Small Intestine Pathology — Malabsorption and Obstruction

MALABSORPTION: Mechanisms of Nutrient Loss

• Mucosal insufficiency: Loss of absorptive epithelium through villous atrophy, decreased brush border enzyme expression, or increased epithelial turnover. The normal small intestinal mucosa presents with 10-40 villi per transverse section and a villus-to-crypt ratio of 3-5:1. In severe mucosal disease (celiac disease, tropical sprue), this ratio may invert to <1:1 as villi flatten and crypts hyperplasia develops. Reduced surface area directly correlates with decreased nutrient absorption; even 30-50% mucosal loss may remain clinically silent until threshold breached.

• Brush border enzyme deficiency: Disaccharidase deficiency (lactase, sucrase, maltase) and peptidase insufficiency prevent terminal breakdown of nutrients into absorbable monosaccharides and amino acids. Primary lactase deficiency (developmental downregulation after weaning) affects 70% of world population; secondary lactase deficiency occurs with mucosal injury. Unabsorbed disaccharides create osmotic diarrhea via osmotic gradient drawing water into lumen.

• Impaired active transport: Loss of Na+-dependent glucose transporters (SGLT1) and amino acid transporters at brush border, or mitochondrial dysfunction in enterocytes reducing ATP availability for active transport. Selective amino acid malabsorption syndromes (Hartnup disease, cystinuria) result from specific transporter mutations.

• Lipid malabsorption pathophysiology: Requires bile acid solubilization (forming micelles), pancreatic lipase digestion, and chylomicron assembly. Defects at any step impair fat-soluble vitamin (A, D, E, K) absorption. Steatorrhea (>7g fat/day stool) indicates >90% of dietary fat unabsorbed. Unabsorbed long-chain fatty acids bind intraluminal calcium, reducing calcium availability and promoting secondary hyperparathyroidism and osteomalacia.

• Bacterial overgrowth pathophysiology: Small intestinal bacterial overgrowth (SIBO) causes deconjugation of bile acids (reducing fat solubilization), competition for vitamin B12 and carbohydrates, and production of gas and short-chain fatty acids causing osmotic diarrhea. Bacteria may also damage mucosa directly or translocate across epithelium.

OBSTRUCTION: Mechanical Compromise and Ischemic Cascade

• Increased intraluminal pressure: Proximal obstruction creates retrograde distension and increased pressure, initially promoting hypertrophic contractions ("obstructive rushes") and fluid/electrolyte secretion into lumen attempting to overcome blockade. Sustained pressure eventually exhausts muscular function, progressing to ileus and bowel dilatation. Pressure gradient across obstruction site determines rate of decompensation.

• Translocation and bacterial overgrowth: Proximal bowel stasis permits rapid bacterial proliferation (reaching 10^6-10^8 CFU/mL compared to normal 10^1-10^3), producing endotoxins and promoting bacterial translocation across injured mucosa. This initiates systemic inflammatory response syndrome, sepsis, and multi-organ dysfunction in prolonged obstruction.

• Ischemic necrosis cascade: Closed-loop obstructions (volvulus, internal herniation, adhesions with torsion) cause both luminal blockade and vascular compromise. Increased intramural pressure compresses capillaries, first impairing mucosal oxygen delivery (most vulnerable to hypoxia due to high metabolic rate), then progressively involving submucosa, muscularis, and serosa. Transmural infarction develops within 6-8 hours at body temperature, leading to mucosal ulceration, bacterial translocation, and perforation.

• Fluid and electrolyte derangement: Obstruction triggers increased secretion of fluid and electrolytes into proximal bowel (up to 8-10L daily), paradoxically causing dehydration and hypochloremic, hypokalemic metabolic alkalosis (from loss of gastric HCl in high obstructions). Third-spacing of fluid in edematous bowel wall and peritoneal cavity compounds hypovolemia.

MALABSORPTION DISORDERS: Luminal, Mucosal, and Post-mucosal Causes

Luminal/Intraluminal Causes

• Pancreatic insufficiency: Chronic pancreatitis (alcohol, cystic fibrosis, chronic idiopathic pancreatitis), pancreatic cancer, post-pancreatectomy
• Bile acid deficiency: Cholestasis, ileal disease/resection, primary biliary cholangitis
• Bacterial overgrowth: Achlorhydria, strictures, diverticula, fistulae, motility disorders (scleroderma, pseudo-obstruction), immunosuppression

Mucosal/Epithelial Causes

• Celiac disease (tissue transglutaminase antibody-mediated): 1% prevalence with higher rates in genetic predisposition (HLA-DQ2/DQ8); autoimmune destruction of villi
• Crohn disease: Patchy transmural inflammation causing mucosal ulceration and stricture formation
• Tropical sprue: Endemic to Caribbean and Southeast Asia; associated with folate deficiency
• Whipple disease: Tropheryma whipplei infection; predominantly in middle-aged white males
• Intestinal lymphangiectasia: Dilated lacteals with protein-losing enteropathy; primary (congenital) or secondary (malignancy, cardiac disease)
• Virus-associated: Rotavirus, norovirus, enteroviruses cause transient mucosal inflammation
• Systemic sclerosis/scleroderma: Smooth muscle atrophy and fibrosis with bacterial overgrowth
• Short bowel syndrome: Surgical resection, infarction, or congenital agenesis reducing absorptive surface

Post-mucosal (Transport) Causes

• Lymphatic obstruction: Lymphoma (blocking lacteals), carcinoma, cardiac dysfunction
• Protein-losing enteropathy: Increased mucosal permeability from inflammation or lymphatic obstruction

Specific Micronutrient Malabsorption

• Vitamin B12: Terminal ileum disease (Crohn's, tuberculosis), pernicious anemia (autoimmune gastritis)
• Folate: Jejunal mucosal disease, SIBO
• Iron: Celiac disease, achlorhydria, post-gastrectomy
• Calcium/Vitamin D: Fat malabsorption, renal disease, dietary deficiency

OBSTRUCTION: Mechanical and Functional Etiologies

Mechanical Obstruction (80% of cases)

• Adhesions: Most common cause overall (60% of small bowel obstruction cases); result from prior abdominal/pelvic surgery, trauma, or peritonitis
• Hernia: Inguinal, femoral, umbilical, incisional; internal herniation through peritoneal defects
• Malignancy: Primary small bowel cancer (adenocarcinoma, lymphoma, sarcoma) or metastatic disease; accounts for 20% of nonoperative SBO
• Crohn disease: Strictures from transmural inflammation and fibrosis; can be multiple and recurrent
• Volvulus: Axial twisting of intestinal segment around mesentery; associated with prior surgery, adhesions, anatomic predisposition
• Intussusception: Telescoping of proximal bowel into distal segment; most common in children but occurs in adults with pathologic lead point (Meckel's diverticulum, lymphoma, lipoma)
• Foreign body and bezoars: Phytobezoars (plant material), trichobezoars (hair), medication concretions
• Gallstone ileus: Erosion of gallstone through fistula into duodenum; rare but accounts for 1-4% of SBO
• Strictures: Inflammatory (Crohn's, radiation, caustic injury), neoplastic, ischemic

Functional Obstruction (20% of cases)

• Ileus: Postoperative (most common), peritonitis, sepsis, electrolyte derangement (hypokalemia, hypocalcemia), medications (anticholinergics, opioids)
• Pseudo-obstruction (Ogilvie syndrome): Massive colonic dilatation without mechanical blockade; risk factors include major surgery, trauma, severe illness
• Motility disorders: Scleroderma, amyloidosis, diabetic neuropathy, Chagas disease (Trypanosoma cruzi)

Risk Factors

• Abdominal/pelvic surgery history (strongest predictor of adhesions)
• Inflammatory bowel disease history
• Prior malignancy
• Chronic opioid use
• Connective tissue disease (scleroderma)

MALABSORPTION: Spectrum of Nutrient Deficiency Manifestations

Cardinal GI Symptoms

• Chronic diarrhea: Typically watery, ≥3-4 stools daily, often with increased volume (>200g/day fecal weight). Steatorrhea appears greasy, floats, and causes fecal urgency. Osmotic diarrhea (from unabsorbed carbohydrates/disaccharides) temporarily improves with fasting, while secretory diarrhea persists. Urgency and postprandial symptoms suggest small bowel origin.
• Abdominal bloating and distension: Secondary to bacterial overgrowth producing hydrogen and methane gas, or osmotic effect of unabsorbed nutrients drawing water intraluminally. Patient reports fullness after small meals.
• Steatorrhea: Objective finding of fatty stools (>7g/day); indicates fat malabsorption and suggests pancreatic, biliary, or mucosal disease

Systemic Nutritional Deficiency Signs (correlate with absorptive pathology)

Physical Examination Findings

• Wasting/cachexia: Temporal muscle atrophy, loss of subcutaneous fat; indicates chronic protein-energy malnutrition
• Dermatitis and skin changes: Eczematous rash over pressure areas (zinc deficiency); follicular hyperkeratosis (vitamin A deficiency); dermatitis herpetiformis (celiac disease with IgA antibodies against epidermal transglutaminase)
• Glossitis and angular cheilitis: Erythematous, atrophic tongue from B12/folate/iron deficiency
• Edema: Dependent edema from hypoproteinemia (plasma albumin <2.5 g/dL); also periorbital edema
• Abdominal distension with hyperactive/rushes of bowel sounds: Small bowel obstruction pattern
• Hepatomegaly: May occur with cirrhosis from portal hypertension (advanced Crohn's) or from steatosis in protein malnutrition

Lab/Imaging Correlates

• Low albumin (<2.5 g/dL) with low prealbumin (<20 mg/dL) indicating malnutrition
• Elevated fecal fat (72-hour fecal fat >7g/day)
• Anemia: Low hemoglobin, microcytic (iron), macrocytic (B12/folate)
• Hypoproteinemia: Total protein <6 g/dL
• Electrolyte derangement: Hypokalemia, hypocalcemia, hypomagnesemia
• Elevated prothrombin time: Vitamin K malabsorption
• Low 25-hydroxyvitamin D: Fat malabsorption with osteomalacia
• Plain abdominal X-ray: In SIBO, may show air-fluid levels, dilated small bowel loops with "mottled" gas pattern (gas mixed with stool)

OBSTRUCTION: Acute Presentation with Anatomic Progression

Proximal (Duodenum/Jejunum) vs. Distal (Ileum) Obstruction Clinical Differentiation

Cardinal Symptoms (with morphologic correlation)

• Colicky abdominal pain: Cramping, intermittent, every 4-5 minutes in proximal obstruction, every 15-20 minutes distally; represents increased peristaltic amplitude attempting to overcome blockade. Constant pain suggests ischemia/necrosis.
• Bilious vomiting: Green/yellow vomitus (bilirubin from bile in proximal small bowel); occurs early in proximal obstruction, develops later in distal disease
• Abdominal distension: Develops progressively as fluid and gas accumulate proximal to obstruction; more prominent in distal obstruction (less proximal dilatation)
• Obstipation: Absence of flatus and stool; develops acutely in complete obstruction, gradually in partial obstruction

Physical Examination Findings

• Visible peristaltic waves: Waves of muscular contraction crossing abdomen; characteristic of high-grade obstruction and indicates hypertrophic musc

Malabsorption — stepwise workup

• Confirm fat malabsorption: qualitative Sudan III stain of stool screens; quantitative 72-hour fecal fat on a defined fat intake confirms steatorrhea. Fecal elastase-1 is low in exocrine pancreatic insufficiency and normal in mucosal disease, separating luminal from mucosal causes.
• D-xylose absorption test: xylose needs no digestion, only intact mucosa. Low urinary/serum xylose implies mucosal disease or SIBO; normal xylose with steatorrhea implies pancreatic or biliary disease. Xylose corrects after antibiotics in SIBO.
• Celiac disease: the ACG celiac guideline makes IgA tissue transglutaminase (tTG-IgA) with a simultaneous total IgA the first-line serology — selective IgA deficiency is over-represented in celiac and yields false negatives (use IgG-based deamidated gliadin peptide/tTG-IgG then). Testing must occur on a gluten-containing diet. Confirmation is EGD with multiple duodenal biopsies including the bulb: intraepithelial lymphocytosis, crypt hyperplasia, villous atrophy, graded by the Marsh (Marsh–Oberhuber) classification. HLA-DQ2/DQ8 testing has value only for its negative predictive value.
• Whipple disease: small bowel biopsy showing PAS-positive, diastase-resistant foamy macrophages in the lamina propria; confirm with **PCR or immunohistochemistry for *Tropheryma whipplei***. CSF PCR is obtained because CNS involvement changes therapy.
• Other: lactose and glucose hydrogen breath tests for lactase deficiency and SIBO; jejunal aspirate culture is the reference standard for SIBO.

Obstruction

• Upright/supine abdominal radiograph: dilated small bowel loops (>3 cm), air–fluid levels, paucity of colonic gas; free air mandates immediate surgery.
• CT abdomen/pelvis with IV contrast is the test of choice per ACR Appropriateness Criteria: identifies the transition point, cause, closed loop, and strangulation signs — small bowel feces sign, mesenteric edema/whirl, reduced bowel wall enhancement, pneumatosis, portal venous gas.
• Intussusception: ultrasound target/donut sign; air or contrast enema is diagnostic and therapeutic in children.
• Suspected midgut volvulus in a bilious-vomiting infant: upper GI series is the gold standard — corkscrew duodenum, ligament of Treitz displaced right.

Malabsorption

• Celiac disease: the ACG celiac guideline specifies a lifelong strict gluten-free diet (wheat, rye, barley) with formal dietitian referral as the only established therapy; repletion of iron, folate, B12, calcium and vitamin D, plus DEXA for metabolic bone disease. Serologies fall with adherence and are used for follow-up. Refractory celiac disease is treated with corticosteroids (budesonide) at referral centers; do not start a gluten-free diet before biopsy, as it invalidates testing.
• Whipple disease: parenteral induction with a third-generation cephalosporin (ceftriaxone), or penicillin G, for roughly two weeks because of the need for CNS penetration, followed by prolonged oral trimethoprim-sulfamethoxazole for about a year. Short courses invite CNS relapse.
• SIBO: a nonabsorbed rifamycin antibiotic (rifaximin); correct the underlying stasis (stricture, blind loop, dysmotility).
• Pancreatic insufficiency: pancreatic enzyme replacement therapy with meals plus fat-soluble vitamin supplementation.
• Lactase deficiency: lactose restriction or exogenous lactase; calcium/vitamin D to protect bone.

Small bowel obstruction — in clinical order

• Immediate stabilization: NPO, large-bore IV isotonic crystalloid resuscitation, correction of the hypokalemic hypochloremic alkalosis, nasogastric decompression for vomiting/distension, foley for urine output, serial abdominal exams and lactate.
• Nonoperative trial: for adhesive, non-strangulated, partial obstruction, EAST guidelines support a nonoperative trial of a few days with a water-soluble contrast (Gastrografin) challenge, which is both prognostic and therapeutic — contrast reaching the colon predicts resolution.
• Surgery (laparotomy/laparoscopic adhesiolysis with resection of nonviable bowel) for peritonitis, closed-loop or strangulated obstruction, complete obstruction, failure of nonoperative management, or obstruction in a "virgin abdomen". Malrotation with midgut volvulus requires emergent Ladd procedure.
• Contraindicated/avoid: antimotility agents and heavy opioid loading, prolonged temporizing when strangulation is suspected, and enema reduction of intussusception in the setting of perforation, peritonitis, or shock.

Complications of malabsorption

• Enteropathy-associated T-cell lymphoma (EATL) and small bowel adenocarcinoma: chronic gluten-driven mucosal lymphoproliferation in celiac disease. Signal — a previously well-controlled patient develops recurrent diarrhea, weight loss, abdominal pain, or obstruction despite dietary adherence; this is refractory celiac disease until lymphoma is excluded by imaging and repeat biopsy.
• Metabolic bone disease: fat malabsorption depletes vitamin D and luminal fatty acids chelate calcium, driving secondary hyperparathyroidism → osteomalacia/osteoporosis with bone pain and fragility fractures.
• Coagulopathy: vitamin K malabsorption → prolonged PT/INR correcting with parenteral vitamin K.
• Functional hyposplenism in celiac disease → risk of encapsulated organism sepsis; pneumococcal vaccination is advised.
• Subacute combined degeneration: B12 deficiency from ileal disease; dorsal column and corticospinal signs may be irreversible — treat before folate to avoid masking.
• Refeeding syndrome (treatment complication): insulin surge drives phosphate, potassium, and magnesium intracellularly. Hypophosphatemia with arrhythmia, heart failure, or respiratory failure is an emergency; repletion must be slow with thiamine.
• Immune reconstitution inflammatory syndrome after starting antibiotics for Whipple disease: fever and worsening inflammation days to weeks into therapy; treated with corticosteroids. CNS relapse (oculomasticatory myorhythmia, dementia, supranuclear gaze palsy) is the feared long-term outcome.

Complications of obstruction

• Strangulation and transmural infarction — surgical emergency: closed-loop physiology raises intramural pressure above capillary perfusion pressure. Signals are constant (rather than colicky) pain, fever, tachycardia, peritoneal signs, leukocytosis, rising lactate/metabolic acidosis, and CT showing nonenhancing bowel wall, pneumatosis, or portal venous gas.
• Perforation with feculent peritonitis and septic shock from bacterial translocation — emergency; free air on imaging.
• Aspiration pneumonitis from vomiting against a distended proximal bowel.
• Hypovolemic shock and acute kidney injury from third-spacing and secretory losses.
• Post-treatment: short bowel syndrome after extensive resection, anastomotic leak, recurrent adhesive obstruction, and recurrence of intussusception after enema reduction (typically within the first day, warranting observation).

• Celiac serology order matters: tTG-IgA plus total IgA, drawn while eating gluten. A negative tTG-IgA in a patient with selective IgA deficiency is the classic trap — the next step is an IgG-based test, not reassurance. Definitive diagnosis still requires duodenal biopsy.
• Buzzword mapping: villous atrophy with crypt hyperplasia and intraepithelial lymphocytes = celiac; PAS-positive foamy macrophages = Whipple disease; dermatitis herpetiformis (pruritic vesicles on extensor surfaces, IgA at dermal papillae) is essentially pathognomonic for celiac and responds to a gluten-free diet, with dapsone for the rash.
• The association examiners love: celiac disease with HLA-DQ2/DQ8, IgA deficiency, type 1 diabetes, autoimmune thyroid disease, and EATL. Note that the USPSTF found evidence insufficient to screen asymptomatic adults — test only when clinically suspected.
• Bilious vomiting in a neonate = malrotation with midgut volvulus until disproven. Best next step is an upper GI series (corkscrew duodenum), then emergent Ladd procedure. Do not order a barium enema first.
• Intussusception: child with currant jelly stool, sausage-shaped mass, and intermittent drawing-up of the legs; ultrasound target sign, then air enema. In an adult, always hunt for a pathologic lead point (tumor, Meckel diverticulum) — adults get resection, not enema.
• D-xylose logic: abnormal = mucosal problem or SIBO; normal with steatorrhea = pancreatic/biliary problem. Low fecal elastase points to the pancreas.
• Colicky pain becoming constant in an obstructed patient, with fever, tachycardia, peritonitis, and rising lactate, means strangulation → operating room, not another day of nasogastric decompression.
• Common distractor: adhesions are the leading cause of small bowel obstruction in adults with prior surgery, but obstruction in a "virgin abdomen" should push you toward hernia, malignancy, or Crohn stricture — and toward operative exploration.