Peptic Ulcer Disease (PUD)

Definition

Common Sites

• First part of the duodenum (most common overall)
• Lesser curve of the stomach (especially the incisura angularis)
• Prepyloric / pyloric channel
• Distal esophagus (acid reflux)
• Post-surgical stoma (marginal ulcer at gastrojejunostomy)
• Meckel's diverticulum (if ectopic gastric mucosa is present)

Epidemiology

• Affects >4 million individuals in the US each year
• Lifetime risk: ~10% in males, ~4% in females
• Duodenal ulcers (DU) are more common than gastric ulcers (GU)
• DU: more common in men; GU: equal gender incidence, older patients
• GU more prevalent in low socioeconomic groups and resource-poor nations
• Robbins & Kumar Basic Pathology, p. 598

Pathogenesis: The Balance Model

Protective Mechanisms

1. Mucus layer and bicarbonate secretion (surface mucous cells, Brunner glands)
2. Mucosal blood flow
3. Epithelial tight junctions and rapid cell turnover
4. Duodenal alkalinization by pancreatic bicarbonate and bile
5. Feedback inhibition of gastric emptying when acid enters the duodenum (secretin release → more pancreatic HCO₃⁻)

Damaging Factors

1. H. pylori infection
2. NSAIDs / aspirin
3. Excess gastric acid secretion
4. Cigarette smoking (reduces mucosal blood flow, impairs healing)
5. High-dose corticosteroids (suppress prostaglandin synthesis)

• Guyton and Hall, p. 825; Robbins & Kumar, p. 598

Etiology

1. Helicobacter pylori

• 70% of all PUD is associated with H. pylori

• Only 5-10% of infected individuals develop ulcers - host factors and bacterial strain virulence matter
• H. pylori breaks down the mucosal barrier and stimulates acid secretion
• Testing and eradication are mandatory in all confirmed PUD cases
• Robbins & Kumar, p. 598

2. NSAIDs / Aspirin

• Increasingly the most common cause of gastric ulcers in developed countries (as H. pylori rates fall)
• Mechanism: inhibit COX-1 → reduce prostaglandin E₂ → reduced mucus and bicarbonate secretion
• Low-dose aspirin use in the aging population is driving this trend

3. Zollinger-Ellison Syndrome (ZES)

• Gastrin-secreting tumors (gastrinomas) cause massive acid hypersecretion
• Multiple ulcers in stomach, duodenum, and even jejunum
• Should be suspected in H. pylori-negative, non-NSAID PUD
• Robbins & Kumar, p. 599

4. Other Risk Factors

• Alcohol-related cirrhosis
• Chronic renal failure (hypercalcemia → gastrin ↑)
• Hyperparathyroidism (hypercalcemia → gastrin ↑)
• Chronic obstructive pulmonary disease

Morphology / Pathology

Macroscopic

• Duodenal ulcers: usually in the first part of the duodenum; often solitary but "kissing ulcers" (anterior + posterior) occur
• Gastric ulcers: tend to be larger; lesser curve, especially at the incisura angularis
• Chronic ulcers penetrate the mucosa into the muscle coat → fibrosis and scarring
• Fibrosis can cause pyloric stenosis or hourglass deformity of the stomach
• Posterior gastric ulcers may erode into the pancreas or splenic artery

Endoscopic Appearance

Microscopic

• Base covered with granulation tissue
• Evidence of endarteritis obliterans in chronic cases
• Epithelial downgrowth during healing can mimic invasion (important not to misinterpret as carcinoma)
• Bailey and Love, p. 1179

Malignancy Risk

• Duodenal ulcers: virtually never malignant
• Gastric ulcers: may be malignant or may coexist with cancer - all gastric ulcers require multiple biopsies
• Bailey and Love, p. 1180

Clinical Features

Investigation

1. Upper GI Endoscopy - gold standard; allows biopsy (mandatory for all gastric ulcers)
2. H. pylori testing - CLO (rapid urease) test on antral biopsy, urea breath test, stool antigen test
3. Barium meal - less common now; shows ulcer crater
4. Serum gastrin - if ZES suspected (H. pylori-negative, non-NSAID, multiple/atypical ulcers)

Treatment

Medical (First-Line)

• Standard-dose PPI (e.g., omeprazole 20 mg BD, lansoprazole 30 mg BD)
• Reduces acid secretion by blocking H⁺/K⁺-ATPase
• Continue for 4-8 weeks (DU) or 8-12 weeks (GU)

• Mandatory in all H. pylori-positive patients, regardless of whether this is first episode or recurrence
• First-line: 14-day triple therapy = PPI + clarithromycin + amoxicillin (or metronidazole)
• Eradication rates: 70-85% with triple therapy
• Eradication reduces recurrence dramatically: from 59-67% → <10-20%
• If triple therapy fails (usually due to clarithromycin resistance), use bismuth quadruple therapy or levofloxacin triple therapy
• Harrison's Principles of Internal Medicine 22E, p. 2570; Textbook of Family Medicine 9e

• Stop NSAIDs if possible
• If NSAIDs must continue: use PPI co-prescription; test and eradicate H. pylori
• Misoprostol (prostaglandin analogue, 200 µg QID) is an alternative mucosal protectant but causes diarrhea in 10-30% and is contraindicated in pregnancy

Surgical Treatment

• Elective surgery for uncomplicated PUD is now very rarely performed - reserved for emergencies
• Historical procedures: Billroth I (gastroduodenostomy), Billroth II/Polya (gastrojejunostomy), vagotomy
• Now only performed for complications

Complications ("PBS")

• Bailey and Love, p. 1178

Rockall Score for Upper GI Bleeding Risk Stratification

• Sleisenger and Fordtran's Gastrointestinal and Liver Disease

Refractory / Non-Healing Ulcers

1. Confirm with repeat endoscopy (mandatory for all gastric ulcers)
2. Check for persistent H. pylori infection (biopsies - breath test may be false-negative soon after treatment)
3. Assess adherence and bacterial culture for resistance
4. Exclude continued NSAID use
5. Measure serum gastrin to rule out ZES
6. Consider rare IgG4-related ulceration

• Bailey and Love, p. 1182

Key Summary Points

• PUD = imbalance between acid/pepsin aggression and mucosal defense
• Two dominant causes: H. pylori (>70%) and NSAIDs
• Diagnosis: upper GI endoscopy + H. pylori testing (all gastric ulcers must be biopsied)
• Treatment: PPI + H. pylori eradication (14-day triple therapy)
• Eradication dramatically reduces recurrence and bleeding
• Complications: perforation, bleeding, stenosis - now mainly managed endoscopically/radiologically; surgical intervention reserved for failures
• Elective surgery for PUD is now obsolete

• Guyton and Hall Textbook of Medical Physiology, Ch. 67
• Robbins & Kumar Basic Pathology
• Bailey and Love's Short Practice of Surgery 28th Ed., Ch. 67
• Harrison's Principles of Internal Medicine 22E (2025), Ch. on PUD
• Textbook of Family Medicine 9e

Malabsorption Syndrome

Definition

Pathogenesis: The Four Phases of Absorption

Causes Classified by Mechanism

A. Intraluminal Maldigestion

• Occurs when >90% of pancreatic secretory function is lost
• Causes: chronic pancreatitis (most often from alcohol), cystic fibrosis, pancreatic duct obstruction, somatostatinoma
• Results in fat, protein, and carbohydrate maldigestion
• Treatment: oral pancreatic enzyme supplementation

• Biliary obstruction or cirrhosis → reduced intraluminal bile acids → impaired micelle formation → fat maldigestion
• Primary bile acid malabsorption (terminal ileal disease/resection, Crohn's ileitis)

• Bacteria deconjugate bile acids → impaired micelle formation
• Occurs in blind loops, multiple small bowel diverticula, motility disorders
• Detected by lactulose or glucose hydrogen breath test; treated with antibiotics

B. Mucosal Malabsorption (Enteropathies)

• Triggered by gluten (wheat, rye, barley) in genetically predisposed individuals
• HLA DQ2 (~90% of cases) or DQ8 required
• Tissue transglutaminase 2 (TG2) deamidates gliadin peptides → bound by DQ2/8 on antigen-presenting cells → CD4+ T cell activation → IFN-γ, IL-2, IL-21 release → CD8+ intraepithelial lymphocyte expansion → epithelial damage
• Histology: villous atrophy, crypt hyperplasia, intraepithelial lymphocytosis
• ~75% concordance in monozygotic twins
• Associated with: type 1 diabetes, thyroiditis, Sjögren's syndrome, IgA nephropathy

• Anti-tissue transglutaminase IgA (anti-TTG IgA) + total IgA level (to exclude IgA deficiency)
• Duodenal/proximal jejunal biopsy (confirmatory)
• Treatment: strict gluten-free diet (lifelong)

• Similar histology to celiac disease (villous atrophy, crypt hyperplasia)
• Occurs in residents of/travelers to tropical climates
• Infectious etiology suspected (abrupt onset, responds to antibiotics + folate)
• Causes folate and B12 deficiency prominently

• Due to Tropheryma whipplei bacillus → macrophage infiltration of small bowel mucosa
• Primarily impairs lymphatic transport
• Typically in young to middle-aged men
• Classic tetrad: diarrhea/steatorrhea, arthralgias, fever, lymphadenopathy + extreme fatigue
• May affect CNS and endocardium
• PAS-positive macrophages in lamina propria (pathognomonic)
• Treatment: antibiotics (usually trimethoprim-sulfamethoxazole)

• Parasites: Giardia lamblia (most common parasitic cause), Cryptosporidium, Cyclospora
• Crohn's disease (especially with ileal involvement)
• Autoimmune enteropathy
• Drug-induced: olmesartan, mycophenolate, colchicine, cholestyramine
• AIDS-related: Mycobacterium avium-intracellulare (similar picture to Whipple's)

C. Post-Mucosal / Lymphatic Obstruction

• Congenital intestinal lymphangiectasia or acquired obstruction (tumor, trauma, cardiac disease, infection)
• Unique pattern: fat malabsorption + protein-losing enteropathy (edema, hypoalbuminemia) + lymphocytopenia
• Carbohydrate and amino acid absorption are preserved
• Harrison's Principles of Internal Medicine 22E, p. 1170

D. Short Bowel Syndrome

• Massive small bowel resection (e.g., mesenteric ischemia, Crohn's)
• Critical mass of absorptive surface lost
• Management: enteral/parenteral nutrition, intestinal adaptation, sometimes transplantation

E. Specific Enzyme Deficiencies

• Lactase deficiency: most common, causes osmotic diarrhea, bloating, flatulence with dairy - abates with fasting
• Disaccharidase deficiencies: impair terminal digestion phase
• Abetalipoproteinemia: rare defect in chylomicron formation → fat malabsorption in children; associated with acanthocytic RBCs, ataxia, retinitis pigmentosa

Clinical Features

GI Symptoms

• Chronic diarrhea (bulky, frothy, offensive, greasy stools = steatorrhea)
• Abdominal bloating, distension, flatulence
• Borborygmi (loud bowel sounds)
• Abdominal cramps
• Weight loss, muscle wasting
• Anorexia

Systemic Manifestations (from nutrient deficiencies)

• Goldman-Cecil Medicine, Table 126-5

Investigations

Diagnostic Flowchart

Blood Tests

• CBC: anemia (microcytic = Fe; macrocytic = B12/folate deficiency)
• Serum iron, ferritin, vitamin B12, folate, vitamin A/D/E/K (PT)
• Serum albumin and total protein
• Anti-TTG IgA + total IgA (celiac screening)
• Serum calcium, magnesium, phosphate

Stool Tests

• Qualitative stool fat: Sudan stain (screening)
• Quantitative stool fat (72-hour collection on 100 g/day fat diet): gold standard; >7 g/24 hr = abnormal; sensitivity 90%, specificity 90%
• Stool ova and parasites + Giardia antigen/PCR
• Fecal calprotectin / leukocytes (if inflammatory cause suspected)
• Fecal elastase-1 (for pancreatic exocrine insufficiency)

Breath Tests

• Hydrogen breath test: lactose, fructose malabsorption or SIBO
• 14C or 13C-triolein breath test: fat malabsorption

Imaging

• CT/MR enterography: structural small bowel disease, Crohn's, lymphoma, diverticula
• MRCP / CT pancreas: pancreatic disease

Endoscopy / Biopsy

• Upper GI endoscopy with duodenal biopsies (multiple): mandatory if mucosal disease suspected
• Key histological patterns:
  • Celiac disease: villous atrophy + crypt hyperplasia + intraepithelial lymphocytosis
  • Whipple's: PAS-positive macrophages in lamina propria
  • Tropical sprue: similar to celiac but less severe
  • Giardia: trophozoites on biopsy

Specific Tests

• Secretin stimulation test: pancreatic function
• Small bowel aspirate/culture: SIBO (>10⁵ organisms/mL)
• Serum gastrin: if Zollinger-Ellison suspected
• Serum 7αC4 or fecal bile acids: bile acid diarrhea

Types of Diarrhea - Distinguishing Features

Management Principles

Key Summary Points

• Malabsorption = failure of one or more of four absorption phases (intraluminal, terminal, transepithelial, lymphatic)
• Hallmark: steatorrhea + weight loss + multiple nutritional deficiencies
• Three most common causes in Western countries: pancreatic insufficiency, celiac disease, SIBO
• Celiac disease: HLA DQ2/8, anti-TTG IgA antibody, villous atrophy on biopsy, treat with gluten-free diet
• Whipple's disease: T. whipplei, PAS-positive macrophages, systemic features (arthralgia, fever, CNS)
• Stool fat test (72-hour collection) = best screening test for fat malabsorption
• Management = treat underlying cause + correct nutritional deficiencies

• Robbins, Cotran & Kumar Pathologic Basis of Disease (10th Ed.), Ch. 17
• Robbins & Kumar Basic Pathology, Ch. 13
• Harrison's Principles of Internal Medicine 22E (2025), Ch. 5
• Goldman-Cecil Medicine International Edition, Ch. 126
• Yamada's Textbook of Gastroenterology 7th Ed., Ch. 27

Preterm Labor

Definition

• Initial examination shows cervix ≥2 cm dilated or ≥80% effaced, or
• Interval examinations document progressive effacement or dilation

Epidemiology

• Preterm birth rate before 34 weeks: 20% in twin pregnancies, 63% in triplet pregnancies (US, 2019)
• 55% of twins are low birth weight (<2500 g); 10% are very low birth weight (<1500 g)
• Not all are spontaneous - many are medically indicated preterm births
• Overdiagnosis of preterm labor occurs in 40-70% of women presenting with symptoms, due to imprecise clinical criteria
• Creasy & Resnik's Maternal-Fetal Medicine

Risk Factors

• Textbook of Family Medicine 9e, Table 20-17

Pathophysiology

1. Infection/inflammation - Intrauterine or decidual infection (most common and important) → cytokines (IL-1, IL-6, TNF-α) → prostaglandin synthesis (PGE₂, PGF₂α) → uterine contractions + cervical ripening
2. Uteroplacental ischemia - Placental insufficiency, abruption, preeclampsia → decidual hemorrhage → thrombin → uterine contractions
3. Uterine overdistension - Multiple gestation, polyhydramnios → mechanical stretch → myometrial activation
4. Cervical insufficiency - Structural weakening of the cervix (congenital or acquired) → silent cervical dilation without contractions
5. Premature activation of the fetal HPA axis - Fetal stress → CRH → prostaglandins → labor

Clinical Features / Diagnosis

Symptoms

• Pelvic pressure
• Increased vaginal discharge
• Low backache
• Menstrual-like cramps
• Uterine contractions (painful or painless)
• Symptoms suggest preterm labor more by their persistence than severity

Contractions against a closed, uneffaced cervix tend to be painful; when cervical effacement precedes contractions, recurrent pressure or tightening may be the only symptom.

Diagnostic Criteria

• Contraction frequency ≥6 per hour AND
• Cervical dilation ≥3 cm OR effacement ≥80%

Diagnostic Tests

1. Transvaginal Ultrasound (TVU) Cervical Length

• Measured at 20-24 weeks for risk stratification
• Cervical length ≥30 mm → preterm labor unlikely despite symptoms
• Cervical length <20 mm → 10-fold positive likelihood ratio for delivery before 32 weeks (in twins)
• Cervical length <15 mm in symptomatic women → associated with delivery within 7 days

2. Fetal Fibronectin (fFN)

• Tested in cervicovaginal fluid at 22-35 weeks
• Released from chorion-decidua interface when disrupted
• Used primarily for its high negative predictive value
• Negative fFN → extremely reassuring; patient will likely not deliver for at least 7-10 days
• Positive fFN → warrants closer surveillance or treatment
• Specimen collected before digital examination (contaminated by lubricants, blood, semen)

3. Combination Protocol

• Cervical length >30 mm: low risk - avoid unnecessary treatment
• Cervical length 15-30 mm: perform fFN testing
• Cervical length + fFN both positive: high risk for imminent delivery

Initial Assessment

1. Uterine contraction monitoring + fetal heart rate monitoring (lateral recumbent position)
2. Full history and physical examination (rule out treatable causes, contraindications to tocolysis)
3. Sterile speculum exam if membrane rupture suspected (nitrazine + ferning test)
4. Digital cervical exam only if no rupture suspected
5. Urinalysis and urine culture (UTI as precipitant)
6. Cervical cultures: GBS, Chlamydia, N. gonorrhoeae, HSV
7. Rule out chorioamnionitis: uterine tenderness, fever, leukocytosis, fetal tachycardia
8. Ultrasound: estimated fetal weight, amniotic fluid index, biophysical profile score (low BPP may contraindicate tocolysis)

Management

Step 1: Identify and Treat Precipitating Causes

• UTI → antibiotics
• BV → metronidazole or clindamycin

Step 2: Evaluate for Contraindications to Tocolysis

• Severe preeclampsia / gestational hypertension
• Hemorrhage / placental abruption
• Chorioamnionitis (infection)
• Significant maternal cardiac disease
• Puerperal infection

• Fetal distress / low BPP
• Intrauterine fetal death
• Lethal fetal anomaly
• Gestational age ≥34 weeks (risk of prematurity < risk of tocolysis side effects)

Step 3: Administer Adjunctive Therapies

A. Antenatal Corticosteroids (MOST IMPORTANT)

• Betamethasone 12 mg IM every 24 hours × 2 doses (preferred)
• OR Dexamethasone 6 mg IM every 12 hours × 4 doses
• Indicated for gestational age 24-34 weeks (consider 22-34 weeks in very preterm)
• Benefits: ↓ neonatal death, ↓ RDS, ↓ IVH, ↓ PDA, ↓ NEC
• Mechanism: promotes surfactant synthesis, increases lung compliance, reduces vascular permeability
• Maturational effects on brain, kidneys, and gut also documented
• Creasy & Resnik, p. 898

B. Magnesium Sulfate for Fetal Neuroprotection

• Recommended for anticipated delivery <32 weeks
• Loading dose: 4-6 g IV over 30 minutes, with or without maintenance 1-2 g/hr for 12-24 hours
• Reduces cerebral palsy: RR = 0.68 (95% CI 0.54-0.85) in meta-analysis of 6 trials
• Reduces moderate-to-severe CP: RR = 0.63 (95% CI 0.45-0.89)
• No significant adverse effects on infants at neuroprotective doses
• Creasy & Resnik, p. 901; ACOG recommendation

C. GBS Prophylaxis

• Penicillin or ampicillin IV for all women in preterm labor (preterm infants at higher risk for neonatal GBS)
• Antibiotic therapy to prolong pregnancy is not recommended for preterm labor with intact membranes (unlike pPROM, where antibiotics reduce perinatal morbidity)

Step 4: Tocolysis

Tocolytic Agents

No tocolytic agent has been shown to definitively improve fetal outcome. Choice of agent is less important than patient selection. - Creasy & Resnik, p. 901

Prevention

1. Progesterone Therapy

• Vaginal progesterone 200 mg nightly: reduces preterm birth in women with mid-trimester cervical shortening (CL <25 mm by ultrasound) - most evidence-based preventive therapy
• 17-hydroxyprogesterone caproate (17-OHPC) 250 mg IM weekly: historically used for women with prior spontaneous preterm singleton birth; the PROLONG trial (2020) showed no benefit vs placebo, casting doubt on this indication
• Mechanism: inhibits proinflammatory cytokines, delays cervical ripening
• Role in multiple gestations remains controversial (meta-analyses show no benefit)

2. Cervical Cerclage

• Indicated for documented cervical insufficiency (painless cervical dilation <24 weeks)
• History-indicated cerclage: prior second-trimester loss with painless dilation
• Ultrasound-indicated: cervical length <25 mm before 24 weeks in singleton with prior preterm birth
• Not beneficial in multiple gestations (meta-analyses show no benefit)

3. Cervical Pessary

• Silicone ring placed around cervix to redirect uterine weight
• Meta-analyses: no significant benefit in multiple gestations or unselected populations

4. Education and Surveillance

• Instruct high-risk women on symptoms of preterm labor
• More frequent prenatal visits
• Transvaginal cervical length screening at 18-24 weeks

Regionalized Care

• Level I: Normal obstetric/neonatal care
• Level II: NICU for infants >1500 g
• Level III: Sickest/smallest infants; complex maternal complications
• Level IV: ECMO, complex cardiothoracic surgery

Fetal Complications of Prematurity

Key Summary Points

• Preterm labor = contractions + cervical change before 37 weeks
• Diagnosis is challenging; overdiagnosis in 40-70% - use TVU cervical length + fFN to avoid unnecessary treatment
• Negative fFN = no delivery for ≥7-10 days (excellent NPV); most useful to rule out preterm labor
• Tocolytics (nifedipine first-line) delay delivery 48 hours - do not reduce preterm birth rates; their purpose is to allow corticosteroids and transfer
• Antenatal corticosteroids (betamethasone 24-34 weeks) are the single most important intervention - reduce RDS, IVH, NEC, and neonatal death
• MgSO₄ before 32 weeks for fetal neuroprotection - reduces cerebral palsy by ~32%
• Vaginal progesterone for women with short cervix (<25 mm) is the best-evidenced preventive strategy

• Creasy & Resnik's Maternal-Fetal Medicine: Principles and Practice, Ch. 38
• Goodman & Gilman's The Pharmacological Basis of Therapeutics 14e, Ch. 48
• Textbook of Family Medicine 9e, Ch. 20
• Pfenninger and Fowler's Procedures for Primary Care 3e
• Morgan and Mikhail's Clinical Anesthesiology 7e, Ch. 6