Unit 1: Physiology of Digestion in Mammals

1. Mechanical and Chemical Events of Digestion of Food

Digestion is the physiological process by which complex, insoluble food molecules are broken down physically and chemically into simpler, soluble components that can be absorbed across the intestinal epithelium into the bloodstream or lymphatic system.

1.1 Digestion in the Oral Cavity (Mouth)

Digestion begins in the oral cavity through both mechanical and chemical processes.

• Mechanical Events: Mastication (chewing) involves the teeth grinding food and mixing it with saliva secreted by the salivary glands (parotid, submandibular, and sublingual). The tongue aids in moving food and forming a cohesive spherical mass called a bolus.
• Chemical Events: Saliva contains water, electrolytes, mucus, and enzymes:
  • Salivary Amylase (Ptyalin): An enzyme that hydrolyzes alpha-1,4-glycosidic bonds in starch, converting complex carbohydrates into disaccharides like maltose, trisaccharide maltotriose, and alpha-limit dextrins. Optimum pH is approximately 6.8.
  • Lingual Lipase: Secreted by Ebner's glands on the tongue; initiates minor digestion of short-chain and medium-chain dietary triglycerides into fatty acids and diglycerides. It remains active in the acidic environment of the stomach.

Definition - Mastication: The mechanical grinding and breakdown of food by teeth, increasing the surface area of food particles for enzymatic action.

1.2 Digestion in the Pharynx and Esophagus

The pharynx and esophagus serve primarily as transit pathways rather than sites of enzymatic digestion.

• Mechanical Events: Deglutition (swallowing) moves the bolus from the oral cavity into the esophagus. Peristalsis—wave-like, rhythmic contractions of smooth muscle layers (outer longitudinal and inner circular)—propels the bolus downward toward the stomach.
• Chemical Events: No digestive enzymes are secreted by the esophagus. Salivary amylase continues working inside the bolus until it encounters gastric acid.

1.3 Digestion in the Stomach

The stomach acts as a temporary storage vessel where food is converted into a semi-fluid mass called chyme.

• Mechanical Events: Churning and mixing waves produced by the three smooth muscle layers (longitudinal, circular, and oblique) physically break down food and blend it with gastric juice. Propulsion and retropulsion pulverize solid food fragments.
• Chemical Events: Gastric glands contain specialized cells that secrete gastric juice:
  • Parietal (Oxyntic) Cells: Secretes hydrochloric acid (HCl) (pH 1.5 to 2.0) and Intrinsic Factor. HCl denatures proteins, kills ingested pathogens, and converts inactive pepsinogen into active pepsin.
  • Chief (Zymogenic) Cells: Secretes pepsinogen (an inactive zymogen) and gastric lipase.
  • Pepsin Action: Pepsin is an endopeptidase that hydrolyzes internal peptide bonds, specifically next to aromatic amino acids (phenylalanine, tyrosine, tryptophan), breaking proteins into proteoses and peptones.
  • Rennin (Chymosin): Found in young mammals (infants); curdles milk protein casein in the presence of calcium to delay gastric emptying.
  • Gastric Lipase: Hydrolyzes butter fat (tributyrin) into fatty acids and monoglycerides; active at pH 4.0 to 5.0.

Important Reaction - Pepsinogen Activation:
Pepsinogen + HCl → Pepsin (Active)
Pepsinogen + Pepsin (Autocatalysis) → Pepsin + Peptide fragments

1.4 Digestion in the Small Intestine

The small intestine (duodenum, jejunum, ileum) is the principal site of both chemical digestion and nutrient absorption.

• Mechanical Events:
  • Segmentation: Localized contractions of circular smooth muscle that mix chyme with digestive secretions and bring it into contact with the mucosal lining.
  • Peristalsis: Migrating motor complexes that slowly propel chyme forward along the intestinal tract.
  • Emulsification: Bile salts (sodium taurocholate and sodium glycocholate) emulsify large lipid droplets into tiny micro-droplets, dramatically increasing the surface area for lipase action.
• Chemical Events: Digestion in the small intestine relies on pancreatic juice, bile, and brush border enzymes of the intestinal mucosa (succus entericus):
  • Pancreatic Enzymes:
    • Pancreatic Amylase: Hydrolyzes remaining starches into maltose, maltotriose, and dextrins.
    • Trypsinogen: Activated to trypsin by enteropeptidase (enterokinase) on the brush border. Active trypsin then activates chymotrypsinogen to chymotrypsin and procarboxypeptidase to carboxypeptidase.
    • Endopeptidases (Trypsin, Chymotrypsin, Elastase): Hydrolyze internal peptide bonds.
    • Exopeptidases (Carboxypeptidases A and B): Cleave amino acids from the carboxyl-terminal end of peptides.
    • Pancreatic Lipase & Colipase: Hydrolyzes triglycerides into 2-monoglycerides and free fatty acids.
    • Nucleases (DNase and RNase): Break down nucleic acids into nucleotides.
  • Brush Border Enzymes (Succus Entericus):
    • Disaccharidases: Maltase (breaks maltose into 2 glucose), Lactase (breaks lactose into glucose and galactose), Sucrase (breaks sucrose into glucose and fructose).
    • Peptidases: Aminopeptidases (cleave amino acids from N-terminal end), Dipeptidases (cleave dipeptides into single amino acids).
    • Nucleotidases & Nucleosidases: Convert nucleotides to nucleosides, and nucleosides to free nitrogenous bases, pentose sugars, and phosphate groups.

1.5 Digestion in the Large Intestine

• Mechanical Events: Haustral churning, peristalsis, and mass peristalsis move remaining undigested residue through the colon.
• Chemical Events: No digestive enzymes are produced by the large intestine. Bacterial fermentation by gut flora digests remaining carbohydrates (producing gases like methane and short-chain fatty acids) and synthesizes vitamins B complex and K.

1.6 Summary of Digestive Events

2. Absorption of Carbohydrates, Lipids, Proteins, Water, Minerals, and Vitamins

Absorption is the passage of digested nutrient molecules from the lumen of the gastrointestinal tract across epithelial cells into blood capillaries or lymph vessels.

2.1 Absorption of Carbohydrates

Carbohydrates are absorbed exclusively as monosaccharides (glucose, galactose, fructose) in the duodenum and jejunum.

• Glucose and Galactose: Transported across the apical (luminal) membrane of enterocytes via Sodium-Glucose Cotransporter 1 (SGLT1) through secondary active transport. Sodium ions move down their electrochemical gradient, carrying glucose/galactose against their concentration gradient.
• Fructose: Transported across the apical membrane via GLUT5 by facilitated diffusion (Na+ independent).
• Basolateral Exit: All three monosaccharides exit the enterocyte across the basolateral membrane into the bloodstream via GLUT2 transporter by facilitated diffusion and enter the hepatic portal circulation.

2.2 Absorption of Proteins

Proteins are absorbed in the small intestine as free amino acids, dipeptides, and tripeptides.

• Amino Acids: Transported across the apical membrane via specific Na+-dependent amino acid transporters through secondary active transport.
• Dipeptides and Tripeptides: Transported across the apical membrane via PepT1 (Peptide Transporter 1) powered by a H+ gradient (secondary active transport driven by Na+/H+ exchanger). Inside enterocytes, intracellular peptidases hydrolyze them into free amino acids.
• Basolateral Exit: Free amino acids exit the basolateral membrane via facilitated diffusion transporters into blood capillaries leading to the hepatic portal vein.

2.3 Absorption of Lipids

Lipid digestion products (free fatty acids, monoglycerides, cholesterol, fat-soluble vitamins) require specialized pathways due to their hydrophobic nature.

1. Micelle Formation: Bile salts and phospholipids assemble around hydrophobic lipids to form amphipathic structures called micelles.
2. Passive Diffusion: Micelles transport lipids to the brush border of enterocytes. Lipids dissociate from micelles and passively diffuse across the lipid bilayer membrane.
3. Re-esterification: Inside the Smooth Endoplasmic Reticulum (SER) of enterocytes, monoglycerides and fatty acids are re-synthesized into triglycerides.
4. Chylomicron Formation: Triglycerides, cholesterol, and phospholipids are packaged with apoproteins (Apo B-48) to form spherical lipoprotein complexes called chylomicrons.
5. Exocytosis to Lacteals: Chylomicrons exit enterocytes across the basolateral membrane via exocytosis and enter central lacteals (lymphatic capillaries), bypass the liver initially, and join the venous blood via the thoracic duct.

Common Mistake to Avoid on Exams: Lipids do not directly enter blood capillaries from intestinal mucosa. They are packaged into chylomicrons and enter lacteals (lymphatic system) first, unlike monosaccharides and amino acids which directly enter blood capillaries.

2.4 Absorption of Water and Minerals

• Water Absorption: Approximately 9 liters of fluid enter the GI tract daily; 90% is absorbed in the small intestine and 8-9% in the colon via osmosis following the active transport of solutes like Na+.
• Sodium (Na+): Absorbed via primary active transport (Na+/K+ ATPase pump on basolateral membrane), co-transport with nutrients (SGLT1), and Na+/H+ exchangers.
• Calcium (Ca2+): Actively absorbed in the duodenum; regulated by Vitamin D3 (calcitriol), which induces the synthesis of intracellular binding protein calbindin, and Parathyroid Hormone (PTH).
• Iron (Fe2+): Absorbed as ferrous iron (Fe2+) via DMT1 (Divalent Metal Transporter 1) on the apical membrane. Regulated by hormone hepcidin secreted by the liver.
• Anions (Cl-, HCO3-): Passively follow Na+ or are exchanged via anion antiport mechanisms.

2.5 Absorption of Vitamins

• Fat-Soluble Vitamins (A, D, E, K): Absorbed along with dietary lipids in micelles via simple passive diffusion into enterocytes and incorporated into chylomicrons.
• Water-Soluble Vitamins (B-complex, C): Absorbed mainly by passive diffusion or Na+-dependent active transport in the small intestine.
• Vitamin B12 (Cobalamin): Requires binding to Intrinsic Factor (IF) produced by parietal cells in the stomach. The B12-IF complex binds to specific receptors (cubilin) in the distal ileum and is absorbed via receptor-mediated endocytosis.

2.6 Summary Table of Nutrient Absorption

3. Gastrointestinal Hormones and Hormonal Control of Secretion

Gastrointestinal hormones are endocrinological peptides secreted by enteroendocrine cells embedded in the mucosal lining of the stomach and intestine. They coordinate secretion, motility, and enzymatic activity throughout digestion.

3.1 Major Gastrointestinal Hormones

• Gastrin: Secreted by G cells located in the pyloric antrum of the stomach and duodenum in response to luminal peptides, amino acids, and vagal stimulation.
  • Functions: Stimulates parietal cells to secrete HCl; stimulates chief cells to secrete pepsinogen; promotes gastric mucosa growth and increases gastric motility.
• Secretin: Secreted by S cells in the mucosal crypts of the duodenum in response to acidic chyme (pH less than 4.5) entering from the stomach.
  • Functions: Stimulates pancreatic centroacinar cells and bile duct epithelium to secrete bicarbonate-rich fluid (HCO3-) to neutralize gastric acid; inhibits gastric acid secretion and slows gastric emptying.
• Cholecystokinin (CCK): Secreted by I cells in the duodenum and jejunum in response to fatty acids, monoglycerides, and peptides in chyme.
  • Functions: Stimulates pancreatic acinar cells to secrete enzyme-rich pancreatic juice; causes gallbladder contraction and relaxation of the Sphincter of Oddi; slows gastric emptying.
• Gastric Inhibitory Peptide (GIP / Glucose-dependent Insulinotropic Peptide): Secreted by K cells in the duodenum and jejunum in response to glucose, amino acids, and fatty acids.
  • Functions: Stimulates insulin release from pancreatic beta cells; weakly inhibits gastric acid secretion and motility.
• Motilin: Secreted by M cells in the duodenum and jejunum during fasting states.
  • Functions: Initiates Migrating Motor Complexes (MMC) to clear undigested debris from the stomach and intestine.

3.2 Hormonal Control of Gastric Secretion

Gastric secretion occurs in three phases regulated by neural and hormonal signals:

1. Cephalic Phase: Triggered by sight, smell, or thought of food. Vagus nerve (CN X) releases acetylcholine (ACh) to stimulate parietal cells and G cells.
2. Gastric Phase: Triggered by food distension and presence of proteins in stomach. Gastrin is released into blood, strongly enhancing HCl and pepsinogen secretion.
3. Intestinal Phase: Triggered by entry of chyme into duodenum. Initially brief gastrin release, followed by inhibition of gastric secretion via secretin, CCK, and GIP to prevent hyperacidity and control transit rate.

3.3 Hormonal Control of Pancreatic and Biliary Secretions

• Pancreatic Enzyme Secretion: CCK acts on pancreatic acinar cells via CCK1 receptors, stimulating exocytosis of zymogen granules containing trypsinogen, chymotrypsinogen, amylase, and lipase.
• Pancreatic Bicarbonate Secretion: Secretin binds to GPCRs on pancreatic ductular cells, raising cAMP levels to activate CFTR chloride channels and Cl-/HCO3- exchangers, producing an alkaline, HCO3--rich secretion that neutralizes gastric acid.
• Biliary Secretion & Gallbladder Contraction: CCK induces gallbladder contraction while simultaneously relaxing the sphincter of Oddi, allowing bile and pancreatic juices to pour into the duodenum.

3.4 Summary Table of GI Hormones