# Lecture 14: Digestion and Absorption — Upper GI
## Anatomy and Physiology II
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## Learning Objectives
By the end of this lecture, students will be able to:
1. Describe the three phases of gastric secretion and their regulation
2. Explain gastric motility and the regulation of gastric emptying
3. Describe the anatomy and histology of the small intestine
4. Explain the mechanical and chemical digestion of carbohydrates, proteins, and lipids in the stomach and small intestine
5. Describe the mechanisms of nutrient absorption in the small intestine
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## Lecture Content
### I. Gastric Secretion and Regulation
The stomach secretes approximately 2 to 3 liters of gastric juice per day, a mixture of hydrochloric acid, pepsinogen, mucus, intrinsic factor, water, and electrolytes.
#### Regulation of HCl Secretion by Parietal Cells
Parietal cells respond to three stimulatory signals. **Acetylcholine (ACh)** from parasympathetic nerve endings (vagus nerve) acts on muscarinic (M3) receptors. **Gastrin** from G cells acts on CCK-B receptors. **Histamine** from ECL cells acts on H2 receptors and is the most potent direct stimulus. All three signals converge to activate the H+/K+-ATPase (proton pump) on the apical membrane, which actively secretes H+ into the stomach lumen in exchange for K+. Chloride follows through dedicated channels, resulting in the net secretion of HCl. Secretion is inhibited by **somatostatin** from D cells, which suppresses G cells, ECL cells, and parietal cells directly, and by **prostaglandins**, which inhibit acid secretion while promoting mucus and bicarbonate production.
#### Three Phases of Gastric Secretion
The **cephalic phase** accounts for about 30% of total secretion and is triggered before food enters the stomach. Stimuli such as the sight, smell, taste, or even thought of food activate pathways from the cerebral cortex and hypothalamus through the vagus nerve to the enteric nervous system, which stimulates parietal cells, chief cells, G cells, and ECL cells. This is a conditioned reflex, famously demonstrated by Pavlov's experiments.
The **gastric phase** produces about 60% of total secretion and begins when food enters the stomach. Stomach distension activates stretch receptors, triggering vagal and local reflexes that stimulate secretion. Peptides and amino acids from partially digested proteins stimulate G cells to release gastrin. The buffering of gastric acid by food raises intragastric pH, which removes the inhibition on G cells. A positive feedback loop develops as HCl activates pepsinogen to pepsin, which digests proteins into peptides, stimulating more gastrin release.
The **intestinal phase** contributes about 10% and is triggered when chyme enters the duodenum. Initially, partially digested proteins stimulate intestinal G cells to release a small amount of gastrin. However, as duodenal content increases, the phase becomes primarily inhibitory. The **enterogastric reflex** decreases gastric motility and secretion. Hormonal inhibitors including secretin (triggered by acid in the duodenum), CCK (triggered by fats and proteins), and GIP (triggered by glucose and fats) slow gastric emptying to prevent duodenal overload.
### II. Gastric Motility
The stomach mixes food with gastric juice to form **chyme**, a semifluid mixture. **Mixing waves**, gentle rippling contractions in the body, blend food with secretions. **Peristaltic waves**, stronger contractions in the pyloric region, propel chyme toward the pylorus. The pyloric sphincter allows only about 3 mL of chyme to pass with each wave; most chyme is forced back through retropulsion, which provides further mixing and mechanical digestion.
**Gastric emptying** is controlled by the pyloric sphincter and is stimulated by gastric distension and gastrin, while being inhibited by the enterogastric reflex, CCK, secretin, GIP, and the presence of fats and acids in the duodenum. A meal typically takes 4 to 6 hours to empty completely, with carbohydrate-rich meals emptying fastest and fatty meals emptying slowest.
### III. Small Intestine — Anatomy
The small intestine is the principal organ of digestion and absorption, measuring approximately 6 meters in length with a diameter of 2.5 to 4 cm. It has three regions. The **duodenum** is approximately 25 cm long, C-shaped, and mostly retroperitoneal. It receives chyme from the stomach, bile from the liver and gallbladder, and pancreatic juice from the pancreas. It contains Brunner's glands in the submucosa that secrete alkaline mucus to neutralize acid. The major duodenal papilla (ampulla of Vater) marks the opening for the common bile duct and main pancreatic duct, controlled by the sphincter of Oddi. The **jejunum**, about 2.5 meters long, is where most chemical digestion and absorption occurs. It has a thicker, more vascular wall and more prominent plicae circulares. The **ileum**, approximately 3.5 meters long, ends at the ileocecal valve at the junction with the large intestine. It contains Peyer's patches (lymphoid tissue) in the submucosa and is the specific site for bile salt and vitamin B12 absorption.
#### Structural Adaptations for Absorption
The small intestine achieves an enormous surface area of approximately 200 square meters through three levels of folding. **Plicae circulares** (circular folds) are permanent deep folds of the mucosa and submucosa, most prominent in the jejunum, that force chyme to spiral through the lumen and slow its passage. **Villi** are finger-like projections of the mucosa, approximately 0.5 to 1 mm tall. Each villus is covered by simple columnar epithelium with absorptive cells (enterocytes) and goblet cells. Its core of lamina propria contains a capillary network that absorbs most nutrients into the blood and a central lacteal (lymphatic capillary) that absorbs lipids into the lymph. **Microvilli** (the brush border) are tiny projections on the apical surface of each enterocyte, numbering 2,000 to 3,000 per cell and measuring approximately 1 micrometer in height. They contain membrane-bound **brush border enzymes** including disaccharidases (maltase, sucrase, lactase) that digest disaccharides to monosaccharides, peptidases (aminopeptidase, dipeptidase) that digest small peptides to amino acids, and nucleosidases and phosphatases.
A diagram of the structural adaptations of the small intestine. Panel A: A segment of the small intestine cut open to reveal plicae circulares (large circular folds) protruding into the lumen. Panel B: A magnified view of one plica showing densely packed villi covering the surface like a carpet. Panel C: A single villus in cross-section showing the simple columnar epithelium with absorptive cells (enterocytes displaying microvilli on their apical surface) and interspersed goblet cells, the lamina propria core containing a capillary network (in red and blue) surrounding a central lacteal (in green), and smooth muscle fibers extending from the muscularis mucosae. Panel D: An electron microscopy-style illustration of the microvilli (brush border) on a single enterocyte, with brush border enzymes labeled on the microvillus surface and the glycocalyx coating.
### IV. Chemical Digestion in the Small Intestine
The small intestine receives enzymes from the pancreas and its own brush border to complete digestion of all macronutrients.
#### Carbohydrate Digestion
Starch digestion begins in the mouth with salivary amylase and continues briefly in the stomach until the enzyme is inactivated by acid. In the duodenum, **pancreatic amylase** resumes starch digestion, producing maltose, maltotriose, and alpha-dextrins. **Brush border enzymes** complete the process: maltase cleaves maltose into two glucose molecules, sucrase cleaves sucrose into glucose and fructose, lactase cleaves lactose into glucose and galactose, and alpha-dextrinase cleaves alpha-dextrins into glucose. The final products are monosaccharides: glucose, fructose, and galactose.
#### Protein Digestion
Protein digestion begins in the stomach with pepsin, which is active at pH 1.5 to 3.5. In the duodenum, **pancreatic proteases** take over. Trypsinogen is activated to **trypsin** by enterokinase (enteropeptidase) from the duodenal brush border. Trypsin then activates chymotrypsinogen to **chymotrypsin**, procarboxypeptidase to **carboxypeptidase**, and proelastase to **elastase**. These enzymes produce short peptides and some free amino acids. **Brush border enzymes** including aminopeptidase, dipeptidase, and carboxypeptidase complete digestion to yield amino acids, dipeptides, and tripeptides.
#### Lipid Digestion
Fat digestion is minimal in the stomach, where lingual lipase and gastric lipase begin the process. In the duodenum, **bile salts** emulsify fats, breaking large fat globules into smaller droplets to increase the surface area available for enzyme action. Bile salts are amphipathic molecules with both hydrophilic and hydrophobic regions. **Pancreatic lipase**, working with colipase as a cofactor, digests triglycerides into monoglycerides and fatty acids. **Phospholipase A2** digests phospholipids, and **cholesterol esterase** digests cholesterol esters. The products of fat digestion (monoglycerides, fatty acids, and cholesterol) combine with bile salts to form **micelles**, small aggregates that transport lipid products to the brush border for absorption.
#### Nucleic Acid Digestion
Pancreatic nucleases (DNase and RNase) digest DNA and RNA into nucleotides, which are further broken down by brush border nucleosidases and phosphatases into nucleosides, bases, sugars, and phosphate groups.
### V. Absorption in the Small Intestine
Most absorption occurs in the duodenum and jejunum.
#### Carbohydrate Absorption
Monosaccharides are absorbed by enterocytes through specific transport mechanisms. Glucose and galactose enter the cell via secondary active transport through the SGLT1 (sodium-glucose symporter) on the apical membrane and exit through the basolateral membrane via GLUT2. Fructose enters by facilitated diffusion via GLUT5 on the apical membrane and also exits via GLUT2. All monosaccharides enter the capillary blood and travel via the hepatic portal vein to the liver.
#### Protein Absorption
Amino acids are absorbed by sodium-dependent cotransporters similar to those for glucose. Dipeptides and tripeptides are absorbed via the H+-dependent peptide transporter (PepT1) and hydrolyzed to amino acids inside the enterocyte. All protein digestion products enter the capillary blood and travel to the liver via the hepatic portal vein.
#### Lipid Absorption
Micelles deliver fatty acids and monoglycerides to the brush border. Short-chain fatty acids are small enough to diffuse directly into the capillary blood. Long-chain fatty acids and monoglycerides diffuse into enterocytes, where they are re-esterified to triglycerides in the smooth endoplasmic reticulum. These triglycerides are combined with cholesterol, phospholipids, and proteins to form **chylomicrons**, which exit the enterocyte by exocytosis and enter the lacteal (lymphatic capillary) rather than the blood capillary. Chylomicrons travel through the lymphatic system to the thoracic duct, which empties into the left subclavian vein, and from there enter the bloodstream.
#### Water and Electrolyte Absorption
Approximately 9 liters of fluid enter the GI tract daily (2 liters ingested plus 7 liters from digestive secretions). The small intestine absorbs about 8 liters, the large intestine absorbs approximately 0.9 liters, and only about 0.1 liters is lost in feces. Water is absorbed by osmosis, following solute absorption. Sodium is absorbed by active transport, and chloride follows passively or via exchangers. Potassium, calcium, iron, and other ions are absorbed by specific mechanisms.
#### Vitamin Absorption
Fat-soluble vitamins (A, D, E, and K) are absorbed along with dietary lipids in micelles. Water-soluble vitamins are absorbed by specific transporters or diffusion. Vitamin B12 has a unique absorption pathway: it binds to intrinsic factor produced by parietal cells and is absorbed in the ileum by receptor-mediated endocytosis.
A summary diagram of nutrient absorption across the enterocyte. Panel A (Carbohydrates): Glucose and galactose entering via SGLT1 cotransporter with Na+ on the apical membrane, and fructose entering via GLUT5; all three exiting via GLUT2 on the basolateral membrane into the capillary. The Na+/K+-ATPase on the basolateral membrane maintaining the Na+ gradient is shown. Panel B (Proteins): Amino acids entering via Na+-dependent cotransporters, and dipeptides/tripeptides entering via PepT1 with H+, being hydrolyzed intracellularly, then exiting into the capillary. Panel C (Lipids): A micelle delivering fatty acids and monoglycerides to the apical membrane, diffusion into the cell, re-esterification to triglycerides in the smooth ER, packaging into chylomicrons with a protein coat, exocytosis from the basolateral side, and entry into the lacteal rather than the blood capillary. Each panel clearly shows the direction of transport and key transport proteins.
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