Notes on Small Intestinal Phase of Digestion

Learning Outcomes

• Understand exocrine pancreas: Functions and regulation.

• Bile components: Main components of bile juice & digestive functions (bile acids & salts).

• Intestinal motility: Patterns, priming and depriming factors, ileocolic sphincter function.

• Small intestine mucosa: Secretory and absorptive cell functions.

• Brush Border Membrane: Definition and role in digestion/absorption.

• Digestion phases: Description of luminal and membranous phases.

Process of Digestion in the Small Intestine

• Chyme composition upon entering small intestine:

  • Highly acidic from previous digestion in the stomach.

  • Contains: polypeptides, large emulsified fat globules, unchanged carbohydrates.

  • Note: None are absorbable in this form.

• Critical events for absorption:

  1. Neutralization of gastric acid (prevents mucosal damage).

  2. Hydrolysis of macromolecules into absorbable micromolecules:

  • Monosaccharides from carbohydrates,

  • Tri/dipeptides & amino acids from proteins,

  • Free fatty acids & monoglycerides from fats.

Role of Pancreas

• Bicarbonate Secretion:

  • 1 liter/day secreted to neutralize gastric acid and enable enzyme function at pH 7.5-8.

• Digestive enzymes:

  • Produced in pancreatic acini; divided into three groups:

  • Amylolytic enzymes (amylase): Digests starches but not structural carbohydrates, breaking polysaccharides into smaller units.

  • Proteolytic enzymes: (e.g., Trypsinogen, Chymotrypsinogen) stored as inactive zymogens to prevent autodigestion until activated in the intestine.

  • Lipases: Hydrolyze triglycerides into fatty acids and monoglycerides, requiring bile salts for effectiveness.

Defense Against Autodigestion

• Inactive storage as zymogens prevents auto-digestion:

  • Ensure strict compartmentalization within pancreas through zymogen granules and inhibitors such as pancreatic secretory trypsin inhibitor.

Control of Pancreatic Secretion

• Phases of secretion:

  • Cephalic Phase: Stimulation via vagal response.

  • Gastric Phase: Mild stimulation through gastrin.

  • Intestinal Phase: Main stimulation via hormones:

  • Secretin: Released due to low pH (<4.5) to stimulate bicarbonate.

  • Cholecystokinin (CCK): Released in response to fats/proteins to stimulate enzyme secretion.

Functions of Bile

• Liver's role: Secretes bile to:

  • Facilitate fat digestion and absorption; neutralize acidic chyme.

  • Bile is stored in the gallbladder and contains bile acids, electrolytes, bicarbonate, and organic compounds.

• Bile Acids: Derived from cholesterol, they emulsify fats and assist in absorption by forming micelles with lipids, keeping them in solution.

Small Intestine Motility Patterns

• Two primary types:

  • Peristalsis: Propels contents through contractions.

  • Segmentation: Mixes contents and enhances contact with absorptive cells.

• Migrating Motility Complex (MMC): Occurs during fasting to clear the GI tract of undigested content and prevent bacterial overgrowth.

Mucosa of the Small Intestine

• Cell types:

  1. Enterocytes:

  • Young enterocytes secrete fluids and convert to absorptive cells with microvilli for nutrient absorption.

  1. Enteroendocrine Cells: Synthesize hormones (e.g., CCK, secretin).

  2. Goblet Cells: Produce mucus for lubrication.

  3. Paneth Cells: Defend against microbes in the gut.

• Brush Border Membrane (BBM):

  • Contains enzymes essential for additional digestion necessary for nutrient absorption.

Implications for Digestion

• Successful digestion/absorption relies on the cooperation between pancreas, liver, and intestinal mucosa to manage pH, provide enzymes, and facilitate absorption through physiological mechanisms.

Pancreas

The exocrine pancreas is the major source of digestive enzymes in dogs. It is composed of acinar cells that synthesize and secrete these enzymes in inactive “zymogen” forms, which are later activated in the duodenum. The main classes of enzymes from the pancreas are:

1. Amylolytic Enzymes (Carbohydrate Digestion)

   • Pancreatic Amylase:

     • Function: Breaks down complex carbohydrates (starch) into simpler sugars (maltose and dextrins).

     • Importance: Although dogs are primarily carnivorous, they still ingest some carbohydrates, and pancreatic amylase helps in their digestion.

2. Proteolytic Enzymes (Protein Digestion)

   • Trypsinogen:

     • Secreted as an inactive precursor; it is converted to active trypsin by the enzyme enterokinase (found on the duodenal mucosal cells).

     • Once active, trypsin not only digests proteins into peptides but also activates other proteolytic zymogens.

   • Chymotrypsinogen, Proelastase, and Procarboxypeptidases:

     • These are also secreted as inactive proenzymes. They become activated (often by trypsin) in the intestinal lumen and help break down proteins into smaller peptides and amino acids.

3. Lipolytic Enzymes (Fat Digestion)

   • Pancreatic Lipase:

     • Function: Hydrolyzes triglycerides into monoglycerides and free fatty acids.

     • It plays a central role in fat digestion.

   • Colipase:

     • An essential cofactor secreted by the pancreas; it binds to lipase and helps anchor it to the lipid-water interface. This is particularly important in the presence of bile salts that otherwise can inactivate lipase.

   • Additional Lipases:

     • Minor enzymes, including phospholipases, also contribute to the breakdown of fat molecules.

4. Bicarbonate Secretion

   • Although not an enzyme, bicarbonate is secreted by the ductal cells of the pancreas.

   • Function: It neutralizes the acidic chyme coming from the stomach into the duodenum, thus creating an optimal pH environment for the pancreatic enzymes to work effectively.

Liver

While the liver is not a source of digestive enzymes in the classical sense (like those that chemically break down food molecules), it plays an indispensable role in digestion by producing bile, which is critical for fat digestion and absorption.

1. Bile Production

   • Bile Synthesis:

     • The liver synthesizes bile acids from cholesterol. The enzyme cholesterol 7α-hydroxylase in hepatocytes catalyzes the rate-limiting step in this pathway.

   • Bile Composition:

     • Bile is a complex mixture containing bile acids (or salts), cholesterol, phospholipids, bilirubin, and water.

   • Bile's Role in Digestion:

     • Emulsification: Bile acids emulsify large fat droplets, increasing their surface area. This emulsification is essential for making fats accessible to pancreatic lipase.

     • Micelle Formation: The emulsified fats are packaged into micelles, aiding in the efficient transport of lipids to intestinal mucosal cells for absorption.

2. Metabolic Functions

   • The liver also contains many enzymes responsible for metabolic, detoxification, and biosynthetic processes, but regarding digestion, its most relevant role is in bile production and secretion.

Integration of Enzymatic Action

• Carbohydrate Digestion:

  • Pancreatic amylase breaks starches into simpler sugars in the duodenum.

• Protein Digestion:

  • Proteolytic enzymes (trypsin, chymotrypsin, etc.) produced by the pancreas work sequentially (with initial activation by enterokinase) to break down proteins into peptides and amino acids.

• Fat Digestion:

  • Pancreatic lipase (aided by colipase) cannot act effectively on intact fat droplets alone. Here, the bile from the liver emulsifies fats, allowing lipase to hydrolyze triglycerides into absorbable fatty acids and monoglycerides.

Together, the pancreas and liver create a coordinated digestive system. The pancreas produces the key enzymes that directly break down macronutrients, while the liver, by producing bile, facilitates the digestion of dietary fats. This integrated approach ensures that dogs (and other mammals) can efficiently derive nutrients from their food.