Physiology

Gastrointestinal System

Dr. LL WangE-mail: wanglinlin@zju.edu.cn

INTRODUCTION

Gastrointestinal System includes GI tract plus the accessory organs.

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Four processes carried out by the GI tract

Functions of Gastrointestinal System

Smooth Muscle of the Gut

(1) General properties

– Low excitability

– High extensibility

– Tonic contraction

– Autorhythmicity

– High sensitivity to temperature, stretch & chemical stimulation

(2) Electrophysiological properties

(a) Resting potential: – between -50 and -60 Mv– Ionic basis

– Em (selective membrane permeability to K+)– Electrogenic Na+-K+ pump

(b) Slow wave (basic electrical rhythm,BER)

– The spontaneous rhythmic, subthreshold

depolarizations of the cell membrane (slow

wave) of the gastrointestinal tract

– Initiated in the interstitial cells of Cajal (ICC)

(pacemaker cell)

• Slow wave (basic electrical rhythm)

– Intensity: 5~15 mV

– Frequency: 3~12 cpm

– Ionic mechanism

• spontaneous rhythmic changes in Na+-K+ pump

activity

cpm: cycles per minute

• Frequencies: 3-12 per minute

• Mechanisms

– BER might be due to spontaneous

rhythmic changes in Na+-K+ pump

activity

– BER not generated by nervous activity

• Features of slow waves

– always present but do not always cause contraction

– dictate frequency of contractions

– frequency and height modulated by

• body temp & metabolic activity

• intrinsic & extrinsic nerves

• circulating hormones

(c) Spike potentials (action potentials)

• only at the peaks of slow waves

• Threshold: –40 mV

• Spike potential (Action potential)

–Duration: 10~20 ms

–Ionic mechanism:

• Depolarization: Ca2+ influx

• Repolarization: K+ efflux

• The higher the slow wave potential

rises, the greater the frequency of the

spike potentials

(3) muscle contraction

• Ca2+ binds to calmodulin (intracellular

protein) activates myosin light chain

kinase phosphorylates myosin light

chain phosphorylated myosin then (in

the presence of ATP) binds to actin

Innervation of the Gut

• Enteric nervous system

• Extrinsic nervous system

• Function

– Myenteric plexus : control over GI motility

– Submucous plexus: regulate gastrointestinal

blood flow and control GI secretion

• Local reflex

• Neurotransmitters secreted by enteric neurons

–Ach: Stimulatory

–NE: inhibitory

–Others: Substance P, Nitric oxide , Vasoactive intestinal polypeptide (VIP), Opioid peptide, serotonin, histamine, ATP…

Gastrointestinal Hormone

• The hormones synthesized by a large number of endocrine cells within the gastrointestinal tract

• Brain-gut peptides: a number of the classical GI hormones are also synthesized in the brain

• Physiological functions

– control of the digestive function

– the release of other hormones

– trophic action

Five major GI hormones• Gastrin• Cholecystokinin• Secretin• Gastric inhibitory polypeptide (GIP)• motilin

DIGESTION IN STOMACH

The abundant smooth muscle in the stomach is responsible for gastric motility.

Specialized cells in the stomachsynthesize andsecrete mucous fluid, enzyme precursors,hydrochloric acid,and hormones.

Gastric Secretion

Parietal cells synthesize and secrete the hydrochloric acid responsible for the acidic pH in the gastric lumen.

Chief cells synthesize and secrete the protease precursor known as pepsinogen.

(i)Composition and Function

• Properties– pH 0.9~1.5– 1~2.5 L/day

• Major components– Hydrochloric acid – Pepsinogen– Mucus– Intrinsic factor

(1) Hydrochloric acid

• Secreted by the parietal cells

• Output

– Basal: 0~5 mmol/h

– Maximal: 20~25 mmol/h

• Mechanism of HCl secretion

• HCl is actively secreted against a huge concentration gradient

• H+/K+ ATPase or "proton pump"

One inhibitory andthree stimulatory signals that alteracid secretion byparietal cellsin the stomach.

Four chemical messengers regulate HCl secretion

p595

• Role of HCl

– Acid sterilization

– Activation of pepsinogen

– Promotion of secretin secretion

– Assisted effect of iron and calcium absorption

(2) Pepsinogen

• Secreted by the chief cells as an inactive precursor of pepsin

• Activated in the stomach, initially by H+ ions and then by active pepsin, autocatalytic activation

• Active pepsin (MW: 35,000)

The acidity in the gastric lumen converts the protease precursor pepsinogen to pepsin; subsequent conversions occur quickly as a result of pepsin’s protease activity.

• Effect of pepsin

Pepsin is an endopeptidase, which attacks peptide bonds in the interior of large protein molecules

ProteinsProteosesPeptonesPolypeptides

Pepsin

(3) Mucus

• Secreted by the epithelial cells all over the mucosa and by the neck mucus cells in the upper portion of the gastric glands and pyloric glands

• a layer ~500 m thick • composed chiefly of mucins

•Role–Lubrication of the mucosal surface–Protection of the tissue from mechanical damage by food particles

Mucus-HCO3- barrier

•Epithelial cells and neck mucus cells secrete a bicarbonate-rich mucus that coats and lubricates the gastric surface

•Serves an important role in protecting the epithelium from acid and other chemical insults. The mucus layer also traps HCO3

- secreted by the mucosal cells and this

buffers, or chemically insulates, the mucosa from the acidic stomach contents.

(4) Intrinsic factor

• A high molecular weight glycoprotein,

synthesized and secreted by the parietal cells

• The intrinsic factor binds to Vit B12 and facilitates

its absorption

(5) Secretion of other enzymes

• Gastric lipase

• Gastric amylase

• Gelatinase

(ii) Regulation of Gastric Secretion

(1) Basic factors that stimulate gastric secretion

– Acetylcholine (+ all secretory cells)

– Gastrin (+ parietal cells)

– Histamine (+ parietal cells)

(2) Nervous regulation

– ‘Short’ reflex pathways

• ‘Short’ excitatory reflexes: mediated by cholinergic

neurons in the plexuses

• ‘Short’ inhibitory reflexes: mediated by non-

adrenergic non-cholinergic (NANC) neurons

(2) Nervous regulation

‘Long’ autonomic pathways

• ‘Long’ excitatory reflexes: parasympathetic

• ‘Long’ inhibitory pathways: sympathetic

(3) Humoral regulation

Excitatory

ACh

Histamine

Gastrin

Inhibitory

Somatostatin

Secretin

5-hydroxytryptamine (5-HT)

Prostaglandin

(4) Phases of gastric secretion

• Cephalic phase

• Gastric phase

• Intestinal phase

(5) Inhibition of gastric secretion

The functional purpose of the inhibition of gastric secretion by

intestinal factors is presumably to slow the release of chyme

from the stomach when the small intestine is already filled or

overactive

Gastric Motility

Proximal stomach

cardia

fundus

corpus (body)

Distal stomach

antrum

pylorus

pyloric sphincter

• Receptive relaxation

– Storage function (1.0~1.5 L)

– Vago-vagal reflex

• Peristalsis

– BER in the stomach

Waves of smooth muscle contraction mix and propel theingested contents of the gastric lumen, but only a small amount of the material enters the small intestine (duodenum) as a result of each wave cycle.

Emptying of the stomach

• Emptying rate

– Fluid > viscous

– Small particle > large particle

– Isosmotic > hyper- & hypo-osmotic

– Carbohydrates > Protein > Fat

– Regular meal 4 ～ 6 hrs

• Regulation of stomach emptying

– Gastric factors that promote emptying

• Gastric food volume

• Gastrin

– Duodenal factors that inhibit stomach emptying

• Enterogastric nervous reflexes

• Fat

• Cholecystokinin

Pancreatic Secretion

The exocrine cells in the pancreas play a central role in the production of digestive enzymes; the endocrine functions of the pancreas will be discussed at length in Chapter 16.

(I) Pancreatic Secretion

• pH 7.8~8.4

• ~1500 ml/day

• Isosmotic

• Components:

– Pancreatic digestive enzymes: secreted by pancreatic acini

– Sodium bicarbonate: secreted by small ductules and larger ducts

Were digestive enzymes synthesized in their active form, they would digest the very cells that make them. Hence, inactive precursors (e.g., trypsinogen) become activated (trypsin).

• Secretion of bicarbonate ions

– Secreted by the epithelial cells of the ductules and ducts

that lead from acini

– Up to 145mmol/L in pancreatic juice (5 times that in the

plasma)

– Neutralizing acid entering the duodenum from the

stomach

• Secretion of pancreatic digestive enzymes

– Carbohydrates -- Pancreatic amylase

Pancreatic lipase (coplipase)

– Fat Cholesterol esterase

Phospholipase

Trypsinogen

– Proteins Chymotrypsinogen

Procarboxypolypeptidase

Proelastase

-RNAase

-DNAase

Starches

Maltose and glucose polymers

Pancreatic amylase

• Trypsin Inhibitor

– Inhibits the activity of trypsin and thus guards

against the possible activation of trypsin and

the subsequent autodigestion of the pancreas

Acute pancreatitis

(II) Regulation of pancreatic secretion

• Basic stimuli that cause pancreatic secretion– Ach– Cholecystokinin:

• Secreted by I cells• Stimulates the acinar cells to secrete large amounts of

enzymes

– Secretin: • Released by S cells• Acts primarily on the duct cells to stimulate the secretion of

a large volume of solution with a high HCO3- concentration

• Phases of pancreatic secretion

– Cephalic Phase: taste of food- ‘long’ parasympathetic pathways

– Gastric Phase: distension of stomach- ‘long’ parasympathetic

reflex pathways

– Intestinal Phase

• The most important regulators are CCK and secretin

• Acid, fats, amino acids, peptides and protein are the main stimulus

for pancreatic production and secretion

Bile Secretion

Composition of bile

• HCO3-

• Bile salts

• Lecithin

• Cholesterol

• Bile pigments

• Trace metals …

Function of bile

(1) Bile are critical for digestion and absorption of fats and fat-soluble vitamins

– Bile salts are facial amphipathic

(2) Eliminate many waste products

– Excrete bile pigments or drug metabolites

"Looking at you with a jaundiced

eye"

Bilirubin (useless and toxic breakdown product of hemoglobin)

(3) Prevent the precipitation of cholesterol in the

gallbladder and eliminate excess cholesterol

90% of gallstones are of cholesterol stones

Up to 95% of the cholesterol-based bile salts are “recycled” by reabsorption along the intestine. -------Enterohepatic circulation

(4) Increasing bile

synthesis & secretion

(5) neutralize the stomach acid

Regulation of bile secretion

Substances increasing bile production

1) Bile salts

2) Secretin

3) Cholecystokinin

4) parasympathetic input

Absorption in the gastrointestinal tract

(I) Basic principle of absorption

Almost all absorption of

nutrients occurs in the

small intestine

1. Absorptive surface of small intestinal mucosa

• Total area of 250 m2:

– Folds: 3-fold– Villi: 10-fold– Microvilli: 20-fold

2. Absorption pathways

• transcellular route

• paracellular route