---

Histology of the Digestive System

---

I. General Wall Structure of the GI Tract

1. Mucosa

• Epithelium: varies by region (stratified squamous, simple columnar, etc.)
• Lamina propria: loose connective tissue with capillaries, lymphatics, free immune cells (macrophages, lymphocytes, IgA-secreting plasma cells), and small glands
• Muscularis mucosae: thin inner circular + outer longitudinal smooth muscle; permits local mucosal movements

2. Submucosa

• Denser connective tissue with larger blood vessels, lymphatics, adipose tissue
• Contains Meissner (submucosal) plexus of autonomic ganglia
• May contain glands (e.g., Brunner's glands in the duodenum) and lymphoid tissue (MALT)

3. Muscularis (Muscularis Externa)

• Two smooth muscle sublayers: inner circular + outer longitudinal
• Myenteric (Auerbach) plexus between the layers: generates and coordinates peristalsis
• Together with the Meissner plexus, forms the enteric nervous system
• Exception: the upper esophagus has striated muscle

4. Serosa / Adventitia

• Stomach and intestines: serosa = loose connective tissue covered by simple squamous mesothelium, continuous with the mesentery
• Esophagus and retroperitoneal portions: adventitia = connective tissue blending with surrounding structures (no mesothelial cover)

---

II. Oral Cavity

Mucosa

• Lining mucosa (cheeks, soft palate, floor of mouth, oral pharynx): nonkeratinized stratified squamous epithelium over a thick submucosa with minor salivary glands
• Masticatory mucosa (hard palate, gingiva): keratinized stratified squamous epithelium; lamina propria attaches directly to periosteum
• Both regions contain antigen-presenting cells and dense sensory innervation

Lips

• Internal surface: nonkeratinized lining mucosa + labial salivary glands
• Vermilion zone: thin keratinized epithelium, richly vascularized (imparts the red color), no sweat or sebaceous glands - prone to dryness
• External surface: typical skin with hair follicles and sweat glands
• Core: striated muscle for mobility

Tongue

• Mass of striated muscle running in three planes, covered by mucosa; lamina propria penetrates between fascicles, making mucosa firmly adherent
• Lower surface: typical lining mucosa
• Dorsal surface: four types of lingual papillae:

• Gustatory (taste) cells: microvilli projecting through apical taste pore; synapse with afferent sensory axons at base
• Supporting cells: poorly understood function
• Basal stem cells: regenerate gustatory and supporting cells

Teeth

• Enamel: covers crown and neck; the hardest tissue in the body; formed by ameloblasts (columnar epithelial cells of the enamel organ) which deposit parallel enamel rods guided by the protein amelogenin; ameloblasts are lost after tooth eruption - enamel cannot regenerate
• Dentin: makes up the roots and extends to the neck; secreted as predentin (with dentinal tubules) by tall odontoblasts lining the pulp cavity; odontoblast processes persist in tubules of the mature tooth
• Cementum: thin bone-like layer surrounding dentin of roots; part of the periodontium
• Periodontal ligament: binds cementum to alveolar bone
• Pulp cavity: vascularized and innervated central cavity lined by odontoblasts

---

III. Salivary Glands (Accessory Organs)

• Serous: pyramidal, basophilic cytoplasm (rER), apical zymogen granules; secrete amylase, lysozyme
• Mucous: columnar; pale cytoplasm (mucin granules displace nucleus basally); secrete mucins

1. Intercalated ducts: lined by low cuboidal epithelium; connect acini to striated ducts
2. Striated (excretory) ducts: columnar cells with prominent basolateral plasma membrane infoldings and mitochondria (visible as striations); active in Na+ reabsorption and K+ secretion, making saliva hypotonic
3. Interlobular ducts: larger; pseudostratified then stratified columnar epithelium

---

IV. Esophagus

• Epithelium: nonkeratinized stratified squamous - protects against abrasion
• Lamina propria: loose CT; contains esophageal cardiac glands near cardia (secrete mucus)
• Submucosa: esophageal glands proper (branched tubulo-acinar mucous glands) scattered along the entire length - produce lubricating mucus
• Muscularis:
  • Superior third: striated muscle (under voluntary control)
  • Middle third: mixed striated + smooth
  • Inferior third: smooth muscle only
• Outer coat: adventitia along most of its length (no mesothelium), merging with mediastinal tissue; becomes serosa at the abdominal segment
• Esophagogastric junction: abrupt transition from stratified squamous to simple columnar epithelium; adventitia replaced by serosa

---

V. Stomach

Regions

Wall layers

• Epithelium: simple columnar (surface mucous cells) lining the lumen and the gastric pits (foveolae gastricae)
• Surface mucous cells: secrete a thick gel of viscous mucus + bicarbonate ions, forming a protective unstirred layer

Gastric Glands (Fundus/Body)

Cardiac and Pyloric Regions

• Cardiac glands: branching tubular; almost entirely columnar mucous cells; absent parietal and chief cells
• Pyloric glands: similar; G cells (gastrin-secreting) abundant here
• Pyloric sphincter: prominent thickening of the inner circular smooth muscle

---

VI. Small Intestine

Three Regions

Mucosa

• Epithelium: simple columnar lining villi and crypts (intestinal glands / crypts of Lieberkühn)
• Villi: finger-like projections of epithelium over a lamina propria core containing capillaries, lymphatics, and a central lacteal (lymph capillary for fat absorption)
• Crypts of Lieberkühn: simple tubular glands between villi base; contain stem cells

Cell Types of the Intestinal Epithelium

Fat Absorption

---

VII. Large Intestine (Colon)

• No villi - flat mucosal surface
• Epithelium: simple columnar
• Intestinal glands: millions of simple tubular crypts, lined by:
  • Colonocytes (absorptive cells): absorb water and electrolytes
  • Goblet cells: very abundant (more than in small intestine); produce copious mucus for lubrication of feces
• Lamina propria: rich in lymphocytes and plasma cells
• Muscularis: outer longitudinal layer condensed into three teniae coli (bands of smooth muscle visible externally); between the bands the wall bulges into haustra
• Serosa: covers the outer surface
• Appendix: blind-ending diverticulum of the cecum; thin mucosa with short crypts; abundant lymphoid nodules in lamina propria and submucosa (MALT organ)

---

VIII. Anal Canal

• Transition zone: simple columnar of rectum abruptly shifts to stratified squamous epithelium (at the pectinate/dentate line)
• Stratified squamous epithelium of the anal canal has no skin appendages, unlike the perianal skin below the anus
• Internal anal sphincter: thickening of the circular smooth muscle of the muscularis
• External anal sphincter: striated (skeletal) muscle under voluntary control

---

IX. Liver

Structural Organization

• Blood flows from portal triads inward to the central vein (portal → sinusoids → central vein)
• Bile flows outward from hepatocytes → bile canaliculi → canal of Hering → interlobular bile ducts in portal triads

Hepatocytes

• Large polygonal cells; one or two round nuclei (often polyploid); abundant rER, sER, Golgi, mitochondria, and glycogen
• Arranged in hepatic plates (1-2 cells thick) that radiate from central vein to portal tracts
• Secretion: bile (exocrine) and plasma proteins - albumin, clotting factors, lipoproteins (endocrine)

Sinusoids

• Wide, fenestrated capillaries lined by sinusoidal endothelial cells (with large fenestrae, no diaphragm or basal lamina) between hepatic plates
• Space of Disse: narrow perisinusoidal space between endothelium and hepatocytes; contains hepatic stellate cells (Ito cells/lipocytes) - normally store vitamin A as lipid droplets; activated in injury they produce collagen (fibrosis/cirrhosis)
• Kupffer cells: resident macrophages lining sinusoids; phagocytose bacteria, debris, old erythrocytes

Bile Canaliculi

• Tiny grooves between adjacent hepatocytes formed by specialized apical membrane domains sealed by tight junctions
• Not separate ducts - simply modified intercellular space
• Bile flows toward portal triads → enters bile ductules (canal of Hering, lined by cholangiocytes)

Portal Triad Contents

• Branch of portal vein (largest, thin wall)
• Branch of hepatic artery (thicker wall, smaller lumen)
• Bile ductule (simple cuboidal epithelium / cholangiocytes)
• Lymphatic vessels and autonomic nerves

---

X. Gallbladder

• Mucosa: simple columnar epithelium with tall cells having apical microvilli; highly folded into irregular rugae (especially when contracted/empty); lamina propria with no glands (except near neck)
• Muscularis: irregularly arranged smooth muscle bundles (no distinct layers)
• Perimuscular connective tissue: replaces submucosa; contains nerves, vessels
• Serosa/adventitia: upper (hepatic) surface is adventitia; free surface is serosa
• Rokitansky-Aschoff sinuses: invaginations of the epithelium through the muscularis into the perimuscular connective tissue - become more pronounced in chronic cholecystitis
• Function: concentrates and stores bile by actively absorbing Na+, Cl-, and water from bile

---

XI. Pancreas

Exocrine Pancreas (~99% of mass)

• Acinar cells: pyramidal; arranged in grape-like acini
  • Basophilic base (abundant rER for enzyme synthesis)
  • Apical zymogen granules (eosinophilic): contain digestive enzyme precursors (trypsinogen, chymotrypsinogen, proelastase, lipase, amylase)
  • Release enzymes into acinar lumen by exocytosis, stimulated by CCK and vagal input
• Centroacinar cells: flattened pale cells that extend from duct epithelium into the acinar lumen; secrete bicarbonate-rich fluid (stimulated by secretin)
• Duct system: intercalated ducts → interlobular ducts → main pancreatic duct

Endocrine Pancreas - Islets of Langerhans (~1% of mass)

• Compact, pale-staining spherical clusters scattered within the exocrine tissue; well vascularized
• Cell types:

---

Summary Table: Epithelial Types at a Glance

---