Physiology: The digestive system

Regulation of the GI Tract continued• Enteric nervous system: • Sites where parasympathetic fibers synapse with postganglionic neurons that innervate smooth muscle.. HCl Production• Pari

The Digestive

System

Physiology

Functions of the GI Tract

Functions of the GI Tract (continued)

Functions of the GI Tract (continued)

• Storage and elimination:

• Temporary storage and elimination of indigestible food

Digestive System (GI)

• Lines the lumen of GI tract.

• Consists of simple columnar epithelium

• Lamina propria:

• Thin layer of connective tissue containing lymph

nodules

• Muscularis mucosae:

• Thin layer of smooth muscle responsible for the folds

• Folds increase surface area for absorption.

• Thick, highly vascular layer of connective tissue.

• Absorbed molecules enter the blood and

lymphatic vessels.

• Submucosal plexus (Meissner’s plexus):

• Provide autonomic nerve supply to the muscularis mucosae

• Responsible for segmental contractions and

peristaltic movement through the GI tract.

• Inner circular layer of smooth muscle

• Outer longitudinal layer of smooth muscle

• Contractions of these layers move food through the tract; pulverize and mix the food.

• Myenteric plexus located between the 2 muscle layers.

• Major nerve supply to GI tract

• Binding and protective outer layer.

• Consists of areolar connective tissue covered with

Regulation of the GI Tract

• Extrinsic innervation:

• Parasympathetic nervous system:

• Vagus and spinal nerves:

• Stimulate motility and GI secretions

• Sympathetic nervous system:

• Postganglionic sympathetic fibers that pass through submucosal and myenteric plexuses and innervate GI tract:

• Reduce peristalsis and secretory activity

Regulation of the GI Tract (continued)

• Enteric nervous system:

• Sites where parasympathetic fibers synapse with

postganglionic neurons that innervate smooth muscle

• Submucosal and myenteric plexuses:

• Local regulation of the GI tract

From Mouth to Stomach

• Mastication (chewing):

• Mixes food with saliva which contains salivary amylase

• Enzyme that can catalyze the partial digestion of starch.

• Deglutition (swallowing):

• Begins as a voluntary activity

• Involves 3 phases:

• Oral phase is voluntary.

• Pharyngeal and esophageal phases are involuntary.

• Cannot be stopped.

From Mouth to Stomach (continued)

• Involuntary muscular contractions and relaxations

in the mouth, pharynx, larynx, and esophagus are coordinated by the swallowing center in the

medulla.

• Esophagus:

• Connects pharynx to the stomach

• Upper third contains skeletal muscle.

• Middle third contains a mixture of skeletal and smooth muscle.

• Terminal portion contains only smooth muscle.

• Peristalsis:

• Produced by a series of

localized reflexes in response

to distention of wall by bolus.

• Wave-like muscular

contractions:

• Circular smooth muscle

contract behind, relaxes in

front of the bolus.

• Followed by longitudinal

contraction (shortening) of

smooth muscle.

Insert 18.4a

• Most distensible part of GI tract.

• Empties into the duodenum

• Functions of the stomach:

Gastric Glands

• Secrete gastric juice:

• Goblet cells: mucus

• Parietal cells: HCl and intrinsic factor

• Chief cells: pepsinogen

• Enterochromaffin-like cells (ECL): histamine and serotonin

• G cells: gastrin

• D cells: somatostatin

• Stomach: ghrelin

HCl Production

• Parietal cells secrete

H + into gastric lumen

Digestion and Absorption in the

Stomach

• Proteins partially digested by pepsin.

• Carbohydrate digestion by salivary amylase is soon inactivated by acidity.

• Alcohol and aspirin are the only commonly

ingested substances absorbed.

Gastric and Peptic Ulcers

Protective Mechanisms of Stomach

• Parietal and chief cells impermeable to HCl.

• Alkaline mucus contains HC03-.

• Tight junctions between adjacent epithelial cells.

• Rapid rate of cell division (entire epithelium

replaced in 3 days).

• Prostaglandins inhibit gastric secretions.

Small Intestine

• Each villus is a fold in the

mucosa

• Covered with columnar

epithelial cells interspersed

with goblet cells

• Epithelial cells at the tips of

villi are exfoliated and

replaced by mitosis in crypt

Absorption in Small Intestine

• Duodenum and jejunum:

• Carbohydrates, amino acids, lipids, iron, and Ca2+

• Ileum:

• Bile salts, vitamin B12, electrolytes, and H20

Intestinal Enzymes

• Microvilli contain brush border enzymes that are not secreted into the lumen.

• Brush border enzymes remain attached to the cell

membrane with their active sites exposed to the chyme

• Absorption requires both brush border enzymes and pancreatic enzymes.

Intestinal Contractions and Motility

• 2 major types of contractions

occur in the small intestine:

Contractions of Intestinal Smooth

▫ Slow waves produced by

interstitial cells of Cajal.

▫ Slow waves spread from 1

smooth muscle cell to

another through nexuses.

Insert fig 18.15

Contractions of Intestinal Smooth Muscles

• When slow waves above threshold, it triggers APs

by opening of VG Ca2+ channels.

• Inward flow of Ca2+:

• Produces the upward depolarization phase

• Stimulates contraction of smooth muscle

• Repolarization:

• VG K+ channels open

• Slow waves decrease in amplitude as they are conducted.

Cells and Electrical Events in the Muscularis

Insert fig 18.16

Large Intestine

• Outer surface bulges outward to form haustra

• Little absorptive function

• Absorbs H20, electrolytes, several vitamin B complexes, vitamin K, and folic acid.

• Intestinal microbiota produce significant amounts of folic acid and vitamin K.

• Bacteria ferment indigestible molecules to produce short-chain fatty acids

• Does not contain villi.

• Secretes H20, via active transport of NaCl into intestinal lumen

Fluid and Electrolyte Absorption in the Intestine

• Small intestine:

• Most of the fluid and electrolytes are absorbed by small intestine

• Absorbs about 90% of the remaining volume.

• Absorption of H20 occurs passively as a result of the

osmotic gradient created by active transport

• Aldosterone stimulates NaCl and H20 absorption in the ileum.

• Large intestine:

• Absorbs about 90% of the remaining volume

• Absorption of H20 occurs passively as a result of the osmotic gradient created by active transport of Na + and Cl -

• Waste material passes to the rectum.

• Occurs when rectal pressure rises and external anal sphincter relaxes

• Defecation reflex:

• Longitudinal rectal muscles contract to increase rectal pressure

• Relaxation of internal anal sphincter.

• Excretion is aided by contractions of abdominal and

pelvic skeletal muscles

Structure of Liver

• Liver largest internal organ.

▫ Hepatocytes form hepatic plates that are 1–2 cells thick.

▫ Arranged into functional units called lobules.

• Plates separated by sinusoids.

▫ More permeable than other capillaries.

• Contains phagocytic Kupffer cells.

• Secretes bile into bile canaliculi, which are drained by bile ducts.

Structure of Liver(continued)

Insert fig 18.20

Hepatic Portal System

• Products of digestion that are absorbed are delivered to the liver.

• Capillaries drain into the hepatic portal vein, which carries blood to liver.

• ¾ blood is deoxygenated

• Hepatic vein drains liver

Enterohepatic Circulation

• Compounds that

recirculate between liver

and intestine

• Many compounds can be

absorbed through small

intestine and enter

hepatic portal blood.

• Variety of exogenous

compounds are secreted

by the liver into the bile

ducts.

Insert fig 18.22

Major Categories of Liver Function

Bile Production and Secretion

• The liver produces and secretes 250–1500 ml of bile/day

• Bile pigment (bilirubin) is produced in spleen, bone

marrow, and liver

• Derivative of the heme groups (without iron) from hemoglobin.

• Free bilirubin combines with glucuronic acid and forms conjugated bilirubin

• Secreted into bile.

• Converted by bacteria in intestine to urobilinogen

• Urobilogen is absorbed by intestine and enters the hepatic vein.

Metabolism of Heme and Bilirubin

Insert fig 18.23

Bile Production and Secretion (continued)

• Bile acids are derivatives of

cholesterol

• Major pathway of cholesterol

breakdown in the body.

• Principal bile acids are:

Detoxification of the Blood

• Liver can remove hormones, drugs, and other

biologically active molecules from the blood by:

• Excretion into the bile

• Phagocytosis by Kupffer cells

• Chemical alteration of the molecules

• Ammonia is produced by deamination of amino acids in the

liver.

• Liver converts it into urea.

• Excreted in urine.

Detoxification of the Blood (continued)

• Inactivation of steroid hormones and drugs.

• Conjugation of steroid hormones and xenobiotics make them anionic

• Can be transported into bile by multispecific organic anion transport carriers.

• Steroid and xenobiotic receptors stimulate production

of cytochrome P450 enzymes

Secretion of Glucose, Triglycerides and Ketones

• Liver helps regulate blood glucose concentration by:

• Glycogenesis and lipogenesis

• Glycogenolysis and gluconeogenesis

• Contains enzymes required to convert free fatty acids into ketone bodies.

Production of Plasma Proteins

• Albumin and most of the plasma globulins (except immunoglobulins) are produced by the liver.

• Albumin:

▫ Constitutes 70% of the total plasma protein

 Contributes most to the colloid osmotic pressure in the

blood.

• Globulins:

• Sac-like organ attached to the inferior surface of the liver.

• Stores and concentrates bile.

• When gallbladder fills with bile, it expands.

• Contraction of the muscularis layer of the gallbladder, ejects bile into the common bile duct into duodenum

• When small intestine is empty, sphincter of Oddi closes.

• Bile is forced up to the cystic duct to gallbladder

• Exocrine:

• Acini:

• Secrete pancreatic juice.

Pancreatic Juice

• Contains H20, HC03- and digestive enzymes

Pancreatic Juice

• Complete digestion of food

requires action of both

pancreatic and brush

Neural and Endocrine Regulation

• Neural and endocrine mechanisms modify the activity of the GI system.

• GI tract is both an endocrine gland, and a target for the action of hormones.

Regulation of Gastric Function

• Gastric motility and secretion are automatic.

• Waves of contraction are initiated spontaneously

Cephalic Phase

• Stimulated by sight, smell, and taste of food

• Activation of vagus:

• Stimulates chief cells to secrete pepsinogen

• Directly stimulates G cells to secrete gastrin

• Directly stimulates ECL cells to secrete histamine

• Indirectly stimulates parietal cells to secrete HCl

• Continues into the 1st 30 min of a meal.

Gastric Phase

• Arrival of food in stomach stimulates the gastric phase

• Gastric secretion stimulated by:

• Distension.

• Chemical nature of chyme (amino acids and short polypeptides).

• Stimulates G cells to secrete gastrin.

• Stimulates chief cells to secrete pepsinogen.

• Stimulates ECL cells to secrete histamine.

• Histamine stimulates secretin of HCl.

• Positive feedback effect.

• As more HCl and pepsinogen are secreted, more polypeptides and amino acids are released.

Gastric Phase (continued)

somatostatin.

• Paracrine regulator to inhibit secretion

of gastrin.

Insert Fig 18.30

• Inhibits gastric motility and secretion.

• In the presence of fat, enterogasterone inhibits gastric motility and secretion.

• Hormone secretion:

Enteric Nervous System

• Submucosal and myenteric plexuses contain 100 million neurons.

• Include preganglionic parasympathetic axons, ganglion cell bodies, postganglionic sympathetic axons; and afferent intrinsic and extrinsic sensory neurons.

Enteric Nervous System (continued)

• Peristalsis:

• ACh and substance

P stimulate smooth

muscle contraction

above the bolus

• NO, VIP, and ATP

stimulate smooth

muscle relaxation

below the bolus

Insert fig 18.31

Paracrine Regulators of the Intestine

• Activates guanylate cyclase, stimulating the production of cGMP.

• cGMP stimulates the intestinal cells to secrete Cl - and H20.

• Inhibits the absorption of Na +

• Uroguanylin:

• May stimulate kidneys to secrete salt in urine.

• Ileogastric reflex:

• Distension of ileum, decreases gastric motility

• Intestino-intestinal reflex:

Secretion of Pancreatic Juice

• Secretion of pancreatic juice and bile is stimulated by:

• Secretin:

• Occurs in response to duodenal pH < 4.5

• Stimulates production of HC03- by pancreas

• Stimulates the liver to secrete HC03- into the bile

Digestion and Absorption of Carbohydrates

Digestion and Absorption of Protein

• Digestion begins in the stomach when pepsin

digests proteins to form polypeptides.

• In the duodenum and jejunum:

▫ Endopeptidases cleave peptide bonds in the interior of the polypeptide:

Digestion and Absorption of Protein (continued)

• Free amino acids

Digestion and Absorption of Lipids

• Arrival of lipids in the duodenum serves as a

stimulus for secretion of bile.

• Emulsification:

• Bile salt micelles are secreted into duodenum to break

up fat droplets

• Pancreatic lipase and colipase hydrolyze

triglycerides to free fatty acids and monglycerides.

• Colipase coats the emulsification droplets and anchors the lipase enzyme to them

• Form micelles and move to brush border

Digestion and Absorption of Lipids (continued)

• Free fatty acids, monoglycerides, and lysolecithin leave micelles and enter into epithelial cells.

• Resynthesize triglycerides and phospholipids within cell

• Combine with a protein to form chylomicrons.

• Secreted into central lacteals.

Transport of Lipids

• In blood, lipoprotein lipase hydrolyzes triglycerides

to free fatty acids and glycerol for use in cells.

• Remnants containing cholesterol are taken to the liver

• Form VLDLs which take triglycerides to cells

• Once triglycerides are removed, VLDLs are converted

to LDLs

• LDLs transport cholesterol to organs and blood vessels.

• HDLs transport excess cholesterol back to liver.

Absorption of Fat

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