Crypt epithelium Cell Loss Villous epithelium Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Absorp- tive cells Villous epithelium Goblet cells Crypt lumen Undifferentiated Crypt epithelium Goblet Mitoses Endocrine cells Endocrine cells Muscularis mucosa

Secretions of the Small Intestine (2000 ml/day) Crypts of Lieberkuhn: Small and Large Intestine Contain Primarily Epithelial Cells, Mucus Goblet Cells, and Endocrine Cells. Water Secretion - VIP Activates Water Secretion by Elevating cAMP and Cl- conductance. Cell Growth and Differentiation: Cell Turnover at the Tip of a Villus is High (3-6 day Cycle).

cAMP Activated Cl- Channel Na+ / K+ / Cl- Co-transport Na-K ATPase Crypt Secretion H2O 2 Cl- Na+ K+ PDte cAMP ? Ca2+ Cl- ATP ADP + Pi 3 Na+ 2 K+ Key Players: cAMP Activated Cl- Channel Na+ / K+ / Cl- Co-transport Na-K ATPase VIP – neurotransmitter Histamine also can activate

Daily Secretions into the Alimentary Canal Daily Volume (ml) pH Saliva 1200 7.0-7.4 Gastric secretion 2000 1.0-3.5 Pancreatic secretion 1200 8.0-8.3 Bile 700 7.8 Intestinal Secretions 2000 7.4-7.8 Brunner’s gland secretion 50 (?) 8.0-8.9 Large intestinal secretion 60 7.5-7.8 Total 7210

Crypt epithelium Cell Loss Villous epithelium Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Absorp- tive cells Villous epithelium Goblet cells Crypt lumen Undifferentiated Crypt epithelium Goblet Mitoses Endocrine cells Endocrine cells Muscularis mucosa

Sugar Absorption LUMEN Brush Border Lactose Sucrose Starch Glycogen a-Amylase Lactose Sucrose Starch Glycogen 30% 70% LUMEN a-Limit Dextrins Oligosaccharides Glucose Glucose Fructose Galactose Na+ Na+ Sucrase a-Dex trinase Glucose Carrier Glucose Carrier Fructose Carrier (Xylose) Gluco- amylase Lactase Brush Border

ABSORPTION Absorption of Nutrients: Carbohydrates Glucose and Galactose - Sodium Co-transporter Across Luminal Membranes Fructose - Facilitated Transport (Na+ Independent) Xylose: Pentose; Uses the Fructose Carrier not Na+ Dependent.

Pepsin, Pancreatic Protease Protein Pepsin, Pancreatic Protease Free Amino Acids Small Peptides Large Peptides Neutral Basic Acidic Carrier Peptidases Carrier Mediated Amino Acids Small Peptides Intracellular Peptidases Amino Acids A.A ? Capillary

Lipid Digestion and Absorption Large oil droplet (TG) Lipase Co-Lipase Emulsion: TG. MG. FFA. B.S. Microvilli Micelles MG. FFA. B.S. MG. FFA Intestinal epithelial cell

Chylomicron Triglyceride Liver Ileum Lacteal Capillary Monoglyceride Free fatty acids Glycerol Pancreatic lipase Liver Conjugated bile salts Micelle Ileum FABP Monoglyceride acylation pathway Phosphatidic acid pathway Protein (Apo B) Phospholipids Cholesterol Chylomicron Lacteal Capillary

Nutrient Digestion and Absorption Only Monomers and small digestion products can be absorbed. For amino acids and carbohydrates, most absorption is Na+dependent Lipids are digested before absorption, then re-synthesized in epithelia cells before packaging and secretion into lymph Glycerol and Monoglycerides diffuse into the blood. Complex fats are packaging into chylomicrons and secreted to the lymph. Lymphatic flow increased 10X during absorption of a high fat meal.

Crypt epithelium Cell Loss Villous epithelium Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Absorp- tive cells Villous epithelium Goblet cells Crypt lumen Undifferentiated Crypt epithelium Goblet Mitoses Endocrine cells Endocrine cells Muscularis mucosa

Relations Between Salt /Water Secretion and Absorption Net Fluid and NaCl Villus Epithelia Absorption Net Fluid and NaCl Crypt Epithelia Secretion

cAMP Activated Cl- Channel CFTR Crypt Secretion H2O 2 Cl- Na+ K+ PDte cAMP Cl- ATP ADP + Pi 3 Na+ 2 K+ Key Player: cAMP Activated Cl- Channel CFTR VIP – neurotransmitter Histamine also can activate formation of cAMP

Concentration in Chyme: Na+ Conc. K+ Conc. Volume Absorption of Na+ Concentration in Chyme: Na+ Conc. K+ Conc. Volume 5 mEq/L 23 mEq/L 80 mEq/L 5 Liters 1 Liter 200 mL Duodenum Ileum Colon (Prox) 140 mEq/L 125 mEq/L 40 mEq/L

Absorption of Na+ Na+ is Absorbed Along the Entire Intestine Na+ Diffuses Down its Electrochemical Gradient into Epithelial Cells Luminal Membrane: Co-transport with Nutrients, Diffusion Through Na+ Channels and Na+/H+ Exchange Transported Across the Basolateral Membrane by the Na-K ATPase. Cl- Moves to the Blood to Maintain Electroneutrality.

Vitamin D3 Liver Kidney Intestine 25-OH-D3 1,25-(OH)2-D3 Ca2+ CaBP Parathyroid Hormone 1,25-(OH)2-D3 RNA Ca2+ CaBP Ca2+ Na+ CaBP Plasma Ca2+ Intestine Ca2+ ATPase

Vitamins and Ileal Transport Fat Soluble – absorbed all along the intestine via normal fat absorptive pathways. (D, K, A) Water Soluble: Specific Transport Most all along the intestine. Several Ileal Specific- Vitamin: B12 also Ileal Specific: Bile Salts.

Where salt goes, so too does water. Absorption of Water 90-95% of Water (re)absorption in the Small Intestine 1-2 L/day is Absorbed in the Colon. A Normal Colon Can Reabsorb a Maximum of About 4.5 liters per day. Mechanism of H2O Absorption- Where salt goes, so too does water.

Pathophysiology of Diarrhea The Causes of Diarrhea Delineate into 3 Categories Motility Based: Limiting Time for Absorption Bacterial Infiltration Malabsorption; Maldigestion: Osmotic Lactase Deficiency Ileal Resection: Biles Salts also stimulate secretion. Celiac Disease (Sprue; Gluten Sensitive) – Xylose Test Secretory: Initiated by Effectors which Alter cAMP Levels in Enterocytes; Bile Salts