Iberogast® for Healthcare Professionals

Malfunctions of the gastrointestinal tract

The gastrointestinal tract is a highly complicated system. If everything goes well, people do not even notice that digestion takes place. Severe malfunctions, however, can result in multiple digestive symptoms.
 
This section provides detailed information on the anatomy of the GI system as well as Functional Gastrointestinal Disorders.

Anatomy & motility of the GI tract

The gastrointestinal (GI) tract can also be named the alimentary tract as the respective anatomical components are related to nourishment or the function of nutrition.

The function of the gastrointestinal system is tripartite:

  1. Ingestion of nutrients and essential substances such as vitamins, minerals, water.
  2. Digestion and absorption of useful ingredients into the blood and the lymphatic system.
  3. Excretion of non-absorbable substances.

The GI tract is a long muscular tube reaching from the mouth to the anus. The tube is surrounded by circular (ring-like) and longitudinal (length-wise) smooth muscles that work together to create a coordinated forward movement of the contents, called peristalsis.

The gut consists of the small intestine and the colon. The small intestine is around 6 m long and roughly 2 cm wide. The colon is about 2m long and 6-7cm wide, ending in the rectum and the anus.

Due to a special fold structure, the surface of the gastrointestinal tract is significantly enlarged. The gastrointestinal mucosa of an adult person occupies up to 400 m2 of surface and is equipped with structures and functions that are specifically adapted for analytical and biochemical examination of substances.

Functionally, the stomach consists of a gastric reservoir and a gastric pump.3

HCP-anatomy-and-motility

Gastric reservoir

When filled with food, the stomach’s gastric reservoir relaxes in three ways to store and evacuate this additional volume:

HCP-gastric-reservoir

  1. Receptive relaxation: The stimulation of receptors in the mouth during chewing induces a reflex for relaxation.
  2. Adaptive relaxation: When the stomach fills, tension receptors are stimulated. The result is prolonged storage until the food is broken down – by gastric acid, enzymes and mechanically.
  3. Feedback relaxation: Induced by nutrients of the small intestine: the prolonged storage of food is a precondition for the adaptation of gastric emptying to the process of digestion and absorption.

Gastric pump

The emptying of the gastric reservoir into the gastric pump is caused by two mechanisms: tonic contractions of the reservoir and peristaltic waves moving over the distal part of the gastric corpus.3

The main feature of the gastric pump is the peristaltic wave. It starts at the proximal stomach and propagates to the pylorus, based on electrical waves originating in the gastric wall. In the region of the corpus the peristaltic waves are shallow. But when they reach the antrum, the circular constriction becomes deeper.

The complex functions of the gastric reservoir and gastric pump indicate that stomach emptying depends on the state of relaxation of the reservoir and the constriction depth of the antral waves. If these phases are not harmonized correctly, digestive symptoms are likely to result.

If, for example, relaxation is not sufficient, patients could experience early satiety, feeling of fullness and heaviness. On the other hand, if the peristaltic waves are too weak and shallow to transport the chyme in a proper and timely manner, gastric pain and bloating could result.

Therefore Iberogast shows region-specific effects with relaxation of the proximal stomach and stimulation of the antrum appear to be highly appropriate to correct gastric motility disorders.7,21

Impaired GI motility plays a major role in Functional Gastrointestinal Disorders (FGID).19

Functional Gastrointestinal Disorders (FGIDs)

Unfortunately 20-25% of the global population experiences problems related to the gastrointestinal tract.15 It is important to know that each patient can experience digestive symptoms in a different way, including but not limited to epigastric pains and cramps, feeling of fullness or heaviness in the stomach, early satiety, bloating, constipation, or diarrhoea. For many people these digestive symptoms return frequently or never completely vanish, resulting in a substantially reduced quality of life.4 They often appear in times of stress, emotional upset, travel or dietary changes.

If patients consult their physicians but no organic causes can be found, the diagnosis of a “Functional Gastrointestinal Disorder” (FGID) will be made. This is an umbrella term comprising of the most important clinical entities including Functional Dyspepsia1 (FD) and Irritable Bowel Syndrome(IBS).23

FD and IBS are also the most common FGIDs diagnosed in gastroenterological practice. Risk factors for both conditions are hormonal effects, post-infectious changes in the colonic microbiome, female gender, stress, and age23.

HCP-frequency-diagnosis-chart
Adapted from Russo, M et al. 1999 (n=500, 1987)
  • Functional Gastrointestinal Disorders (FGIDs) is an umbrella term used to comprise Functional Dyspepsia (FD) and Irritable Bowel Syndrome (IBS), as well as similar medical conditions which are disorders of gut–brain interaction. Since 1987, scientists and clinicians have attempted to understand and categorize FGIDs and have recently developed the Rome IV criteria which are now applied in diagnosis2. They classify FGIDs into several categories according to the regional location of symptoms, the predominant symptoms, and the age. In total, there are 22 adult and 10 pediatric FGIDs.

    Rome IV: list of Functional Gastrointestinal Disorders:
    • A. Esophageal Disorders
      • A1. Functional chest pain
      • A2. Functional heartburn
      • A3. Reflux hypersensitivity
      • A4. Globus
      • A5. Functional dysphagia
    • B. Gastroduodenal disorders
      • B1. Functional dyspepsia
        • B1a. Postprandial distress syndrome (PDS)
        • B1b. Epigastric pain syndrome (EPS)
      • B2. Belching disorders
        • B2a. Excessive supragastric belching
        • B2b. Excessive gastric belching
      • B3. Nausea and vomiting disorders
        • B3a. Chronic nausea vomiting syndrome (CNVS)
        • B3b. Cyclic vomiting syndrome (CVS)
        • B3c. Cannabinoid hyperemesis syndrome (CHS)
      • B4. Rumination syndrome
    • C. Bowel disorders
      • C1. Irritable bowel syndrome (IBS)
        • IBS with predominant constipation (IBS-C)
        • IBS with predominant diarrhoea (IBS-D)
        • IBS with mixed bowel habits (IBS-M)
        • IBS unclassified (IBS-U)
      • C2. Functional constipation
      • C3. Functional diarrhoea
      • C4. Functional abdominal bloating/distension
      • C5. Unspecified functional bowel disorder
      • C6. Opioid induced constipation
  • Compared to the old definition of Functional Dyspepsia, only minor changes have been introduced in the new Rome IV criteria, with the purpose of improving the specificity of definitions. FD remains the accepted umbrella term and refers to a patient who fulfills diagnostic criteria for Postprandial Distress Syndrome (i.e. meal-related symptoms) and/or Epigastric Pain Syndrome (EPS). That means, both sub-entities of FD can occur separately or co-exist in the same patients.

    Diagnostic criteria of Functional Dyspepsia (B1)28

    • 1. One or more of the following:
      • a. Bothersome postprandial fullness
      • b. Bothersome early satiation
      • c. Bothersome epigastric pain
      • d. Bothersome epigastric burning
    • 2. No evidence of structural disease (including at upper endoscopy) that is likely to explain the symptoms.

    Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis.

    Must fulfill criteria for Postprandial Distress Syndrome (B1a) and/or Epigastric Pain Syndrome (B1b).

    The former definition of the Postprandial Distress Syndrome (PDS) was slightly modified by acknowledging that – beyond postprandial fullness and early satiety that occur postprandially by definition – other digestive symptoms, including epigastric pain and epigastric burning, can be perceived by the patient as being induced or worsened by a meal. Epigastric bloating, belching, and nausea can be present in both, PDS and EPS, and should be considered as possible adjunctive features of the 2 subgroups. Vomiting, on the other hand, is unusual and should prompt the search for other diagnoses.

    B1a. Postprandial Distress Syndrome

    • 1. Diagnostic criteria must include one or both of the following at least 3 days per week:
      • a) Bothersome postprandial fullness (ie, severe enough to impact on usual activities)
      • b) Bothersome early satiation (ie, severe enough to prevent finishing a regular-size meal)
    • 2. No evidence of organic, systemic, or metabolic disease that is likely to explain the symptoms on routine investigations (including at upper endoscopy)


    Supportive remarks:
    - Postprandial epigastric pain or burning, epigastric bloating, excessive belching, and nausea can also be present
    - Vomiting warrants consideration of another disorder
    - Heartburn is not a dyspeptic symptom but may often coexist
    - Symptoms that are relieved by evacuation of faeces or gas should generally not be considered as part of dyspepsia
    - Other individual digestive symptoms or groups of symptoms, eg. from gastroesophageal reflux disease and the irritable bowel syndrome may coexist with PDS

    B1b. Epigastric Pain Syndrome

    • 1. Diagnostic criteria must include at least 1 of the following symptoms at least 1 day a week:
      • a. Bothersome epigastric pain (ie. severe enough to impact on usual activities) AND/OR
      • b. Bothersome epigastric burning (ie. severe enough to impact on usual activities)
    • 2. No evidence of organic, systemic, or metabolic disease that is likely to explain the symptoms on routine investigations (including at upper endoscopy).


    Supportive remarks:
    - Pain may be induced by ingestion of a meal, relieved by ingestion of a meal, or may occur while fasting
    - Postprandial epigastric bloating, belching, and nausea can also be present
    - Persistent vomiting likely suggests another disorder

  • IBS is a functional bowel disorder in which recurrent abdominal pain is associated with defecation or a change in bowel habits. Disordered bowel habits are typically present (ie. constipation, diarrhoea, or a mix of constipation and diarrhoea), as are symptoms of abdominal bloating/distention. In contrast to the former Rome III criteria, the term discomfort has been eliminated from the current definition because not all languages have a word for “discomfort,” it has different meanings in different languages, and the term is ambiguous to patients.

    Diagnostic criteria of Irritable Bowel Syndrome29

    Recurrent abdominal pain, on average, at least 1 day per week in the last 3 months associated with two or more of the following criteria:

    •    a Related to defecation
    •    b. Associated with a change in frequency of stool
    •    c. Associated with a change in form (appearance) of stool


    The criteria have to occur for the last 3 months with symptom onset at least 6 months before diagnosis.

    Diagnostic criteria for IBS subtypes:

    Predominant bowel habits are based on stool form on days with at least one abnormal bowel movement.*

    • - IBS with predominant constipation (IBS-C):
      • More than one fourth (25%) of bowel movements with Bristol stool form types 1 or 2 and less than one-fourth (25%) of bowel movements with Bristol stool form types 6 or 7.
      • Alternative for epidemiology or clinical practice: Patient reports that abnormal bowel movements are usually constipation (like type 1 or 2 in the Bristol Stool Form Scale, BSFS).
    • - IBS with predominant diarrhoea (IBS-D):
      • More than one fourth (25%) of bowel movements with Bristol stool form types 6 or 7 and less than one-fourth (25%) of bowel movements with Bristol stool form types 1 or 2.
      • Alternative for epidemiology or clinical practice: Patient reports that abnormal bowel movements are usually diarrhoea (like type 6 or 7 in the BSFS).
    • - IBS with mixed bowel habits (IBS-M):
      • More than one fourth (25%) of bowel movements with Bristol stool form types 1 or 2 and more than one-fourth (25%) of bowel movements with Bristol stool form types 6 or 7.
      • Alternative for epidemiology or clinical practice: Patient reports that abnormal bowel movements are usually both constipation and diarrhoea (more than one-fourth of all the abnormal bowel movements were constipation and more than one-fourth were diarrhoea, using BSFS).
    • - IBS unclassified (IBS-U):
      • Patients who meet diagnostic criteria for IBS but whose bowel habits cannot be accurately categorised into 1 of the 3 groups above should be categorized as having IBS unclassified.
      • For clinical trials, subtyping based on at least 2 weeks of daily diary data is recommended, using the “25% rule.”


    *IBS subtypes related to bowel habit abnormalities (IBSC, IBS-D, and IBS-M) can only be confidently established when the patient is evaluated without medications used to treat bowel habit abnormalities.

    By definition, no mechanical, biochemical or overt inflammatory condition explains the symptoms observed in FGIDs. Therefore a ‘diagnosis of exclusion’ is necessary by elimination of any organic reasons. This process can be very laborious and costly, since it requires multiple tests1.

Diagnosis of exclusion is often the consequence of the uncertainty created by overlapping symptoms, pressure from certain patients ‘to rule out anything bad‘, or the physician’s fear of making a mistake. It is therefore very helpful to know the ‘warning signs and symptoms‘ that may point to an organic cause.

These warning symptoms are:

- Age over 50 at the onset of symptoms
- Hematochezia (passage of blood into the stool)
- Severe and persistent diarrhoea
- Significant, unexplained weight loss
- Fever
- Family history of certain digestive diseases (inflammatory bowel disease, celiac disease, colon or rectal cancer)

FGIDs - Malfunctions, mechanisms, and symptoms

Unfortunately the various symptoms of FGIDs have multiple and very diverse causes. These disorders can be caused by disturbed gut-brain interactions, charaterised by altered function of the CNS or enterie nervous system. Several malfunctions in the gastrointestinal tract may result, leading to IBS and FD. These malfunctions often occur in combination and result in the typical disorders.34

HCP-gastric-diagram
  • In healthy subjects, strong emotional or environmental stress can lead to increased motility in the esophagus, stomach, small intestine and colon. FGIDs, however, are characterised by an even greater motility response to stressors (psychological or physiological) when compared to normal subjects.23 These responses are partially correlated with bowel symptoms, particularly vomiting, diarrhoea and constipation, but are not sufficient to explain reports of chronic or recurrent abdominal pain.

  • Slow gastrointestinal transport often causes bloating, ascending pressure and feelings of fullness.19

  • Visceral hypersensitivity helps explain the poor association of pain with GI motility in many of the FGIDs.23 These patients have a lower pain threshold of the bowel (visceral hyperalgesia) or they have increased sensitivity even to normal intestinal function (allodynia).

    Visceral hypersensitivity may be amplified in patients with FGIDs, a process called sensitisation or stimulus hyperalgesia. Hypersensitivity and sensitisation may occur through altered receptor sensitivity at the gut mucosa and myenteric plexus, which may be caused by mucosal inflammation, degranulation of mast cells close to enteric nerves or increased serotonin activity.

  • Excessive gas formation can result in flatulence and feeling of bloating and discomfort. This may occur when patients eat foods that are difficult to digest, e.g. cabbage or onions. Gas formation can also be the result of disturbed gastrointestinal function, e.g. decreased muscle movement. Feeling of fullness, heaviness and distention may ensue.

  • Only a few years ago it was recognised that about 50% of patients with IBS have an increased number of activated mucosal inflammatory cells.23 This information appears to be related to other clinical observations: About one third of patients with IBS or dyspepsia describe that their symptoms began after an acute enteric infection. Likewise, up to 25% of patients presenting with an acute enteric infection will go on to develop IBS-like or dyspeptic symptoms.23 The mucosa of these individuals typically shows an increase of inflammatory cells and cytokine expression, as well as lower levels of anti-inflammatory interleukin 10 (IL-10). In this context, altered gut microbiota might also play a role.