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GI Motility Disorders: Why are Women at Risk?. Henry P. Parkman, MD Professor of Medicine Director – Gastrointestinal Motility Laboratory Temple University School of Medicine Philadelphia, PA. Topics to Cover.

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Gi motility disorders why are women at risk l.jpg
GI Motility Disorders:Why are Women at Risk?

Henry P. Parkman, MD

Professor of Medicine

Director – Gastrointestinal Motility Laboratory

Temple University School of Medicine

Philadelphia, PA


Topics to cover l.jpg
Topics to Cover

  • GI Motility and Functional GI Disorders are common and are associated with poor quality of life.

  • GI Motility and Functional GI Disorders are more common in women than in men.

  • Focus on gastric motility and gastroparesis to discuss gender effects on gastric motility.


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Normal GI Tract Motility

Peristalsis:Involuntary wave-like muscular contractions that move materials through the gastrointestinal tract

  • Esophagus

    • Swallowing initiates esophageal peristalsis and

      relaxation of the lower esophageal sphincter, which

      propels food bolus into the stomach

  • Stomach

    • The fundus relaxes to accommodate the ingested food

    • Food is broken down and mixed with gastric secretions

    • Contents are slowly emptied into the small intestine

  • Small bowel

    • Food is mixed, digested, and absorbed;chyme is propelled by peristalsis

  • Colon

    • Water and electrolytes are absorbed, and stoolis concentrated and stored until defecation


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GI Motility and Functional GI DisordersPathophysiology

  • Dysmotility

    • Disturbed regulation and coordination of the muscles and nerves in the GI tract, leading to:

      • Decreased

      • Increased

      • Chaotic motility

  • Altered sensation

    • Hypersensitivity

    • Hyposensitivity


Gi motility and functional gi disorders l.jpg
GI Motility and Functional GI Disorders

Noncardiac chest pain (NCCP)

Achalasia

Gastroesophageal

Reflux Disease

Dyspepsia

Gastroparesis

Irritable bowelsyndrome (IBS)

Biliarydyskinesia

Chronic constipation

Levator anisyndrome

Fecal incontinence


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Importance of GI Motility Disorders - 1

Gastrointestinal motility and its disorders are important areas for the health of the United States.

GI motility and functional bowel disorders affect up to 25% of the US population.

These disorders comprise about 40% of GI problems for which patients seek health care.

GI motility disorders pose a heavy burden of illness, decreased quality of life, and decreased work productivity.


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Prevalence of Upper GI SymptomsIn the United States

Percent of US Population

> 1 episode Clinically Relevant

per month Symptoms (> 1-2/week)

Heartburn 21.6% 6.3%

Regurgitation 16.4% 2.9%

Dysphagia 7.8% 4.6%

Bloating 10.7% 4.5%

Postprandial Fullness 20.9% 3.6%

Early Satiety 23.0% 5.3%

Nausea 9.5% 2.2%

Vomiting 2.7% 0.4%

Belching/Burping 6.3% 3.0%

Abdominal Pain / Discomfort 4.8%

From: Camilleri, Dubois, et al. Clinical Gastroenterology and Hepatology 2005;3:543-552.


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Effect of Gender on Upper GI SymptomsIn the United States

Percent of US Population

With Clinically Relevant Symptoms

Total Males Females

(n=17,484) (n=8,408) (n=9,076)

Heartburn 6.3% 5.7 6.9

Regurgitation 2.9% 2.7 3.1

Dysphagia 4.6% 4.4 4.7

Bloating 4.5% 3.4 5.6

Postprandial Fullness 3.6% 3.1 4.0

Early Satiety 5.3% 3.7 6.7*

Nausea 2.2% 1.4 3.0*

Vomiting 0.4% 0.4 0.5

Belching/Burping 3.0% 2.5 3.4

From: Camilleri, Dubois, et al. Clinical Gastroenterology and Hepatology 2005;3:543-552.


Prevalence of gi motility and functional gi disorders compared to some chronic non gi disorders l.jpg
Prevalence of GI Motility and Functional GI DisordersCompared to Some Chronic Non-GI Disorders

Dyspepsia 20-25%

Irritable bowel syndrome 10-25%

Functional heartburn (GERD) 15.5%

Chronic constipation 12-19%

Gastroparesis 4%

Hypertension 28%

Migraine Headache 6-18%

Asthma 8%

Diabetes 8%

The GI disorders, IBS, chronic constipation, and gastroparesis

but not dyspepsia, are more common in females than males.

Sources – several articles from 2000-2005


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Motor Events During Gastric Emptying

Horowitz M, et al. Nature Clinical Practice 2005;2:454.


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Gastric Emptying ScintigraphyThe Gold Standard Test to Measure Gastric Emptying

Normal Gastric Emptying Delayed Gastric Emptying


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Clinical Characteristics of Patients With Gastroparesis (146 Patients at Tertiary Motility Centers)

Gender: Female 82%

  • Male 18%

    Onset of Symptoms: 34 years

    Symptoms: Nausea 92%

    • Vomiting 84%

    • Abdominal bloating 75 %

      • Early Satiety 60 %

        Abdominal pain 46%



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Influence of Gender on the Myoelectric ActivityElectrogastrogram in Normal Subjects

Effect of Gender on

EGG Dominant Frequency

Effect of the Female Menstrual Cycle

on EGG Dominant Frequency

Parkman et al. AJG 1996;91: 127.


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?Hormonal Causes of GI Dysmotility Myoelectric Activity

  • Progesterone

    • Calcium Channels

    • G proteins

    • Nuclear transcription

  • Estrogen

  • Estrogen priming of Progesterone


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Gender Effects on Gastric Emptying Myoelectric Activity

Effects of gender on gastric emptying remain controversial.

Some studies have reported delayed gastric emptying in premenopausal women compared with men, especially in later phase of the menstrual cycle with progesterone and estrogen levels are high.

Other studies have reported no difference between women and men or between women in different phases of the menstrual cycle.

The majority of patients with symptoms of dyspepsia and gastroparesis are female. To evaluate these patients, it is important to determine the normal physiologic parameters of gastric emptying for women.


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Gender Effects on Gastric Emptying Myoelectric ActivityLinda C. Knight, Henry P. Parkman, Jean-Luc Urbain, Alan H. Maurer, Robert S. Fisher

AIMS

To determine whether gender affects gastric emptying by characterizing gastric emptying for normal women and age matched men.

To see if observed differences correlate with alterations in antral motility measured by dynamic antral scintigraphy (DAS) and cutaneous electrogastrography (EGG).

STUDY POPULATION

13 normal men age 27.5 ± 1.7 yr

9 normal women* age 27.9 ± 2.2 yr

*studied in the first 10 days of the menstrual cycle


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FEMALES Myoelectric Activity

100

%

R

E

M

A

I

N

I

N

G

MALES

80

60

40

Lag (F)

T 1/2 (M)

20

T 1/2 (F)

Mean: Lag (M)

0

0

0

30

60

90

120

150

180

Time (min)

Gastric Emptying Curves - Whole Stomach


Gastric emptying parameters l.jpg

150 Myoelectric Activity

0.03

120

0.02

90

60

0.01

30

0.00

0

MALE

FEMALE

MALE

FEMALE

Gastric Emptying Parameters

T 1/2

* P <0.05

*

*


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Gender Affects Gastric Emptying Myoelectric Activity

Male Subject

Female Subject

T=20

min

T=60

min

T=90

min

T=120

min

T=0


Proximal gastric emptying curves l.jpg

FEMALES Myoelectric Activity

100

MALES

%

R

E

M

A

I

N

I

N

G

80

60

40

20

0

0

0

30

60

90

120

150

180

Time (min)

Proximal Gastric Emptying Curves


Distal gastric emptying curves l.jpg

60 Myoelectric Activity

FEMALES

MALES

%

R

E

M

A

I

N

I

N

G

50

40

30

20

10

0

0

0

30

60

90

120

150

180

TIME (MIN)

Distal Gastric Emptying Curves


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1 Myoelectric Activity

3

5

7

9

11

13

15

17

19

Visualization of Antral ContractilityUsing Dynamic Antral Scintigraphy

time (sec)


Data analysis das l.jpg

1200 Myoelectric Activity

1000

COUNTS

800

600

400

0

0

60

120

180

240

Time (seconds)

Data Analysis - DAS

The oscillating data were analyzed:

• for dominant frequency by fast Fourier transform

• for mid-antral ejection fraction by determining the percentage of

basal content displaced by each contraction.


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Examples of DAS Data: Myoelectric ActivityEjection Fraction Analysis


Effect of time post meal on mid antral ejection fraction and egg power l.jpg

FEMALES Myoelectric Activity

MALES

Effect of Time Post Meal on Mid-Antral Ejection Fraction and EGG Power

p

o

w

e

r

EF

(%)


Frequency analysis by dynamic antral scintigraphy l.jpg

Raw Data Myoelectric Activity

fast Fourier transform

30

1200

a

m

p

l

i

t

u

d

e

25

1000

c

o

u

n

t

s

20

800

15

600

10

400

5

200

0

0

0

0

60

120

180

240

0

2

4

6

8

10

12

14

16

Frequency (cycles/minute)

Frequency Analysis by Dynamic Antral Scintigraphy

Time (sec)


Examples of das data fourier analysis l.jpg

30 Myoelectric Activity

4

25

3

20

15

2

10

1

5

0

0

0

2

4

6

8

10

12

14

16

0

2

4

6

8

10

12

14

16

Examples of DAS data: Fourier Analysis

MALE SUBJECT

FEMALE SUBJECT

FFT

FFT

3.0 cycles/min

3.6 cycles/min

Frequency (cycles/min)

Frequency (cycles/min)


Summary of this temple study l.jpg
Summary of this Temple Study Myoelectric Activity

• Gastric emptying of solid food in normal young women is slower than in age-matched men, even in the first 10 days of the menstrual cycle when estrogen and progesterone levels are low.

• Higher gastric retention in women was associated with normal proximal gastric emptying but a decreased rate of distal gastric emptying.

• Females had decreased antral contractility as recorded by dynamic antral scintigraphy.


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Conclusions of this Temple Study Myoelectric Activity

• The delay in gastric emptying of solids in women appears to be primarily due to altered distal gastric motor function.

• One explanation may be that less vigorous antral contractions may contribute to slower breakdown of food particles and thus delay the rate of emptying.

• This hypothesis was corroborated by finding decreased antral contractility as recorded by DAS.

• This study emphasizes the need to evaluate symptomatic females using gastric emptying parameters derived in normal women.


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Gender Affects Many Aspects of Health Care in Gastroenterology

  • Presentation of Illness

    Higher prevalence of symptoms in females

  • Different Physiology

    Neural pathways – Gastrocolonic reflex

    Sensory pain pathways and neurotransmission

  • Evaluation of the Patient

    Different Normal Values – Gastric Emptying, Colonic Transit

  • Prevalence of GI Motility Disorders and Functional GI Disorders

    Higher prevalence in females

  • Response to Treatment

    Different Response to Therapy

    IBS: Allosetron, Tegaserod


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Importance of GI Motility Disorders GastroenterologyRelates to Other FunctionsDo These Areas Also Have Gender-Related Effects?

GI motility also plays an important role in issues outside of traditional gastroenterology. Examples of this include nutrition, obesity, and drug delivery.

Nutrition depends on the controlled delivery of food for optimal assimilation from the gastrointestinal tract.

Signaling of satiety is dependent on proper control of GI motility and release of GI hormones. Obesity can result when satiety and GI motility are altered.

Bioavailability of orally administered drugs is controlled in large part by GI motility.


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Decreased Electromechanical Activity of Guinea Pig Circular Muscle During Pregnancy

During the third trimester of pregnancy in guinea pigs,

The force of both spontaneous and bethanechol-induced antral circular muscle contractions is decreased

The electrical slow waves displayed decreased upstroke amplitude, plateau amplitude, and number of spikes during the plateau potential.

The diminished gastric contractility during pregnancy is due to a change in electromechanical activity of the gastric muscle.

(Parkman, Wang, Ryan. Gastroenterology 1993;105:1306.)


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Delayed Gastric Emptying Muscle During Pregnancyin Normal Women is Associated with Decreased Antral Contractility

Linda C. Knight, Henry P. Parkman,

Jean-Luc Urbain, Alan H. Maurer, Robert S. Fisher

Gastroenterology Section; Department of Medicine

Nuclear Medicine Section; Department of Radiology

Temple University School of Medicine

Philadelphia, PA


Protocol l.jpg
PROTOCOL Muscle During Pregnancy

• Study starts at 7:30 AM after an overnight fast.

• Fasting EGG recording for 1 hour.

• Ingest standard test meal:

99mTc egg sandwich (2mCi 99mTc-SC in 2 eggs)

and 300 ml nonlabeled water.

• Perform the following tests for 3 hr:

  • Gastric Emptying Scintigraphy (GES):

    Anterior/posterior images every 10-15 minutes.

  • Dynamic Antral Scintigraphy (DAS):

    256 images of 1 sec each, every 10-15 minutes.

  • Cutaneous Electrogastrography (EGG):

    Continuous recordings with time stamp at start of DAS


Data analysis l.jpg
DATA ANALYSIS Muscle During Pregnancy

GES:

Geometric mean counts were fit to a modified power exponential function: %Retention = 100(1-(1-e-kt)ß)

DAS:

A region was drawn across the mid-antrum and a time-activity curve was generated. The oscillating data were analyzed for dominant frequency by fast Fourier transform and for mid-antral ejection fraction by determining the percentage of basal content displaced by each contraction.

EGG:

The signals were analyzed during the fasting period and during the postprandial period at time periods corresponding to DAS recordings, using fast Fourier transform to determine dominant frequency (DF) of contractions and the power of DF.


Data analysis ges l.jpg

200 Muscle During Pregnancy

ß

%

R

E

T

E

N

T

I

O

N

100

50

-slope =

Lag =

( ln ß) /

20

T1/2

10

0

30

60

90

120

150

180

TIME (MIN)

Data Analysis - GES

Geometric mean counts were fit to a modified power exponential function: %Retention = 100(1-(1-e-t)ß)


Ejection fraction analysis by dynamic antral scintigraphy l.jpg

Raw Data Muscle During Pregnancy

Normalized Data

1200

120

1000

100

c

o

u

n

t

s

800

80

600

60

EFi = MAX-MIN / MAX

400

40

= 29%

EF = average EFi

200

20

0

0

0

0

60

120

180

240

0

0

60

120

180

240

Time (sec)

Time (sec)

Ejection Fraction Analysis by Dynamic Antral Scintigraphy


Data analysis egg l.jpg
Data Analysis-EGG Muscle During Pregnancy

EGG signals were analyzed using fast Fourier transformation

  • during the fasting period and

  • during the postprandial period at time periods corresponding to DAS recordings

    Parameters determined:

  • dominant frequency (DF) of contractions

  • the power of DF.


Frequency of contractions vs time post meal l.jpg

FEMALES Muscle During Pregnancy

MALES

Frequency of Contractions vs time post meal

DF

(cpm)

DF

(cpm)


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