Physiology of Digestion and Absorption

Physiology of Digestion and Absorption

Key Concepts

• The small intestinal absorptive surface is designed to maximize transport capacity.
• Enzymatic processes are required for effective digestion of carbohydrates, lipids, and proteins.
• Specific transport and carrier mechanisms are required for nutrient movement across the gut wall.

Overview of Digestion and Absorption

The primary function is the transfer of nutrients, water, and electrolytes from food into the body. This involves:

• Chewing and swallowing.
• Digestion.
• Absorption.
• Elimination (pooping).

The Gastrointestinal (GI) Tract

Structure

• Pharynx
• Esophagus
• Stomach
• Small intestine
• Large intestine

Accessory Organs

• Teeth
• Tongue
• Salivary glands
• Liver
• Gall bladder
• Pancreas

Processes

• Digestion: Breaking down food into smaller molecules.
• Absorption: Transferring nutrients from the GI tract into the body.
• Secretion: Release of enzymes, hormones, and other substances to aid digestion.
• Motility: Movement of food through the GI tract.

Other Functions

• Fluid balance.
• Protection against pathogens.

Food Disintegration

• Fragmentation: Breaking food into smaller bits.
• Abrasion: Erosion of the surface by shear stress.
• Dissolution: Nutrients dissolving into solution for absorption.

Hydrolysis

• Carbohydrates are broken down into monosaccharides.
• Proteins are broken down into amino acids.
• Lipids are broken down into monoacylglycerides.

Digestion Throughout the GI Tract

Small Intestine - Perfect for Absorption

• The absorption rate is very fast due to the huge surface area.
• Three structures increase the surface area:
  • Plicae circulares (small circular bowel folds)
  • Villi
  • Microvilli

Surface Area

Functional Unit - The Villus

• Villi are lined by specialized epithelial cells called enterocytes.
• Enterocytes have a brush border containing microvilli.
• The brush border contains key digestive enzymes.
• Villi contain absorptive vasculature and lymphatics (lacteal).

The Enterocyte

• Apical membrane: The surface facing the intestinal lumen.
• Basal membrane: The surface facing the bloodstream.
• Tight junctions: Seal between enterocytes.
• Glycocalyx: A layer of carbohydrates on the surface of the microvilli.

Carbohydrate Digestion

• Digestion starts in the mouth with salivary amylase.
• Further digestion occurs in the small intestine with pancreatic amylase.
• Enzymes in the microvilli (glycocalyx) break down disaccharides into monosaccharides:
  • Sucrase: sucrose → glucose + fructose
  • Lactase: lactose → glucose + galactose
  • Maltase: maltose → glucose + glucose

Monosaccharide Absorption

• Glucose, galactose, and fructose are absorbed by the small intestine in a two-step process:

  • Step 1: Across the apical cell membrane
    • Glucose and galactose via SGLT1 (Sodium/Glucose Transporter 1), driven by the $Na^+$ current produced by the $Na^+/K^+/ATPase$ pump.
    • Fructose via GLUT5 (facilitated sugar transporter).
  • Step 2: Across the basal cell membrane
    • Glucose, galactose, and fructose via GLUT2 (facilitated sugar transporter).

Lactose Intolerance

• A genetically acquired condition resulting in a deficiency of the enzyme lactase.
  lactose
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  ightharpoonup[lactase] glucose + galactose
• Lactose accumulation in the gut:
  • Acts as an osmotic laxative → water is retained in the gut.
  • Acts as a nutrient for bacteria in the large intestine → increased gas production.
• Leads to osmotic diarrhea, bloating, and excessive gas production.
• Can potentially lead to malnutrition and failure to thrive in children.

Protein Digestion

• Digestion of dietary protein starts in the stomach with pepsin.

• The majority of protein digestion occurs in the small intestine by proteases found in three locations:

  • In the lumen (70%): Luminal proteases, secreted from the pancreas, hydrolyze proteins to oligo-peptides, short peptides, and free amino acids.
  • At the brush border (30%): Brush border peptidases, membrane proteins that digest peptides to short (di- and tri-) peptides and single amino acids.
  • Within the enterocyte: Cytoplasmic peptidase, digests short peptides to free amino acids after absorption across the enterocyte membrane.

Protein Absorption - Apical Membrane

• Short peptide transport via $H^+$-dependent peptide co-transporter (PepT1).
  • Active transporter driven by the $H^+$ electrochemical gradient.
• Amino acid transport via $Na^+$-dependent amino acid co-transporters.
  • Seven different transporters are located in the apical membrane, specificity based on the chemical properties of the amino acids:
    • Basic: $b^{0,+}$ amino acid transporter (BAT1)
    • Acidic: excitatory amino acid transporter 3 (EAAT3)
    • Neutral: alanine-serine-cysteine transporter (ASCT2)

Protein Absorption - Basal Membrane

• Amino acid transport across the basal membrane is mediated by $Na^+$-independent amino acid transporters.
  • Five known different transporters:
    • Three responsible for amino acid transport out of the enterocyte.
    • Two responsible for amino acid transport into the enterocyte.
• 90% of apically absorbed amino acids are transported across the basal membrane and into the circulation.
• The other 10% are utilized by the enterocyte for intracellular protein synthesis.

Coeliac Disease

• Autoimmune disease that can lead to damage to the small intestine, leading to possible problems with nutrient absorption.
• Intolerance to gluten, a protein found in wheat, rye, barley, and oats.
• The immune response leads to damage to the small intestine mucosa, resulting in the loss of intestinal villi (atrophy).
• Common symptoms: diarrhea, abdominal pain, and bloating.
• Can result in malnutrition, anemia, fatigue, and skin rash.

Lipid Digestion

• Digestion of lipids begins in the mouth with lingual lipase (<5%).
• The vast majority of lipid digestion occurs in the small intestine with pancreatic lipase.
• However, lipids are hydrophobic and therefore not soluble in the aqueous lumen of the GI tract.
• Lipids must be emulsified by bile salts for efficient digestion to occur.
• Lipases required for lipid digestion (lingual lipase, pancreatic lipase & bile salt-dependent lipase) are all found in breast milk, aiding digestion of milk lipids in infants.

Emulsification of Lipids by Bile Salts

• A layer called the unstirred water layer surrounds the brush border.
• Micellar emulsification by bile salts increases the water solubility of lipids.
• Bile salts are produced by the liver.
• Aids enzymatic digestion.
• Allows entry into enterocyte for absorption.
• Without bile salts, lipids pass through the GI tract undigested and unabsorbed, causing steatorrhea (foul-smelling fatty stools).

Hydrolysis of Lipids by Enzymes

**Orlistat (Xenical) is a pancreatic lipase inhibitor - approved treatment for obesity.

Absorption and Exocytosis of Lipids

• Following digestion by pancreatic enzymes, lipid digestion products (e.g., MAG and fatty acids) are absorbed by diffusion across the apical membrane of the enterocyte.
• Digestion products are converted back to ingested fats in the SER (e.g., MAG back to TAG).
• Lipids are then packaged/coated with proteins to form chylomicrons.
• Chylomicrons cross the basal membrane by exocytosis.
• Enter lymph via the lacteal.
• The lymphatic system empties into the systemic bloodstream via the hepatic artery to the liver.

Nutrient Malabsorption

Several disorders can result in nutrient malabsorption and failure to thrive:

• Enteric infections.
• Parasites.

Nutrient malabsorption can result from anything that interferes with the digestion and absorption of nutrients, the delivery of bile, or factors that damage the intestinal mucosa.

Absorption of Vitamins

• Fat-soluble vitamins (A, D, E, and K): Absorbed along with lipids (micelles, chylomicrons, etc.).
• Water-soluble vitamins (C and B-complex): Require transport proteins (active transport or facilitated diffusion).
• Vitamin B12: Requires intrinsic factor protein secreted from the gastric parietal cells. The IF-B12 complex is transported to the ileum where absorption occurs.

Absorption of Sodium/Potassium

• Sodium is absorbed by several different processes:
  • From lumen as a solute in $H_2O$ through tight junctions (solvent drag).
  • Co-transport with nutrient carriers (e.g., SGLT1).
  • $Na^+/H^+$ exchanger.
  • $Na^+$-selective ion channels in the epithelium (e.g., ENac).
• Potassium Absorption of potassium is a passive process through tight junctions:
  • Driven by the difference in luminal $[K^+]$ and blood $[K^+]$. As $H_2O$ is absorbed from the lumen, the luminal $[K^+]$ increases, leading to increased absorption.
  • Prolonged diarrhea can produce considerable loss of $K^+$ (hypokalemia), which can be life-threatening.

Absorption of Calcium

• Takes place predominantly in the duodenum.
• The absorption of $Ca^{2+}$ is regulated by plasma $Ca^{2+}$ levels.
• When levels are low, calcium absorption can be promoted by the Vitamin D derivative 1,25-dihydroxy vitamin D3.
• Low vitamin D levels can lead to decreased $Ca^{2+}$ absorption and rickets in children.

Absorption of Iron

• Iron is actively absorbed in the ferrous form ($Fe^{2+}$) via divalent metal transporter (DMT-1) on the apical surface.
• Once inside the enterocyte, iron is either stored as ferritin or transported across the basal membrane by the ferroportin transporter.
• Iron is transported in the blood bound to transferrin.
• Iron is released from enterocytes according to need/plasma concentrations.

Absorption of Water

• Water absorption is driven by osmotic gradients.
• The direction is determined by the osmolarity difference between the lumen and blood.
• Water can move in either direction.
• After eating, water often moves from blood to lumen.
• After absorption of the nutrients, lumen osmolarity falls, and water is absorbed.
• Absorption of water mainly occurs in the small intestine, around 9 liters total each day.