Digestive System: Comprehensive Guide

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1. MOUTH (Oral Cavity)

Anatomy

• Teeth: Incisors (cutting force ~55 lbs), molars (grinding force ~200 lbs)
• Tongue: Manipulates food, initiates the voluntary phase of swallowing
• Salivary glands (parotid, submandibular, sublingual): secrete saliva (~1.5 L/day)

Mechanical Digestion: Mastication (Chewing)

Chemical Digestion

• Salivary amylase (ptyalin): begins starch hydrolysis (cleaves α-1,4 glycosidic bonds)
• Lingual lipase: minor initial fat digestion
• Saliva maintains oral pH (~6.8–7.0) and lubricates the bolus with mucin

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2. PHARYNX

Anatomy

• Nasopharynx (above soft palate)
• Oropharynx (behind mouth)
• Laryngopharynx (connects to larynx and esophagus)
• Key structures: soft palate, epiglottis, palatopharyngeal folds, tonsillar pillars, upper esophageal sphincter (UES)

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3. DEGLUTITION (Swallowing)

Stage 1 — Voluntary

Stage 2 — Pharyngeal (Involuntary)

1. Soft palate elevates → closes posterior nares (prevents nasal reflux)
2. Palatopharyngeal folds approximate → form a slit (food filter)
3. Vocal cords approximate; larynx pulled upward and anteriorly; epiglottis tips backward over the glottis (prevents aspiration)
4. UES relaxes → food enters esophagus
5. Respiration is inhibited throughout this stage

Stage 3 — Esophageal (Involuntary)

Sphincters

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4. ESOPHAGUS

• A muscular tube ~25 cm long
• Upper third: striated muscle; lower two-thirds: smooth muscle; middle third: mixed
• Lined by non-keratinized stratified squamous epithelium
• Produces no digestive enzymes — purely transport
• Peristalsis (primary and secondary) drives bolus to stomach

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5. STOMACH

Anatomy

• Corpus/fundus: Parietal cells + chief cells + ECL cells + mucus neck cells
• Antrum: G cells (gastrin) + D cells (somatostatin) — no parietal cells

Cell Types and Secretions

Gastric Acid Secretion

1. Gastrin → G receptor on parietal cell + ECL cell → ↑Ca²⁺ signaling
2. Histamine → H₂ receptor on parietal cell → ↑cAMP → activates proton pump
3. Acetylcholine (vagal) → M₃ receptor → ↑Ca²⁺ signaling

Gastric Motor Functions

1. Receiving food (receptive relaxation of fundus — VIP-mediated)
2. Mixing (antral contractions grind food into chyme)
3. Grinding (retrograde peristalsis)
4. Emptying through pylorus into duodenum (regulated by duodenal feedback — CCK, secretin slow emptying)

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6. PANCREAS

Exocrine Pancreas

• Secretin (from S cells of duodenum, triggered by acid): stimulates bicarbonate-rich pancreatic secretion
• CCK (from I cells, triggered by fats and proteins): stimulates enzyme-rich secretion

Endocrine Pancreas (Islets of Langerhans)

• α cells → Glucagon
• β cells → Insulin
• δ cells → Somatostatin

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7. LIVER AND GALLBLADDER

Liver

• Hepatocytes produce ~600–1000 mL bile/day
• Primary bile acids: cholic acid and chenodeoxycholic acid (conjugated with glycine or taurine → bile salts)
• Bile salts emulsify dietary fats → form micelles → dramatically increase surface area for lipase action
• Bile also contains: bilirubin, cholesterol, phospholipids, water, ions

Gallbladder

• Stores and concentrates bile (10× concentration by absorbing water and electrolytes)
• Contraction triggered by CCK (released when fat/protein enters the duodenum)
• Bile is released via common bile duct → ampulla of Vater → duodenum
• Sphincter of Oddi regulates flow into the duodenum

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8. SMALL INTESTINE

Anatomical Adaptations for Absorption

1. Plicae circulares (circular folds) — permanent mucosal folds
2. Villi — finger-like projections of mucosa (~1 mm tall)
3. Microvilli (brush border) — on each enterocyte, expressing digestive enzymes

Duodenum

• Receives chyme + pancreatic juice + bile
• Brunner's glands secrete alkaline mucus (protects from acid)
• Site of iron absorption and calcium absorption

Jejunum

• Principal site for absorption of most nutrients (carbohydrates, proteins, fats, fat-soluble vitamins)
• High density of villi

Ileum

• Absorbs vitamin B₁₂–intrinsic factor complex (specific receptor: cubam)
• Bile salt reabsorption (enterohepatic circulation — ~95% recycled)
• Contains Peyer's patches (lymphoid tissue, immune surveillance)

Intestinal Motility

• Segmentation contractions: mixing
• Peristalsis: propulsion
• Migrating motor complex (MMC): housekeeping between meals

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9. LARGE INTESTINE

Functions

1. Water and electrolyte absorption (~1.5 L/day absorbed; only ~100–200 mL excreted in feces)
2. Na⁺ absorption mechanisms (Medical Physiology):
   • Nutrient-coupled (jejunum/ileum)
   • Electroneutral NaCl absorption via parallel Na-H/Cl-HCO₃ exchangers (ileum + proximal colon)
   • Electrogenic Na⁺ absorption via ENaC (distal colon — aldosterone-regulated; key in Na⁺ conservation)
3. Fermentation of undigested carbohydrates by colonic bacteria → short-chain fatty acids (SCFAs), gases (CO₂, H₂, CH₄)
4. Feces formation: bacteria, sloughed epithelial cells, undigested material, water

The Appendix

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10. PHASES OF DIGESTION

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11. MECHANICAL DIGESTION

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12. CHEMICAL DIGESTION

Carbohydrates

• Mouth: salivary amylase → maltose + dextrins
• Small intestine: pancreatic amylase → disaccharides; brush border enzymes (maltase, sucrase, lactase) → monosaccharides (glucose, fructose, galactose)

Proteins

• Stomach: pepsin (endopeptidase) begins denaturation and cleavage
• Small intestine: trypsin, chymotrypsin, elastase (endopeptidases) + carboxypeptidase A/B (exopeptidases) → dipeptides/tripeptides + amino acids; brush border peptidases → free amino acids

Fats

• Mouth/stomach: lingual + gastric lipase (minor)
• Small intestine: bile salts emulsify → pancreatic lipase + colipase → fatty acids + 2-monoglycerides → incorporate into micelles → absorbed by enterocytes → re-esterified into triglycerides → packaged into chylomicrons → secreted into lymph (lacteals)

Nucleic Acids

• Pancreatic DNase and RNase → nucleotides
• Brush border nucleotidases + nucleosidases → bases + sugars + phosphate

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13. ABSORPTION OF NUTRIENTS

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14. DISORDERS

14.1 Gastroesophageal Reflux Disease (GERD)

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14.2 Peptic Ulcer Disease (PUD)

1. H. pylori infection (~70–90% of duodenal ulcers; ~60–70% of gastric ulcers) — urease → ammonia → mucosal damage; disrupts protective mucus layer; upregulates gastrin
2. NSAIDs — inhibit COX-1 → ↓prostaglandin synthesis → ↓mucus/bicarbonate secretion + ↓mucosal blood flow
3. Zollinger-Ellison syndrome — gastrin-secreting tumor → massive acid hypersecretion

• H. pylori eradication: Triple therapy — PPI + clarithromycin + amoxicillin (×14 days); or bismuth quadruple therapy
• NSAID ulcers: stop NSAID + PPI (4–8 weeks); misoprostol for prevention
• Complications: surgical intervention for perforation, uncontrolled bleeding

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14.3 Celiac Disease

• Tissue transglutaminase (tTG) deamidates gliadin peptides
• Deamidated gliadin is presented by HLA-DQ2/DQ8 on antigen-presenting cells to CD4⁺ T cells
• Cytokine release → CD8⁺ T-cell activation → epithelial damage
• Result: villous atrophy + crypt hyperplasia + increased intraepithelial lymphocytes (IELs)
• Loss of villous surface area → malabsorption

• Classic: chronic diarrhea, steatorrhea, weight loss, abdominal bloating, failure to thrive (children)
• Atypical: iron deficiency anemia, osteoporosis, infertility, dermatitis herpetiformis (10%), neurological symptoms
• Silent: positive serology + villous atrophy, no symptoms
• Associations: type 1 DM, Down syndrome, Turner syndrome, IgA deficiency, autoimmune thyroid disease
• Worldwide prevalence ~1%; women 2–3× more affected than men

1. Serology: anti-tTG IgA (most sensitive/specific); anti-endomysial (EMA-IgA); anti-deamidated gliadin (DGP) IgG if IgA-deficient
2. Duodenal biopsy: gold standard — villous atrophy, crypt hyperplasia, ↑IELs (Marsh classification)
3. HLA typing: DQ2/DQ8 (high negative predictive value — rules out disease if absent)

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Summary: The Digestive Tract at a Glance

Mouth → Pharynx → Esophagus → Stomach → Duodenum → Jejunum → Ileum → Colon → Rectum → Anus
 ↓          ↓           ↓          ↓           ↓           ↓          ↓         ↓
Amylase   Swallowing  Peristalsis  HCl        Bile +     Main       B₁₂/      Water/
Lipase    reflex      LES         Pepsin      Pancreatic  nutrient   Bile salt  electrolyte
(mech)    (medulla)               Gastrin     enzymes    absorption absorption  absorption

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