Small Intestine

UBERON:0002108 · Atlas One / Scale 06 — Organ · Digestive

The principal site of nutrient digestion and absorption — spanning from the pyloric sphincter to the ileocaecal valve. Three hierarchical surface amplifications achieve ~250 m² from a 2.5–3 cm diameter tube: plica circulares (Kerckring folds), villi (0.5–1.5 mm finger-like projections with central lacteals), and microvilli (brush border, ~2 µm). Each villus is renewed every 3–5 days from LGR5+ intestinal stem cells (ISCs) in crypts of Lieberkühn. Enterocytes absorb sugars (SGLT1/GLUT5 apical → GLUT2 basolateral), amino acids (PepT1, multiple SLC family transporters), and fats (chylomicrons → lacteals → thoracic duct). The ileum specifically absorbs vitamin B12 (cubilin/amnionless receptor) and bile acids (ASBT, 95% recovery per cycle). The enteroendocrine system constitutes the body's largest endocrine organ by cell number.

Overview

The small intestine is a 6–7 m convoluted tube spanning from the pyloric sphincter to the ileocaecal valve — the principal site of nutrient digestion and absorption in the human body. Divided into three anatomically and functionally distinct segments: the duodenum (25–30 cm, C-shaped, fixed retroperitoneal), jejunum (~2.5 m, proximal mobile small bowel), and ileum (~3.5 m, distal mobile small bowel). Despite its modest luminal diameter (2.5–3 cm), the small intestine achieves a total absorptive surface area of approximately 250 m² through three hierarchical surface amplifications.

The small intestine is not merely an absorptive tube. Its enteroendocrine system constitutes the largest endocrine organ in the body by cell number, secreting more than 20 peptide hormones — including CCK, secretin, GIP, GLP-1, GLP-2, and PYY — that coordinate digestion, appetite, and metabolic homeostasis. Its immune apparatus (Peyer's patches, intraepithelial lymphocytes, lamina propria lymphocytes) provides the intestinal mucosal firewall against luminal pathogens while maintaining tolerance to dietary antigens.

Anatomy — Three Segments and Wall Structure

Duodenum (25–30 cm, C-shaped, retroperitoneal): The superior (first) part — duodenal cap — is most vulnerable to peptic ulceration. Second (descending) part receives bile and pancreatic juice via the major duodenal papilla (ampulla of Vater, sphincter of Oddi) and minor papilla (accessory pancreatic duct). Fourth part passes the ligament of Treitz (upper/lower GI bleeding landmark). Brunner's glands in the submucosa secrete alkaline mucus (pH 8.1–9.3) to neutralise acid chyme. Iron and calcium absorbed primarily here.

Jejunum (~2.5 m): Wider lumen, thicker wall, more prominent plica circulares and villi per cm². Majority of carbohydrate, protein, and fat absorbed here. Fewer goblet cells, more enterocytes per villus than ileum.

Ileum (~3.5 m): Narrower, less prominent folds. Specialised for vitamin B12-intrinsic factor complex absorption (cubilin/amnionless [CUBAM] receptor → transcytosis → transcobalamin II), bile acid reabsorption (ASBT/SLC10A2 apical → IBABP intracellular → OSTα/β basolateral → portal circulation → hepatic NTCP reuptake — ~95% recovery per enterohepatic cycle), and immune surveillance (20–30 Peyer's patches in terminal ileum).

Layer	Key features
Mucosa	Epithelium (enterocytes, goblet, Paneth, enteroendocrine, tuft, M-cells) + lamina propria (capillaries, lacteal, immune cells, IgA plasma cells) + muscularis mucosae
Submucosa	Meissner's (submucosal) plexus; Brunner's glands (duodenum only)
Muscularis externa	Inner circular + outer longitudinal; Auerbach's (myenteric) plexus; interstitial cells of Cajal (ICCs) as pacemakers for peristalsis
Serosa	Visceral peritoneum (absent over retroperitoneal duodenum)

Cell type	Proportion	Location	Function
Enterocytes	~80%	Villus surface	Absorption; brush border enzymes (lactase, sucrase-isomaltase); SGLT1, GLUT5, PepT1, CD36
Goblet cells	~15%	Villi + crypts	MUC2 mucin secretion → gel-forming mucus layer
Paneth cells	Rare	Crypt base only	α-defensins (cryptdins), lysozyme, REG3γ — antimicrobial; support LGR5+ ISC niche
Enteroendocrine cells	~1%	Villi + crypts	Hormone secretion (CCK, secretin, GIP, GLP-1/2, PYY, serotonin)
Tuft cells	~0.4%	Villi	Chemosensory; IL-25 → ILC2 → Th2 immunity against helminths/protozoa
M-cells	Rare	Follicle-associated epithelium over Peyer's patches	Antigen sampling for Peyer's patches; entry site for some pathogens

Function — Nutrient Absorption and Enteroendocrine Axis

CARBOHYDRATE ABSORPTION (Enterocyte — Brush Border → Basolateral)
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Luminal starch → salivary + pancreatic amylase → dextrins + maltose
Brush border:
  Lactase (LCT)           : lactose → galactose + glucose
  Sucrase-isomaltase (SI) : sucrose → glucose + fructose; maltose → glucose
  Glucoamylase            : maltooligosaccharides → glucose

Apical uptake:
  SGLT1 (SLC5A1) — Na⁺-coupled glucose/galactose (against gradient; driven by Na⁺/K⁺-ATPase)
  GLUT5 (SLC2A5) — facilitated fructose uptake (concentration gradient)

Basolateral export to portal blood:
  GLUT2 (SLC2A2) — all three monosaccharides → portal vein → liver

PROTEIN ABSORPTION
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Gastric pepsin + pancreatic endopeptidases (trypsin, chymotrypsin, elastase)
+ carboxypeptidases → oligopeptides + amino acids

Brush border peptidases → dipeptides, tripeptides, amino acids

  PepT1 (SLC15A1) — H⁺-coupled di/tripeptide uptake (high capacity)
    Clinically exploited by prodrugs: valacyclovir, enalapril
  Amino acid transporters: rBAT/b⁰,+AT (cationic), ASCT2 (neutral), SLC6A19/B0AT1
    (neutral — mutated in Hartnup disease → niacin deficiency + pellagra-like symptoms)

FAT ABSORPTION
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
TG → emulsified by bile salts (micelles) → pancreatic lipase + colipase
  → fatty acids + 2-monoacylglycerol

Enterocyte apical uptake:
  Passive diffusion of FFA + CD36/FAT (long-chain FA)
  Re-esterification in ER → TG → assembled into CHYLOMICRONS
    (TG core + ApoB-48, ApoA-I/IV, ApoE; MTP essential — abetalipoproteinaemia = MTP mutation)
  Chylomicrons exocytosed basolaterally → enter lacteal (central villus lymphatic)
    → thoracic duct → left subclavian vein (bypass portal circulation entirely)

Fat-soluble vitamins A, D, E, K absorbed with fat → same chylomicron route

ENTEROENDOCRINE HORMONES
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
CCK       (I-cell, duodenum/jejunum): fat + protein → gallbladder contraction + pancreatic enzymes + satiety
Secretin  (S-cell, duodenum): luminal acid (pH <4) → pancreatic HCO₃⁻ + ↓gastric acid
GIP       (K-cell, duodenum/jejunum): glucose + fat → incretin (↑insulin glucose-dependently) + ↓gastric motility
GLP-1     (L-cell, ileum/colon): glucose + fat + SCFAs → potent incretin + ↓glucagon + ↑satiety + slow gastric emptying
           → TARGET of semaglutide (GLP-1 receptor agonist — type 2 diabetes + obesity)
GLP-2     (L-cell): nutrients → intestinal trophism + ↑blood flow + ↑epithelial proliferation
PYY       (L-cell, ileum/colon): fat + protein → ileal brake (↓appetite, ↓gastric motility)
5-HT      (EC-cell, throughout): mechanical/chemical → peristaltic reflex via 5-HT3/4 on ENS neurons

Motility — Migratory Motor Complex

Two patterns coordinate digestion: Segmental contractions (fed state) — rhythmic, non-propagating contractions of circular muscle → mixing chyme with digestive secretions and repeated contact with absorptive surface. Peristalsis — aboral propagating contractions (ascending excitation + descending inhibition, via myenteric plexus) → net aboral movement of chyme.

Migratory Motor Complex (MMC, fasted state) — cyclic ~90 min activity complex: Phase I (quiescence, ~45 min) → Phase II (irregular contractions, ~30 min) → Phase III ("housekeeper wave," 5–10 min): intense high-amplitude contractions sweep residue, bacteria, and sloughed cells from stomach to ileum; driven by motilin (duodenum, every 90 min during fasting) + 5-HT. Loss of MMC (e.g., opioids, scleroderma autonomic neuropathy) → small intestinal bacterial overgrowth (SIBO).

Pathology

Coeliac Disease (Gluten-Sensitive Enteropathy)

Immune-mediated enteropathy in HLA-DQ2 (~90%) or HLA-DQ8 (~5%) individuals triggered by gluten (gliadin from wheat, rye, barley). Tissue transglutaminase (tTG) deamidates gliadin → enhanced HLA-DQ2/8 binding → CD4+ T cell activation → Th1 → mucosal inflammation. Histology: villous atrophy (Marsh III), crypt hyperplasia, ↑intraepithelial lymphocytes (IELs). Malabsorption of fat (steatorrhoea), iron (anaemia), Ca²⁺ (osteoporosis), B vitamins. Serology: anti-tTG IgA (>90% sensitivity/specificity). Treat: lifelong gluten-free diet → villous restoration within 2 years. Complications: refractory coeliac, EATL (enteropathy-associated T-cell lymphoma).

Crohn's Disease (Small Bowel)

Transmural, granulomatous, chronic inflammatory bowel disease; predilection for terminal ileum and ileocolon. Pathogenesis: NOD2/CARD15, ATG16L1, IL23R mutations + dysbiosis + mucosal barrier defect → aberrant innate + adaptive immune activation → transmural inflammation. Features: skip lesions, cobblestone mucosa, deep fissuring ulcers, non-caseating granulomata (histological hallmark), strictures (fibrosis), fistulae (enterocutaneous, enteroenteric, enterovesical, perianal). Complications: SBO (strictures), B12 malabsorption + bile acid depletion with terminal ileal disease, abscesses. Treat: steroids (acute), azathioprine/6-MP (maintenance), anti-TNF (adalimumab, infliximab), anti-integrin (vedolizumab), anti-IL-12/23 (ustekinumab).

SIBO (Small Intestinal Bacterial Overgrowth)

Overgrowth of colonic-type bacteria (>10⁵ CFU/mL on jejunal aspirate; H₂ breath test). Causes: anatomical (strictures, Roux-en-Y, small bowel diverticula), motility disorders (diabetes autonomic neuropathy — ICC dysfunction; scleroderma — MMC loss), achlorhydria, immune deficiency. Consequences: bile acid deconjugation → fat malabsorption + diarrhoea; B12 consumption → megaloblastic anaemia; gas production → bloating. Treat: rifaximin (first-line); address underlying cause.

Small Intestinal NET / Carcinoid

Most common primary small intestinal malignancy; arise from enterochromaffin cells, predominantly distal ileum, often multifocal. Secrete serotonin (5-HT), substance P, bradykinin → carcinoid syndrome (flushing, diarrhoea, right-sided valvular disease [carcinoid plaques], bronchospasm) — occurs when hepatic metastases secrete directly into systemic circulation. Diagnose: plasma chromogranin A, 24h urine 5-HIAA, ⁶⁸Ga-DOTATATE PET. Treat: surgical resection; somatostatin analogues (octreotide/lanreotide); PRRT for metastatic disease.

Cross-Atlas Connections

Part ofDigestive System Receives fromStomach Delivers toLiver (portal vein) RegulatesPancreas (CCK, secretin, GIP) ContainsIntestinal Epithelium Infected byNorovirus Infected byRotavirus Infected byGiardia lamblia

References

Hall JE, Hall ME. Guyton and Hall Textbook of Medical Physiology. 14th ed. Elsevier; 2021. elsevier.com
Berg JM, Tymoczko JL, Stryer L. Biochemistry. 9th ed. W.H. Freeman; 2019. macmillanlearning.com
Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab. 2018;27(4):740–56. doi:10.1016/j.cmet.2018.03.001
Barker N, van Es JH, Kuipers J, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007;449(7165):1003–7. doi:10.1038/nature06196