Irritable Bowel Syndrome

Epidemiology and Pathophysiology

Epidemiology

• The onset of symptoms usually begins in adolescence and young adulthood. Approximately 50% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship report symptoms before the age of 35.
• 60%–70% of cases are women.
• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency in North America is 10%–15%.

Pathophysiology

Although no specific organic cause has been identified, there are several possible pathogenic mechanisms.

• Abnormal motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility:
  • ↑ Frequency of luminal contractions in the intestines
  • Irregularity of luminal contractions
  • Slow transit → irritable bowel syndrome (IBS) with constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
  • ↑ Motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology response to cholecystokinin Cholecystokinin A peptide, of about 33 amino acids, secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. Gastrointestinal Secretions and meals → IBS with diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
• Visceral hyperalgesia Hyperalgesia An increased sensation of pain or discomfort produced by minimally noxious stimuli due to damage to soft tissue containing nociceptors or injury to a peripheral nerve. Pain: Types and Pathways:
  • Hypothesized to be due to ↑ receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors stimulation in the gut wall
  • ↑ Sensitivity to abdominal and rectal distension 
  • ↑ Sensitivity to bloating Bloating Constipation and gas
• Intestinal inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation:
  • ↑ Lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes: Histology and mast cells Mast cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Innate Immunity: Phagocytes and Antigen Presentation have been noted in the bowel → possible ↑ release of mediators that stimulate the enteric nervous system Enteric nervous system Two ganglionated neural plexuses in the gut wall which form one of the three major divisions of the autonomic nervous system. The enteric nervous system innervates the gastrointestinal tract, the pancreas, and the gallbladder. It contains sensory neurons, interneurons, and motor neurons. Thus the circuitry can autonomously sense the tension and the chemical environment in the gut and regulate blood vessel tone, motility, secretions, and fluid transport. The system is itself governed by the central nervous system and receives both parasympathetic and sympathetic innervation. Autonomic Nervous System: Anatomy
• Post-infectious changes:
  • ↑ T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions and enteroendocrine cells Enteroendocrine cells Cells found throughout the lining of the gastrointestinal tract that contain and secrete regulatory peptide hormones and/or biogenic amines. Gastrointestinal Secretions → ↑ serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS levels → ↑ gastrointestinal (GI) motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility and sensitivity
  • Antibiotic use may also play a role.
• Psychosocial abnormalities:
  •  > 50% of IBS patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have underlying depression, anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder, or somatization Somatization Somatic Symptom Disorder disorders. 
  • Stress → may ↑ corticotropin-releasing factor activity (mediator of the stress response) → ↑ abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and colonic motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility → ↑ IBS symptoms
• Other factors that are being investigated:
  • Altered fecal flora or small intestinal bacterial overgrowth Bacterial overgrowth Lactose Intolerance
  • Food allergies Allergies A medical specialty concerned with the hypersensitivity of the individual to foreign substances and protection from the resultant infection or disorder. Selective IgA Deficiency, malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion, and sensitivity
  • Genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics

Clinical Presentation

Classification

Irritable bowel syndrome is classified based on the clinical presentation.

• IBS with predominant diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea (IBS-D):
  • Loose or watery stools 
  • Frequent bowel movements (> 3/day)
  • Fecal urgency +/- incontinence
• IBS with predominant constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation (IBS-C):
  • Hard or lumpy stools 
  • Infrequent bowel movements (< 3/week) 
  • Straining during defecation Defecation The normal process of elimination of fecal material from the rectum. Gastrointestinal Motility 
• IBS with mixed bowel habits (IBS-M): presents with both diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea and constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
• Unclassified IBS: insufficient abnormality in the stool consistency Consistency Dermatologic Examination or frequency to meet criteria for the other types

Other signs and symptoms

• Chronic abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Intermittent, crampy, and frequently in the lower abdomen 
  • Associated with altered bowel habits
  • May improve or worsen with defecation Defecation The normal process of elimination of fecal material from the rectum. Gastrointestinal Motility
  • Abdominal tenderness is commonly present in the lower abdomen.
• Abdominal distension or bloating Bloating Constipation
• Mucousy stools
• Extraintestinal symptoms:
  • Somatic symptoms Somatic symptoms Major Depressive Disorder (e.g. generalized pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia)
  • Dyspareunia Dyspareunia Recurrent genital pain occurring during, before, or after sexual intercourse in either the male or the female. Primary Ovarian Insufficiency
  • Increased urinary frequency and urgency
• Alarm features that suggest an alternative diagnosis and warrant further investigations:
  • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery or anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
  • Nocturnal diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
  • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types
  • Severe constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation or diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
  • Progressive symptoms
  • Acute onset of disease, or onset in older patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship 

Diagnosis

Criteria for diagnosis

Irritable bowel syndrome is a diagnosis of exclusion, but the Rome IV criteria Rome Iv Criteria Elimination Disorders help provide a standardized diagnosis:

• Recurrent abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways that lasts at least 1 day per week during the previous 3 months
• Onset of abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways is ≥ 6 months prior to diagnosis.
• Is associated with ≥ 2 of the following:
  • Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways related to defecation Defecation The normal process of elimination of fecal material from the rectum. Gastrointestinal Motility
  • Change in stool frequency
  • Change in stool appearance or form

Tests to rule out organic disease

Work-up will be guided by the patient’s clinical presentation.

• Laboratory tests:
  • Complete blood count → screen for iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements deficiency anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types → malignancy Malignancy Hemothorax, celiac disease Celiac disease Celiac disease (also known as celiac sprue or gluten enteropathy) is an autoimmune reaction to gliadin, which is a component of gluten. Celiac disease is closely associated with HLA-DQ2 and HLA-DQ8. The immune response is localized to the proximal small intestine and causes the characteristic histologic findings of villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Celiac Disease
  • Fecal calprotectin or fecal lactoferrin → screen for inflammatory bowel disease (IBD)
  • Immunoglobulin A ( IgA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions) tissue transglutaminase → screen for celiac disease Celiac disease Celiac disease (also known as celiac sprue or gluten enteropathy) is an autoimmune reaction to gliadin, which is a component of gluten. Celiac disease is closely associated with HLA-DQ2 and HLA-DQ8. The immune response is localized to the proximal small intestine and causes the characteristic histologic findings of villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Celiac Disease
  • Thyroid-stimulating hormone Thyroid-stimulating hormone A glycoprotein hormone secreted by the adenohypophysis. Thyrotropin stimulates thyroid gland by increasing the iodide transport, synthesis and release of thyroid hormones (thyroxine and triiodothyronine). Thyroid Hormones → hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism or hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism
  • Stool test for Giardia Giardia A genus of flagellate intestinal eukaryotes parasitic in various vertebrates, including humans. Characteristics include the presence of four pairs of flagella arising from a complicated system of axonemes and cysts that are ellipsoidal to ovoidal in shape. Nitroimidazoles
• Abdominal radiography:
  • Performed in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
  • Rules out stool impaction
  • Determines the severity of constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
• Colonoscopy Colonoscopy Endoscopic examination, therapy or surgery of the luminal surface of the colon. Colorectal Cancer Screening with biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma:
  • All patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship should have age-appropriate cancer screening Screening Preoperative Care. 
  • Use is based on the patient’s presentation to exclude malignancy Malignancy Hemothorax, IBD, and microscopic colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis.

Management

General measures

• Reassurance Reassurance Clinician–Patient Relationship, education, and support
• Involve the patient in the treatment process.
• Encourage physical activity.

Dietary modifications

• Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship can follow a normal diet.
• May exclude gas-producing foods (e.g., beans, brussel sprouts)
• Low-FODMAP (fermentable oligosaccharides Oligosaccharides Carbohydrates consisting of between two (disaccharides) and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. Basics of Carbohydrates, disaccharides Disaccharides Oligosaccharides containing two monosaccharide units linked by a glycosidic bond. Basics of Carbohydrates, monosaccharides Monosaccharides Single chain carbohydrates that are the most basic units of carbohydrates. They are typically colorless crystalline substances with a sweet taste and have the same general formula CNH2NON. Basics of Carbohydrates, and polyols) diet
• Dietary or supplemental fiber
• Avoid/restrict alcohol and caffeine Caffeine A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine’s most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. Stimulants.
• Maintain proper hydration.

Pharmacologic agents, based on symptoms

IBS-D:

• Loperamide Loperamide One of the long-acting synthetic antidiarrheals; it is not significantly absorbed from the gut, and has no effect on the adrenergic system or central nervous system, but may antagonize histamine and interfere with acetylcholine release locally. Antidiarrheal Drugs ( antidiarrheal Antidiarrheal Antidiarrheal agents include several drug classes, including opioid agonists, somatostatin analogues, adsorbents, and bile acid sequestrants. These medications mainly work through antimotility and/or antisecretory effects. Antidiarrheal Drugs):
  • Reasonable 1st-line treatment
  • Acts on the μ-opioid receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors ( opioid Opioid Compounds with activity like opiate alkaloids, acting at opioid receptors. Properties include induction of analgesia or narcosis. Constipation receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors agonist):
  • ↑ Intestinal transit time, ↓ peristalsis Peristalsis A movement, caused by sequential muscle contraction, that pushes the contents of the intestines or other tubular organs in one direction. Gastrointestinal Motility and secretion Secretion Coagulation Studies
• Bile acid sequestrants Bile Acid Sequestrants Antidiarrheal Drugs:
  • Options: cholestyramine Cholestyramine A strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium cl(-) anion. Lipid Control Drugs, colesevelam Colesevelam An allylamine derivative that binds bile acids in the intestine and is used as an anticholesteremic agent in the treatment of hypercholesterolemia and hyperlipidemias. Lipid Control Drugs IBS-D may have idiopathic Idiopathic Dermatomyositis bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy acid malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion (I-BAM) contributing to symptoms. 
• 5-Hydroxytryptamine 5-hydroxytryptamine A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS 3 (5-HT3) receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors antagonists:
  • Options: ondansetron Ondansetron A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and has reported anxiolytic and neuroleptic properties. Antiemetics, alosetron 
  • Slow colonic transit and decrease secretion Secretion Coagulation Studies
• Eluxadoline:
  • Mixed opioid Opioid Compounds with activity like opiate alkaloids, acting at opioid receptors. Properties include induction of analgesia or narcosis. Constipation receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors drug: 
  • 2nd-line option for severe IBS-D (not responding to initial treatments
• Rifaximin Rifaximin A synthetic rifamycin derivative and anti-bacterial agent that is used for the treatment of gastroenteritis caused by Escherichia coli infections. It may also be used in the treatment of hepatic encephalopathy. Hepatic Encephalopathy:
  • Oral, nonabsorbable antibiotic (active against gram-negative and gram-positive Gram-Positive Penicillins aerobic and anaerobic bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology)
  • Helps with diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea and bloating Bloating Constipation

IBS-C:

• Polyethylene glycol Polyethylene Glycol Laxatives (osmotic laxative Laxative Agents that produce a soft formed stool, and relax and loosen the bowels, typically used over a protracted period, to relieve constipation. Hypokalemia):
  • 1st-line therapy (over-the-counter) for occasional constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation, though efficacy in relieving IBS-C abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways has not been proven^[15]
  • Long-chain polymer of ethylene oxide
• Lubiprostone ( chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes channel activator):
  • 2nd-line treatment
  • ↑ Chloride-rich intestinal fluid secretion Secretion Coagulation Studies
• Linaclotide (guanylate cyclase-C [GC-C] agonist):
  • 2nd-line treatment
  • Nonabsorbed 14-amino acid peptide → stimulates the GC-C receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors on enterocytes → intestinal chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes and bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes secretion Secretion Coagulation Studies
• Plecanatide (guanylate cyclase-C [GC-C] agonist):
  • 2nd-line treatment
  • 16-amino acid peptide → stimulates the GC-C receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors on enterocytes → fluid and electrolyte secretion Secretion Coagulation Studies
• Tegaserod ( 5-hydroxytryptamine 5-hydroxytryptamine A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS 4 (5-HT4) receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors partial agonist):
  • Stimulates GI motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility and ↑ fluid in the intestine
  • Was previously withdrawn from the market, but now with limited use (safety in men or women > 65 not established; ↑ cardiovascular event)
• Tenapanor:
  • Other therapy options have failed
  • ↓ Sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption, ↑ water secretion Secretion Coagulation Studies 

Abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and bloating Bloating Constipation:

• Peppermint oil Peppermint Oil Antispasmodics:
  • ↑ Smooth muscle relaxation (blocks calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channels Channels The Cell: Cell Membrane)
  • ↓ Abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
• Antispasmodic agents Antispasmodic agents Antispasmodics are a group of medications used to reduce excessive GI smooth muscle contractility and spasm. These medications may be helpful in those with abdominal pain due to conditions such as irritable bowel syndrome, although their efficacy is controversial. Antispasmodics:
  • Options: hyoscyamine Hyoscyamine The 3(s)-endo isomer of atropine. Anticholinergic Drugs, dicyclomine Dicyclomine A muscarinic antagonist used as an antispasmodic and in urinary incontinence. It has little effect on glandular secretion or the cardiovascular system. It does have some local anesthetic properties and is used in gastrointestinal, biliary, and urinary tract spasms. Anticholinergic Drugs 
  • ↓ Smooth muscle contraction Smooth muscle contraction Smooth muscle is primarily found in the walls of hollow structures and some visceral organs, including the walls of the vasculature, GI, respiratory, and genitourinary tracts. Smooth muscle contracts more slowly and is regulated differently than skeletal muscle. Smooth muscle can be stimulated by nerve impulses, hormones, metabolic factors (like pH, CO2 or O2 levels), its own intrinsic pacemaker ability, or even mechanical stretch. Smooth Muscle Contraction and visceral hypersensitivity
• Tricyclic antidepressants Tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants ( TCAs TCAs Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants):
  • Options: amitriptyline Amitriptyline Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the reuptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antagonize cholinergic and alpha-1 adrenergic responses to bioactive amines. Tricyclic Antidepressants, nortriptyline Nortriptyline A metabolite of amitriptyline that is also used as an antidepressant agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions. Tricyclic Antidepressants 
  • Gut-brain modulators → improve visceral and central pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways by acting on norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS and dopaminergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
• Probiotics:
  • Not given routinely, but ↓ abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • No specific strain or species recommended.

Differential Diagnosis

• Celiac disease Celiac disease Celiac disease (also known as celiac sprue or gluten enteropathy) is an autoimmune reaction to gliadin, which is a component of gluten. Celiac disease is closely associated with HLA-DQ2 and HLA-DQ8. The immune response is localized to the proximal small intestine and causes the characteristic histologic findings of villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Celiac Disease: an immunologically mediated disease resulting in mucosal inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and villous atrophy Villous Atrophy Giardia/Giardiasis in the small bowel Small bowel The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy due to gluten Gluten Prolamins in the endosperm of seeds from the triticeae tribe which includes species of wheat; barley; and rye. Celiac Disease. Symptoms include abdominal bloating Bloating Constipation and foul-smelling diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may also have nutritional deficiencies and weight loss Weight loss Decrease in existing body weight. Bariatric Surgery due to malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion, which is not found in IBS. The diagnosis is established with serologic markers and small bowel Small bowel The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Treatment requires a strict, gluten-free diet.
• Inflammatory bowel disease: includes Crohn’s disease and ulcerative colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis. The disease is characterized by chronic inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the GI tract due to a cell-mediated immune response to the GI mucosa. Symptoms include diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, weight loss Weight loss Decrease in existing body weight. Bariatric Surgery, and extraintestinal manifestations, which help differentiate IBD from IBS. Diagnosis includes imaging, endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) and biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Treatment involves steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors, aminosalicylates, immunomodulators, and biologic agents Biologic Agents Immunosuppressants.
• Microscopic colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis: a chronic inflammatory disease of the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy, which can be categorized as collagenous or lymphocytic colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship tend to be middle-aged. Symptoms include chronic, watery diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, and bloating Bloating Constipation. A colonoscopy Colonoscopy Endoscopic examination, therapy or surgery of the luminal surface of the colon. Colorectal Cancer Screening will appear normal, but inflammatory cells, cryptitis, or a subepithelial Subepithelial Membranoproliferative Glomerulonephritis collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology band will be seen on biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma, differentiating microscopic colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis from IBS. Treatment includes trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation avoidance, glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids, and symptom management.
• Small intestinal bacterial overgrowth Bacterial overgrowth Lactose Intolerance: defined as excessive bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology growing in the small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy, and can result due to alteration in the intestinal anatomy or motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility. Symptoms can range from mildly symptomatic to chronic diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, weight loss Weight loss Decrease in existing body weight. Bariatric Surgery, and malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion. Bacterial cultures and breath tests can distinguish this condition from IBS. Treatment includes antibiotics and correction of nutritional deficiencies.
• Lactose intolerance Lactose intolerance Lactose intolerance (LI) describes a constellation of symptoms due to lactase deficiency (LD), the enzyme located in the brush border of the absorptive cells in the small intestine. Lactose is the disaccharide present in milk and requires hydrolysis by lactase to break it down into its 2 absorbable constituents, glucose and galactose. Lactose intolerance typically presents with bloating, abdominal cramping, diarrhea, and flatulence. Lactose Intolerance: an intolerance to lactose-containing foods due to lactase Lactase An enzyme which catalyzes the hydrolysis of lactose to d-galactose and d-glucose. Defects in the enzyme cause lactose intolerance. Digestion and Absorption of Carbohydrates deficiency. Symptoms include crampy abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, bloating Bloating Constipation, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, and diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea. Diagnosis is based on the association with lactose-containing foods and a lactose hydrogen breath test Hydrogen breath test Lactose Intolerance, which will differentiate the condition from IBS. Management includes restriction of dietary lactose and enzyme replacement Enzyme replacement Therapeutic replacement or supplementation of defective or missing enzymes to alleviate the effects of enzyme deficiency (e.g., glucosylceramidase replacement for gaucher disease). Severe Combined Immunodeficiency (SCID).
• Giardiasis Giardiasis An infection of the small intestine caused by the flagellated protozoan giardia. It is spread via contaminated food and water and by direct person-to-person contact. Giardia/Giardiasis: an intestinal infection due to Giardia Giardia A genus of flagellate intestinal eukaryotes parasitic in various vertebrates, including humans. Characteristics include the presence of four pairs of flagella arising from a complicated system of axonemes and cysts that are ellipsoidal to ovoidal in shape. Nitroimidazoles duodenalis. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may be asymptomatic or have watery, foul-smelling diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea; abdominal cramping Abdominal cramping Norovirus; and distension. Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery and evidence of malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion may be present and will differentiate this condition from IBS. Stool studies for Giardia Giardia A genus of flagellate intestinal eukaryotes parasitic in various vertebrates, including humans. Characteristics include the presence of four pairs of flagella arising from a complicated system of axonemes and cysts that are ellipsoidal to ovoidal in shape. Nitroimidazoles will establish the diagnosis, and treatment includes metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess, tinidazole Tinidazole A nitroimidazole alkylating agent that is used as an antitrichomonal agent against trichomonas vaginalis; entamoeba histolytica; and giardia lamblia infections. It also acts as an antibacterial agent for the treatment of bacterial vaginosis and anaerobic bacterial infections. Nitroimidazoles, or nitazoxanide.