2018.02.23.

1

Evening seminar:

GASTROINTESTINAL PHYSIOLOGY

Zoltán Lelkes

2

Hierarchy in GI track control

2018.02.23.

2

EXTRINSIC INNERVATION OF THE GI TRACT

PARASYMPATHETIC(Preganglionic)

SYMPATHETIC

somatic

somatic

Postganglionic fibres

2018.02.23.

3

Spinal cord

LOCAL SHORT LONG

Parasympathetic(vagus, sacral s.c.)Protective reflexes

inhibiting GI activity

Parasympathetic

reflexes

stimulating

GI activity

Unique reflexes

regulating GI

activity without

involving CNS

GASTROINTESTINAL REFLEXES

2018.02.23.

4

GI HORMONES, PARACRINES AND NEUROCRINES

1. HORMONES

Gastrin family: gastrin and CCK

Secretin family: secretin, GIP, VIP, enteroglukagon

Motilin family: motilin and ghrelin

2. HORMONE CANDIDATES

Neuropeptide Y family: PPP, peptide YY

Neurotensin

Guanylyn

(Villikinin)

3. PARACRINES

Somatostatin

Histamine

4. NEUROCRINES

GRP

Substance P

Enkephalins

VIP

8

Glucose administration

4

8

12

16

20

24

-60 0 60 120 180 240 300

Pla

sm

a g

luco

se

[m

mo

l/l]

min

Postprandial

(postalimentary)

hyperglycemia

Postprandial

(postalimentary)

hypoglycemia

no GIP

Diabetes mellitus

The oral glucose tolerance test

2018.02.23.

5

9

Ghrelin: a member of the somatotropic axisfrom the fundus cells (P/D1 cells) in the stomach

GHRHNPY

hypothalamus:nucl. arcuatus

GH

hunger

appetite

feeding

Stimulation ofHCl secretion?

releaseunder circadian control?

released when GI empty, peaks

before feeding

10

Ghrelin:

increases hunger

supresses fat utilization

stimulates gastric emptying

stimulates growth hormone secretion

2018.02.23.

6

11

12

Overview of appetite and satiety

2018.02.23.

7

ELECTRICAL ACTIVITY OF GI SMOOTH MUSCLE

GI smooth muscle cells, particularly in the circular layer:

- are linked via gap junctions

- the resting potential is less negative and oscillates

- include mesenchymal pacemaker cells (interstitial cells of Cajal)

Resting Ach

Stretch

Noradrenaline

• BER: Basic

Electrical Rhythm

(slow waves) triggered

by pacemaker cells

and propagated

by smooth muscle.

• Spikes = action

potentials superimposed

on slow waves. Spikes

are associated with

Ca influx.

BAYLISS’ LAW OF THE GUT

Stimulation in the GI tract elicits:

1. Contraction on the orad

side of the stimulation, and

2. Relaxation on thecaudad side, and

3. The contractile ring preceded by

dilatation moves in aboral direction.

Stimulation

2018.02.23.

8

EXNER’S PHENOMENON

Needle thrown

into the wall causes

stimulation.

Peristalsis

Peristalsis turns

the needle.

Peristalsis pulls

out needle.

Sharp objects turn

in the GI tract.

TYPES OF MOVEMENTS IN THE GI TRACT

1. Tonic contraction with intermittent relaxation: sphincters2. Segmentation3. Peristalsis

2018.02.23.

9

MIGRATING MOTOR COMPLEXES (MMC)

1. Electrical and motor activity occurring during fasting.

2. Activity lasts for 3-5 min and recurs at 90 min periods.

3. Activity starts in the stomach and moves aborally.

CHEWING (MASTICATION)

Chewing deficit does not compromise digestion but the process is greatly

prolonged and large particles may hurt gastric mucosa.

Unilateral stretch reflex:• Opening the mouth activates stretch reflex → jaw rises.

• Stimulation of mechanoreceptors in the mucosa inhibits

stretch reflex → jaw drops.

Food intake

SUCKING (innate brainstem reflex)

BITING

m. temporalis

m. masseter

mm. pterygoidei

2018.02.23.

10

FUNCTIONS OF SALIVA, SALIVARY GLANDS

• Digestion (amilase, lipase)

• Excretion

• Protection of mucosa

• Bacteriostatic action

• Lubricant, moisturizing

• Promoting taste

• Alkalic pH (fresh salival)

gl. parotis

gl. sublingualis

gl.submandibularis

Secretion of saliva

2018.02.23.

11

SWALLOWING (DEGLUTITION)

1. Voluntary stage: mouth → pharynx

2. Pharyngeal stage

3. Esophageal stage

Primary peristalsis:

Peristaltic wave initiated

from the pharynx.

Secondary peristalsis:

residual bolus left in the

esophagus initiates new

peristalsis.

MOTILITY OF THE PROXIMAL PORTION OF THE STOMACH

1. During filling:

RECEPTIVE RELAXATION

(Vago-vagal reflex,

local reflex,

stress relaxation

2. After filling:

TONIC CONTRACTION

The proximal portion does

not participate in peristalsis.

MOTILITY OF THR DISTAL PORTION OF THE STOMACH

1. Fasted state: MMC

2. Filled state: PERISTALSIS

2018.02.23.

12

Phases of gastric juice secretion

Parietal

cell

Receptor

CNS

Stimulus

(chemical, mechanical)

Blood

Mechanisms enhancing gastric acid secretion

2018.02.23.

13

Regulation of gastric acid secretion (gastrin, histamine,

somatostatin)

Parietal cell

CA

Mechanism of gastric acid secretion

2018.02.23.

14

Measurement of gastric acid secretion

BAO (basal acid output) 2 (0-10) mmol/h

Stimulation (histamine, pentagastrin)

MAO (maximal acid output, the output of gastric acid for 1 hour after the stimulation) 20 (5-45) mmol/h

PAO (peak acid output, the sum of the two consecutive highest 15-minute outputs of gastric acid after the

stimulation multiplied by 2,) 8-60 mmol/h

28

2018.02.23.

15

SECRETION OF EXOCRINE PANCREAS

1. Enzymes necessary for digestion of all food stuffs

2. Serous alkaline fluid providing appropriate pH for enzyme

activity.

Enzyme secretion:

1. Vesicular secretion (zymogen

granules)

2. All proteolytic and many lipolytic

enzymes are in inactive pro-forms.

3. Enzyme secretion is stimulated by

- CCK (pancreozymine)

- vagus

The secretion of HCO3- is enhanced by

- Secretin

- N. Vagus

Phases of pancreas secretion:

1. cephalic, 2. gastric, 3. intestinal

Amylase

Peptidases:

trypsinogen

chymotrypsinogen

procarboxypeptidases

proelastase

Lipolytic enzymes:

prophospholipase 2

lipase (procolipase)

cholesterol estarase

Nucleases:

ribonuclease

deoxyribonuclease

PANCREARIC DIGESTION ENZYMES

2018.02.23.

16

Pancreatic secretions

Trypsinogen

Enterokinase

(enteropeptidase)Trypsin

Chymotrypsinogen

Procarboxypeptidases

Proelastase

Procolipase

Prophospholipase

Chymotrypsin

Carboxipeptidases

Elastase

Colipase (not an enzyme!)

Phospholipase

THE ROLE OF THE ENTEROKINASE-TRYPSINE ACTIVATION

BILE

Functions:

• Promotion of digestion and absorption of lipids (micelles)

• Excretion of endogenous substances, e.g.

- bilirubin

- cholesterol

• Excretion of exogenous substances (drugs, heavy metals)

Components:

• Primary and secondary bile acids

• Phospholipids (e.g. lecithin)

• Cholesterol

• Bilirubin

• HCO3 rich fluid

2018.02.23.

17

Liver

A. hepatica Bile ductV. portae

V. hepatica

V.centralis

REGULATION OF SECRETION AND EXPULSION OF BILE

Stimulation of bile

Secretion = Choleretic

factors:

• Recirculated bile acids

• Secretin

Stimulation of expulsion

of bile = Cholekinetic

factors:

• CCK

• Vagus

• (gastrin)

Simultaneous

• contraction of gallbladder

• relaxation of sphincter

of Oddi.

2018.02.23.

18

THE LARGEST SURFACE BETWEEN THE BODY AND THE

ENVIRONMENT

Structure Surface

(m2)

cylinder 0.33

Folds of

Kercking

1.0

Villi 10.0

Microvilli 200.0

MECHANISM OF Cl- SECRETION BY CRYPT CELLS

2 Cl-

Na+

K+

~ K+

Cl-

Na+

H2O

cAMP

VIP

ENTEROGLUCAGON

CHOLERA TOXIN

Lumen

CRYPT CELL

Simultanously with the stimulation of Cl secretion in the crypt cells,

cAMP inhibits Cl absorption (NaCl absorption) in the enterocytes.

Massive loss of

water and

electrolytes.

2018.02.23.

19

Na+

~K+

Na+

Electrogenic Ileum,

Colon

Na+

Glucose

Amino acids

Bile acids

Vitamins

~K+

Na+ Glucose

Amino acids

Bile acids

Vitamins

Cotransportwith

organic solute

MECHANISMS OF Na+ ABSORPTION

Na+

Cl-

~K+

Na+

Cl-

CotransportwithCl-

Distal

Jejunum,

Ileum

Na+

H+

Cl-

HCO3-

H2O

Carbonic

anhydrase

OH-

+

CO2

~K+

Na+

Cl-

Na-H

exchange

with net

NaCl

absorption

Colon

Brush border enzymes

Cytoplasma Blood

Lactose

Glucogen

Lactase

Glucose

Digestion and absorption of carbonhydrates

2018.02.23.

20

Absorption of peptides

Glycerol3-phosphate

Phosphatidicacid

FA-bindingprotein

• Lipids are re-synthesized from FA, cholesterol and MG

• Lipids are incorporated in chylomicrons and transported by the lymph

ABSORPTION OF LIPIDS

2018.02.23.

21

Pathways of the parasympathetic mechanism

for enhancing the defecation reflex