Certificate Course in Gastroenterology & Hepatology

Peptic Ulcer Disease (PUD)

Introduction

Peptic ulcer disease refers to the formation of ulcers in the lining of the stomach or the first part of the small intestine (duodenum), where the mucosal layer is eroded and the lesion penetrates at least through the muscularis mucosa. It results from an imbalance between mucosal defense mechanisms and aggressive luminal factors such as gastric acid and pepsin.

Definitions and Classification

• Peptic ulcer: A mucosal break ≥ 0.5 cm deep that extends through the muscularis mucosae in the stomach or duodenum.

• Gastric ulcer: Occurs in the stomach, most commonly along the lesser curvature.

• Duodenal ulcer: Usually seen in the duodenal bulb (first part), more often anteriorly.

• Erosions: Superficial defects limited to mucosa, unlike ulcers which penetrate deeper.

Epidemiology

• Annual incidence: ∼ 1 case per 1,000 person-years.

• Prevalence in the US: ~6 million annually.

• Duodenal ulcers occur 10–20 years earlier than gastric ulcers.

• Median age of diagnosis: 18–30 years.

• Sex distribution: Equal in males and females.

Etiology and Risk Factors

• Main causes:

  • Helicobacter pylori infection (duodenal > gastric ulcers).

  • Chronic NSAID use (impairs mucosal defense).

• Shared risk factors with GERD/gastritis: Smoking, alcohol, caffeine, steroids, stress.

• Rare causes:

  • Hypersecretory states: Zollinger-Ellison syndrome, systemic mastocytosis.

  • Other drugs: SSRIs, bisphosphonates, chemotherapeutics.

  • Infections: CMV, HSV, EBV.

  • Inflammatory: Crohn's disease, sarcoidosis.

  • Mechanical: foreign bodies, surgery.

Pathophysiology

• Normal physiology: Gastric mucosa secretes HCl, pepsinogen, and mucus. Mucus and bicarbonate protect epithelium.

• Protective factors: Prostaglandins, mucus, bicarbonate, mucosal blood flow.

• Disruption mechanisms:

  • H. pylori damages mucosa by urease (raises pH), cytotoxins (cagA), and immune response.

  • In duodenum, it increases gastrin → more acid → overwhelms bicarbonate.

  • NSAIDs inhibit COX → less prostaglandin → less mucus/blood flow.

  • Hypergastrinemia: seen in ZES → increased H+ output and mucosal injury.

Clinical Presentation

• Asymptomatic: Up to 70% (especially NSAID-induced).

• Symptomatic:

  • Epigastric pain (burning, gnawing).

  • Gastric ulcer pain worsens with food → weight loss.

  • Duodenal ulcer pain relieved with food → weight gain.

  • Nocturnal pain (more common in duodenal ulcer).

  • Nausea, bloating, belching, reflux, anemia.

Diagnosis

• Noninvasive tests:

  • H. pylori detection: Urea breath test, stool antigen test.

• Endoscopy (EGD):

  • Best diagnostic tool.

  • Biopsies essential for gastric ulcers to rule out malignancy.

  • Look for visible ulcers, irregular borders, or ulcerated masses.

• Alarm features for early EGD: Age >60, weight loss, vomiting, anemia, bleeding.

• Special studies: Serum gastrin + secretin test (for ZES), PTH (if hyperparathyroidism suspected).

Differential Diagnosis

• GERD

• Gastric cancer

• Gastritis

• Pancreatitis

• Functional dyspepsia

• Biliary disease

Treatment

• General measures: Stop NSAIDs, avoid alcohol/smoking, stress reduction.

• H. pylori positive:

  • Quadruple therapy: PPI + bismuth + metronidazole + tetracycline.

• H. pylori negative:

  • PPI monotherapy for 4–8 weeks.

• Cytoprotective agents:

  • Sucralfate (mucosal coating, avoid simultaneous PPI).

  • Misoprostol (prostaglandin analog).

• Surgery (if indicated):

  • For refractory ulcers, ongoing NSAID need, or complications.

  • Options: Vagotomy (truncal + pyloroplasty or antrectomy), Billroth I/II, Roux-en-Y reconstruction.

Follow-up

• Indications for repeat EGD:

  • Refractory symptoms

  • Initial gastric ulcer with suspicious features

  • No biopsy during first EGD

  • Ulcer diagnosed on imaging only

• Test for cure: H. pylori eradication confirmed ≥ 4 weeks after therapy.

Complications

• Bleeding ulcer:

  • Posterior duodenal ulcer → gastroduodenal artery.

  • Signs: hematemesis, melena, anemia.

  • Forrest classification guides endoscopic treatment.

• Perforation:

  • Anterior duodenal ulcer most common.

  • Sudden severe pain, rigidity, free air on X-ray.

  • Surgical repair with Graham patch.

• Penetration:

  • Ulcer invades neighboring organs (pancreas, colon, liver).

  • Symptoms vary with organ: eg., copremesis, diarrhea, abscess, hemorrhage.

• Gastric outlet obstruction (GOO):

  • Vomiting, succussion splash, weight loss.

  • Labs: metabolic alkalosis.

  • Management: NG decompression, fluids, surgery/dilation.

• Malignant transformation:

  • More likely in gastric ulcers.

  • Requires biopsy and surveillance.

Subtypes: Stress Ulcers

• Types:

  • Curling ulcer: burns → reduced blood flow.

  • Cushing ulcer: brain injury → vagal stimulation → increased acid.

• Prevention: PPIs or H2 blockers in high-risk ICU patients.

• Risks: Ventilation, coagulopathy, shock, liver disease.

NSAID-Induced Ulcers

• Mechanism: Inhibition of COX → reduced prostaglandins → less mucus, more acid.

• Risk factors: Age >60, H. pylori, steroids, anticoagulants, high-dose NSAIDs.

• Prevention:

  • Use lowest effective dose.

  • Eradicate H. pylori.

  • Add PPI or misoprostol in high-risk patients.

Summary Pearls for Boards

• Duodenal ulcer pain improves with food; gastric ulcer worsens with food.

• H. pylori and NSAIDs are the most common causes.

• Always biopsy gastric ulcers.

• Anterior ulcers tend to perforate; posterior tend to bleed.

• Zollinger-Ellison causes multiple refractory ulcers.

• Eradicate H. pylori and reduce acid to promote healing.

Introduction

Inflammatory Bowel Disease (IBD) refers to two distinct but related chronic autoimmune gastrointestinal disorders: Crohn disease (CD) and ulcerative colitis (UC). Both are characterized by chronic intestinal inflammation resulting from dysregulated immune responses to intestinal flora in genetically predisposed individuals. However, their anatomical involvement, histological features, clinical presentation, and management strategies differ.

Epidemiology

• Crohn Disease:

  • Prevalence: ~1 per 500 individuals.

  • Incidence: ~6 per 100,000 annually.

  • Bimodal age distribution: Peaks at 15–35 and 55–70 years.

  • Equal prevalence in males and females.

  • Higher prevalence among those of Northern European and Ashkenazi Jewish descent.

• Ulcerative Colitis:

  • Affects ~600,000 adults in the US.

  • Peak incidence: 15–35 years; secondary peak > 55 years.

  • Higher prevalence in Whites and Ashkenazi Jewish individuals.

  • No significant sex difference.

Etiology and Risk Factors

• Immune Dysregulation and Dysbiosis form the core pathogenesis in both diseases.

• Crohn Disease:

  • Genetic predisposition: NOD2 gene mutations, HLA-B27.

  • Familial clustering.

  • Tobacco smoking is a major modifiable risk factor.

• Ulcerative Colitis:

  • Genetic link: HLA-B27 association.

  • Risk factors: Prior GI infections, high-fat diet, oral contraceptive use.

  • NSAIDs can worsen disease.

  • Smoking and appendectomy are paradoxically protective.

Pathophysiology

• Crohn Disease:

  • Involves full-thickness (transmural) intestinal inflammation.

  • IL-23/Th17 dysregulation → unrestrained inflammation → ulceration, strictures, fistulas.

  • Aphthous ulcers → fissures → fistulae and abscess formation.

• Ulcerative Colitis:

  • Inflammation begins in the rectum and spreads proximally in a continuous pattern.

  • Limited to mucosa and submucosa.

  • Th2-mediated response with upregulation of cytokines (IL-6, TNF-α).

  • Autoantibodies (pANCA) may be present.

Clinical Features

• Crohn Disease:

  • Chronic intermittent course with acute flares.

  • Abdominal pain (typically RLQ), weight loss, chronic non-bloody diarrhea.

  • Palpable RLQ mass.

  • Malabsorption symptoms, anemia, vitamin deficiencies.

  • Perianal fistulas or abscesses may be the first sign.

• Ulcerative Colitis:

  • Bloody diarrhea with mucus, fecal urgency, tenesmus.

  • Pain in the LLQ.

  • Rectum is always involved.

  • Intermittent flares and remissions.

Extraintestinal Manifestations (Both CD and UC)

• Musculoskeletal: Peripheral arthritis, ankylosing spondylitis, sacroiliitis.

• Skin: Erythema nodosum, pyoderma gangrenosum.

• Eyes: Uveitis, episcleritis, iritis.

• Hepatobiliary: Cholelithiasis (CD), PSC (UC).

• Oral lesions: Aphthous ulcers, pyostomatitis vegetans.

• Renal: Urolithiasis, especially calcium oxalate stones in CD.

Diagnosis

• Initial Approach:

  • Detailed history and physical exam.

  • Identify extraintestinal features.

  • Check for perianal disease (especially in CD).

• Laboratory Evaluation:

  • CBC, CRP, ESR, CMP, B12, folate, iron studies.

  • Stool studies: rule out infections, measure fecal calprotectin/lactoferrin.

  • Serology: ASCA (CD), pANCA (UC).

• Endoscopy:

  • CD: Ileocolonoscopy shows skip lesions, linear ulcers, cobblestone appearance, strictures.

  • UC: Continuous mucosal inflammation starting from rectum, friable mucosa, pseudopolyps.

  • Biopsies are essential for histology.

• Imaging:

  • CD: Cross-sectional enterography (CTE/MRE) preferred.

    • Findings: wall thickening, creeping fat, abscess, fistula.

    • String sign on small bowel follow-through.

  • UC: X-ray/CT for complications like toxic megacolon, perforation.

• Histopathology:

  • CD: Transmural inflammation, noncaseating granulomas, lymphoid aggregates.

  • UC: Mucosal inflammation, crypt abscesses, epithelial dysplasia.

Differential Diagnosis

• Appendicitis

• Celiac disease

• Infectious colitis (C. difficile, TB, CMV)

• Microscopic colitis

• Diverticulitis

• IBS

• Radiation or ischemic colitis

• GI malignancies

Treatment Principles

• Goals: Induce and maintain remission, prevent complications, preserve quality of life.

• Crohn Disease:

  • Induction: Corticosteroids, anti-TNF agents, budesonide (ileal disease).

  • Maintenance: Anti-TNF agents, immunomodulators (azathioprine, methotrexate).

  • Surgery for complications or localized disease (not curative).

• Ulcerative Colitis:

  • Induction: Rectal/oral 5-ASA (mild), corticosteroids, biologics (moderate-severe).

  • Maintenance: 5-ASA, immunomodulators, biologics.

  • Surgery (proctocolectomy with IPAA) is curative.

• Supportive Measures (Both):

  • Nutritional support.

  • Micronutrient supplementation (iron, B12, folate, vit D).

  • Pain control (avoid opioids).

  • Smoking cessation (especially CD).

  • Avoid NSAIDs.

Complications

• Crohn Disease:

  • Fistulas (enterocutaneous, perianal, enteroenteric).

  • Abscesses, strictures, bowel obstruction.

  • Malnutrition, short bowel syndrome.

  • Small bowel cancer.

• Ulcerative Colitis:

  • Toxic megacolon.

  • Colonic perforation.

  • Colorectal cancer (especially pancolitis).

  • Primary sclerosing cholangitis.

Long-Term Management

• Monitoring Disease Activity: Objective markers (CRP, fecal calprotectin, endoscopy).

• Cancer Screening: Colonoscopy every 1–5 years starting 8–10 years after diagnosis (UC, or CD with >30% colonic involvement).

• Osteoporosis Screening: DXA if >3 months cumulative steroid exposure.

• Vaccinations & Preventive Care: As per IBD protocols.

Special Groups

• Pregnancy in IBD:

  • Aim for remission before conception.

  • Most therapies (5-ASA, immunomodulators, biologics) are safe.

  • Avoid methotrexate (teratogenic).

  • Steroids reserved for flares.

• Pediatrics:

  • Growth failure and delayed puberty may occur.

  • Nutritional support and aggressive disease control are vital.
    
    Key Differences Between Crohn’s Disease and Ulcerative Colitis )

    Crohn’s disease and ulcerative colitis, though both forms of inflammatory bowel disease (IBD), differ significantly in their clinical and pathological characteristics. Crohn’s disease can affect any part of the gastrointestinal tract from the mouth to the anus, whereas ulcerative colitis is limited strictly to the colon and always involves the rectum. The pattern of inflammation in Crohn’s disease is discontinuous or “skip lesions,” with affected segments interspersed with normal tissue. In contrast, ulcerative colitis exhibits a continuous spread of inflammation starting at the rectum and extending proximally.

    In terms of tissue involvement, Crohn’s disease causes transmural inflammation, meaning all layers of the intestinal wall are involved. Ulcerative colitis, on the other hand, is restricted to the mucosa and submucosa. Noncaseating granulomas, which are hallmark histological findings, are commonly seen in Crohn’s disease but are absent in ulcerative colitis.

    Fistula formation, strictures, and perianal disease are frequent complications in Crohn’s disease, while they are rare in ulcerative colitis. Smoking worsens the course of Crohn’s disease but is paradoxically protective in ulcerative colitis. Serologically, patients with Crohn’s disease are more likely to have ASCA (anti-Saccharomyces cerevisiae antibodies), whereas those with ulcerative colitis often have positive p-ANCA (perinuclear anti-neutrophil cytoplasmic antibodies).

    From a surgical perspective, ulcerative colitis can be cured with colectomy, while surgery in Crohn’s disease is often required for complications but is not curative, since the disease can recur in other parts of the GI tract.
    
    Summary Pearls

    • Crohn skips, UC creeps.

    • CD affects full thickness; UC is mucosal.

    • Cobblestone + creeping fat + granulomas = CD.

    • Pseudopolyps, lead pipe colon = UC.

    • Steroids for flares only — maintenance needs immunomodulators or biologics.

    • Surveillance colonoscopy is key in long-term care.

Introduction: What is Malabsorption?

Malabsorption is a condition in which the small intestine fails to absorb nutrients efficiently. This can involve carbohydrates, fats, proteins, vitamins, minerals, and electrolytes. When absorption is impaired, the body doesn't get what it needs to function properly — leading to a wide range of systemic symptoms. These include chronic diarrhea, weight loss, steatorrhea, fatigue, edema, anemia, osteomalacia, and neurologic manifestations due to vitamin deficiencies.

Clinical Approach: The 3-Step Diagnostic Strategy

When evaluating a patient suspected of having a malabsorption disorder, follow a structured and logical 3-step clinical approach:

Step 1: Recognize Clinical Clues

• Chronic diarrhea

• Bulky, greasy, foul-smelling stools (steatorrhea)

• Bloating and abdominal discomfort

• Progressive weight loss

• Fatigue and signs of micronutrient deficiency:

  • Night blindness → Vitamin A deficiency

  • Bleeding tendency → Vitamin K deficiency

  • Paresthesia or ataxia → Vitamin B12 or Vitamin E deficiency

  • Bone pain or fractures → Vitamin D or calcium deficiency

Step 2: Screen for Evidence of Malabsorption

• Quantitative stool fat test (gold standard): Measures fat excretion in stool.

• Sudan stain: Rapid bedside screening for fat droplets in stool.

• Serum nutritional markers:

  • Low albumin, prealbumin

  • Low levels of fat-soluble vitamins (A, D, E, K)

  • Low iron, folate, B12

• Functional tests:

  • D-xylose test: Evaluates mucosal absorption (abnormal in celiac disease).

  • Hydrogen breath test: Suggests lactose intolerance or bacterial overgrowth (SIBO).

Step 3: Establish the Cause

• Endoscopic biopsy: To identify villous atrophy, mucosal inflammation, or infiltration.

• Imaging (CT/MRI enterography): To assess for structural abnormalities (Crohn's, lymphangiectasia).

• Serologic tests:

  • Anti-tTG/EMA antibodies for celiac disease

  • PCR or PAS stain for Whipple disease

? Classification of Malabsorption Disorders

Malabsorption is classified based on the level of impairment in the digestive/absorptive process:

1. Intraluminal (Pre-Mucosal) Disorders These disorders affect digestion before absorption by damaging the enzymes or bile necessary to break down food.

• Pancreatic insufficiency (e.g., chronic pancreatitis, cystic fibrosis):

  • Deficiency of digestive enzymes (lipase, protease)

  • Leads to maldigestion of fats and proteins

• Bile acid deficiency (e.g., primary biliary cholangitis, cholestasis, ileal resection):

  • Impairs micelle formation, reducing fat solubility and absorption

• Small intestinal bacterial overgrowth (SIBO):

  • Bacteria deconjugate bile acids → impaired fat digestion

  • May also damage the mucosa and consume B12

2. Mucosal (Intestinal Wall) Disorders These involve damage to the intestinal epithelium, preventing nutrients from being absorbed efficiently.

• Celiac disease:

  • Autoimmune destruction of villi

  • Leads to impaired absorption of iron, folate, calcium

• Tropical sprue:

  • Post-infectious condition in residents/travelers to tropical regions

  • Mimics celiac disease

• Lactase deficiency:

  • Deficiency in brush-border enzyme

  • Causes osmotic diarrhea from unabsorbed lactose

• Crohn disease:

  • Chronic inflammation with ulceration and fibrosis

  • Leads to patchy malabsorption, especially in the terminal ileum

3. Post-Mucosal (Transport) Disorders These impair transport of absorbed nutrients into the lymphatic or portal circulation.

• Intestinal lymphangiectasia:

  • Loss of chylomicrons into interstitium

  • Causes protein-losing enteropathy and edema

• Whipple disease:

  • Caused by Tropheryma whipplei

  • Systemic illness involving joints, CNS, and lymphatics

• Abetalipoproteinemia:

  • Genetic disorder

  • Prevents formation of apolipoprotein B-containing lipoproteins (chylomicrons)

  • Fat malabsorption and acanthocytosis

Clinical Pearls: Anatomic Correlation & Nutrient Deficiencies

Understanding which nutrient is absorbed where helps localize the disease:

• Iron deficiency anemia → Think proximal small bowel (duodenum) — common in celiac disease.

• Vitamin B12 deficiency → Think terminal ileum (Crohn disease or ileal resection).

• Fat-soluble vitamin deficiency (A, D, E, K) → Suggests fat malabsorption — seen in pancreatic insufficiency, bile salt disorders, or mucosal injury.

• Calcium and Vitamin D → Deficiency leads to osteopenia, fractures, and secondary hyperparathyroidism.

• Vitamin K deficiency → Can cause bleeding tendency and prolonged PT.

• Zinc deficiency → May cause rash, diarrhea, alopecia, and delayed healing.

Summary Points

• Stepwise evaluation: symptoms → screen for malabsorption → establish cause.

• Pancreatic and bile dysfunction = pre-mucosal.

• Mucosal damage (e.g., celiac, Crohn’s) = absorptive surface loss.

• Post-mucosal (transport) = rare but important (e.g., lymphangiectasia).

• Always correlate nutritional deficiency patterns with bowel segment function.

• Don’t forget serologic tests for celiac and special stains for Whipple.

Disorders of Absorption | Gastroenterology

Introduction: What are Absorptive Disorders?

Disorders of absorption refer to a group of conditions where the intestinal lining is unable to properly absorb one or more key nutrients. This leads to a broad range of systemic issues, including chronic diarrhea, steatorrhea (fatty stools), weight loss, anemia, fatigue, and deficiencies in vitamins and minerals. On USMLE Step 2 CK, these conditions are often presented through clinical vignettes involving unexplained nutritional deficiencies or long-standing gastrointestinal complaints.

Physiology of Nutrient Absorption: Segment-Wise Overview

Before diving into disorders, it's important to know which part of the small intestine absorbs what:

• Duodenum: Primary site for iron, calcium, and folate.

• Jejunum: Absorbs carbohydrates, proteins, and water-soluble vitamins (e.g., B-complex, vitamin C).

• Ileum: Crucial for vitamin B12 and bile salt reabsorption.

Understanding this layout helps correlate clinical signs with affected anatomical segments.

High-Yield Disorders of Absorption

Each of the following syndromes affects one or more of the above segments or mechanisms.

1. Celiac Disease

Celiac disease is an autoimmune condition triggered by gluten (a protein found in wheat, barley, and rye). It leads to immune-mediated destruction of the villi in the duodenum and proximal jejunum, reducing absorptive capacity.

• Key clinical features:

  • Diarrhea, bloating, flatulence

  • Iron deficiency anemia (due to duodenal involvement)

  • Dermatitis herpetiformis (pruritic vesicles on elbows, knees)

• Diagnosis:

  • Positive anti-tissue transglutaminase (tTG) IgA antibodies

  • Duodenal biopsy: villous atrophy, crypt hyperplasia, intraepithelial lymphocytosis

• Treatment: Lifelong strict gluten-free diet

2. Lactose Intolerance

Lactose intolerance results from deficiency of lactase, the enzyme that breaks down lactose (milk sugar) on the intestinal brush border.

• Presentation:

  • Bloating, flatulence, crampy abdominal pain

  • Osmotic diarrhea following dairy consumption

• Diagnosis:

  • Hydrogen breath test (positive = ↑ hydrogen from colonic fermentation of undigested lactose)

  • Symptom resolution after lactose withdrawal

• Treatment: Avoid dairy or use lactase enzyme supplements

3. Pancreatic Insufficiency

Seen in conditions like chronic pancreatitis, cystic fibrosis, or pancreatic surgery, this results in impaired secretion of digestive enzymes (especially lipase and protease).

• Key signs:

  • Steatorrhea (bulky, greasy stools)

  • Weight loss despite adequate intake

  • Deficiencies in fat-soluble vitamins (A, D, E, K)

• Diagnosis:

  • Qualitative/quantitative stool fat test

  • Low fecal elastase (pancreatic marker)

• Management: Pancreatic enzyme replacement therapy (e.g., pancrelipase)

4. Small Intestinal Bacterial Overgrowth (SIBO)

SIBO occurs when colonic bacteria abnormally colonize the small intestine, interfering with bile salt activity and villi integrity.

• Clinical signs:

  • Bloating, flatulence, malabsorption, weight loss

  • Vitamin B12 deficiency (bacteria compete for it)

• Diagnosis:

  • Glucose hydrogen breath test

  • Small bowel aspirate with bacterial culture (gold standard but rarely done)

• Treatment: Non-absorbed antibiotics like rifaximin, address predisposing factors (e.g., motility disorders, strictures)

5. Tropical Sprue

A post-infectious malabsorption disorder seen in tropical regions, mimicking celiac disease but involving the entire small bowel.

• Symptoms: Diarrhea, weight loss, megaloblastic anemia (due to folate and B12 deficiency)

• Diagnosis: Clinical suspicion + small bowel biopsy showing villous atrophy (like celiac)

• Treatment: Antibiotics (e.g., tetracycline) + folate supplementation

6. Whipple Disease

A rare systemic illness caused by Tropheryma whipplei, affecting small bowel, joints, CNS, and lymphatics.

• Symptoms:

  • Malabsorption, diarrhea, steatorrhea

  • Migratory arthralgias

  • Lymphadenopathy, cognitive impairment, oculomotor dysfunction

• Diagnosis:

  • PAS-positive foamy macrophages in small bowel lamina propria

• Treatment:

  • IV ceftriaxone, followed by prolonged oral TMP-SMX

7. Abetalipoproteinemia

A congenital disorder affecting chylomicron and apolipoprotein B production. Results in defective fat transport.

• Clinical presentation (usually infancy):

  • Steatorrhea, fat-soluble vitamin deficiency

  • Neurologic signs: Ataxia, retinitis pigmentosa

  • Acanthocytosis on peripheral smear

• Diagnosis:

  • Low serum cholesterol, triglycerides

  • Absent apolipoprotein B

• Treatment: High-dose vitamin E and fat-soluble vitamin supplementation

Diagnostic Tools for Absorptive Syndromes

• Stool Fat Analysis: Confirms fat malabsorption

• D-xylose test: Evaluates mucosal absorption (normal in pancreatic insufficiency; low in celiac)

• Hydrogen breath test: Identifies lactose intolerance or SIBO

• Serologic tests: Anti-tTG (celiac), PAS stain (Whipple)

• Endoscopic biopsy: Definitive for mucosal diseases

Segment-Based Diagnostic Clues

• Iron deficiency anemia: Think duodenum (Celiac)

• Folate deficiency: Proximal small bowel

• Vitamin B12 deficiency: Ileum (Crohn, resection, SIBO)

• Fat-soluble vitamin deficiencies: Pancreatic or mucosal disease

• Megaloblastic anemia: B12 and folate (Tropical sprue, Whipple)

• Neurologic symptoms + steatorrhea: B12 or vitamin E deficiency (Abetalipoproteinemia, Whipple)

Summary Pearls

• Celiac = anti-tTG + villous atrophy + iron deficiency anemia

• Pancreatic insufficiency = fat malabsorption + enzyme deficiency + normal D-xylose test

• Lactose intolerance = osmotic diarrhea + positive H2 breath test

• SIBO = B12 deficiency + bloating + rifaximin responsive

• Tropical sprue = folate/B12 deficiency + tropical residence + antibiotic responsive

• Whipple disease = PAS-positive macrophages + multisystem involvement

• Abetalipoproteinemia = infant with steatorrhea + acanthocytes + fat-soluble vitamin deficiency

Irritable Bowel Syndrome (IBS)

Introduction: Why IBS Matters

Irritable Bowel Syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by abdominal pain and altered bowel habits in the absence of any structural, infectious, or inflammatory abnormality. It is one of the most commonly encountered conditions in outpatient GI practice and a frequently tested diagnosis on USMLE Step 2 CK, especially in clinical scenarios involving normal investigations but persistent symptoms.

Diagnostic Criteria: Rome IV Explained

IBS is a clinical diagnosis made using the Rome IV criteria:

To diagnose IBS, the patient must have:

• Recurrent abdominal pain, on average at least one day per week in the last 3 months, associated with ≥2 of the following:

  • Related to defecation (improves or worsens)

  • Associated with a change in stool frequency

  • Associated with a change in stool form (appearance)

Symptoms should have started at least 6 months ago for Rome IV application.

Classification of IBS Subtypes

Understanding the IBS subtype helps tailor treatment:

• IBS-C (Constipation-predominant)

• IBS-D (Diarrhea-predominant)

• IBS-M (Mixed type): alternating diarrhea and constipation

• IBS-U (Unclassified): does not fit the above categories

? Pathophysiology: Multifactorial and Complex

The pathogenesis of IBS is not fully understood but involves:

• Visceral hypersensitivity: heightened perception of gut stimuli

• Abnormal GI motility: altered colonic transit

• Post-infectious changes: especially after bacterial gastroenteritis

• Altered gut-brain axis: central nervous system amplifies GI sensations

• Psychosocial stressors: anxiety, depression, trauma

Importantly, while there is no structural damage, the symptoms are real and can significantly affect quality of life.

Red Flags: When to Investigate Further

IBS is typically diagnosed clinically in patients with typical symptoms and no alarm signs. Investigations (e.g., colonoscopy) should be considered if any of the following are present:

• Weight loss

• Iron deficiency anemia

• Rectal bleeding

• Nocturnal symptoms (e.g., diarrhea waking the patient)

• Family history of colon cancer or IBD

• Age > 50 with new onset of symptoms

In the absence of red flags, young patients with classic symptoms do not need endoscopy or imaging.

Clinical Presentation

• Abdominal pain (improves or worsens with defecation)

• Altered bowel habits:

  • Diarrhea, constipation, or both

• Bloating, excessive gas, mucus in stool

• Normal physical exam

• Normal lab and imaging findings

Management: Symptom-Based, Subtype-Specific

General measures for all patients:

• Patient reassurance: emphasize that symptoms are real but not life-threatening

• Dietary modification:

  • Low-FODMAP diet (reduces fermentable carbs)

  • Avoid triggers (e.g., caffeine, alcohol, fatty foods)

• Psychological support:

  • CBT, mindfulness-based therapy

IBS-C (Constipation Predominant)

• Fiber supplementation (psyllium)

• PEG (polyethylene glycol) for osmotic laxative effect

• Lubiprostone, linaclotide: for refractory cases

IBS-D (Diarrhea Predominant)

• Loperamide: reduces stool frequency

• Rifaximin: especially useful in bloating and diarrhea

• Eluxadoline: opioid receptor modulator

• Bile acid sequestrants (e.g., cholestyramine) if bile acid diarrhea suspected

Abdominal Pain Management (All Subtypes)

• Antispasmodics: dicyclomine, hyoscyamine

• Tricyclic antidepressants (TCAs): especially in IBS-D

• SSRIs: may help in IBS-C and mood-related symptoms

USMLE Step 2 CK Strategy

On the exam, identify classic presentation:

• Young woman with intermittent crampy abdominal pain, bloating, and altered stool pattern

• Normal colonoscopy or labs

• No weight loss, no blood in stool

Ask yourself:

• Are red flags absent? → No further workup needed

• What is the predominant symptom? → Directs treatment choice

Summary Pearls

• IBS = chronic abdominal pain + altered bowel habits with normal tests

• Use Rome IV criteria to diagnose

• Rule out red flags: weight loss, anemia, bleeding, nocturnal symptoms

• Treatment is subtype-specific and includes diet, medications, and CBT

• Loperamide for IBS-D, PEG for IBS-C, TCAs for pain and diarrhea

• Don’t order colonoscopy in young patients with typical symptoms and no alarm features