GUT PHYSIOLOGY Introduction Dr. Jack Grider Rm 12-004 Sanger Hall 828-1853 jgrider@vcu.edu 2009

Digestive Processes

ANATOMY red denotes a sphincter Salivary Glands Liver Pancreas duodenum, jejunum, ileum Rectum Pancreas red denotes a sphincter

SPHINCTERS

Summary of Gut Physiology

Layers of the Gut Wall

Fourth mechanism: autocrine Control Mechanisms Fourth mechanism: autocrine

Neural Control Mechanisms Hormone/Paracrine agent

CNS Control - Extrinsic - Autonomic N.S. ANS

Extrinsic Control Mechanisms P.S.N.S. is excitatory

Extrinsic/Autonomic S.N.S. is inhibitory

Sympathetic Nervous System Presynaptic Inhibition

Sympathetic Nervous System

Afferent/Sensory Neurons Extrinsic Primary Afferent

REFLEXES THAT CONTROL GUT FUNCTION Long Arc Reflexes: PSNS

Extrinsic/Autonomic N.S. Long Arc Reflexes: PSNS Vago-Vagal Reflex CNS

Extrinsic/Autonomic N.S. Long Arc Reflexes: SNS 3 pathways

Extrinsic/Autonomic N. S Extrinsic/Autonomic N.S. Long Arc Reflexes: SNS Intestino-Intestinal reflex

Intrinsic/Enteric N.S. The “little brain” or “mini-brain”

Intrinsic/Enteric N.S.

Intrinsic/Enteric N.S. Short Arc Reflexes

Intrinsic/Enteric N.S. Many neuronal types IPANs (sensory) Intestinofugal Interneurons & motor neurons Transmitters: Ach/ TKs (~45%) VIP/NO (~25%) Enk, GRP, SSt,. …….

Hormonal Control Mechanisms Blood vessel

Hormonal Control Mechanisms All gut hormones are polypeptides All are amidated at C-terminal end Importance varies: proximal vs. distal Criteria Candidates vs. putative hormones

Hormonal Control Mechanism Gastrin Multiple forms: G-17, G-14, G-34 etc. Tyr-12 can be sulfated (equal amounts) C-terminal end Synthesized in G-cells of terminal antrum, minor amounts in duodenum. Released by: protein digestion products antral distension(direct, vagal & ENS) vagal stimulation (cephalic phase)

Hormonal Control Mechanism Gastrin Physiological Action: Gastric HCl secretion growth of mucosa (trophic) stimulation of gastric motility (?) Negative feedback regulates release Pharmacological effects (impt. sulfation) Zollinger-Ellison Syndrome

Hormonal Control Mechanism Cholecystokinin Multiple forms: CCK-8, CCK-33, CCK-39, CCK-58 etc. Sulfated in 7th AA from C-terminal end. C-terminal end Synthesized in I cells of duodenum (CCK-8, -4 in neurons of ENS and CNS) Released by:protein digestion products monoglycerides/FFA, HCl (minor)

Hormonal Control Mechanism Cholecystokinin Physiological Action: pancreatic enzyme secretion gallbladder contraction mucosal growth & pancreatic growth (trophic) inhibit gastric emptying in high conc. Pharmacological Action

Hormonal Control Mechanism Secretin Single form: 27 AA Structure similar to GIP, VIP, Glucagon Released from S cell in proximal small intestine. Released by: HCl monglyceride/FFA (minor)

Hormonal Control Mechanism Secretin Physiological Action stimulate bicarbonate ion secretion from duodenal glands, duct cells of biliary and pancreatic system, growth of pancreatic tissue inhibits acid secretion and gastric emptying.

Hormonal Control Mechanism Glucose-dependent Insulinotrophic Peptide (GIP) Singular form: 42 AA Structure similar to Secretin, VIP, Glucagon Synthesized in K cells of proximal small intestine Released by: nutrients in proximal small intestine. Physiological action: Stimulate insulin secretion by the pancreas inhibit gastric acid secretion (?)

Hormonal Control Mechanism Candidate Hormones Enteroglucagon Pancreatic polypeptide family (PP, PYY, NPY) Somatostatin Motilin & Ghrelin Many more ...

Paracrine Control Mechanisms Local control Somatostatin, Histamine, GRP