
oranges, sausage, pizza, peppers,onions, tomato juice, lettuce,
coffee, salsa, broccoli, bacon, roast beef, were generally fatty,
acidic, spicy,roughage-based.
• A high-fat solid meal significantly increased overall symptoms
• Saltine crackers, Jell-O,graham crackers moderately improved
symptoms, and 12
• Additional foods were tolerated without provoking symptoms;
ginger ale, gluten-free foods, tea,sweet potatoes, pretzels, white fi
sh, clear soup, salmon,potatoes, white rice, popsicles, applesauce.
• A small particle size diet reduces upper gastrointestinal symptoms
(nausea, vomiting, bloating, postprandial fullness, regurgitation,
heartburn) in patients with diabetic gastroparesis

34. Standard medications:
• The only approved drugs for treatment of gastroparesis target
dopamine D2 receptors; metoclopramide (a D2 -receptor
antagonist with some 5-HT4 receptor agonism) & Domperidone.
• Tardive dyskinesia risk is overstimated.
• Metochlopromide nasal spray, reduced symptoms of gastroparesis
in women, but not in men.
• Domperidone risk of SCD from prolonged QT.
• Motilin agonists; erythro,azithro & clarithro also prolong QT &
should not be combined with prokinetics.
• Tachyphylaxis is a problem.
• All should not be given for > 3 months.

35. Novel medications:
• Novel Motilin Agonist : GSK962040 (or camicinal) is a small
molecule, selective motilin receptor agonist.
• Ghrelin agonist; Relamorelin accelerated gastric half-emptying
time of solids in patients with type 2 or type 1 diabetes with
delayed gastric emptying.
• New 5-HT4 Receptor Agonists: prucalopride; Velusetrag is a
selective 5-HT4 receptor agonist, YKP10811 is a novel benzamide
derivative, selective 5-HT4 receptor agonist.
• In nonobese diabetic mice phosphodiesterase 5 inhibitor,
sildenafil reversed gastric emptying.

36. Intrapyloric Botox inj:
• It directly inhibits smooth muscle contractility, as evidenced by a
decreased contractile response to acetylcholine.
• Not approved yet.
• It can improve gastric emptying & symptoms,> with 200-
unit,second inj, female,< 50 years& idiopathic cause.

37. Transpyloric FCMS:
• Improvements in gastric emptying & clinical outcomes in 75% ,
with greater efficacy in predominant nausea/or vomiting (79%)
rather than those with predominant pain (21%).

38. Gastric Per-Oral or lap Endo Myotomy:
• Extended to include patients with gastroparesis secondary to
vagal injury.

39. Gastric Electrical Stimulation:
• Approved for diabetic & idiopathic gastroparesis, for persistence
of symptoms despite antiemetic/prokinetics for at least 1 year.
• NICE in 2014: current evidence is adequate to support its use.

40. Endoscopic GES implantation:
• Temporary gastric stimulators placed endoscopically to
determine response to GES before permanent implantation
• A novel, wirelessly powered miniature GES implanted into the pig
stomach through an overtube & attached to the gastric mucosa
with endoclips needs validation in humans.