7.2 Absorption of Nutrients

Absorption of Nutrients

Absorption is the process by which digested nutrients move from the lumen of the GI tract into the blood or lymph. Without it, all the mechanical and chemical digestion that came before would be pointless. The small intestine handles the bulk of this work, while the large intestine finishes up by reclaiming water and electrolytes.

Small Intestine Structure and Function

Anatomy and Sections

The small intestine has three sections, and each one contributes differently to digestion and absorption:

• Duodenum: Receives chyme from the stomach along with pancreatic secretions and bile from the liver. Most chemical digestion is completed here.
• Jejunum: The primary absorption site for carbohydrates, proteins, and fats. Its walls are thick with villi, giving it the greatest absorptive capacity of the three sections.
• Ileum: Absorbs remaining nutrients, bile salts, and vitamin B12 (via intrinsic factor). Connects to the large intestine at the ileocecal valve.

Surface Area Enhancement

The small intestine maximizes its absorptive surface area through three levels of folding. This is a favorite exam topic, so know all three:

1. Plicae circulares (circular folds): Large, permanent folds in the intestinal wall that force chyme to spiral as it moves through, slowing transit and increasing contact time.
2. Villi: Finger-like projections covering the plicae. Each villus contains a capillary network (for absorbing most nutrients into the blood) and a central lacteal, a lymphatic vessel that absorbs fats.
3. Microvilli: Microscopic projections on the apical surface of each epithelial cell. They contain brush border enzymes (like lactase and peptidases) and transport proteins. Collectively, the microvilli form the brush border membrane.

Together, these three structures increase the surface area of the small intestine to roughly 200 square meters, about the size of a tennis court.

Primary Site of Nutrient Absorption

The epithelial cells (enterocytes) lining the villi are specialized for absorption. Tight junctions between adjacent cells create a selective barrier that prevents large molecules and pathogens from passing between cells (paracellular route).

Once nutrients cross the enterocyte, they take one of two routes:

• Hepatic portal vein: Carries water-soluble nutrients (monosaccharides, amino acids, water-soluble vitamins) directly to the liver for processing.
• Lymphatic system: Fats are packaged into chylomicrons inside the enterocyte and released into lacteals, eventually draining into the bloodstream via the thoracic duct.

Nutrient Absorption Mechanisms

Passive Transport

Passive transport moves substances down their concentration gradient with no energy cost.

• Simple diffusion: Small, nonpolar molecules like fatty acids, monoglycerides, and fat-soluble vitamins pass directly through the phospholipid bilayer of the cell membrane.
• Facilitated diffusion: Larger or polar molecules need carrier proteins to cross. Fructose, for example, crosses the apical membrane via the GLUT5 transporter and exits through the basolateral membrane via GLUT2. No ATP is required because movement follows the concentration gradient.
• Osmosis: Water follows solute gradients passively, moving into or out of cells wherever solute concentration is higher.

Active Transport

Active transport moves substances against their concentration gradient and requires energy.

• Primary active transport: Uses ATP directly. The $Na^+/K^+$ ATPase pump on the basolateral membrane of enterocytes pumps 3 $Na^+$ out and 2 $K^+$ in, maintaining a low intracellular sodium concentration. This pump is the engine that drives most secondary active transport.
• Secondary active transport: Uses the sodium gradient created by the $Na^+/K^+$ ATPase to co-transport other molecules.
  • Symport (co-transport): $Na^+$ and another molecule move in the same direction. SGLT1 on the apical membrane brings glucose and $Na^+$ into the cell together.
  • Antiport (counter-transport): $Na^+$ and another molecule move in opposite directions. The $Na^+/H^+$ exchanger is one example, helping regulate intracellular pH.

Endocytosis

Some large molecules are absorbed by endocytosis, where the cell membrane wraps around the substance and pulls it inside as a vesicle.

• Receptor-mediated endocytosis: Specific receptors bind target molecules (e.g., immunoglobulins in breast milk absorbed by neonatal intestinal cells), triggering vesicle formation.
• Pinocytosis: Nonspecific uptake of extracellular fluid and small dissolved molecules.

Major Nutrients and Destinations

Carbohydrates

By the time carbohydrates reach the absorptive epithelium, they've been broken down into monosaccharides: glucose, fructose, and galactose.

• Glucose and galactose are absorbed via SGLT1 (secondary active transport with $Na^+$) on the apical membrane, then exit through GLUT2 on the basolateral membrane.
• Fructose is absorbed by facilitated diffusion via GLUT5 on the apical side and GLUT2 on the basolateral side.

All three monosaccharides travel through the hepatic portal vein to the liver. The liver converts fructose and galactose into glucose. Glucose is then used for energy (glycolysis/cellular respiration) or stored as glycogen.

Proteins

Proteins arrive at the brush border as amino acids, dipeptides, and tripeptides.

• Amino acids are absorbed via $Na^+$-dependent secondary active transport (similar to glucose).
• Dipeptides and tripeptides are absorbed via $H^+$-dependent co-transporters (PepT1) and then broken down into individual amino acids inside the enterocyte.

Amino acids enter the hepatic portal vein and travel to the liver. From there, they're distributed for protein synthesis (enzymes, hormones, structural proteins) or, if in excess, deaminated and converted to glucose (gluconeogenesis) or fatty acids.

Fats

Fat absorption is unique because it involves the lymphatic system rather than direct entry into the blood.

1. Bile salts emulsify fat globules into smaller droplets, increasing the surface area for pancreatic lipase.
2. Lipase breaks triglycerides into fatty acids and monoglycerides.
3. These products combine with bile salts to form micelles, which ferry them to the brush border.
4. Fatty acids and monoglycerides diffuse across the apical membrane (simple diffusion, since they're lipid-soluble).
5. Inside the enterocyte, they're reassembled into triglycerides and packaged with cholesterol, phospholipids, and proteins into chylomicrons.
6. Chylomicrons are too large to enter capillaries, so they enter the lacteals and travel through the lymphatic system before reaching the bloodstream.

Short- and medium-chain fatty acids are an exception. They're small enough to pass directly into the capillary blood and travel via the hepatic portal vein without being packaged into chylomicrons.

Vitamins

• Fat-soluble vitamins (A, D, E, K) are absorbed along with dietary fats. They travel in micelles to the brush border, enter enterocytes by simple diffusion, and are packaged into chylomicrons for lymphatic transport.
  • A: vision, immune function, cell differentiation
  • D: calcium and phosphorus regulation, bone health
  • E: antioxidant protecting cell membranes
  • K: blood clotting factors and bone metabolism
• Water-soluble vitamins (B-complex and C) are absorbed directly into the blood, mostly in the jejunum. Most cross via specific carriers or $Na^+$-dependent co-transport.
  • B-complex: coenzymes for energy metabolism, red blood cell formation, and DNA synthesis
  • C: antioxidant, collagen synthesis, immune function
  • Vitamin B12 is a special case. It requires intrinsic factor (secreted by gastric parietal cells) and is absorbed specifically in the ileum via receptor-mediated endocytosis.

Minerals

Mineral absorption occurs primarily in the duodenum and jejunum, and each mineral has its own transport mechanism:

• Calcium: Absorbed in the duodenum. Active absorption is regulated by calcitriol (active vitamin D), which increases the synthesis of calcium-binding proteins (calbindin) in enterocytes. When dietary calcium is high, some is absorbed passively via the paracellular route.
• Iron: Absorbed in the duodenum as $Fe^{2+}$ (ferrous iron). The protein DMT1 transports it across the apical membrane. Inside the cell, iron binds to ferritin for storage or is exported to the blood via ferroportin, where it binds transferrin for transport. Absorption is regulated by hepcidin.
• Magnesium: Absorbed in the ileum and colon through both active and passive mechanisms. Involved in energy metabolism, enzyme function, and neuromuscular signaling.

Water and Electrolyte Absorption in the Large Intestine

Water Absorption

About 1.5 liters of chyme enters the large intestine (colon) each day. The colon absorbs roughly 90% of this remaining water, converting liquid chyme into semisolid feces.

Water absorption here is entirely passive, driven by osmosis. As electrolytes (especially $Na^+$) are actively absorbed, water follows the osmotic gradient. Goblet cells throughout the colon secrete mucus that lubricates the fecal mass and protects the intestinal lining.

Electrolyte Absorption

The colon recovers key electrolytes to maintain fluid balance and blood pH:

• Sodium ($Na^+$): Absorbed actively via the $Na^+/K^+$ ATPase on the basolateral membrane and through epithelial sodium channels (ENaC) on the apical membrane. Water follows sodium osmotically.
• Chloride ($Cl^-$): Absorbed passively through paracellular pathways (following the electrical gradient created by sodium absorption) and via $Cl^-/HCO_3^-$ exchange.
• Bicarbonate ($HCO_3^-$): Secreted into the lumen in exchange for chloride, helping neutralize acids produced by bacterial fermentation in the colon.

Hormonal Regulation

Two hormones fine-tune water and electrolyte absorption in the colon:

• Aldosterone: Released by the adrenal cortex in response to low blood volume or high $K^+$ levels. It upregulates ENaC and the $Na^+/K^+$ ATPase, increasing $Na^+$ (and therefore water) reabsorption while promoting $K^+$ secretion.
• ADH (antidiuretic hormone / vasopressin): Released by the posterior pituitary when blood osmolarity rises. It increases water reabsorption in both the kidneys and the colon by inserting aquaporin channels.

Disorders of Water and Electrolyte Absorption

When colonic absorption is disrupted, two common conditions result:

• Diarrhea: Excess water remains in the feces due to impaired absorption or excessive secretion (as with bacterial toxins like cholera toxin, which locks $Cl^-$ channels open). This can rapidly cause dehydration and dangerous electrolyte imbalances.
• Constipation: Too much water is absorbed, often because transit time through the colon is too slow. The result is hard, dry stool that's difficult to pass.

Treatment depends on the cause but commonly includes oral rehydration solutions (water plus electrolytes and glucose to drive $Na^+$ co-transport), dietary fiber adjustments, and medications such as laxatives or antidiarrheal agents.