Comprehensive Notes on Digestion and Absorption

Regulation of Stomach Secretions

Cephalic Phase ("Get ready!")

• Initiated by taste, smell, thoughts of food, or tactile sensations in the mouth.
• These stimuli activate the medulla oblongata.
• Vagus nerves transmit parasympathetic action potentials to the stomach, activating enteric plexus neurons.
• This stimulation leads to:
  • Increased secretion of HCl and pepsinogen from parietal and chief cells.
  • Secretion of gastrin and histamine from endocrine cells
• Gastrin is transported through the circulation back to the stomach.
• Gastrin and histamine further stimulate the secretion of HCl and pepsin.

Gastric Phase ("Go for it!")

• Triggered by:
  • Distention of the stomach.
  • Presence of amino acids/peptides (also caffeine, alcohol).
• Activates a parasympathetic reflex where action potentials are carried by the vagus nerves to the medulla oblongata.
• The medulla oblongata further stimulates stomach secretions.
• Local reflexes are also stimulated by distention, amplifying stomach secretions.
• Gastrin is carried via bloodstream back to the stomach where, along with histamine, it stimulates secretion.
• Negative feedback mechanism: When the pH in the stomach falls below 2, gastric secretions are inhibited, limiting the secretion of gastric juice.

Intestinal Phase ("Slow down!")

• Chyme entering the duodenum (with a pH less than 2 or containing lipids) inhibits gastric secretions through three mechanisms:
  1. Sensory input to the medulla inhibits motor input from the medulla to the stomach, stopping pepsin and HCl secretion.
  2. Local reflexes inhibit gastric secretion (enterogastric reflex).
  3. Hormones (secretin and cholecystokinin) produced by the duodenum decrease gastric secretions.
• Secretin is released in response to acidic solutions in the duodenum.
  • Inhibits gastric secretions by inhibiting both parietal and chief cells.
• Cholecystokinin is released in response to lipids (and to a lesser degree, proteins).
  • Inhibits gastric secretions.
• These negative-feedback loops ensure that acidic chyme entering the duodenum is neutralized.
  • Important for preventing peptic ulcers and ensuring proper digestive enzyme activity in the small intestine.

Movements of the Stomach

• Mixing waves and peristaltic waves work together to mix chyme and move it toward the pyloric sphincter.
• Mixing waves:
  • Occur approximately every 20 seconds.
  • Constitute about 80% of stomach contractions.
  • Esophageal and pyloric sphincters both remain closed.
• Peristaltic waves:
  • Less frequent but stronger than mixing waves.
  • Push a few milliliters of chyme through the partially relaxed pyloric sphincter (pyloric pump).
• The amount of time food remains in the stomach depends on the type and volume of food.
  • A typical meal remains in the stomach for 3-4 hours.
• Hormonal and neural mechanisms that decrease gastric secretions also decrease gastric motility and prevent relaxation of the pyloric sphincter, delaying gastric emptying.

Vomiting Mechanism

• Vomiting is a protective mechanism against toxic or harmful substances; can result from irritation anywhere along the GI tract.
• Action potentials travel to the vomiting center in the medulla oblongata via the vagus and spinal accessory nerves.
• Steps of the vomiting reflex:
  1. A deep breath is taken.
  2. The hyoid bone and larynx elevate, opening the upper esophageal sphincter.
  3. The opening of the larynx is closed.
  4. The soft palate elevates, closing the connection between the oropharynx and the nasopharynx.
  5. The diaphragm and abdominal muscles forcefully contract, compressing the stomach and increasing intragastric pressure.
  6. The lower esophageal sphincter relaxes.
  7. Gastric contents are forced out through the esophagus and oral cavity.

Small Intestine

• Site of greatest amount of digestion and absorption of nutrients and water.
• Parts:
  • Duodenum: The first 25 cm beyond the pyloric sphincter.
  • Jejunum: 2.5 m long.
  • Ileum: 3.5 m long.
• Duodenum and jejunum are the major sites of nutrient and water absorption.

Anatomy and Histology of the Duodenum

• Structural modifications of the lining increase surface area by approximately 600-fold:
  • Circular folds (plicae): Folds of the mucosa and submucosa perpendicular to the long axis.
  • Villi: Finger-like projections of the mucosa, about 1mm in length.
    • Each villus is covered by simple columnar epithelium and contains a blood capillary network and a lymphatic lacteal.
  • Microvilli: Cytoplasmic extensions on the apical surface of the absorptive cells covering the villi; collectively form the brush border.

Cell Types of the Simple Columnar Epithelium

1. Absorptive cells:
   • Possess microvilli.
   • Produce digestive enzymes.
   • Absorb digested food.
2. Goblet cells:
   • Produce protective mucus.
3. Granular cells (Paneth cells):
   • May help protect from bacteria.
4. Endocrine cells:
   • Produce regulatory hormones.

• Intestinal glands (crypts of Lieberkühn):
  • Tubular invaginations of the mucosa at the base of the villi.
• Duodenal glands (Brunner glands):
  • Tubular mucous glands of the submucosa.
  • Open into the base of the intestinal glands.

Duodenum, Jejunum and Ileum

Duodenum

• Arcs around the head of the pancreas.
• Major and minor duodenal papillae: Openings to ducts from the liver and pancreas.

Jejunum

• Major site of nutrient absorption.
• Gradual decrease in diameter, thickness of the intestinal wall, number of circular folds, and number of villi the farther away from the stomach

Ileum

• Peyer patches: Lymphatic nodules numerous in the mucosa and submucosa.
• Ileocecal junction: Where the ileum meets the large intestine; contains a ring of smooth muscle (ileocecal sphincter) and a one-way ileocecal valve.

Secretions of the Small Intestine

• Fluid primarily composed of water, electrolytes, and mucus.
• Mucus:
  • Secreted by duodenal glands and goblet cells.
  • Protects against digestive enzymes and stomach acids.
• Electrolytes and water from the epithelium keep the chyme in an aqueous solution to facilitate chemical digestion.
• Digestive enzymes of the small intestine:
  • Bound to the membranes of the absorptive cell microvilli; collectively called brush border enzymes.
  • Disaccharidases: Break down disaccharides to monosaccharides.
  • Peptidases: Hydrolyze peptide bonds.
  • Products are absorbed.
  • Large surface area promotes digestion and absorption.

Movement in the Small Intestine

• Mixing and slow propulsion over short distances.
• Segmental contractions:
  • Mix chyme.
• Peristalsis:
  • Propels chyme.
• Generally takes 3-5 hours for chyme to move from the pyloric sphincter to the ileocecal junction.
• Ileocecal sphincter remains slightly contracted until peristaltic waves reach it.
• It relaxes, allowing chyme to move into the cecum.
• Cecal distention causes a local reflex: strong constriction of the ileocecal sphincter.
  • Prevents more chyme from entering the cecum.
  • Increases digestion and absorption in the small intestine by slowing the progress of chyme.
  • Prevents backflow.

Accessory Organs: Liver, Gallbladder, and Pancreas

Anatomy of the Liver

• Located in the right-upper quadrant of the abdomen; largest internal organ.
• Lobes:
  • Major: Left and right lobes separated by the falciform ligament (C.T. septum).
  • Minor: Caudate and quadrate lobes.
• Porta hepatis: On the inferior surface.
  • Vessels, ducts, and nerves enter/exit the liver.
  • Hepatic portal vein and hepatic artery enter.
  • Lymphatic vessels and two hepatic ducts exit.

Flow of Bile and Pancreatic Secretions

1. The right and left hepatic ducts (carrying bile from the liver lobes) combine to form the common hepatic duct.
2. The common hepatic duct joins the cystic duct (from the gallbladder) to form the common bile duct.
3. The common bile duct joins the pancreatic duct at the hepatopancreatic ampulla (an enlargement where the two ducts merge).
4. The hepatopancreatic ampulla empties into the duodenum at the major duodenal papilla. A smooth muscle sphincter surrounds the common bile duct where it enters the hepatopancreatic ampulla.
5. The accessory pancreatic duct empties pancreatic secretions into the duodenum at the minor duodenal papilla.

Histology of the Liver

• The connective tissue capsule and visceral peritoneum cover most of the surface.
• Connective tissue septa branch from the porta into the interior.
  • Nerves, vessels, and ducts follow the septa.
• Divides the liver into hepatic lobules:
  • Hexagonal-shaped regions with a portal triad at each corner:
    • Three vessels: hepatic portal vein, hepatic artery, and hepatic duct.
    • Central vein in the center of the lobule.
  • Central veins unite to form hepatic veins that exit the liver and empty into the inferior vena cava.
• Hepatic cords:
  • Radiate out from the central vein.
  • Composed of hepatocytes.
  • Hepatocytes take up nutrients from portal blood, store, detoxify, and synthesize new compounds.
• Hepatic sinusoids:
  • Located between cords.
  • Lined with endothelial cells and hepatic phagocytic cells (Kupffer cells).
• Bile canaliculus:
  • Located between cells within cords.

Blood and Bile Flow Through the Liver

1. The hepatic artery carries oxygenated blood from the aorta into the porta of the liver.
2. Hepatic artery branches become part of the portal triads, enter the hepatic sinusoids, and supply hepatocytes in the hepatic cords with oxygen.
3. The hepatic portal vein carries nutrient-rich, deoxygenated blood from the intestines into the porta of the liver. Hepatic portal vein branches become part of the portal triads, enter the hepatic sinusoids, and supply hepatocytes in the hepatic cords with nutrients.
4. Blood in the hepatic sinusoids picks up plasma proteins, processed molecules, and waste products produced by hepatocytes in the hepatic cords.
5. The hepatic sinusoids empty into central veins, which converge to form hepatic veins that connect to the inferior vena cava.
6. Bile produced by hepatocytes in the hepatic cords enters bile canaliculi, which connect to hepatic duct branches that are part of the portal triads.
7. The hepatic duct branches converge to form the left and right hepatic ducts, which carry bile out of the porta hepatis of the liver.

Functions of the Liver

• Bile production: 600 to 1000 mL/day.
  • Contains bile salts, bile pigments, cholesterol, fats, and fat-soluble hormones.
  • Bicarbonate neutralizes stomach acid.
  • Bile salts emulsify lipids; most are reabsorbed in the ileum.
  • Secretin (from the duodenum) stimulates bile secretions, increasing water and bicarbonate ion content of the bile.
• Storage of nutrients:
  • Glycogen, fat, vitamins (A, B12, D, E, K), copper, and iron.
• Processing of nutrients:
  • Amino acids to energy-producing compounds.
  • Hydroxylation of vitamin D (which then travels to the kidney to be hydroxylated again into its active form).
• Detoxification:
  • Hepatocytes remove ammonia and convert it to urea.
  • Hepatic phagocytic cells remove worn-out blood cells, bacteria, and other debris.
• Synthesis of new molecules:
  • Albumins, fibrinogen, clotting factors, and cholesterol.

Control of Bile Secretion and Release

1. Parasympathetic stimulation through the vagus nerves increases bile secretion from the liver.
2. Two hormones released from the duodenum increase bile in the duodenum:
   • Secretin: Stimulates bile secretion from the liver, primarily by increasing the water and bicarbonate content of bile.
   • Cholecystokinin: Stimulates gallbladder contractions.
3. Over 90% of bile salts are reabsorbed in the ileum.
   • They are carried back to the liver via the hepatic portal circulation and are again secreted into the bile.
   • This recycling process reduces the loss of bile salts in the feces.
   • Bile secretion into the duodenum continues until the duodenum empties.

Gallbladder

• Sac-like structure for bile storage.
• Lined with mucosa folded into rugae, muscularis, outer serosa.
• Bile arriving constantly from the liver is stored and concentrated.
• Stimulated by cholecystokinin (from the intestine) and vagal stimulation.
• Bile exits through the cystic duct and then into the common bile duct.
• Gallstones: Precipitated cholesterol; can block the cystic duct.
  • Can occur because of drastic dieting.

Anatomy of the Pancreas

• The pancreas functions as both an endocrine and exocrine gland.
• It has a head (in the curvature of the duodenum), body, and tail.
• Endocrine function: Pancreatic islets (islets of Langerhans) produce insulin and glucagon.
• Exocrine function: Acini (grape-like clusters) form lobules separated by septa.
• Secretions from acini flow into intercalated ducts, intralobular ducts, and interlobular ducts to the pancreatic duct.
• The pancreatic duct joins the common bile duct and enters the duodenum at the hepatopancreatic ampulla, controlled by the hepatopancreatic ampullar sphincter.

Pancreatic Secretions

Pancreatic juice containing aqueous and enzymatic components.

• Aqueous portion: Produced by columnar epithelium lining smaller ducts; contains Na^+, K^+, HCO_3^-, and water.
  • Bicarbonate raises the pH, inhibiting pepsin and providing the proper pH for pancreatic and brush border enzymes.
• Enzymatic portion: Contains enzymes that digest all major food classes:
  • Trypsinogen: Activated by enterokinase (brush border) to trypsin.
  • Chymotrypsinogen: Activated by trypsin to chymotrypsin.
  • Procarboxypeptidase: Activated by trypsin to carboxypeptidase.
  • Pancreatic amylase.
  • Pancreatic lipase.
  • Deoxyribonucleases and ribonucleases.

Interaction of Duodenal and Pancreatic Enzymes

• Enterokinase (from the duodenal mucosa, attached to the brush border) activates trypsinogen to trypsin.
• Trypsin activates chymotrypsinogen to chymotrypsin.
• Trypsin activates procarboxypeptidase to carboxypeptidase.
• Trypsin, chymotrypsin, and carboxypeptidase digest proteins (proteolytic).
• Pancreatic amylase continues the digestion of starch.
• Pancreatic lipase digests lipids.
• Deoxyribonucleases and ribonucleases digest DNA and ribonucleic acid, respectively.

Regulation of Pancreatic Secretion

• Parasympathetic stimulation (vagus nerve) causes the release of enzyme-rich pancreatic juice.
• Secretin (from the duodenum) causes the release of aqueous pancreatic juice rich in bicarbonate.
• Cholecystokinin (from the duodenum) causes the release of enzyme-rich pancreatic juice.

Control of Pancreatic Secretion

1. Parasympathetic stimulation through the vagus nerves stimulates the secretion of enzyme-rich pancreatic juices; sympathetic stimulation inhibits secretion. Vagal stimulation on pancreatic juice secretion is greatest during the cephalic and gastric phases of stomach secretion.
2. The hormones secretin and cholecystokinin are released from the duodenum in response to specific stimuli; each hormone stimulates the secretion of a specific type of pancreatic juice.
3. Acidic chyme in the duodenum stimulates the release of secretin, which stimulates the secretion of the bicarbonate-rich aqueous juice.
4. The major stimulus for the release of cholecystokinin is the presence of fatty acids and other lipids in the duodenum, which stimulates the secretion of the enzyme-rich pancreatic juice. Cholecystokinin also stimulates the release of bile from the gallbladder, which aids in the digestion of lipids.

Functions of the Major GI Hormones

Large Intestine

• Extends from the ileocecal junction to the anus.
• Consists of the cecum, colon, rectum, and anal canal.
• Movements are sluggish (18 to 24 hours); chyme is converted to feces.
• Involved in the absorption of water and salts, secretion of mucus, and extensive action of microorganisms.
• Approximately 1500 mL of chyme enter the cecum, and 90% of the volume is reabsorbed, yielding 80 to 150 mL of feces.

Anatomy of the Large Intestine

Cecum

• A blind sac with the vermiform appendix attached.
• Appendix walls contain numerous lymph nodules.

Colon

• Ascending, transverse, descending, and sigmoid portions.
• The circular muscle layer is complete, and the longitudinal layer is incomplete (3 teniae coli bands).
• Contractions of the teniae form pouches called haustra.
• Small, fat-filled pouches called omental appendages are attached to the outer surface.

Histology of the Large Intestine

• The mucosa is simple columnar epithelium with numerous straight tubular glands called crypts.
• Goblet cells predominate, but there are also absorptive and granular cells.

Rectum

• Straight muscular tube with a thick muscular tunic.

Anal Canal

• The last few centimeters of the digestive tract.
• The superior epithelium is simple columnar, and the inferior epithelium is stratified squamous.
• Contains the internal anal sphincter (smooth muscle) and the external anal sphincter (skeletal muscle).
• Hemorrhoids: Vein enlargement or inflammation.

Secretions of the Large Intestine

• The major secretion is mucus, which provides lubrication.
  • Irritation, tactile stimulation, and parasympathetic stimulation increase goblet cell secretion.
• Water leaves the lumen of the colon by osmosis as Na^+ and Cl^- move into epithelial cells.
• Bacteria in the microbiota produce vitamin K, which is then passively absorbed.
• Also, produce gases (flatus) from particular kinds of carbohydrates.
• Feces consist of water, undigested food (cellulose), microorganisms, and sloughed-off epithelial cells.

Movement in the Large Intestine

• Mass movements:
  • Common after meals.
  • Initiated by the presence of food in the stomach and duodenum.
  • Integrated by ENS reflexes.
  • Gastrocolic: Initiated by stomach distention.
  • Duodenocolic: Initiated by distention of the duodenum.
• Defecation reflex stimulated by distension of the rectal wall by feces.
  • Parasympathetic reflexes are responsible for most of the defecation reflex.
  • Can also be initiated voluntarily through the Valsalva maneuver.
  • This straining includes a large inspiration of air, followed by closure of the larynx and forceful contraction of abdominal muscles.
  • The increased intra-abdominal pressure forces feces into the rectum, where the stretching initiates a defecation reflex.

Defecation

• Contractions moving feces toward the anus must be coordinated with the relaxation of the internal and external anal sphincters.
• Parasympathetic reflexes are responsible for most of the defecation reflex.
• There is also conscious control of the defecation reflex.
  • Action potentials from the sacral spinal cord get sent to the brain, where parts of the brainstem and hypothalamus inhibit or facilitate reflexes in the spinal cord.
  • Action potentials are sent to the cerebrum, where awareness of the need to defecate is realized.
  • The external anal sphincter is composed of skeletal muscle and is under conscious control.
  • If this sphincter is relaxed, feces are expelled.
  • Increased contraction prevents defecation.
• The defecation reflex persists for only a few minutes and quickly declines.

Control of Defecation

1. Distension of the rectum by feces stimulates local defecation reflexes that cause contractions of the large intestine and rectum, which move feces toward the anus.
2. Distension of the rectum stimulates parasympathetic reflexes. Action potentials are propagated to the defecation reflex center. Input from the defecation reflex center causes contraction of the large intestine and rectum but causes relaxation of the internal anal sphincter.
3. Voluntary control of the external anal sphincter from motor nerve fibers contracts or relaxes it.

Digestion and Absorption

Digestion

• Breakdown of food molecules for absorption into the circulation.
  • Mechanical: Breaks large food particles into small particles.
  • Chemical: Breaks covalent bonds by digestive enzymes.

Absorption and Transport

• Molecules are moved out of the digestive tract and into circulation for distribution throughout the body.
• Some molecules are absorbed by diffusion; others are transported across the intestinal wall using transport proteins.
• Absorbed water, ions, and water-soluble digestion products (such as glucose and amino acids) enter the hepatic portal system and travel to the liver.
• Lipids are coated with proteins and move into lymphatic capillaries (lacteals), which become lymphatic vessels that drain into the thoracic duct, which empties into the left subclavian vein. The protein-coated lipid products then travel in the blood to adipose tissue or to the liver.

Carbohydrates

• Polysaccharides, disaccharides, and monosaccharides.
• A small amount is digested in the oral cavity due to salivary amylase, which is inactivated in the stomach by acid.
• Carbohydrate digestion continues in the small intestine with pancreatic amylase and disaccharidases, resulting in glucose, galactose, and fructose.
• Absorption:
  • Glucose and galactose are taken up by symport with sodium (secondary active transport).
  • Fructose is absorbed via facilitated diffusion.

Transport of Glucose Across the Intestinal Epithelium

1. The monosaccharides glucose and galactose are taken up into intestinal epithelial cells by symport, powered by a Na^+ gradient. The Na^+ gradient is generated by the Na^+-K^+ pump located on the basolateral membrane. Diffusion of Na^+ down its concentration gradient provides the energy to transport glucose or galactose across the plasma membrane. Fructose is taken up by facilitated diffusion.
2. Once inside the intestinal epithelial cell, monosaccharides are transported by facilitated diffusion to the capillaries of the intestinal villi.
3. Monosaccharides are then carried by the hepatic portal system to the liver, where the non-glucose monosaccharides are converted to glucose.

Lipids

• Include triglycerides (fats), phospholipids, steroids, and fat-soluble vitamins.
• Lipases digest lipid molecules; products include free fatty acids and monoglycerides (lingual lipase, pancreatic lipase, gastric lipase).
• Emulsification: Bile salts turn large lipid droplets into smaller droplets, increasing the surface area for better lipase access.
• Micelles: Lipid droplets surrounded by bile salts.
• Micelles are absorbed by epithelial cells, and lipid contents are repackaged into chylomicrons.
• Chylomicrons enter lacteals and eventually the blood, travel to adipose tissue. In blood, triglycerides are converted back into fatty acids and glycerol, transported into the adipose cells, and then converted back into triglycerides.

Transport of Lipids Across Intestinal Epithelium

1. Bile salts surround fatty acids and monoglycerides to form micelles.
2. When micelles contact the plasma membranes of intestinal epithelial cells, the fatty acids and monoglycerides pass by simple diffusion into the intestinal epithelial cells.
3. Within intestinal epithelial cells, fatty acids and monoglycerides are converted to triglycerides; proteins coat the triglycerides to form chylomicrons, which move out of the intestinal epithelial cells by exocytosis.
4. Chylomicrons enter the lacteals of the intestinal villi and are carried through the lymphatic system to the general circulation and then to adipose tissue.

Lipoproteins

• Lipids are transported in the blood in combination with protein to make them soluble in plasma.
  • This combination is a lipoprotein. Types: VLDL, LDL, and HDL; vary in the amount of lipid vs. protein and serve different functions.
• Chylomicrons enter the lymph (99% lipid, 1% protein - extremely low density).
• VLDL: The form in which lipids leave the liver (92% lipid, 8% protein).
  • Triglycerides are removed from VLDL and stored in adipose cells, which converts VLDL to LDL.
• LDL: Transports cholesterol to cells (75% lipid, 25% protein).
  • Cells have LDL receptors, allowing cells to take in cholesterol and other lipids.
  • The number of LDL receptors becomes less once the cells' lipid/cholesterol needs are met.
• HDL: Transports excess cholesterol from cells to the liver for removal from the body (55% lipid, 45% protein).
• Cholesterol: 15% comes from ingestion; 85% is manufactured in the liver and intestinal mucosa.

Protein Digestion and Transport Across Intestinal Epithelium

• Pepsin breaks proteins into smaller polypeptide chains in the stomach.
• Pancreatic proteases (trypsin, chymotrypsin, and carboxypeptidase) produce small peptide chains.
• Peptidases from the intestinal brush border produce amino acids as products (as well as dipeptides and tripeptides).
• Transport of amino acids across the epithelium depends on charge.
  • Acidic and neutral amino acids are symported with the Na^+ gradient
  • Basic enter by facilitated diffusion.
• Amino acids then enter the hepatic portal system, which transports them to the liver.
• The amino acids may be modified in the liver or released to the blood for distribution to all cells in the body.

Digestion of Carbohydrates, Lipids, and Proteins

• Oral Cavity: Complex carbohydrates and disaccharides broken down by salivary amylase into smaller polysaccharides and disaccharides.
• Stomach: Proteins broken down by pepsin into polypeptides
• Duodenum: With pancreatic secretions and bile, bile salts emulsify lipids. Lipase from the pancreas breaks down triglycerides into fatty acids and monoglycerides,. Simultaneously, pancreatic amylase breaks down polysaccharides into disaccharides. Trypsin, chymotrypsin, and carboxypeptidase from the pancreas also break down polypeptides into peptides
• Epithelium of Small Intestine: Disaccharides broken down by disaccharides in the epithelium of the small intestine, Bile salts, with the help of pancreatic lipase further emulsify triglycerides.

Water and Ions

Water:

• Can move in either direction across the wall of the small intestine, depending on osmotic gradients.
• Diarrhea results from a decrease in fluid absorption or an increase in fluid secretion by the intestines.
• Oral rehydration therapy involves water containing sodium and glucose; water follows by osmosis.

Ions:

• Sodium, potassium, calcium, magnesium, and phosphate are actively transported.
• Chloride ions move passively, following Na^+.
• Calcium transport requires vitamin D3.

Representative Diseases and Disorders of the Digestive System