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Guyton & Hall - Chapters 63, 64 & 65: GIT Physiology (Detailed)

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CHAPTER 63 - Propulsion and Mixing of Food in the Alimentary Tract

Overview of GI Motility

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The Enteric Nervous System

• Myenteric (Auerbach's) plexus: Located between the outer longitudinal and inner circular muscle layers. Controls GI movements.
• Submucosal (Meissner's) plexus: Located in the submucosa. Controls local intestinal secretion, absorption, and blood flow.

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Peristalsis - The Basic Propulsive Movement

1. Contraction of circular muscle proximal to the food bolus (pushes it forward)
2. Relaxation of circular muscle distal to the food bolus (the "receptive relaxation" or the "law of the intestine")

• Distension of the gut wall
• Epithelial irritation
• Parasympathetic (vagal) stimulation
• Certain GI hormones

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Motility of the Esophagus

• Primary peristalsis: Continuation of the swallowing reflex that travels down the esophagus.
• Secondary peristalsis: Initiated by distension from food that remains in the esophagus after the primary wave; it does not require a swallowing act.
• The lower esophageal sphincter (LES) normally remains tightly closed but relaxes as the peristaltic wave approaches. Failure to relax causes achalasia.
• The LES also prevents acid reflux from the stomach.

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Stomach Motility

• Fundus/body: Storage reservoir; shows receptive relaxation (via vagovagal reflex and VIP) as food enters.
• Antrum: The powerful mixing/grinding pump.

• Gastric factors promoting emptying: Increased gastric volume → stretch → local myenteric reflexes → increased pyloric pump activity.
• Gastrin (released from antral G-cells by proteins and distension) slightly increases antral motility.

1. Distension
2. Mucosal irritation
3. Acidity (pH < 3.5-4)
4. Osmolality (hypo- or hypertonic chyme)
5. Protein/fat breakdown products

• Enteric nervous system (direct gut-to-gut reflex)
• Sympathetic fibers via prevertebral ganglia
• Vagus nerve (to the brain stem and back)

• Secretin (released by S-cells when pH < 4.5): Inhibits gastric motility and stimulates pancreatic bicarbonate.
• CCK (cholecystokinin) (released by I-cells when fats/proteins arrive): Inhibits gastric emptying and stimulates gallbladder contraction + pancreatic enzyme secretion.
• GIP (gastric inhibitory peptide / glucose-dependent insulinotropic peptide): Released in response to fat and carbohydrates; inhibits gastric acid secretion and motility.

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Small Intestinal Movements

• Most characteristic movement of the small intestine.
• Ring-like contractions divide the intestinal content into segments, then relax while new contractions form between the previous ones - effectively "chopping" and mixing chyme with digestive juices and exposing it to the absorptive mucosa.
• Frequency: ~12 per minute in the duodenum, ~8-9 per minute in the terminal ileum.

• True peristaltic waves move chyme forward 10-15 cm at a time.
• Peristaltic rush: A strong, rapid peristalsis that can sweep contents from the duodenum to the colon in minutes - triggered by intense irritation (e.g., cholera toxin, severe mucosal injury).

• Distension (most important)
• Mucosal irritation
• Parasympathetic stimulation (enhances)
• Sympathetic stimulation (inhibits)

• Villous contractions (1-6 times/minute): Compress the central lacteal and squeeze absorbed lymph into the lymphatic system, then relax to allow fresh chyme to contact the villi.

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Ileocecal Valve

• Prevents backflow of colonic bacteria-rich contents into the ileum.
• Normally slightly constricted.
• Ileocecal sphincter relaxes (allows flow into colon) when peristaltic waves approach from the ileum.
• Reflexes from the cecum: Distension or inflammation of the cecum causes the ileocecal sphincter to contract further, slowing ileal emptying.

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Movements of the Colon

• Occur only 1-3 times daily.
• A large segment of the colon contracts en masse, propelling feces toward the rectum.
• Triggered most powerfully by the gastrocolic reflex (filling of the stomach) and the duodenocolic reflex (filling of the duodenum).
• Also triggered by distension of the colon and irritation.
• The stimulus leads to a strong peristaltic ring that sweeps colonic contents 20+ cm distally in seconds.

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Defecation

1. Intrinsic reflex (myenteric): Distension of rectum → peristaltic waves in descending colon, sigmoid colon, rectum → relaxation of the internal anal sphincter (smooth muscle, involuntary).
2. Parasympathetic defecation reflex (S2-S4 sacral cord): Greatly amplifies the intrinsic reflex. Signals go to sacral cord via pelvic nerves → return signals intensify peristalsis throughout left colon and rectum, and relax the internal anal sphincter more powerfully.
3. External anal sphincter (skeletal muscle, voluntary): Under voluntary conscious control. When the person is ready to defecate, the external sphincter relaxes and defecation occurs. If defecation is suppressed, the reflex diminishes after a few minutes.

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CHAPTER 64 - Secretory Functions of the Alimentary Tract

General Principles of Alimentary Tract Secretion

1. Single-cell mucous cells (goblet cells) - found throughout the GI mucosa
2. Crypts of Lieberkühn (intestinal glands)
3. Compound tubular glands (stomach, Brunner's glands)
4. Complex alveolar glands (salivary, pancreas, liver)

• Tactile/mechanical stimulation: Direct contact of food with epithelium stimulates mucus secretion via local myenteric reflexes.
• Nervous stimulation: Parasympathetic signals (acetylcholine) greatly increase secretion of almost all glands; sympathetic signals generally decrease secretion or have a secondary effect.
• Hormonal stimulation: GI hormones (gastrin, secretin, CCK) stimulate specific glands.

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Salivary Secretion

• Volume: ~1 liter/day
• Composition: Mostly water + electrolytes (Na+, K+, Cl-, HCO3-) + salivary amylase (ptyalin) + mucin
• Saliva is hypotonic to plasma (K+ and HCO3- are secreted; Na+ and Cl- are partially reabsorbed in the ducts).
• Salivary amylase: Begins starch digestion in the mouth; continues in the stomach until inactivated by acid.
• Parotid glands: Serous (watery, enzyme-rich)
• Submandibular and sublingual glands: Mixed (serous + mucous)
• Control: Entirely by the autonomic nervous system - both parasympathetic (dominant) and sympathetic. There is NO hormonal control. Parasympathetic (CN VII, IX) stimulates copious, watery saliva; sympathetic causes thick, protein-rich saliva.
• Salivary reflex: Conditioned (sight/smell of food) and unconditioned (food in mouth).

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Esophageal Secretion

• Entirely mucous.
• The esophagus has compound mucous glands near the gastroesophageal junction that protect the lower esophageal mucosa from gastric acid.

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Gastric Secretion

• Parietal cells pump H+ (using H+/K+-ATPase proton pump) into the canaliculi at a concentration of ~150 mEq/L (pH ~0.8 in pure acid).
• For each H+ secreted into the lumen, one HCO3- is released into the blood ("alkaline tide").
• HCl: Activates pepsinogen to pepsin, kills bacteria, denatures proteins, and creates the acid environment needed by pepsin (optimal pH 1.8-3.5).

• Pepsinogen (inactive) → pepsin (active) at pH < 5; autocatalytically activated at low pH.
• Proteolytic enzyme - cleaves peptide bonds.
• Inactivated at pH > 5.

1. Cephalic phase (~20% of total acid): Triggered by sight, smell, taste, chewing. Mediated entirely by the vagus nerve. Vagal stimulation releases ACh → directly stimulates parietal cells + releases gastrin from G-cells.
2. Gastric phase (~70% of total acid):
   • Distension of the stomach → long vagovagal reflexes + local enteric reflexes → stimulate acid and pepsin secretion.
   • Proteins/peptides in food → directly stimulate G-cells → gastrin release → stimulates parietal cells via the bloodstream and via ECL cells (histamine release).
   • Gastrin also stimulates ECL cells to release histamine, which binds H2 receptors on parietal cells (potent stimulator of HCl).
3. Intestinal phase (~5-10% of total acid):
   • Entry of chyme into the duodenum initially stimulates a small amount of gastrin secretion.
   • However, duodenal factors (secretin, GIP, somatostatin, enterogastrones) soon inhibit gastric secretion.

• Somatostatin (from D-cells): Inhibits gastrin and directly inhibits parietal cells.
• Secretin: Strongly inhibits gastric acid when duodenal pH falls.
• GIP, CCK, VIP: Also inhibit acid secretion.
• Low pH in the antrum: Directly inhibits G-cells via somatostatin feedback.

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Pancreatic Secretion

• Proteolytic enzymes (secreted as inactive proenzymes/zymogens):
  • Trypsinogen → activated to trypsin by enterokinase (enteropeptidase) on the brush border
  • Chymotrypsinogen → chymotrypsin (by trypsin)
  • Proelastase → elastase (by trypsin)
  • Procarboxypeptidase → carboxypeptidase (by trypsin)
  • Trypsin inhibitor is secreted along with trypsinogen to prevent premature activation inside the pancreatic ducts.
• Amylase: Digests starch to maltose and dextrins (only pancreatic enzyme secreted in active form).
• Lipase: The primary fat-digesting enzyme; hydrolyzes triglycerides to monoglycerides and fatty acids. Requires colipase (also secreted by pancreas) and bile salts.
• Cholesterol esterase
• Phospholipase A2
• Ribonuclease, deoxyribonuclease

• Creates the high-volume alkaline juice (pH ~8) that neutralizes acid chyme arriving from the stomach.
• Bicarbonate secretion is via a Cl-/HCO3- exchanger driven by cAMP.

1. Cephalic phase: Vagal stimulation → moderate enzyme secretion (little HCO3-).
2. Gastric phase: Gastric distension → vagovagal reflexes → enzyme secretion.
3. Intestinal phase (dominant, ~80% of total):
   • Secretin (from S-cells, duodenum): Released by acid (pH < 4.5). Stimulates ductal cells to pour out large volumes of HCO3--rich juice. This is the primary neutralizing mechanism.
   • CCK (from I-cells, duodenum): Released by fats and proteins. Powerfully stimulates acinar cells to secrete enzyme-rich juice. Also potentiates the effect of secretin.
   • CCK and secretin are synergistic: Together they produce a much greater response than either alone.

• Proenzymes secreted (not active enzymes)
• Trypsin inhibitor secreted with zymogens
• Ductal mucus prevents contact with pancreatic cells
• In acute pancreatitis, these mechanisms fail - trypsin activates inside the pancreas, triggering autodigestion.

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Secretion of Bile (Liver and Gallbladder)

• Synthesized from cholesterol in hepatocytes (~6 g/day).
• Primary bile acids: cholic acid and chenodeoxycholic acid.
• Conjugated with glycine or taurine → conjugated bile salts (glycocholate, taurocholate, etc.) → more water-soluble, less absorbable in upper GI.
• In the colon, bacteria deconjugate and dehydroxylate → secondary bile acids (deoxycholic, lithocholic).
• Enterohepatic circulation: ~94-95% of bile salts are reabsorbed in the terminal ileum → portal blood → liver → re-secreted. This recycling occurs 6-10 times/day. Loss in stool: only ~0.5 g/day (replaced by new synthesis).

1. Emulsification of fats: Hydrophobic tail associates with fat droplets; hydrophilic head associates with water. Reduces fat droplet size to ~1 mm diameter → greatly increases surface area for lipase.
2. Micelle formation: Bile salts aggregate around fatty acids and monoglycerides to form micelles (3-6 nm). Micelles shuttle fat breakdown products to the brush border for absorption. Without micelles, only ~40-50% of fat is absorbed (vs. ~97% normally).

• End product of heme catabolism from senescent red blood cells.
• Unconjugated bilirubin → conjugated (glucuronidated) in liver → secreted in bile → reduced to urobilinogen by gut bacteria → mostly excreted in stool (as stercobilin) or reabsorbed and excreted in urine (as urobilinogen).

• Stores and concentrates bile (10-fold concentration by absorbing water, Na+, Cl-, HCO3-).
• Emptying: Triggered primarily by CCK (in response to fats and proteins in the duodenum). CCK causes rhythmic contractions of the gallbladder wall AND relaxes the sphincter of Oddi, allowing bile to flow into the duodenum. Vagal stimulation (ACh) also promotes gallbladder contraction.
• Gallbladder fills between meals when the sphincter of Oddi is closed.

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Small Intestinal Secretion

• Large volume of watery fluid (~1.8 L/day in the small intestine): Acts as a vehicle for absorption - nutrients are absorbed from this fluid as villi take it up.
• The secretion is neutral to slightly alkaline.
• Paneth cells (at the base of crypts in the small intestine): Secrete lysozyme and defensins - antimicrobial peptides that protect against pathogens.

• Secrete alkaline mucus (pH 8-9) to protect the duodenal mucosa from gastric acid.
• Stimulated by: tactile irritation, vagal stimulation, secretin.
• Inhibited by: sympathetic stimulation (explaining duodenal ulcers under stress).

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Large Intestinal Secretion

• The colon secretes almost entirely mucus (no digestive enzymes).
• Mucus protects the colonic wall from trauma, provides a medium for holding bacteria, and seals fecal material to allow water absorption.
• Stimulated by direct tactile stimulation and pelvic parasympathetic nerves.
• In extreme parasympathetic stimulation (emotional stress) → massive mucus secretion → contributes to mucous colitis.

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CHAPTER 65 - Digestion and Absorption in the Gastrointestinal Tract

Overview

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Digestion of Carbohydrates

• Starch (polysaccharide; the largest portion ~50% of total calories)
• Sucrose (disaccharide: glucose + fructose)
• Lactose (disaccharide: glucose + galactose)
• Cellulose and other fibers (not digested)

1. Salivary amylase (ptyalin): Begins starch hydrolysis in the mouth; continues in the stomach until inactivated by acid (~30-40% of starch digested).
2. Pancreatic amylase: The most important. Hydrolyzes starch in the small intestine → maltose, maltotriose, and alpha-limit dextrins.
3. Brush border (intestinal) enzymes (final digestion at the apical surface of enterocytes):
   • Maltase: Maltose → glucose + glucose
   • Sucrase: Sucrose → glucose + fructose
   • Lactase: Lactose → glucose + galactose
   • Dextrinase (isomaltase): Alpha-limit dextrins → glucose

• Glucose and galactose: Absorbed by secondary active transport - co-transported with Na+ via the SGLT1 transporter on the apical membrane. Na+-K+-ATPase on the basolateral membrane maintains the Na+ gradient. Energy is indirectly used (ATP for Na+-K+-ATPase). Then glucose/galactose exit via GLUT2 on the basolateral membrane into portal blood.
• Fructose: Absorbed by facilitated diffusion via GLUT5 on the apical membrane, then exits via GLUT2.
• Lactase deficiency: Undigested lactose → osmotic diarrhea + bacterial fermentation → bloating, gas, cramps.

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Digestion of Proteins

1. Gastric pepsin: Cleaves about 10-20% of proteins. Active at pH 1.8-3.5. Inactivated in the alkaline duodenum.
2. Pancreatic proteases (the main agents):
   • Trypsin + Chymotrypsin (endopeptidases): Cleave interior peptide bonds. Together hydrolyze most protein.
   • Elastase: Cleaves bonds adjacent to small amino acids.
   • Carboxypeptidase (exopeptidase): Cleaves from the C-terminal end.
3. Intestinal brush border enzymes:
   • Aminopeptidase: Cleaves from the N-terminal end.
   • Dipeptidases, tripeptidases

• Active transport via Na+-dependent amino acid co-transporters (multiple systems for different amino acid types: neutral, basic, acidic, imino acids).
• Di- and tripeptides absorbed via PepT1 (H+-coupled transporter) → hydrolyzed inside the cell.
• Exit the enterocyte via facilitated diffusion into portal blood.
• Absorption is essentially complete by the end of the jejunum.

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Digestion of Fats

1. Lingual lipase (minor): Begins in the mouth; important in neonates.
2. Gastric lipase (minor): Hydrolyzes some short- and medium-chain TG.
3. Emulsification in the duodenum: Bile salts coat fat droplets → reduce surface tension → reduce droplet size from mm to ~1 mm diameter → dramatic increase in surface area for lipase.
4. Pancreatic lipase (the key enzyme): Hydrolyzes TG at positions sn-1 and sn-3 → 2-monoglyceride + 2 free fatty acids. Requires colipase (pancreatic) to anchor to the fat droplet surface (bile salts otherwise displace lipase).
5. Micelle formation: 2-monoglycerides + free fatty acids + bile salts + phospholipids + cholesterol → mixed micelles. These diffuse to the brush border and release their fat contents at the membrane surface.

• Long-chain fatty acids and 2-monoglycerides: Diffuse passively into the enterocyte. Inside the cell:
  • Re-esterified to TG by the smooth ER.
  • Packaged with apolipoprotein B-48, cholesterol, phospholipids → chylomicrons.
  • Exocytosed from the basolateral surface → enter lacteals (lymphatics) → thoracic duct → bloodstream.
• Short- and medium-chain fatty acids (< 10-12 carbons): Absorbed directly into portal blood (do not need re-esterification or chylomicron packaging). This is exploited in patients with fat malabsorption.

• Pancreatic exocrine insufficiency (no lipase)
• Bile salt deficiency (no emulsification/micelles)
• Intestinal mucosal disease (Crohn's, celiac)

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Absorption of Water

• ~9-10 liters of fluid enter the gut daily (2 L ingested + ~7-8 L secretions).
• Only ~100-200 mL is lost in stool.
• Mechanism: Water is absorbed by osmosis, driven passively by the absorption of solutes (especially Na+ and glucose). This is the basis of oral rehydration therapy (ORS).
• The small intestine absorbs ~8 L/day; the colon absorbs ~1-1.5 L/day (maximum colonic reabsorptive capacity ~5-6 L/day).

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Absorption of Electrolytes

• Most actively absorbed Na+ ion drives most other absorption.
• Mechanisms:
  • Co-transport with glucose, amino acids (SGLT1, Na+-amino acid transporters)
  • Na+-H+ exchanger (NHE3) on brush border - very important in the ileum and colon
  • Na+ channels in the colon (aldosterone-regulated ENaC channels)
• Na+-K+-ATPase on the basolateral side is the primary energy-consuming driver.

• Absorbed passively (follows Na+)
• In the ileum/colon: via Cl-/HCO3- exchanger (secretes HCO3- into lumen, accounting for alkaline stool)

• Absorbed passively in the small intestine (high luminal concentration drives absorption).
• Actively secreted in the colon (aldosterone increases K+ secretion by colon - important for K+ balance).

• Absorbed primarily in the duodenum (proximal small intestine).
• Heme iron (from meat): Absorbed intact via a heme transporter (HCP1); highly bioavailable.
• Non-heme iron (Fe2+): Absorbed via DMT1 (Divalent Metal Transporter 1). Fe3+ must first be reduced to Fe2+ by duodenal cytochrome b (ferroreductase). Vitamin C (ascorbic acid) enhances reduction.
• Inside enterocyte: iron is stored as ferritin, or transported to the basolateral side via ferroportin → oxidized to Fe3+ by hephaestin → bound to transferrin in portal blood.
• Regulation: By body iron stores (via hepcidin). In iron overload, hepcidin increases → degrades ferroportin → iron stays trapped in enterocytes → reduced absorption.

• Absorbed in the duodenum and jejunum (active transport) and throughout the small intestine (passive diffusion).
• Active absorption: Ca2+ enters via apical TRPV6 channel → bound to calbindin D-9k inside the cell → transported to basolateral membrane → pumped out by PMCA (plasma membrane Ca2+ ATPase) and NCX.
• Regulated by 1,25-(OH)2 vitamin D (calcitriol), which upregulates TRPV6, calbindin, and PMCA. PTH indirectly increases Ca2+ absorption by stimulating calcitriol production.

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Absorption of Vitamins

• Absorbed with fats - require micelle formation (bile salts needed).
• Deficiency in fat malabsorption syndromes or cholestasis.

• Most absorbed by Na+-dependent co-transport in the jejunum.
• Vitamin B12 (cobalamin): Unique - requires intrinsic factor (IF) from gastric parietal cells. B12-IF complex binds to cubilin receptors in the terminal ileum → receptor-mediated endocytosis → B12 transported to portal blood via transcobalamin II.

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Absorption in Different Parts of the GI Tract

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Clinical Correlates

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Quick Chapter Map

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Key High-Yield Points to Remember

• The pyloric pump + enterogastric reflex (duodenal pH, osmolality, distension, proteins/fats) regulates stomach emptying - acid pH < 3.5 blocks it.
• Three phases of gastric secretion: Cephalic (vagal, 20%), gastric (gastrin/histamine, 70%), intestinal (5-10%).
• Secretin = "nature's antacid" - released by acid, stimulates pancreatic HCO3-.
• CCK = enzyme releaser + gallbladder contractor; released by fat and protein.
• Trypsin is the master activator of all other pancreatic proteases.
• Bile salts are recycled via enterohepatic circulation 6-10x/day through the terminal ileum.
• Glucose/galactose absorption = SGLT1 (Na+ co-transport, active); fructose = GLUT5 (facilitated diffusion).
• Fat absorption: Long-chain → chylomicrons → lymphatics; short/medium-chain → portal blood directly.
• B12 needs intrinsic factor + cubilin receptors in the terminal ileum.
• Iron absorption = duodenum via DMT1; regulated by hepcidin via ferroportin.