Digestive System — Small Intestine, Large Intestine, Pancreas, Bile & Liver

Small Intestine (Gut) – General Layout

• Follows the stomach; overall length ≈ $6-7\,\text{m}$.
• Regions (proximal ➜ distal):
  • Duodenum
  • Jejunum
  • Ileum
• Principal vascular supply (branches of abdominal aorta):
  • Celiac trunk ➜ common hepatic ➜ gastroduodenal ➜ right gastro-omental artery (duodenum/head of pancreas).
  • Superior mesenteric artery (SMA): jejunal, ileal, ileocolic, ileal branch, straight arteries (vasa recta), arterial arcades.
• Venous drainage largely parallels arteries into the portal system (superior mesenteric vein).

Duodenum – Detailed Anatomy

• Vertebral relations: T$12$ ➜ L$1-L3$.
• Four parts:
  1. 1st / Superior (duodenal cap): common ulcer site.
  2. 2nd / Descending: receives hepatopancreatic ampulla of Vater (union of common bile duct + main pancreatic duct) at major duodenal papilla; surrounded by sphincter of Oddi; minor papilla superiorly drains accessory pancreatic duct.
  3. 3rd / Horizontal.
  4. 4th / Ascending.

Duodenum – Physiological Functions & Hormones

• Acts as a “gate-keeper,” coordinating gastric emptying & gall-bladder release in response to acidic chyme.
• Endocrine secretions from mucosal enteroendocrine cells:
  • Secretin – released when luminal $[H^+]$ & fatty acids ↑; actions: ↓ gastric HCl secretion, ↑ pancreatic/ductal $HCO_3^-$.
  • Cholecystokinin (CCK) – released to fatty chyme; triggers gall-bladder contraction & pancreatic enzyme secretion.
  • Enterogastrone – inhibits gastric peristalsis, slowing delivery.

Small Intestine – Key Function & Enzymology

• Primary site for digestion & absorption of carbohydrates ➜ monosaccharides, proteins ➜ amino acids, fats ➜ fatty acids + glycerol.
• Pancreas supplies majority of hydrolytic enzymes; enteroendocrine hormones regulate pancreatic secretion, gall-bladder emptying & motility.

Electrical & Motor Patterns of the Small Intestine

• Basic Electrical Rhythm (BER): slow waves at ≈ $12\,/\,\text{min}$; spikes on peak produce contractions.

1. Segmental (Mixing) Contractions

• Alternating rings of circular muscle contract over ~$1\,\text{cm}$ segments at $8-12\,/\,\text{min}$.
• Produce back-and-forth “chopping” ➜ thorough mixing without net propulsion (segmentation).

2. Propulsive Contractions (Peristalsis)

• Commence once digestion/absorption mostly complete.
• Stereotyped pattern: contraction behind bolus + relaxation ahead ➜ unidirectional (caudad) flow.
• Each peristaltic wave travels $3-5\,\text{cm}$ then dies out; transit time pylorus ➜ ileocecal valve ≈ $3-5\,\text{h}$.
• Controlled by enteric nervous system.

3. Gastro-Ileal Reflex

• Mediated by autonomic nervous system + Gastrin.
• Gastric distension ➜ ↑ ileal peristalsis + relaxation of ileocecal sphincter.

4. Peristaltic Rush

• Powerful, rapid peristalsis triggered by mucosal irritation (e.g., infectious diarrhea) & strong neural input to expel irritants.

5. Migrating Motor Complex (MMC)

• Occurs during fasting every $1.5-2\,\text{h}$.
• Sweeps sequentially along ~$40\,\text{cm}$ segments for $6-10\,\text{min}$ each – “intestinal housekeeper” clearing residual secretions & debris.

Ileocecal Valve – Structure & Control

• Tonic closure prevents reflux of colonic bacteria.
• Normally opens transiently after meals via gastro-ileal reflex (Gastrin-mediated).
• Approx. $1500\,\text{ml/day}$ of chyme enters cecum.
• Cecal distension ➜ colono-ileal reflex: ↑ sphincter tone, ↓ ileal peristalsis.
• Appendix irritation (appendicitis) elicits massive reflex spasm ➜ blockage, upstream distension, RUQ pain, vomiting.

Structural Adaptations: Folds & Villi

• Muscularis mucosae forms transient folds to churn chyme & expand surface area.
• Each villus contains smooth-muscle fibers ➜ rhythmic squeezing empties lacteals (“milking”) & stirs adjacent fluid layer.

Vomiting Reflex

• Reverse peristaltic wave originates in small intestine, moves orad.
• If upper esophageal sphincter (UES) remains closed ➜ retching; pressure > UES tone ➜ vomit.
• Central control: vomiting center in medulla activated by
  • Oropharyngeal stimulation (touch posterior pharynx).
  • Gastric/duodenal distension.
  • Vestibular input (motion sickness).
  • Chemoreceptor trigger zone (area postrema, 4th ventricle) – sensitive to emetics, radiation.

Large Intestine – Gross Anatomy

• Length ≈ $1\,\text{m}$; segments: Cecum, Ascending, Transverse, Descending, Sigmoid, Rectum, Anal canal.
• Distinctive features: teniae coli (3 longitudinal ribbons), haustra (sacculations), omental (epiploic) appendices; note rectum lacks teniae & appendices; longitudinal coat becomes continuous.
• Arterial supply: ileocolic & appendicular (cecum/appendix), right & left colic flexures, mesocolic & omental teniae branches.

Large-Intestinal Motility

1. Cecum & Proximal Colon
   • Distension ➜ ileocecal sphincter contraction (anti-reflux).
   • Segmentation (“haustral churning”) mixes contents.
   • Mass movements (1–3 ×/day) propel feces large distances (e.g., transverse ➜ sigmoid).
2. Distal Colon
   • Contents become semi-solid as water absorbed proximally; slow propulsion until next mass movement.
3. Rectum & Anal Canal – Defecation Sequence
   • Rectum filling ➜ rectosphincteric reflex: rectal contraction + internal anal sphincter relaxation.
   • At ≈ $25\%$ capacity urge appears; external anal sphincter (voluntary, striated) maintains continence.
   • When convenient: relax external sphincter, contract rectum & abdominal wall (Valsalva) ➜ expulsion.

Pancreas – Anatomy

• Retroperitoneal, length $14-18\,\text{cm}$, weight $65-75\,g$.
• Parts: Head (within C-loop of duodenum), Uncinate process (inferior head extension), Neck, Body, Tail (reaches hilum of spleen in front of left kidney).

Pancreatic Exocrine Secretion

A. General Properties

• High volume, isotonic; $[Na^+]$ & $[K^+]$ ~ plasma.
• Very high $[HCO_3^-]$ to neutralize gastric acid; low $[Cl^-]$.
• Contains digestive enzymes: pancreatic lipase, amylase, proteases (trypsinogen, chymotrypsinogen, proelastase, procarboxypeptidases).

B. Flow-Rate Dependence

• Low flow: fluid mainly $Na^+$ & $Cl^-$.
• High flow: fluid mainly $Na^+$ & $HCO_3^-$ (still isotonic regardless of rate).

C. Cellular Origin

• Acinar cells: secrete small volume, enzyme-rich, $Na^+/Cl^-$-rich primary fluid.
• Ductal/centroacinar cells: add $HCO<em>3^-$, absorb $Cl^-$ via luminal $Cl^-$/$HCO</em>3^-$ exchanger; water follows osmotically ➜ final isotonic juice.

D. Regulation

1. Secretin (from duodenal S cells, stimulated by luminal $H^+$) ➜ ↑ ductal $HCO_3^-$.
2. CCK (from I cells, stimulated by peptides, AAs, fatty acids) ➜ ↑ acinar enzyme secretion.
3. Acetylcholine (vagovagal reflex) ➜ ↑ acinar enzymes; potentiates Secretin on ductal $HCO_3^-$.

Bile Production, Storage & Composition

• Components: bile salts, phospholipids, cholesterol, bilirubin pigments, electrolytes, water.
• Hepatocytes synthesize primary bile acids (cholic, chenodeoxycholic) from cholesterol.
• Intestinal bacteria convert fraction ➜ secondary bile acids (deoxycholic, lithocholic).
• Conjugation with glycine/taurine forms bile salts (e.g., taurocholate).
• Electrolytes & water added ➜ canalicular bile ➜ hepatic ducts.
• Interdigestive period: sphincter of Oddi closed; gall-bladder relaxed & fills; concentrates bile via isosmotic absorption of salt + water.

Gallbladder – Contraction Control

• CCK: released by duodenal I cells when fatty acids/peptides present; causes gall-bladder contraction + Oddi relaxation.
• Acetylcholine (parasympathetic) also contracts gall-bladder.

Bilirubin Metabolism & Clinical Correlates

• Source: hemoglobin breakdown by reticulo-endothelial macrophages.
  • Heme ➜ biliverdin ➜ free bilirubin (albumin-bound) in plasma.
• Hepatic uptake ➜ conjugation (≈$80\%$ to bilirubin glucuronide via UDP-glucuronyl transferase; $10\%$ sulfate; rest other conjugates) ➜ excreted in bile.
• Intestinal bacteria convert bilirubin ➜ urobilinogen:
  • Most oxidized to stercobilin (brown feces).
  • ~$50\%$ reabsorbed ➜ enterohepatic return; 95 % resecreted in bile, 5 % escapes liver ➜ kidneys ➜ urine (converted to urobilin, yellow).

Jaundice (Hyperbilirubinemia)

• Normal plasma bilirubin $\approx0.5\,\text{mg/dl}$; yellow skin appears ≥$1.5\,\text{mg/dl}$; survival possible up to $40\,\text{mg/dl}$.
• Hemolytic (pre-hepatic): ↑ RBC lysis ➜ excess unconjugated bilirubin; ↑ urobilinogen ➜ dark urine.
• Obstructive (post-hepatic): bile duct blockage/hepatic damage ➜ conjugated bilirubin regurgitates into blood; pale stools, dark urine.

Gallbladder Pathology

• Gallstones (cholelithiasis): precipitation of cholesterol ± pigment when bile salt:cholesterol ratio imbalanced.
  • Types: cholesterol, pigment, mixed.
• Acute cholecystitis: inflammation, usually cystic-duct blockage; RUQ/transpyloric pain, Murphy’s sign, guarding, vomiting.
• Cholecystectomy indicated for severe biliary colic or recurrent cholecystitis.

Liver – Microscopic & Macroscopic Anatomy

• Functional unit: liver lobule (≈$50-100\,000$ per liver).
  • Plates of hepatocytes radiate around central vein.
  • Portal triads (portal vein branch, hepatic artery, bile ductule) in fibrous septa.
  • Between plates: sinusoidal capillaries lined by endothelial cells & Kupffer macrophages; bile canaliculi between hepatocytes flow opposite to blood.
  • Space of Disse drains lymph ➜ interlobular lymphatics.

Hepatic Blood Flow & Filtration

• Total inflow ≈ $1450\,\text{ml/min}$:
  • Portal vein $\approx1100\,\text{ml/min}$ (nutrient-rich, oxygen-poor).
  • Hepatic artery $\approx350\,\text{ml/min}$.
• Kupffer cells phagocytose >$99\%$ of bacteria in portal blood within $10^{-2}$ s, preventing systemic bacteremia.

Liver – Metabolic Functions

Carbohydrate Metabolism

• Glycogenesis (glucose ➜ glycogen), Glycogenolysis, Gluconeogenesis, Glycogen storage.
• Degradation of insulin & other peptide hormones.

Vitamin & Iron Storage

• Vitamin A store ≈ $10\,\text{months}$; D ≈ $3-4\,\text{months}$; B$12$ ≈ $1\,\text{year}$.
• Iron stored as ferritin/hemosiderin; mobilized on demand.

Plasma Protein & Coagulation Factor Synthesis

• Produces most plasma proteins; vitamin K–dependent clotting factors: prothrombin, VII, IX, X, protein S & Z.

Detoxification & Excretion

• Biotransforms/excretes drugs (sulfonamides, penicillins, erythromycin, etc.).
• Metabolizes steroid/thyroid hormones; excretes excess $Ca^{2+}$ via bile.
• Clinical implication: hepatic failure ➜ drug accumulation/toxicity or hormonal imbalance.

Common Hepatic Pathologies

• Jaundice (sign of bilirubin accumulation).
• Hepatitis (viral, toxin, autoimmune).
• Cirrhosis: fibrotic replacement of hepatocytes, often post-hepatitis or alcoholism.
• Hemochromatosis: genetic iron overload ➜ hepatocellular damage.
• Primary & metastatic liver tumors (hepatocellular carcinoma, cholangiocarcinoma).
• Wilson’s disease: hereditary copper accumulation causing liver & neurologic damage.