Gastrointestinal Disorders - Comprehensive Overview

Gastrointestinal disorders encompass a broad range of conditions affecting the digestive tract from esophagus to anus, as well as the liver, gallbladder, and pancreas. They account for significant morbidity worldwide, with diverse pathophysiology ranging from acid-peptic diseases to autoimmune inflammatory conditions and malignancies. This article provides comprehensive coverage of major GI conditions.

Gastroesophageal Reflux Disease (GERD)

Parameter	Detail
Definition	Condition of symptoms and/or mucosal damage resulting from abnormal reflux of gastric contents into the esophagus
Prevalence	10-20% of adults in Western countries
Pathophysiology	Transient lower esophageal sphincter relaxations (most common), hypotensive LES, hiatal hernia, impaired esophageal clearance, delayed gastric emptying

GERD Classification (Los Angeles Classification)

Grade	Endoscopic Finding
A	One or more mucosal breaks <5 mm, not extending between two mucosal folds
B	One or more mucosal breaks >5 mm, not extending between two mucosal folds
C	Mucosal breaks extending between two or more mucosal folds, involving <75% of circumference
D	Mucosal breaks involving >=75% of esophageal circumference

GERD Treatment

Severity	Initial Treatment	Maintenance	Refractory Options
Mild/intermittent	Lifestyle modifications (elevate head of bed, avoid trigger foods, weight loss), antacids, H2RAs (famotidine)	On-demand PPI or H2RA	–
Moderate	PPI once daily (omeprazole, pantoprazole, esomeprazole, lansoprazole, rabeprazole)	Continue PPI (lowest effective dose); consider step-down to on-demand	Double PPI dose, switch to different PPI
Severe/complicated (stricture, Barrett esophagus)	PPI twice daily	Long-term PPI + surveillance endoscopy	Fundoplication (Nissen), LINX device, Roux-en-Y gastric bypass (if obese)

Peptic Ulcer Disease (PUD)

Parameter	Detail
Definition	Mucosal defects in the stomach or duodenum extending through the muscularis mucosae
Causes	H. pylori infection (70-80%), NSAIDs (15-20%), acid hypersecretion (Zollinger-Ellison, 1%)
Duodenal vs Gastric Ulcers	Duodenal: common, nocturnal pain, relieved by food; Gastric: pain worsened by food, associated with gastric cancer risk

PUD Risk Factors

Risk Factor	Relative Risk
H. pylori infection	3-6x (duodenal), 2-3x (gastric)
NSAID use	4x (overall); 10x (high dose, >65 years, comorbid)
Smoking	2-3x
Alcohol	Modest increase
Corticosteroids	2x (when combined with NSAIDs)
Previous ulcer history	3-4x for recurrence
Zollinger-Ellison syndrome	Rare but high risk

H. pylori Diagnosis and Treatment

Test	Sensitivity	Specificity	Notes
Urea breath test	>95%	>95%	Gold standard for active infection; post-eradication testing
Stool antigen test	>90%	>90%	Good for initial and post-treatment
EGD with biopsy	>95%	100%	Allows histology, culture, and sensitivity
Serology	~80-90%	~80-90%	Cannot distinguish active from past infection
Rapid urease test (CLO test)	90-95%	95-100%	Requires biopsy

H. pylori Eradication Regimens

Regimen	Duration	Eradication Rate	Notes
Triple therapy: PPI + clarithromycin + amoxicillin (or metronidazole if penicillin-allergic)	14 days	65-85%	Declining efficacy (clarithromycin resistance)
Bismuth quadruple therapy: PPI + bismuth + metronidazole + tetracycline	14 days	85-95%	Good alternative; increasing use due to clarithromycin resistance
Concomitant therapy: PPI + clarithromycin + amoxicillin + metronidazole	14 days	85-95%	Simplified quadruple
Levofloxacin triple therapy: PPI + levofloxacin + amoxicillin	14 days	80-90%	Second-line
Rifabutin triple: PPI + rifabutin + amoxicillin	14 days	80-90%	Third-line

Inflammatory Bowel Disease (IBD)

Crohn Disease vs Ulcerative Colitis

Feature	Crohn Disease	Ulcerative Colitis
Location	Any part of GI tract (mouth to anus); skip lesions	Colon only; continuous from rectum proximally
Inflammation pattern	Transmural	Mucosal (superficial)
Endoscopic findings	Aphthous ulcers, cobblestoning, strictures, fistulas, deep fissuring ulcers	Continuous erythema, friability, granularity, pseudopolyps, superficial ulcers
Histology	Granulomas (non-caseating, 50%), focal cryptitis, transmural inflammation	Crypt abscesses, basal plasmacytosis, mucin depletion, crypt architectural distortion
Rectal sparing	Common	Rare
Terminal ileum involvement	Common (70%)	Not involved (backwash ileitis in pancolitis)
Perianal disease	Common (fistulas, fissures, abscesses, skin tags)	Rare
Fistulas	Common	Not a feature
Strictures	Common	Rare (can occur in long-standing disease)
Colon cancer risk	Increased (especially with colonic involvement)	Increased (duration and extent-dependent)
Smoking	Exacerbates	Protective (may reduce risk)

IBD Extra-Intestinal Manifestations

System	Conditions	Association
Musculoskeletal	Peripheral arthritis, ankylosing spondylitis, sacroiliitis	Most common; may correlate with disease activity (type 1) or be independent (axial, type 2)
Dermatologic	Erythema nodosum, pyoderma gangrenosum, Sweet syndrome, psoriasis	EN correlates with disease activity; PG may be independent
Ocular	Episcleritis, uveitis (anterior), scleritis	Episcleritis correlates with activity; uveitis often independent
Hepatobiliary	Primary sclerosing cholangitis (PSC), fatty liver, cholelithiasis, autoimmune hepatitis	PSC strongly associated with UC (2-5%), progresses to cirrhosis/cholangiocarcinoma
Thromboembolic	DVT, PE, mesenteric ischemia	Increased risk especially during flares
Metabolic	Osteoporosis, vitamin deficiencies	Steroid use, malabsorption
Renal	Nephrolithiasis (oxalate stones, uric acid), amyloidosis	More common in Crohn

IBD Treatment

Drug Class	Examples	Mechanism	Crohn	UC
5-ASA (aminosalicylates)	Sulfasalazine, mesalamine, balsalazide, olsalazine	Topical anti-inflammatory; inhibit NF-kB, PPAR-gamma	Mild-moderate (colonic disease)	First-line for mild-moderate
Corticosteroids	Budesonide (MMX), prednisone, hydrocortisone	Broad anti-inflammatory	Moderate-severe (induction)	Moderate-severe (induction)
Immunomodulators	Azathioprine, 6-MP, methotrexate	Purine synthesis inhibition	Maintenance, steroid-sparing	Maintenance, steroid-sparing
Anti-TNF	Infliximab, adalimumab, certolizumab, golimumab	Neutralize TNF-alpha	Moderate-severe (induction + maintenance)	Moderate-severe (induction + maintenance)
Anti-integrin	Vedolizumab	Block alpha-4-beta-7 integrin (gut-specific)	Moderate-severe	Moderate-severe
Anti-IL12/23	Ustekinumab	Block IL-12/IL-23 p40 subunit	Moderate-severe	Moderate-severe
JAK inhibitors	Tofacitinib, upadacitinib	Block JAK-STAT signaling	–	Moderate-severe (tofacitinib, upadacitinib)
S1P receptor modulator	Ozanimod	Lymphocyte sequestration	–	Moderate-severe
Antibiotics	Metronidazole, ciprofloxacin	Antibacterial; anti-inflammatory	Perianal disease, pouchitis	–
Surgery	Resection, strictureplasty, colectomy	–	For complications (stricture, fistula, abscess, refractory disease)	Colectomy (cure)

Irritable Bowel Syndrome (IBS)

Parameter	Detail
Definition	Chronic functional GI disorder characterized by recurrent abdominal pain associated with defecation or change in bowel habits
Prevalence	10-15% of adults; female > male (2:1)
Pathophysiology	Visceral hypersensitivity, altered gut motility, brain-gut axis dysfunction, gut microbiota alterations, low-grade inflammation, post-infectious

IBS Subtypes (Rome IV Criteria)

Subtype	Stool Consistency (Bristol Stool Form Scale)	Frequency
IBS-C (constipation)	>25% of bowel movements: type 1-2 (hard/lumpy)	30-40%
IBS-D (diarrhea)	>25% of bowel movements: type 6-7 (mushy/watery)	20-30%
IBS-M (mixed)	>25% type 1-2 AND >25% type 6-7	30-40%
IBS-U (unclassified)	Does not meet criteria for other subtypes	5-10%

IBS Treatment

Category	Intervention	Evidence
Lifestyle	Dietary modification (low FODMAP, fiber for IBS-C), exercise, stress reduction	Moderate-strong
Psychological	CBT, gut-directed hypnotherapy, mindfulness	Strong
IBS-C	Soluble fiber (psyllium), PEG, linaclotide, plecanatide, lubiprostone, tenapanor, prucalopride	Moderate-strong
IBS-D	Loperamide, rifaximin, eluxadoline, alosetron (women only, restricted), ondansetron	Moderate-strong
IBS pain	Antispasmodics (hyoscyamine, dicyclomine), peppermint oil, TCAs (low dose), gabapentinoids	Moderate

Celiac Disease

Parameter	Detail
Definition	Immune-mediated enteropathy triggered by gluten ingestion in genetically predisposed individuals
Prevalence	1% of population; higher in first-degree relatives (10-15%)
Genetics	HLA-DQ2 (90-95%), HLA-DQ8 (5-10%)
Pathophysiology	Gluten peptides (gliadin) deamidation by tissue transglutaminase (tTG) presentation by DQ2/DQ8 T-cell activation Th1 response enteropathy

Celiac Disease Presentation

Phenotype	Features	Age
Classical	Diarrhea, steatorrhea, weight loss, failure to thrive, abdominal distension	Infants/toddlers (after gluten introduction)
Non-classical	Iron deficiency anemia (most common), fatigue, osteoporosis, dermatitis herpetiformis, elevated LFTs, neuropathy, infertility, short stature	Older children and adults
Subclinical/silent	No symptoms; found by screening in at-risk populations	Any
Potential	Positive serology, normal biopsy, genetic susceptibility	Any

Celiac Serology

Test	Sensitivity	Specificity	Notes
tTG-IgA (tissue transglutaminase)	>95%	>95%	First-line screening test
EMA-IgA (endomysial antibody)	>90%	>99%	Confirmatory if tTG positive
DGP-IgG (deamidated gliadin peptide)	80-90%	90-95%	For IgA deficient patients
Total IgA	–	–	Must check to rule out IgA deficiency
HLA DQ2/DQ8	>99% negative predictive value	Low specificity	Useful to rule out disease (negative test excludes with >99% certainty)

Celiac Disease Management

Intervention	Detail
Gluten-free diet	Strict, lifelong avoidance of wheat, barley, and rye; consult with dietitian
Nutritional supplementation	Iron, calcium, vitamin D, B12, folate as needed
Monitoring	Follow-up serology (tTG-IgA) to confirm dietary adherence; consider repeat biopsy if persistent symptoms
Non-responsive celiac disease	Evaluate for gluten exposure (intentional or inadvertent), refractory celiac disease (type I: treat with steroids/immunosuppression; type II: high risk of EATL)
Vaccinations	Pneumococcal, influenza (due to hyposplenism risk)

Hepatitis and Cirrhosis

Causes of Hepatitis

Type	Etiology	Key Features
Viral hepatitis A	HAV (fecal-oral)	Acute only; vaccine-preventable
Viral hepatitis B	HBV (blood/sexual/perinatal)	Can become chronic (risk depends on age of acquisition)
Viral hepatitis C	HCV (blood)	Chronic in 55-85%; curable with DAAs
Viral hepatitis D	HDV (requires HBV)	Coinfection or superinfection; more severe
Viral hepatitis E	HEV (fecal-oral)	Usually acute; severe in pregnancy
Alcoholic hepatitis	Ethanol toxicity	Acute-on-chronic; high mortality
Autoimmune hepatitis	Autoimmune (type 1: ANA/anti-SMA; type 2: anti-LKM1)	Female predominance; responds to steroids/immunosuppression
Drug-induced liver injury	Acetaminophen (most common), many others	Dose-dependent (acetaminophen) or idiosyncratic
Metabolic	NAFLD/NASH	Most common cause of elevated LFTs; associated with obesity, diabetes, metabolic syndrome

Cirrhosis Complications

Complication	Pathophysiology	Treatment
Portal hypertension	Increased resistance to portal flow	Non-selective beta-blockers (propranolol, nadolol, carvedilol), TIPS
Esophageal varices	Portosystemic collaterals	Endoscopic band ligation, beta-blockers, TIPS
Ascites	Portal HTN + hypoalbuminemia	Sodium restriction, diuretics (spironolactone + furosemide), paracentesis, TIPS
Spontaneous bacterial peritonitis (SBP)	Bacterial translocation into ascitic fluid	Antibiotics (cefotaxime, ceftriaxone), albumin
Hepatorenal syndrome (HRS)	Renal vasoconstriction in cirrhosis	Terlipressin + albumin, TIPS, liver transplant
Hepatic encephalopathy	Accumulation of neurotoxins (ammonia)	Lactulose, rifaximin
Coagulopathy	Reduced synthesis of clotting factors	Vitamin K, FFP (if bleeding), TPO agonists
Hepatocellular carcinoma (HCC)	Malignant transformation in cirrhosis	Surveillance every 6 months (ultrasound + AFP); treatment: resection, ablation, TACE, systemic therapy (atezolizumab/bevacizumab, sorafenib, lenvatinib)

Child-Pugh Score for Cirrhosis Severity

Parameter	1 Point	2 Points	3 Points
Bilirubin (mg/dL)	<2	2-3	>3
Albumin (g/dL)	>3.5	2.8-3.5	<2.8
INR	<1.7	1.7-2.3	>2.3
Ascites	None	Mild/moderate (diuretic-responsive)	Severe (refractory)
Hepatic encephalopathy	None	Grade I-II	Grade III-IV

Interpretation: Child-Pugh A (5-6 points): well-compensated; B (7-9): significant compromise; C (10-15): decompensated.

Pancreatitis

Feature	Acute Pancreatitis	Chronic Pancreatitis
Definition	Acute inflammation of pancreas with variable involvement of peripancreatic tissues	Progressive inflammatory disease with irreversible morphologic changes leading to exocrine and endocrine insufficiency
Most common causes	Gallstones (40%), alcohol (30%), hypertriglyceridemia, hypercalcemia, drugs, autoimmune, ERCP, trauma, genetic	Alcohol (60-70%), genetic (PRSS1, SPINK1, CFTR), obstructive, autoimmune, idiopathic
Presentation	Epigastric pain (radiating to back), nausea/vomiting, epigastric tenderness	Epigastric pain (may be chronic or recurrent), steatorrhea, weight loss, diabetes
Key labs	Elevated amylase and/or lipase (>3x ULN)	Normal amylase/lipase (in end-stage); low fecal elastase, increased fecal fat
Severity scoring	Ranson criteria, APACHE II, BISAP, CT severity index	Cambridge classification (imaging)
Imaging	Contrast-enhanced CT (best for assessing necrosis)	CT, MRCP, ERCP, EUS

Ranson Criteria for Acute Pancreatitis

At Admission	During Initial 48 Hours
Age >55 years	Hematocrit fall >10%
WBC >16,000/mL	BUN increase >5 mg/dL
Glucose >200 mg/dL	Calcium <8 mg/dL
LDH >350 IU/L	PaO2 <60 mmHg
AST >250 IU/L	Base deficit >4 mEq/L
	Fluid sequestration >6 L

Interpretation: 0-2: mild (0% mortality); 3-4: moderate (15%); 5-6: severe (40%); >7: very severe (near 100%).

Gallbladder Disease

Condition	Pathophysiology	Presentation	Diagnosis	Treatment
Cholelithiasis (gallstones)	Supersaturation of bile with cholesterol or bilirubin	Often asymptomatic (80%); biliary colic (RUQ pain, postprandial, radiating to back/shoulder)	Ultrasound (sensitivity >95%)	Asymptomatic: observation; Symptomatic: cholecystectomy
Acute cholecystitis	Gallstone obstruction of cystic duct + inflammation	RUQ pain, fever, Murphy sign, leukocytosis	Ultrasound (gallstone, gallbladder wall thickening >4mm, pericholecystic fluid, sonographic Murphy sign)	Cholecystectomy (early, within 72 hours); antibiotics if infected
Choledocholithiasis	Common bile duct stones	Biliary colic, jaundice, cholangitis	MRCP, EUS, ERCP	ERCP + sphincterotomy + stone extraction + cholecystectomy
Ascending cholangitis	CBD obstruction + infection	Charcot triad (RUQ pain, fever, jaundice); Reynolds pentagon (adds shock + confusion)	Clinical + labs (elevated bilirubin, ALP, GGT, LFTs)	Urgent ERCP + antibiotics (piperacillin-tazobactam, ceftriaxone + metronidazole)
Gallstone pancreatitis	Stone obstruction at ampulla of Vater	Epigastric pain, elevated lipase	Labs + imaging (MRCP/EUS)	Supportive care; ERCP if severe/cholangitis; cholecystectomy
Acalculous cholecystitis	Gallbladder stasis + ischemia (critical illness)	Fever, RUQ pain (may be absent in ICU)	Ultrasound (sludge, gallbladder wall thickening); HIDA scan if needed	Cholecystostomy (percutaneous) or cholecystectomy
Gallbladder polyps	Cholesterol polyp or adenoma	Incidental on ultrasound	Ultrasound	>1 cm or symptomatic: cholecystectomy
Gallbladder cancer	Adenocarcinoma (rare, poor prognosis)	RUQ pain, weight loss, jaundice	Ultrasound, CT, MRI	Cholecystectomy (early); chemotherapy (advanced)

Colorectal Cancer

Refer to the Cancer Overview article for detailed coverage.

Topic	Summary
Screening age	Start at 45 years (USPSTF)
Screening modalities	Colonoscopy (every 10 years), FIT (annually), CT colonography (every 5 years), sigmoidoscopy (every 5-10 years)
Hereditary syndromes	Lynch syndrome (HNPCC): MSI testing, MLH1/MSH2/MSH6/PMS2; FAP: APC gene, hundreds of polyps
Staging and treatment	Stage I: surgery; Stage II: surgery +/- chemo; Stage III: surgery + chemo; Stage IV: systemic therapy +/- metastasectomy