1. Functional Gastrointestinal Disorders (FGID)
Qing Zheng Department of Gastroenterology Shanghai Institute of Digestive Disease

2. Definition of FGID
Chronic and recurrent symptoms of the gastrointestinal (GI) tract:
pain nausea vomiting
bloating diarrhea constipation…
Without detectable structural or biochemical abnormalities
FGD are characterized by chronic and recurrent symptoms of the gastrointestinal (GI) tract without detectable structural or biochemical abnormalities. In the absence of universal biologic markers, the diagnosis is based on consensus symptom criteria.

3. Rome Criteria Multinational Working Teams
Rome Committees:
Multinational Working Teams
Symptom-based diagnostic criteria:
Rome I
Rome II
Rome III
In the absence of universal biologic markers, the diagnosis is based on consensus symptom criteria.
For characterizing and classifying the FGIDs, a Multinational Working Teams ( Rome Committees) developed a diagnostic criteria in With the growing knowledge in this field, in 1999, the updated criteria - Rome II criteria was published, which is in currently using.

4. Classification FGIDs ( classified by anatomic region) (A) Esophageal
(B) Gastroduodenal (B1: FD)
(C) Bowel (C1: IBS)
(D) Functional abdominal pain
(E) Biliary
(F) Anorectal.
Patients with FGIDs report a wide variety of symptoms affecting different regions of the gastrointestinal tract. These symptoms have in common disturbances in sensory and/or motor gastrointestinal function, which may overlap across anatomic regions. Within each anatomic category site, there can be several disorders, each with specific clinical features. The clinical value of the classification is that they can be reliably diagnosed and more specifically treated.

5. Common Features of FGIDs
1. Pathophysiology
2. Role of psychosocial factors
3. The treatment strategy
despite differences in location and symptom patterns, the FGIDs share common features.

6. 1. Pathophysiology Abnormal motility Visceral hypersensitivity
Inflammation
Brain-gut interactions
Brain-gut peptides:
5-hydroxytryptamine 5-羟色胺
enkephalins 脑啡肽,
substance P, p-物质
calcitonin gene related polypeptide 降钙素,
cholecystokinin 缩胆囊素
The FGIDs have an even greater motility response to stressors (psychological or physiological) when compared with responses in normal subjects
These patients may have a lower pain threshold, or increased sensitivity even to normal intestinal function and an increased or unusual area of somatic referral of visceral pain.
Increased inflammation in the enteric mucosa or neural plexi may contribute to symptom development. This may occur by peripheral sensitization, and/or hypermotility activated by induction of mucosal inflammatory cytokines.
Brain-gut axis dysfunction may also play a role.
Some neuropeptides have integrated activities on gastrointestinal function and human behavior depending upon their location, including: 5-hydroxytryptamine and its congeners, the enkephalins and opioid agonists, substance P, calcitonin gene related polypeptide, and cholecystokinin

7. 2. Role of psychosocial factors
1)Psychological stress exacerbates GI symptoms.
2)Psychological disturbances modify the experience of illness and illness behaviors such as health care seeking.
3) Psychosocial factors affect health status and clinical outcome.

8. FGID—biopsychosocial model
The FGIDs seem to be understood as dysregulation of brain–gut function,
Early in life, genetics and environmental influences may affect one’s psychosocial development or the development of gut dysfunction
In addition, the presence and nature of a FGID is determined by the interaction of psychosocial factors and altered physiology via the brain–gut axis.
So, one individual afflicted with a bowel disorder, but with no psychosocial disturbances and good coping skills and social support, may not experience the symptoms as distressing enough to seek medical care.
Another, having co-existent psychosocial disturbance, high life stress, and poor social support, may experience the symptoms as severe and unmanageable, may see physicians frequently, and have a generally poor outcome.

9. 3. Treatment Strategy
General treatment approach establish therapeutic relationship
education and reassurance
dietary and lifestyle modifications
2) Pharmacological therapies
symptomatic treatment
antidepressant
Psychological therapies
cognitive-behavioral treatment hypnosis
1 For all patients, the physician should establish an effective therapeutic relationship, provide patient education and reassurance, and help with dietary and lifestyle modifications when needed.
2 aim at relieving the predominant symptoms//Antidepressants are recommended for moderate to severe symptoms
3. Psychological treatments are initiated when symptoms are severe enough to impair health-related quality of life.

10. Functional dyspepsia (FD)

11. Definition
Persistent or recurrent pain or discomfort centered in the upper abdomen:
including pain,  early satiety, nausea, vomiting, abdominal distension, bloating, and anorexia
Evidence of organic disease likely to explain the symptoms is absent.

12. Social Impact of Dyspepsia70 60 50 40 30 20 10
Not At All
Slightly
Moderately
Quite A Lot
Extremely
Extent to which dyspepsia has interfered with normal social activities
(DIGEST, 1996)

13. Pathophysiological mechanisms
1. Gastrointestinal motor abnormalities
2. Altered visceral sensation
3.Psychosocial factors
4. Helicobacter pylori infection ?
the exact pathogenesis of FD still remain poorly understood so far. But the major pathophysiological mechanisms responsible for functional dyspepsia include psychosocial factors and alterations in motility and visceral sensation.

14. Putative Pathogenesis of Dyspepsia
Stress
ANS Imbalance
Increased Sensitivity
Sensory Inhibition
Sensitivity
. . .
Increased Afferent
Activity
Low Grade
Inflammation
± HP Infection
Impaired Motor Activity
Accommodation
Altered Motor & Sensory Function
DYSPEPSIA

15. 1. Alterations in Motility
Delayed emptying
Impaired accommodation to a meal
Antral hypomotility
Gastric dysrhythmias
Altered duodenojejunal motility
These conditions have all been identified in subgroups of patients with FD.

16. 2. Altered visceral sensation
Hypersensitivity to gastric balloon distention:
suggesting abnormal afferent function
Reflex hyporeactivity:
suggesting either abnormal afferent or abnormal efferent function
Hypersensitivity to gastric balloon distension is highly specific for functional dyspepsia,
Impaired gastric and intestinal reflexes have also been observed in functional dyspepsia.
These finding suggest that dyspeptic symptoms may be a consequence of antral hypersensitivity and antral overload, which is caused by impaired reflex relaxation of the proximal stomach.

17. 3. Psychosocial factors
The personality profile impacts on patients with functional dyspepsia.
Higher levels of anxiety and depression have been found.
A link between childhood abuse and functional gastrointestinal disorders.

18. 4. Helicobacter pylori infection?
Strictly controlled studies have failed to identify any real relationship between Helicobacter pylori infection and FD.
The role of H pylori in functional dyspepsia has long been a subject of controversy.
strictly controlled studies have failed to identify any real relationship between the two.
A comprehensive evaluation of the motor and sensory function of the stomach in H pylori positive and negative patients with functional dyspepsia showed that gastric accommodation to meal ingestion was reduced in patients with dyspepsia, independent of their H pylori status.

19. Clinical Features Dyspepsia:
Pain or Discomfort centered in the upper abdomen
The symptoms may be intermittent or continuous, and may or may not be related to meals.
Centered implies that the pain or discomfort is mainly in or around the midline.

20. Definitions of the symptom
Pain: a subjective, unpleasant sensation
Discomfort: a subjective, unpleasant sensation or feeling that is not interpreted as pain according to the patient, including upper abdominal fullness, early satiety, bloating, or nausea
centered in the upper abdomen: the pain or discomfort is mainly in or around the midline
Centered implies that the pain or discomfort is mainly in or around the midline.

21. Dyspepsia subgroup classification -based on the predominant single symptom
Ulcer-like dyspepsia
2. Dysmotility-like dyspepsia
3. Unspecified (non-specific) dyspepsia

22. 1. Ulcer-like dyspepsia
Pain centered in the upper abdomen is the predominant (most bothersome) symptom.

23. 2. Dysmotility-like dyspepsia
An unpleasant or troublesome non-painful sensation (discomfort) centered in the upper abdomen is the predominant symptom; this sensation may be characterized by or associated with upper abdominal fullness, early satiety, bloating, or nausea.

24. 3. Non-specific dyspepsia
Symptomatic patients whose symptoms do not fulfill the criteria for ulcer-like or dysmotility-like dyspepsia.

25. Diagnosis Rome II Criteria:
At least 12 weeks, which need not be consecutive, within the preceding 12 months of:
1. Persistent or recurrent dyspepsia (pain or discomfort centered in the upper abdomen);

26. Diagnosis Rome II Criteria:
2. No evidence of organic disease (including at upper endoscopy) that is likely to explain the symptoms;

27. Diagnosis Rome II Criteria:
3. No evidence that dyspepsia is exclusively relieved by defecation or associated with the onset of a change in stool frequency or stool form (i.e., not irritable bowel).

28. Diagnostic process FD remains a diagnosis of exclusion:
Careful history and physical examination
Upper endoscopy is necessary
The others: exclusion of
chronic peptic ulcer disease,
gastroesophageal reflux disease,
esophagitis,
pancreatico-biliary disease
malignancy
Patients need to have been investigated to rule out relevant organic disease. Functional dyspepsia therefore remains a diagnosis of exclusion.

30. Major Causes of Dyspepsia
Williams 1988 Stanghellini 1996 Heikkinen (n=1386) (n=1057) (n=766)
% of Patients with Diagnosis
Gastric Cancer Peptic Ulcer Esophagitis/ Functional
GERD Dyspepsia

31. Differential Diagnosis
GERD:
Heartburn is the predominant symptom
Upper endoscopy
Prolonged esophageal pH monitoring
Twenty-four hour esophageal pH monitoring
only about one third of patients with reflux have visual evidence of esophagitis at endoscopy, and patients without macroscopic esophagitis are often misclassified as having FD. If heartburn and acid regurgitation are dominant complaints, they are reasonably specific in detecting the presence of acid reflux disease, as defined by prolonged esophageal pH monitoring;
Twenty-four hour esophageal pH monitoring is useful for making a diagnosis and may be positive in up to one third of cases with unexplained dyspepsia who are not suspected of having pathologic gastroesophageal reflux

32. Differential Diagnosis
IBS: overlap symptom
co-exist with FD
Irritable bowel syndrome (IBS) is a very common disorder that is characterized by recurrent abdominal pain associated with an erratic disturbance of bowel habit and often bloating; approximately one third of patients with FD also manifest typical symptoms of IBS. Inflation of balloons in different parts of the large bowel can produce upper abdominal pain, and esophageal or small bowel dysmotility occurs in some patients with IBS, which may explain the link between dyspepsia and IBS

33. Treatment
The goal is to accept, diminish, and cope with symptoms rather than eliminate them.
The most important aspects include explanation that the symptoms are not imaginary, evaluation of relevant psychosocial factors, and dietary advice.

34. Pharmacological therapies
H. pylori therapy ? controversial
Acid suppression and prokinetic agents (digestive agents) ? may help
Gut analgesics ? Relaxants of the nervous system of the gut may be beneficial
Antidepressant? May help

35. Management of Ulcer-like Functional Dyspepsia
Ulcer-like Symptoms Dominant
Education/lifestyle modification
Test Hp + -
Eradicate Hp
Trial of acid suppression
Reassess
Success
Failure
Investigate
Trial of prokinetic

36. Management of Dysmotility-like Functional Dyspepsia
Dysmotility-like Symptoms Dominant
Educate/lifestyle modification
Trial of prokinetic medication
Success
Failure
Continue with cyclic therapy
Investigate
Test H. pylori
Gastroscopy or UGI + -
Eradicate
Consider H2 antagonists, tricyclics
Success
Failure

37. Irritable bowel syndrome (IBS)

38. Definition
Irritable bowel syndrome (IBS) is a functional GI disorder characterized by abdominal pain or discomfort and altered bowel habits
In the absence of demonstrable organic disease.

39. Pathophysiological mechanisms
1 Altered gut reactivity (motility, secretion) in response to luminal (e.g., meals, gut distention, inflammation, bacterial factors) or provocative environmental stimuli (psychosocial stress),
resulting in symptoms of diarrhea and/or constipation
the exact pathogenesis of FD still remain poorly understood so far. But the major pathophysiological mechanisms responsible for functional dyspepsia include psychosocial factors and alterations in motility and visceral sensation.

40. Pathophysiological mechanisms
2 A hypersensitive gut with enhanced visceral perception and pain
the exact pathogenesis of FD still remain poorly understood so far. But the major pathophysiological mechanisms responsible for functional dyspepsia include psychosocial factors and alterations in motility and visceral sensation.

41. Pathophysiological mechanisms
3 Dysregulation of the brain-gut axis, possibly associated with greater stress-reactivity and altered perception and/or modulation of visceral afferent signals
the exact pathogenesis of FD still remain poorly understood so far. But the major pathophysiological mechanisms responsible for functional dyspepsia include psychosocial factors and alterations in motility and visceral sensation.

42. Pathophysiological mechanisms
4 Inflammation: gut inflammatory and immune factors persisting following infection or inflammation of the bowel
the exact pathogenesis of FD still remain poorly understood so far. But the major pathophysiological mechanisms responsible for functional dyspepsia include psychosocial factors and alterations in motility and visceral sensation.

43. Pathophysiological mechanisms
5 Autonomic dysfunction: the role of autonomic dysfunction in IBS requires further evaluation
the exact pathogenesis of FD still remain poorly understood so far. But the major pathophysiological mechanisms responsible for functional dyspepsia include psychosocial factors and alterations in motility and visceral sensation.

44. Role of psychosocial factors
1)Psychological stress exacerbates GI symptoms.
2)Psychological disturbances modify the experience of illness and illness behaviors such as health care seeking.
3) Psychosocial factors affect health status and clinical outcome.

46. Possible causes of IBS

47. The biopsychosocial model of IBS

48. Nerve cell communication in the wall of the colon.

49. Clinical Features Abdominal discomfort or pain is
associated with defecation or a
change in bowel function and with
features of disordered defecation.

50. Clinical Features Classifying IBS patients based on their
symptomatology:
Diarrhea-predominant pattern:
IBS associated with abdominal discomfort, fecal urgency, and diarrhea

51. Clinical Features 2. Constipation -predominant pattern:
IBS associated with abdominal
discomfort, bloating, and constipation

52. Clinical Features 3. Mixed pattern:
IBS alternating between diarrhea and constipation

53. Symptoms and signs

55. Diagnosis Rome II Criteria
patients must have the following continuous or
recurrent symptoms for at least 12 weeks of
abdominal pain or discomfort characterized by the
following:
Relieved by defecation
Associated with a change in stool frequency
Associated with a change in stool consistency

58. Treatmemt General treatment approach
Establish therapeutic relationship
Education and reassurance
Dietary and lifestyle modifications

59. Physician-Patient Relationship
Reassure the patient that they are not unusual
Identify why the patient is currently presenting
Obtain a history of referral experiences
Examine patient fears or agendas
Ascertain patient expectations of physician
Determine patient willingness to aid in treatment
Uncover the symptom most impacting quality of life and the specific treatment designed to improve management of that symptom
Patients suffering from IBS often present for medical care only after frustrating self-diagnostic attempts to determine symptom causation and resolution. It is very important, therefore, that the responsible physician foster a positive relationship with the patient in order to aid in successful clinical management. A positive, confident diagnosis, accompanied by a clear explanation of possible mechanisms and an honest account of probable disease course, can be critical in achieving desired management goals. In order to facilitate a positive relationship, it is important that the physician practice the following principles:

60. Pharmacological therapies
Dietary and drug therapy for IBS can be considered in two categories:
1.End organ treatment aimed at relieving abdominal pain (antispasmodic drugs) or disturbed bowel habit (antidiarrhoeal and bulking agents).
2. Central treatment (antidepressants) targeted at patients with associated affective disorder.

61. Loperamide is an opioid analogue which slows small and large intestinal transit and decreases stool frequency and urgency in patients with IBS at doses of 4–12 mg each day.

62. Psychological therapies
Cognitive-behavioral treatment
Hypnosis……
1 For all patients, the physician should establish an effective therapeutic relationship, provide patient education and reassurance, and help with dietary and lifestyle modifications when needed.
2 aim at relieving the predominant symptoms//Antidepressants are recommended for moderate to severe symptoms
3. Psychological treatments are initiated when symptoms are severe enough to impair health-related quality of life.
5-HT =serotonin 3

64. Functional dyspepsia
Definition: pain or discomfort without the evidence
of organic disease
Pathophysiological mechanisms
Alterations in Motility and visceral sensation;
Psychosocial factors; Hp infection?
Clinical Features
Ulcer-like dyspepsia; Dysmotility-like dyspepsia;
Non-specific dyspepsia.
Diagnosis (a diagnosis of exclusion):Rome II Criteria:
Treatment: Goal;
Pharmacological therapies;
Psychological therapies

65. Irritable bowel syndrome
Definition:abdominal pain or discomfort and altered
bowel habits without demonstrable organic disease.
Pathophysiological mechanisms
Clinical Features: Diarrhea-predominant;
2. Constipation-predominant;
3. Mixed
Diagnosis: Rome II Criteria
Treatment: 1.General treatment approach;
2. Pharmacological therapies
3.Psychological therapies