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Home , Duodenum, G cell, Lumen (anatomy), Parietal cell

Overview of Gastrointestinal Function

George N. DeMartino, Ph.D.

Department of Physiology University of Texas Southwestern Medical Center Dallas, TX 75390 The gastrointestinal system Functions of the gastrointestinal system

• • Absorption •

• Motility

• Immune surveillance and tolerance

GI-OP-13 Histology of the GI tract

Blood or Lumenal Serosal Side or Mucosal Side Structure of a villus

Villus

Lamina propria Movement of substances across the epithelial layer

Tight junctions X Lumen Blood

Apical membrane Basolateral membrane X X transcellular

X X paracellular

GI-OP-19 Histology of the GI tract

Blood or Lumenal Serosal Side or Mucosal Side Motility in the gastrointestinal system

Propulsion net movement by Mixing for digestion and absorption Separation Storage decreased pressure

GI-OP-42 Intercellular signaling in the gastrointestinal system

• Neural

• Hormonal

• Paracrine

GI-OP-10 Neural control of the GI system

• Extrinsic nervous system autonomic central nervous system

• Intrinsic (enteric) nervous system entirely with the GI system

GI-OP-14 The extrinsic nervous system The intrinsic nervous system forms complete functional circuits

Sensory neurons

Interneurons

Motor neurons

(excitatory and inhibitory) Parasympathetic regulate functions of the intrinsic nervous system Y Reflex control of gastrointestinal functions

Vago-vagal Afferent reflex Salivary Glands Composition of

O α− RNase lysozyme et al O Electrolyte solution water Na+ , K + - HCO3 Functions of saliva

• Oral protection buffering of hot, cold, acid, base

• Oral hygiene bacteriostatic

• Lubrication

• Digestion carbohydrates and lipids

GI-ME-11 Structure of the

Pharynx Upper Esophageal Skeletal (UES) muscle

Skeletal and smooth muscle

Smooth muscle Diaphragm

Lower Esophageal Sphincter GI-010 (LES) Regulation of the UES during a swallow

Reflex Reflex relaxation contraction (neural) (neural)

Persistalsis Regulation of the UES during a swallow

Reflex Reflex relaxation contraction (neural) (myogenic) VIP (NO ?) Anatomical and functional divisions of the stomach LES Fundus

Pyloric Oxyntic gland Orad gland area area Gastric juice Oxyntic gland G Caudad Body (Corpus) Antrum

GI-S-15 Mechanism of acid secretion by the

H O 2 Lumen - Cl-

H+ K+ H2O Cl- - + ATP Cl K ADP K+ ATP ADP Na+ H 0 H+ + OH - HCO - Na+ 2 3 CO2

Blood + GI-S-07 Stimulation of acid secretion in parietal cells

Receptors (H2) Gastrin ACh G G G AC PL-C PL-C

H+

H+

Lumen GI-S-13 Stimulation of acid secretion in parietal cells

Receptors Histamine (H2) Gastrin ACh G G G AC PL-C PL-C

cAMP

IP3 + DAG kinase A Ca2+ Protein kinase Substrates C Sequestered H+ / K+ pumps Substrates Sequestered H+ / K+ pumps H+ Membrane-exposed H+ / K+ pumps Lumen GI-S-13

Cephalic phase vagal nucleus of acid secretion vagus thought, sight, smell, taste, or chewing of food H+

ACh Parietal cell

GRP ECL cell Histamine

Gastrin Efferent pathways

circulation

GI-S-05 Gastric phase vagal nucleus of acid secretion distension sensed by mechanoreceptors distension in the stomach, presence of amino acids and H+ Amino acids and peptides ACh Parietal cell G cell GRP ECL cell

ACh Histamine

Gastrin Efferent pathways

Afferent pathways circulation

GI-S-06 Protection of the epithelial lining of the stomach

pH 2 Gastric lumen

- - Mucus layer HCO3 HCO3 pH 7

Mucus

GI-S-19 Motility in the stomach

• Reservoir storage without increased pressure • Grinding and mixing mechanical disruption for digestion and absorption • Regulated pumping optimal delivery to duodenum

GI-S-32

The gastrointestinal system

Small Intestine

Digestion Absorption Secretion Motility Pancreatic Secretion

Aqueous Component (ductule cells)

water Function: acid neutralization

Enzymatic Component (acinar cells)

Function: digestion saccharidases Intestinal phase vagal nucleus of pancreatic secretion vagus nerve afferent pathways acid and digestion products for vagal in the duodenum reflex protein amino acids I cells peptides fat H+ efferent S cells pathways for circulation vagal reflex

HCO - CCK 3 H O 2 Ach

ductule cells acinar cells

GI-SILPGB-02 Secretion from the and

Figure15 NaNa++ ClCl -- KK++ CaCa2+2+ Liver BileBile wwaatteerr acidsacids

Figure11 PortalPortal

- circulationcirculation HCO3 Gallbladder Secretin Na+ -- HCOHCO3 H20 3 ClCl-- NaNa++

HH2200 Figure14 CCK Ach

BileBile BileBile acidsacids Duodenum Functions of

• Emulsification of dietary lipids required for lipid digestion

• Solubilization of lipid digestion products

required for lipid absorption

• Excretion of waste products bilirubin and cholesterol GI-SILPGB-30 Organic components of bile

• Bile acids / bile salts 70%

• Phospholipids 20% • Cholesterol 5%

• Bilirubin 1%

• Everything else 4%

GI-SILPGB-40 Components of bile Bile acids package products of lipid digestion into mixed micelles for absorption

Products of lipid digestion Mixed micelle + - - + - + - --

Free fatty acid Lysolecithin

- + - Cholesterol Monoglyceride

GI-SILPGB-36

Digestion and absorption in the

Proteins degradation to amino acids and peptides combined action of lumenal and membrane- bounds proteases absorption by multiple transporters

Carbohydrates degradation to monosaccharides combined action of lumenal and membrane- bounds proteases absorption by several transporters

Lipids Absorption of monosaccharides in the small intestine

Na+/ K+ ATPase SGLT1 K+ ATP¤ADP Na+ Na+ Glucose / Glucose / Glut 2 Galactose Galactose

Fructose Fructose Glut 5

Lumen Blood

(Apical) (Basolateral) GI-SILPGB-16

Fluid balance in the GI tract

9000 ml 8900 ml

VolumeVolume VolumeVolume enterenteriinngg absorbedabsorbed intestinesintestines byby intestinesintestines

~ 20% total 100 ml body water ! Volume excreted Important Principle

The absorption of water is dependent on and proportional to the absorption of solutes

GI-LI-25 Bad things happen when solutes are not absorbed

Colon Ileum

Na+

Lactose glucose + galactose H2O H2O

Normal

Diarrhea SCFA CO2

Lactose Lactose H2OLactose H2O

Lactase deficiency

GI-LI-24 H2O