Sandbox MWH

Irritable Bowel Syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Muhammad Waleed Haider, M.D.[2]

Synonyms and Keywords: Spastic colon, functional bowel disorder, IBS

Historical Perspective

Irritable Bowel syndrome (IBS) was first mentioned in the Rocky Mountain Medical Journal in 1950. IBS was described as a psychosomatic disorder, not explained by any biochemical or structural abnormalities. Apley and Nash conducted a famous study on 1000 children in Bristol, United Kingdom and were the first to describe recurrent abdominal pain (RAP) as the predominant feature of IBS. In 1978, the first diagnostic criteria i.e. the Manning criteria was described. It did not specify any required duration for the symptoms of IBS. The subsequent criteria saw a reduction in the required duration of symptoms to facilitate early diagnosis and treatment. In Rome in 1995, an international group of gastroenterologist defined the diagnostic criteria for IBS and this was published in 1999 under the title of the Rome II criteria. This criteria underwent modification and was described as the Rome III criteria. Since June 2016, the criteria being followed is the Rome IV criteria.

Discovery

• In 1950, the concept of irritable bowel syndrome (IBS) was mentioned for the first time without the recognition of any particular etiology, in the Rocky Mountain Medical Journal.
• IBS was described as a psychosomatic disorder, not explained by any biochemical or structural abnormalities.
• In 1958, Apley and Nash conducted a study on 1000 children in Bristol, United Kingdom and were the first to describe Recurrent abdominal pain (RAP), as the predominant feature of IBS.
• Recurrent abdominal pain was defined as pain in the abdomen occurring over a duration of at least 3 months, with the severity enough to cause significant impairment of function.
  

Classificatiion

Irritable bowel syndrome (IBS) may be classified according to Rome IV criteria into 4 sub-types based on predominant type of bowel habits:

• IBS with predominant constipation
• IBS with predominant diarrhea
• IBS with mixed bowel habits:
  • Alternating patterns of stool passage which is not in conjuncture with the normal bowel movements.
• IBS unclassified:
  • Patients who meet the diagnostic criteria for IBS but whose bowel habits do not fit into any of the above subtypes.

• Post infectious IBS (PI-IBS):
  • Post-infectious IBS is an additional sub-type that is acute in onset and occurs subsequent to an infectious illness of the gastrointestinal tract. Post-infectious IBS is characterized by two or more of the following:
    • Vomiting
    • Fever
    • Positive stool culture
    • Diarrhea

Subtype	Hard or Lumpy Stools	Soft (Mushy) or Watery Stools
IBS with Constipation	≥ 25 percent	≤ 25 percent
IBS with Diarrhea	≤ 25 percent	≥ 25 percent
Mixed IBS	≥ 25 percent	≥ 25 percent
Unsubtyped IBS	Insufficient abnormality of stool consistency to meet criteria for IBS with constipation, diarrhea or mixed sub types

Pathophysiology

Pathogenesis

IBS occurs as a result of an interplay between four main factors:

CNS dysregulation and psychosocial factors

Intrinsic gastrointestinal factors: • Motor abnormalities • Visceral hypersensitivity • Immune activation and mucosal inflammation • Altered gut microbiota • Abnormal serotonin pathways

Irritable Bowel Syndrome

Genetic factors: • Twin concordance • Familial aggregation • Single nucleotide polymorphisms(SNPs) • TNF polymorphism

Environmental factors: •Diet •Infections

Diet

• Fermentable oligosaccharides, monosaccharides, disaccharides, and polyols (FODMAPs) are present in stone fruits, artificial sweeteners, lactose-containing foods, and legumes. Changes in diet such as increased amounts (FODMAPs) can alter gut microflora.
• Fermentation and osmotic effects of FODMAPs produce abdominal discomfort and diarrhea in IBS.
• FODMAPs yield carbon dioxide, methane, and hydrogen that are responsible for bloating.
• Osmotically active carbohydrate by products lead to diarrhea by enhancing intestinal contractions and precipitating fluid secretion.

Infection

• Infectious gastroenetritis triggers micro inflammation and up to one third of irritable bowel syndorme cases follow acute gastroenteritis.
• Micro inflammation of the gut causes activation of the lymphocytes, mast cells and pro inflammatory cytokines that stimulate the enteric nervous system and lead to abnormal visceral and motor responses within the gastrointestinal tract.

Intrinsic gastrointestinal factors[edit | edit source]

• Motor abnormalities:
  • IBS is referred to as ‘spastic colon’ due to changes in colonic motor function.
  • Manometry recordings from the transverse, descending and sigmoid colon have shown that IBS leads to altered colonic and small intestinal tumor function, such as increased frequency and irregularity of luminal contractions.
  • Motor changes lead to symptoms of diarrhea and constipation.
    • Diarrhea-prone IBS patients have increased responses to ingestion, CRH (corticotropin releasing hormone), CCK (cholecystokinin), which increase the peak amplitude of high-amplitude propagating contractions (HAPCs) and lead to abdominal discomfort with accelerated transit through the colon.
    • Constipation-prone IBS patients show fewer high-amplitude propagating contraction (HAPCs) as compared to diarrhea prone IBS patients, delayed transit through the colon and decreased motility.

Visceral hypersensitivity:

• IBS is associated with a decreased threshold for perception of visceral stimuli (i.e. visceral hypersensitivity)
• Rectal distension produces painful and non-painful sensations at lower volumes in IBS patients as compared to healthy controls, suggesting the presence of afferent pathway disturbances in visceral innervation.
• Visceral hypersensitivity contributes to IBS by involving the following:
  • Spinal hyperexcitability
    • Secondary to activation of neurotransmitters such as:
    • NDMA receptor
    • Nitric oxide
  • Activation of specific gastrointestinal mediators that lead to afferent nerve fiber sensitization:
    • Kinins
    • Serotonin
  • Central (brainstem and sortical) modulation with increased activation of anterior cingulate cortex, thalamus and insula.
    • These structures are involved in processing of pain.
    • Cortical and brainstem modulation translate into long term hypersensitivity due to neuroplasticity.
    • Semi permanent changes(seen on functional MRI and PET scan) in the neural response to visceral stimulation contribute to visceral hypersensitivity.
  • Recruitment of peripheral silent nocireceptors cause increased end organ sensitivity due to
    • Hormonal activation ( increased serotonin affects gastrointestinal and visceral pain perception)
    • Immune activation(recruitment of inflammatory mediators)

• IBS in patients with history of inflammatory bowel disease, celiac disease or microscopic colitis points towards the fact that immune activation and local gastrointestinal mucosal inflammation play an important role in its pathogenesis.
• IBS patients have high mucosal counts of lymphocytes (T cells, B cells), mast cells and immune mediators such as prostanoids, proteases, cytokines and histamines.

Gross Pathology

• On gross pathology, the GI tract appears normal in IBS.

Microscopic Pathology

Microscopic changes that may be found in IBS patients are as follows:

Location	Layer of Intestine involved	Mast Cells	T Lymphocytes	Enterochromaffin Cells
Rectum	Mucosa	+++/-	+/-	+/-
Terminal Ileum	Mucosa	-	++	-
Cecum	Mucosa	++	-	-
Colon	Muscularis Externa	+/-	-	-
Jejunum	Myenteric Plexus	++	-	-