📚 Gastroenterology (Git) — L5: Functional Gi Disorders & Ibs

📚 Lecture Overview

This lecture covers Functional Gastrointestinal Disorders (FGIDs), recently renamed Disorders of Gut-Brain Interaction (DGBI), with a primary focus on Functional Dyspepsia (FD) and Irritable Bowel Syndrome (IBS). Understanding these conditions is crucial because they are among the most prevalent disorders encountered in gastroenterology, heavily influenced by the bidirectional brain-gut axis and requiring symptom-based diagnostic criteria like the Rome IV criteria.

🎯 Key Concepts & Definitions

• Disorders of Gut-Brain Interaction (DGBI): Formerly known as FGIDs, these are conditions classified by GI symptoms related to motility disturbances, visceral hypersensitivity, altered mucosal/immune function, gut microbiota, and central nervous system processing.
• Brain-Gut Axis: A bidirectional communication network linking the emotional and cognitive centers of the brain with peripheral intestinal functions, regulated via neural, hormonal, and immunological pathways.
• Functional Dyspepsia (FD): The presence of symptoms originating from the gastroduodenal region in the absence of any organic, systemic, or metabolic disease, divided into Postprandial Distress Syndrome (PDS) and Epigastric Pain Syndrome (EPS).
• Irritable Bowel Syndrome (IBS): A chronic, relapsing, and remitting functional bowel disorder characterized by abdominal pain linked to changes in bowel habits, classified into subtypes based on stool consistency (IBS-C, IBS-D, IBS-M, IBS-U).
• Dysbiosis: An alteration in the composition and function of the gut microbiota, heavily implicated in the pathogenesis of IBS and DGBIs.
• Visceral Hypersensitivity: Increased sensitivity of visceral afferent nerve fibers in the gut wall triggered by normal physiological events like bowel distention or bloating.

📖 Main Content

1. Disorders of Gut-Brain Interaction & The Brain-Gut Axis

• Definition & Scope: FGIDs are diagnosed using symptom-based criteria (Rome IV classification system), encompassing 33 adult and 20 pediatric disorders.
• The Brain-Gut Axis Mechanisms:
• Direct physical connections exist between the central nervous system and nerve plexuses in visceral muscles.
• Neurotransmitters transmit signals regarding thoughts, feelings, and pain regulation.
• Negative emotions (fear, anxiety, anger, stress) can delay gastric emptying, alter transit times, and induce diarrhea or defecation.
• Psychosocial distress activates the hypothalamic-pituitary-adrenal (HPA) axis, elevating corticotropin-releasing hormone (CRH) and cortisol.

2. Functional Dyspepsia (FD)

• Subtypes:
• Postprandial Distress Syndrome (PDS): Characterized by postprandial fullness, early satiety, and bloating.
• Epigastric Pain Syndrome (EPS): Characterized by focal burning or pain localized to the epigastric region unrelated to meals or biliary causes.
• Risk Factors: Female sex, smoking, NSAID use, H. pylori infection, coexisting DGBIs (like IBS), and psychological comorbidity.
• Diagnostic Workup:
• Exclude alarm symptoms (red flags).
• Apply Rome IV criteria.
• Full blood count for patients aged $≥ 55$ years.
• Non-invasive 'test and treat' strategy for Helicobacter pylori.

3. Irritable Bowel Syndrome (IBS) Pathogenesis

• Multifactorial Etiology:
• Genetic predisposition: Positive family history in 33% of patients.
• Intestinal hypersensitivity: Afferent nerve fiber overstimulation.
• Altered intestinal motility: Accelerated transit in IBS-D; delayed transit in IBS-C. Driven partly by serotonin (5-HT) dysregulation.
• Enteric infection/inflammation: Post-infectious IBS involving residual mast cells and immunocytes.
• Food intolerance: Gluten sensitivity altering intestinal permeability.
• Altered gut microbiota: Decreased beneficial Lactobacilli and Bifidobacteria.

4. IBS Diagnosis and "Red Flags"

• Mandatory screening for warning symptoms prior to labeling a disorder as functional:
• Change in bowel habit to looser/more frequent stools persisting $> 6$ weeks in individuals aged $> 60$.
• Rectal or abdominal masses, and rectal bleeding.
• Anemia or raised inflammatory markers.
• Unintentional and unexplained weight loss.
• Age over 50 without prior colon cancer screening.
• Nocturnal passage of stools.
• Family history of IBD or colorectal cancer.

5. Management and Treatment of IBS

• Non-pharmacological: Regular meals, adequate fluids (at least 8 glasses/day), limiting caffeine ($≤ 3$ cups/day), managing fiber, reducing resistant starch, and avoiding artificial sweeteners like Sorbitol in IBS-D.
• Pharmacological Subtypes & Agents:
• Antidiarrheals: Loperamide (reduces frequency/urgency, does not relieve pain) and Cholestyramine (for bile acid malabsorption in IBS-D).
• Antispasmodics (Anticholinergics): Mebeverine, Hyoscyamine butylbromide, and peppermint oil; block acetylcholine to relieve abdominal pain and smooth muscle spasms.
• Serotonin Modulators: Alosetron (5-HT3 antagonist for severe IBS-D in women; risk of ischemic colitis), Prucalopride (5-HT4 agonist for constipation), Linaclotide (GC-C agonist), and Lubiprostone (chloride channel activator).
• Antibiotics: Rifaximin (nonabsorbable antibiotic approved for IBS-D at 550 mg TID for 14 days).
• Probiotics: Modify mucosal immunity and normalize gut flora (Bifidobacterium, Lactobacillus, VSL#3, E. coli Nissle 1917).
• Fecal Microbiota Transplantation (FMT): Considered for refractory IBS.
• Psychological Therapies: Tricyclic Antidepressants (TCAs) (Trimipramine, Imipramine, Amitriptyline) for pain and motility modification; SSRIs for constipation acceleration; Benzodiazepines for prominent anxiety.

📊 Visual Learning

💡 Important Points to Remember

• Rome IV Criteria form the international diagnostic backbone for functional gastrointestinal disorders (FGIDs/DGBIs).
• Functional Dyspepsia is split strictly into PDS (postprandial fullness, early satiety) and EPS (epigastric pain/burning).
• Serotonin (5-HT) levels are reduced in IBS-C and raised in IBS-D.
• Alosetron is restricted strictly to women with severe IBS-D due to the dangerous side effect of ischemic colitis.
• Rifaximin is a nonabsorbable antibiotic given at 550 mg TID for 14 days for IBS-D.
• Loperamide improves stool consistency and urgency in IBS-D/IBS-M, but does not relieve pain or bloating.
• Red flag symptoms (e.g., nocturnal stools, rectal bleeding, unexplained weight loss, age $> 50$ without screening) mandate immediate structural workup to rule out IBD or cancer.
• H. pylori test and treat is the preferred strategy for management of dyspepsia.
• Hyoscyamine works by blocking acetylcholine action at parasympathetic sites, providing powerful antispasmodic effects.
• Tricyclic antidepressants (TCAs) slow intestinal transit and relieve abdominal pain, making them ideal for IBS-D, whereas SSRIs accelerate transit and suit IBS-C.

⚠️ Common Exam Questions

• Classic MCQ Trap: Examiners will state that a drug like Loperamide or Alosetron cures all IBS symptoms including global pain and bloating. Correction: Loperamide does not relieve pain or bloating; Alosetron is reserved exclusively for severe female IBS-D cases due to ischemic colitis risks.
• Diagnostic Confusion: Distinguishing the pain location and triggers. FD pain is upper abdominal (fasting or food-related, not related to defecation), whereas IBS pain directly correlates with altered bowel habits and defecation.
• Red Flag Overlook: Questions testing whether a patient presenting with weight loss and nocturnal diarrhea can be diagnosed with IBS. Answer: No, red flags require exclusion of organic pathology first.

📝 Quick Review Checklist

I can explain the brain-gut axis and its bidirectional mechanisms
I understand the diagnostic criteria and subtypes of Functional Dyspepsia (PDS vs. EPS)
I can define the core pathogenetic factors contributing to IBS
I know the key red flag symptoms that rule out functional disorders
I can match IBS pharmacological treatments to their appropriate subtypes (e.g., Alosetron, Rifaximin, Linaclotide, Loperamide)