Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University1
GASTROINTESTINAL TRACT
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University2
serosis (adventicia)
epithelium
muscularis mucosae
longitudinal
layer
circular layer
plexus
submucosus
(Meissner)
plexus
myentericus
(Auerbach)
ENS
muscularisexterna
submucosa
Modified according to: J. Švíglerová: Fyziologie gastrointestinálního traktu, LF UK Plzeň, 2012
coordination of motility
secretion and absorption
+ glands
+ lymphatic tissue
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University3
Circular muscle layer: inhibitory fibers, contraction – gut is longer and smaller in diameter
Longitudinal muscle layer : no inhibitory fibers, contraction – gut is shorter and bigger in diameter
GIT motility – mainly nervous control
Secretion in GIT – mainly humoral control
+
PARASYMPATICUS
(preganglionic cholinergic fibres)
n.VII, n.IX, n.X, nn.pelvici (S2-S4)
-
SYMPATICUS
(postganglionic adrenergic fibres)
Th5-L2
(tonus and motility –)
(vasoconstriction)
(musc.mucosae, sphincters +)
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University4
GIT INNERVATION
ENTERIC NERVOUS SYSTEM
SYMPATICUS PARASYMPATICUS
Local (short) reflex
Central (long) reflex
CNS
+-
mechanoreceptors
chemoreceptors
osmoreceptors
thermoreceptors
Vagovagal reflex
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University5
ENTERIC NERVOUS SYSTEM
(plexuses + endings of sympathetic and parasympathetic nervous system + other GIT neurons)
Local (short) reflexes
Mediators and modulators: Ach, peptides and bioactive amines
Ach, VIP, NOR, DOPA, serotonin, histamine, AT II, PG
somatostatin, enkephalin, GABA, TRH, neuropeptide Y, substance P
secretin, GIP, glucagon, gastrin, CCK, G-releasing peptide
(Secretin group)
(Gastrin group)
Chemoreceptors, mechanoreceptors, thermoreceptors…
(mucosa, musc. externa)
Central (long) reflexes
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University6
Continuous tonus of
S, PS
FORWARD SIGNALS:
SPEED UP, OPEN THE WAY
BACKWARD SIGNALS:
SLOW DOWN, CLOSE THE WAY
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University7
CONTRACTIONS tonic (stomach, colon)
rhythmic
MOVEMENTS propulsive (peristalsis, myenteric reflex)
mixing
Receptive relaxation.
These contractions and movements are responsible for churning, peristalsis and reservoir action in GIT.
GIT MOTILITY
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University8
ELECTROPHYSIOLOGY OF GI SMOOTH MUSCLE
Resting potential: from - 40 to - 80mV ( gNa : gK)
Lower activity of Na+/K+-ATPase
Slow waves (oscillation of rest.MP) 3 (stomach) – 12(duodenum)/min – basal electric rhythm
Spike (AP) low voltage, depolarisation – Na+ and Ca2+, 1-10/sec
Pacemaker cells in ENS automacy
Variability neurohumoural regulation
Innervations: nexus, innervations of circular muscle >> longitudinal muscle
No motor endplate Ach, ENS, exceptions
0
-40
ICa direct activation of contraction (binding to calmodulin)
0
-40
5s
Basal muscle tonus, basal rhythm (time summation)
Spike -10 -20ms
F
E
5s
Contractions triggered by slow waves (no AP!!!)
F
E
Stomach
Modulation of slow waves – amplitude (less by frequency)
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University9
SWALLOWING
• Oral phase (voluntary)
• Pharyngeal phase (reflex)<1s
• Oesophageal phase (peristaltic)
Food – chewing (voluntary and reflex)
Frequency of swallowing – approx. 600x / day
Saliva (1.5 litres / day)
SWALLOWING CENTRE
(oblongata, pons)
X., ….
REC
(touch)
Plexus myentericus
Parasympathetic NS (VIP)
Sympathetic NS
V.X.
Proximal sphincter
(somat.motoneurons – X.
striated muscles)
Peristalsis – 3-5cm/s
(primary - swallowing centre,
secondary - ENS)
Mouth
Pharynx
Central
reflexes
Junction
Distal sphincter (cardia)
(smooth muscle) – opened by secondary peristalsis
Local
reflexes
Reflex relaxation of cardia (PS)
Achalasia (cardiospasmus)
Gastrooesophageal reflux
IX.
Oesophagus
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University10
GASTRIC MOTILITY
Reflex relaxation of distal oesophageal sphincter (cardia)
Receptive relaxation of fundus and body
(X. – VIP) (Laplace: P = T . R)
Pacemaker zone (3/min)
Motoric gradient
(F <<< A)
Chyme stratification
1,5 l
A
B
F
D
P
C
O
Migrating myoelectric complex
(„hungry“ contractions)
Reservoir
Mixer (3/min)
1-2 hour: rest
10-20 min: activity, during fasting is stronger
PYLORUS = sphincter ???
Common ENS with bulbus duodeni
Smooth muscle
sympaticus +++, n.X. --- (VIP)
N. vagus +
Plexus cealicus prominent
circular layer
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University11
EMPTYING OF STOMACH
CNS
PACEMAKER
CONTRACTIONS OF ANTRUM
CONTRACTIONS OF PYLORUS
DUODENUM:
pH < 3,5
Lipids
Peptides
secretin
CCK, GIP
gastrin
Oddi
gastrin
chemoreceptors
osmoreceptors
slowed emptying
(entorogastric reflex)
Symp. Paras.
FA, H+, osmotically
active substances,
tryptophan
Modulation:
•Peristaltic movements
•Continuous tonus
(summation of contractions
of antrum – relaxation)
pressure, distension, pH, pain
VIP
Ach
SYMP.
x.
Coordination of contractions of antrum
and relaxation of bulbus
Duodenogastric reflux
A/D reciprocal
activity
-
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University12
VOMITING (PROTECTION)
HIGHER CENTRES
CENTRE FOR VOMITING
IN MEDULLA OBLONGATA
Afferentation: X., symp.
Taste
Smell
Vision
Labyrinths
Central
Mechanoreceptors
of pharynx
Peripheral
Mechano- a chemoreceptors
of stomach and duodenum
Peripheral
Trigger zone – bottom of 4.chamber
Area postrema – circ. ventric.
organisation
• Antiperistalsis in jejunum and duodenum
• Relaxation of pylorus and antrum
• Contractions of diaphragm (increased intraabdominal pressure)
• Inverse Valsalva manoeuvre (decreased intrathoracal pressure)
• Contractions of pylorus and antrum
• Relaxation of cardia
• Relaxation of upper pharyngeal sphincter
Emetics: central
peripheral
Antiemetics
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University13
MOTILITY OF SMALL INTESTINE
• Slow waves – approx.11-13/min in duodenum, 8-9 - ileum
• „Minute“ rhythm (jejunum) – salvos approx. every minute
• Hour rhythm (migrating myoelectric complex, MOTILIN)
hours
100%
1 2 3
fasting food
5
10
12/min
duodenum jejunum ileum
Distance from pylorus
in vitro 7/min
in situ
Segmentation >>> peristalsis (up to 10 cm)
LAW OF INTESTINE
INTESTINO-INTESTINAL REFLEX
GASTRO-ILEAL R.
GASTRO-COLIC R.
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University14
MOTILITY OF COLON
• Slow waves with frequency 4 – 6 / min
• Segmentation = haustra; 5-10 cm/hour– pendulum movements
• Mass peristalsis; 1-3/day – „sweeping“
• Reverse peristalsis – in proximal colon („delay“ – absorption of water
and ions)
• Control of anal sphincter: int. – reflex, ext. – voluntary (+reflex)
• Defecation: abdominal muscles +++, muscles of pelvic bottom –
• Reflex: colono-colonic, gastro-colic
• Parasympaticus + (X. till FL)
• Sympaticus – (L2 – L4)
4-8 hod
12-72 hod
VIC
parasympaticus.
sacral sympaticus
Int.
Ext. sphincter
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University15
GIT REFLEXES
SYMP.
Voluntary control
Voluntary control
pharynx
oesophagus
stomach
small intestine
colon
rectum
A
Superimposed on
continuous basal tonus
PS and S
(sphincters S PS )
a1
10´´
2-3 hrs
2-4 hrs
10-20 hrs
Signalling:
relax, move on!
slow down!
PARASYMP.
VI
P
Achswallowing
lower oesophagus
local
pyloric
gastroileal
enterogastric
internal anal sphincter
gastrocolic
receptive relaxation of fundus
colonoileal
colonocolonic
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University16
SECRETION in GIT
GIT glands:
• Salivary glands
• Gastric glands
• Small glands of esophagus and intestine
• Exocrine pancreas
• Liver
Stimulation of secretory functions in GIT:
1. Neurocrine
2. Endocrine
3. Paracrine
Function of GIT secretion:
• Lubrication of food
• Swallowing
• Mechanical protection of GIT
• Chemical protection of GIT
• Enzymes
• Immune function(s)
• Articulation
Common features of GIT secretion:
water, ions, HCO3-, mucin
Marie Nováková, Department
of Physiology, Faculty of
Medicine, Masaryk University
17
PRODUCTION OF SALIVA
• Mucinous vs. serous secretion
• Gl. parotis, gl. submandibularis, gl. sublingualis, small salivary glands in mouth
• 1 liter / day ( 1ml/min/g )
• High resting blood flow – 10 x contracting muscle, high metabolic exchange
• pH: 7 – 8 (at rest rather acidic, increase in HCO3- - alkalization)
• Parasympathetic stimulation – Ach, VIP, VII. and IX.n.; vasodilatation
ACINES
Serous secretion (H2O, ions; isotonic)(gl. parotis)
Salivary amylase (zymogenic granules – exocytosis)
Over pH 4!!!
PRIMARY SALIVA
Mucinous secretion (glycoproteins)
(gll. submandibularis and sublingualis)
Resembles exocrine pancreas
DUCTUS
Na+
Cl-
HCO3-
K+
SECONDARY SALIVA
(hypotonic, after stimulation – increased tonus)
pH ~ 8
Xerostomia
Trophic influence of PS
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University18
REGULATION OF SALIVA PRODUCTION
Transmitter 2. messenger Final secretion
SYMPATHETIC NS
Only transient effect !!!
amylase
vasoconstriction
secretion of K+, HCO3-
Na+
ClH2O
volume
PARASYMPATHETIC NS
(dominant) - n.fac.,
n. glossoph.
amylase, mucin
vasodilatation
VIP cAMP
NOR
b
a
IP3Ach
Subst.P
K+
Na+
Na+
(antiport)
Ca2+
Ca2+
amylase
= + amylase
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University19
SECRETION OF GASTRIC JUICE
Mucus (pH 7-8)
Gastric pits (glands)
pH 2, high concentration of K+ (vomiting) a ClSurface
epithelia
Lamina propria
Mucous neck cells
Parietal cells (HCl, intrinsic factor)
Main cells - zymogenic granules (pepsinogen)
G cells (gastrin)
Area:
• Subcardial (mucus)
• Fundus (HCl)
• Pyloric (mucin, G)
Gastric juice: water, salts, HCl, pepsin, intrinsic factor, mucus
Production increases after meal
Higher secretion – lower pH, lower secretion – more Na+, (always more K+ than in plasma)
pepsinogen pepsin
HCl
Gastric mucinous barrier
Gastric ulcers
Stimulation of a-receptors – decreased secretion of HCO3
NSA
– decreased secretion of HCO3
- and mucus
Ach, G, CCK, secretin
+
(individual number!!!)
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University20
HCl PRODUCTION IN PARIETAL CELL
AP
SP
SP
H2O+CO2=HCO3-+ H+ (CA)
Cl-
Cl-
Na+
Na+
K+
K+
H+
K+
Cl-
HCl
Tubulovesicular system (rest, 10% – secretion)
Proton pump
Basolateral
membrane
Apical
membrane
blood
„alkaline tide“
(1 000 000 : 1 )
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University21
CONTROL OF HCl PRODUCTION IN PARIETAL CELL
H+K+
(cholinergic fibres) Ach H G (antrum, duodenum)
(mast cells)
PK
IP3 cAMP ?
Ca2+
Potentiation of stimulation!!!
muscarin rec H2
Phases of gastric secretion:
• Cephalic (vision, smell, taste)(X.)(directly, G, H)
• Gastric (distension of stomach; peptides, AA)(mechanorec.-local and central reflexes; tryptophan, phenylalanine, caffeine, alcohol – G)
• Intestinal (distension of duodenum, peptides, AA)(G from duodenum and jejunum)
Inhibition of gastric secretion:
Low pH, FA, hypertonia v duodenum and jejunum; secretin, bulbogastron, GIP, CCK
PGE, somatostatin –
inhibition of HCl secretion
Marie Nováková, Department of
Physiology, Faculty of Medicine, Masaryk
University
22
CONTROL OF PANCREATIC JUICE SECRETION
PANCREAS:
100 gr
Exocrine and endocrine part
n. X. Acinus
Ductus
(epithelium)
Proteins
Proenzymes
Digestion products
(lipids, peptides)
Na+
K+
HCO3-
Cl-
H2O
CCK
Ach
G
Subst. P
ISOTONIC
HCO3
-
Cl-
HCO3
-
Na+
K+
Cl-
H2O
Decrease of pH
Secretion of VIP
1. Trypsinogen (trypsin activates 1, 2, 3)
2. Chymotrypsinogen
3. Prokarboxypeptidase
4. Trypsin-inhibitor
5. a-amylase
6. Pancreatic lipases
• Enterokinase – activates trypsinogen
PANCREATIC JUICE: approx. 1 l/day
1. Water phase (HCO3
-) – secretin; ductal cells
2. Enzymatic phase - CCK
Oddi sphincter (X. – relaxation, secretin - contraction)
Regulation of secretion
1. Phase cephalic (n.X. – gastrin)
2. Phase gastric (distension of stomach – gastrin)
3. Phase intestinal (acid in duodenum and jejunum – secretin;
peptides, AA = tryptophan., phenylalanine, FA – CCK)
Acute pancreatitis
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University23
LIVER FUNCTION
• Regulation of metabolism (saccharides – glycogenolysis, gluconeogenesis;
lipids – chylomicrons, lipoprotein lipase, VLDL, cholesterol and triglycerides;
ketone bodies; proteins – synthesis of urea)
• Proteosynthesis (non-essential AA, lipoproteins, albumins, globulins, fibrinogen
and other proteins of blood clotting cascade)
• Storage (glycogen, vitamins – A, D, B12, iron)
• Degradation (hormones – epinephrine, norepinephrine, steroids, polypeptide
hormones)
• Inactivation and excretion (remedies, toxins) – detoxication by conjugation with
glucuronic acid, glycine and glutathione
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University24
BILE PRODUCTION
LOBULUS
hepatocytes (1-2 layers), fenestration
v. portae
bile ductus
sinusoides
a. hepatica
Bile
• 250-1500ml/day, isotonic, primary secretion – resembles plasma, CCK; modification - secretin
• bile acids (salts – Na+) – conjugated (glycin, taurin) – soluble in H2O, 50% of dry, micels
• cholesterol (crystals, lithiasis)
• lecithins
• bile pigments (bilirubin – glucuronid) – yellow colour of bile (lithiasis)
• Na+, K+, Cl•
H2O, HCO3
- (secretin)
Secretion resembles exocrine pancreas
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University25
ENTEROHEPATIC CIRCULATION of BILE ACIDS
CCK
X.
(G)
D IJ
20%
conjugated bile acids
secretion
HCO3
-
H2O
35ml
portal circulation
G, CCK, S
G, CCK
X. Intestinal phase
bile acids
Na+
Cl-
HCO3
-
H2O
Between meals –
thickening up to 5-20x
Active transport –
other ions keep
electroneutrality
Oddi
Cephalic phase
Gastric phase
Intestinal phase
deconjugated bile acids
Marie Nováková, Department of Physiology,
Faculty of Medicine, Masaryk University
26
REGULATION OF SECRETORY
FUNCTIONS IN GIT
HCl G
Ach H
peptides
H2 receptors (mast cells)
GRP
subst.P
(axon. reflex)
(motility)
ENS VIP
GIP
glucose
lipids
INSULIN
(b-cells, endocrine pancreas)
enzymes
HCO3
-
CCK,GIP
peptides
AA, FA
HCl
SS (d-cells)
motility
electrolytes
H2O
exocrine pancreas
* CEPHALIC PHASE
(taste, smell…)
* GASTRIC PHASE
(Ach, H, S, G, CCK stimulation
of
production
INTESTINAL PHASE OF
SECRETION
* mediated by gastrin
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University27
SELECTED QUESTIONS – related to ABSORPTION, IONS AND WATER
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University28
TRANSPORT MECHANISMS in GIT
Diffusion
Facilitated diffusion
Co-transport
Active transport
Marie Nováková, Department of Physiology, Faculty of Medicine,
Masaryk University29
DAILY WATER BALANCE
INTAKE
OUTPUT
saliva
gastric juice
pancreatic juice
bile
small intestine
colon
~ 2 - 3
~ 1,5
~ 1 - 2
~ 1,5
~ 0,5
~ 1,5
~ 0,4
~ 0,2
(~7,5)
(~1,3)
(~0,2)
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University30
WATER ABSORPTION (small intestine, gallbladder, stomach, colon)
(duodenum – osmotic draft of H2O)
Continuous osmotic gradient
brush border H2O
H2O
FILTRATION
Na+
Na+, K+, Cl-
+10m
V
Na+
K+
Cl-
TRANSPORT
•Transcellular
•Paracellular
Brush border
Tight junctions
Basal membrane
Lateral membrane
F
STIMULATION: digestion products (AA, sugars)
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University31
TRANSPORT OF IONS
K
+
Na+
K
+
K
+
Na+
Na+
IL
IL
glucose, galactose,
AA
Cl-
H2O+CO2
H+ HCO3
-
H2CO3
H2O + CO2
ClLieberkühn
cryptes: matured cells –
absorption, immature cells – secretion
of Na+, Cl- a H2O
JEJUNUM
ILEUM
brush border
basolateral membrane
J
glucose, galactose,
AA
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University32
TRANSPORT OF IONS
K+
Na+ (120mM/l)
K+
Na+
Na+(25mM/l)+H2O
Cl-
H2O+CO2
H+ HCO3
-
H2CO3
H2O + CO2
COLON
K+
ClALDOSTERONE
ALDOSTERONE
ALDOSTERONE – synthesis of transport
systems (as in proximal tubule)
basolateral membrane
brush border
K+
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University33
REGULATION OF TRANSPORT OF WATER AND IONS
1. Autonomous nervous system: SYMP (noradrenaline, enkefalins) + somatostatin –
increase of absorption of water, sodium and chlorine
2. Aldosterone: colon – stimulation of secretion of potassium and absorption of sodium and
water (up-regulation of Na/K-ATPase, Na-channel)
3. Glucocorticoids: small intestine and colon - absorption of sodium, chlorine and water
(up-regulation of Na/K-ATPase)
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University34
ABSORPTION OF Ca2+
INTAKE: 1000mg/day
ABSORPTION: 350mg/day
Absorption against
concentration gradient (1:10)
in all GIT (D, J), 50x slower
than absorption of Na+
Ca2+
Ca BP
Ca2+-ATPase Na+/Ca2+-antiporter
VIT.D
ER
Mch
1,25-dihydrocholecalciferol
Calbindin – prevention of
formation of insoluble salts
(phosphates, oxalates)
[Ca2+]pl.
Basolateral membrane
brush border
TRPV6Ca2+
K+
Na+
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University35
RACHITIS
(rickets)
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University36
ABSORPTION OF Fe2+
endocytosis
2 Fe2+
TRANSFERIN
INTAKE: 15-20mg/day
ABSORPTION:
Men: 0,5 - 1mg/day
Women: 1 – 1,5mg/day
D, J
pH: Fe3+ Fe2+
70% - Hb
25% - F
Insoluble salts and complexes (20:1) – limitation of absorption
Decrease of pH
Fe – up-regulation
Fe2+ stimulates
synthesis of TF – regulation!
Hemosiderin – deposits of Fe in desmosomes
PLAZMATIC TRANSFERIN
(Apo)-Feritin Excess of Fe2+ – loss with epithelium
Fe2+ stimulates synthesis of apoferitin
(translation) – regulation!
basolateral membrane
brush border
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University37
VITAMIN B12
• Daily need is close to its absorption capacity
• Synthesised by bacteria in colon – BUT there is not absorption mechanism
• Store in liver (2-5mg)
• In bile 0.5-5mg / day, reabsorbed
• Daily loss – 0.1% of stores stores will last for 3-6 years
ABSORPTION
1. Gastric phase: B12 is bound to proteins, low pH and pepsin release it; bound to glycoproteins –
R-proteins (saliva, gastric juice), almost pH-undependable; intrinsic factor (IF) – parietal cells of
gastric mucosa; most of vitamin bound to R-proteins
2. Intestinal phase: pancreatic proteases, cleavage of R-B12, bound to IF (resistant to pancreatic
proteases)
Marie Nováková, Department of Physiology,
Faculty of Medicine, Masaryk University
38
ABSORPTION OF B12 VITAMIN
IF B12
B12
B12
IF
IF
Intrinsic Factor
IF-B12
receptor
complex
?
B12
B12 B12
v.portae
ILEUM
B12
transcobalamin II
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University39
Pernicious anaemia
(megaloblastic)
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University40
DIGESTION AND ABSORPTION
OF SACCHARIDES
POLYSACHARIDES
(a-glycosyled s.)
OLIGOSACCHARIDES
MONOSACHARIDES FRUCTOSE GLUCOSE GALACTOSE
AMYLOPECTIN
GLYCOGENa-amylase
DEXTRIN
TRICHACHARIDES
DISACHARIDES: SACCHAROSE MALTOSE LACTOSE
isomaltase
maltase
saccharase
lactase
Saliva
Pancreatic juice
Na+
Epithelium of duodenum and jejunum
• Lactase intolerance
• Diarrhoea
salivary amylase
2 binding sites for Na+
1 binding site for saccharide
facilitated transport + diffusion
GLUT-5 SGLT-1
GLUT-2
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University41
DIGESTION AND ABSORPTION
OF PROTEINS
STOMACH
Pepsin
DUODENUM
Trypsin
Chymotrypsin
Carboxypeptidase
JEJUNUM
Membrane peptidases
(brush border)
CYTOPLASM of epithelial cell
di-, tri-peptidases
PEPTIDES > 4 AA
DI-, TRI-PEPTIDES
AA
AA
PROTEASES
15%
50%
PEPTIDASES (exo-, endo-)
NUCLEASES
Na+-cotransport Diffusion
Purine, pyrimidine bases
– active transport
100g food + 30g GIT juices + epithelial cells
enterokinase
Marie Nováková, Department of Physiology,
Faculty of Medicine, Masaryk University
42
DIGESTION AND ABSORPTION
OF LIPIDS
Triglycerides (TAG)
Sterols (-esters)
Phospholipids (lecithin)
LIPID DROPS
EMULSIFICATION (+lecithin, +monoglycides)
Ø 1mm
BILE ACIDS SALTS
DEESTHERIFICATION
PANCREATIC LIPASE (colipase)
CHOLESTEROL-ESTHERASE
PHOSPHOLIPASE A2
ENTERIC LIPASE
Glycerol FA MAG CH LFL
MICELLES
Ø 5nm, 20-30
molecules
polar stratification, hydrophilic
disintegration of micelles
TAG
unstirred water layer
200-500mm
bile acids
resorption (diffusion)
reesterification (FA >12c, in endopl.retic.)
CHE PL
PROT.
EXOCYTOSIS
CHYLOMICRA Ø 10nm
LYMPHATIC CIRCULATION
NEFA (<12c)
GLYCEROL
capillaries (fenestration)
Na+
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University43
ABSORPTION IN COLON
• Na+ (active transport, aldosteron) H2O (90% water in colon)
• ClREST
OF CHYME
1. Cellulose, collagen
2. Bile acids, epithelia, mucin, leucocytes
• Bacteria fermenting: fibre (pectin, cellulose) – lactate, alcohol, acetate, CO2, methane
• Bacteria putrescent: residues of AA – NH3, SH2, phenol, indole, solatol (carcinogenic)
Production of vitamin K and vitamins of B group – BUT NO ABSORPTION MECHANISMS
NUTRITION
PASSAGE EUMICROBIA
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University44
REGULATION OF FOOD INTAKE AND NUTRITIONAL STATE
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University45
INTAKE OUTPUT
CENTER OF SATIETY CENTER OF HUNGER
(permanently active)
ncl.
ventromedialis in hypothalamus
lateral hypothalamus
(nucleus under fasciculus telencephalicus medialis)
Marie Nováková, Department of Physiology, Faculty of Medicine,
Masaryk University
46
FEELING OF SATIETY
FOOD INTAKE
Chewing
movements
Receptors in
nose, mouth,
oesophagus,
intestine
Mechanoreceptors
in stomach
GIT
chemoreceptor
s
SATIETY
PRERESORPTIVE FEEDING
Central
gluco-
thermo-
lipo-
receptors
COMPILING THE INFORMATION IN CNS
(CENTER OF SATIETY = ncl. ventromedial in hypothalamus)
RESORPTIVE FEEDING
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University47
FEELING OF HUNGER
LACK OF FOOD
Hungry
contractions
of stomach
Decreased
glucose
availability
Decreased
heat
production
Changes of lipid
metabolism
Mechanoreceptors Glucoreceptors Internal termoreceptors
(hypothalamus)
„Liporeceptors“
HUNGER
SHORT-TERMED REGULATION
LONG-TERMED REGULATION
Compensation of dietary mistakes
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University48
HYPOTHESIS:
1. Lipostatic
2. GIT peptides
3. Glucostatic
4. Thermostatic
REGULATION OF FOOD INTAKE
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University49
OREXIGENIC FACTORS
• Neuropeptide Y
• Orexin A and B (hypocretin 1 and 2)
• ARP (agouti-related peptide)
• Ghrelin (lenomorelin) – s.-c. hormone of hunger (released from „empty“ stomach)
• Motilin
• Sugars (fructose)
ANOREXIGENIC FACTORS
• Leptin - – s.-c. hormone of satiety
• POMC – derivative MC4-R
• CRH (corticoliberin)
• CART (cocaine- and amphetamine-regulated transcript)
• Peptide YY (pankreatic peptide; L-cells in ileum and colon, suppresses
gastric motility, increases absorption)
• CCK (cholecystokinin)
• glucagon
MEDICAMENTS !!!
50 Compendium of Physiology, Marie Nováková
Hormone Source Site of Action Effect
Insulin Pancreatic beta cells Hypothalamus
↓Appetite
↑Metabolism
Leptin
Fat cells
Endocrine cells of the
stomach
Hypothalamus
↓NPY, AgRP
↑POMC
Vagal afferents
↓Appetite
↑Metabolism
↓Ghrelin release
CCK I cells of the duodenum Vagal afferents
↓Appetite
↓Gastric emptying
PYY
L cells of the ileum and
colon
Hypothalamus
↓NPY, AgRP
↑POMC
Stomach
↓Appetite
↑Metabolism
↓Gastric emptying
Ghrelin
Endocrine cells of the
stomach, hypothalamus,
large and small
intestines
Hypothalamus
↑NPY, AgRP
Vagal afferents
↑Appetite
↓Metabolism
↓Leptin release
↓, Inhibits; ↑, stimulates AgRP, agouti-related peptide; CCK, cholecystokinin; NPY,
neuropeptide Y; POMC, proopiomelanocortin; PYY, peptide YY.
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University51
LEPTIN (ob-protein)
Secreted by adipocytes into the blood
Binding proteins
Effect on CNS (regulation of body mass and stability of adipose tissue)
• Pulsatile and diurnal character of plasmatic levels
• Free and bound form (in serum)
• SLIM PEOPLE HAVE 2x MORE OF BOND FORM THAN OBESE PEOPLE
• LEPTIN REZISTANCE: often in obese patient with insulin resistance
RECEPTORS from cytokine family
• Peripheral (gonads)
• Central (hypothalamus, pituitary)
Modulates expression of genes for oestrogens.
Regulation of obesity by leptin mediated by NPY and MSH.
Leptin controls adipose tissue by coordination of food intake, metabolism, autonomous nervous system
and energy balance.
Marie Nováková, Department of Physiology,
Faculty of Medicine, Masaryk University
52
ADIPOSE TISSUE
INCREASE OF BODY MASSLOSS OF BODY MASS
- LEPTIN
+LEPTIN
HYPOTHALAMUS
HYPOTHALAMUS
NPY
RESPONSE TO FASTING
MSH
RESPONSE TO OBESITY
NPY RECEPTOR
MSH RECEPTOR
+ Food intake
- Reproduction
- Temperature
- Energy expenditure
- Food intake
+ Energy expenditure
PARASYMPATHETIC
ACTIVITY
SYMPATHETIC
ACTIVITY
POMC derivatives
LEPTIN RESISTANCE
(MC4-R)(Y1, Y2, Y5)
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University53
• The GIT is a tube, specialized along its length for the sequential processing of food
• Assimilation of substrates from food requires both digestion and absorption
• Digestion requires enzymes, which are secreted in various parts of GIT
• Food ingestion triggers complex whole-body responses (endocrine, neural, paracrine)
• GIT plays an important role also in homeostasis (absorption vs. excretion, izovolemia,
izoionia, etc.) and immunity
THM
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University54
The regulation of GI function results from an interplay of neural and hormonal influences on effector cells that
have intrinsic activities.
The GI tract is innervated by the ANS, which is composed of nerves that are extrinsic and nerves that are intrinsic
to the tract.
Extrinsic nerves are distributed to the GI tract through both parasympathetic and sympathetic pathways.
Intrinsic nerves are grouped into several nerve plexuses, of which the myenteric and submucosal plexuses are the
most prominent. Nerves in the plexuses receive input from receptors within the GI tract and from extrinsic nerves.
This input can be integrated within the intrinsic nerves such that coordinated activities can be effected.
ACh is one of the major excitatory neurotransmitters, and NO and VIP are two of the major inhibitory
neurotransmitters at effector cells. Serotonin and somatostatin are two important neurotransmitters of intrinsic
interneurons.
THM
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University55
THM
Striated muscle comprises the musculature of the pharynx, the oral half of the esophagus, and the external anal
sphincter. Smooth muscle makes up the musculature of the rest of the GI tract.
Adjacent smooth muscle cells are electrically coupled to one another and contract synchronously when
stimulated. Some smooth muscles contract tonically, whereas others contract phasically.
In phasically active muscle, stimulation induces a rise in intracellular Ca2+, which in turn induces phosphorylation
of the 20,000-dalton light chain of myosin. ATP is split, and the muscle contracts as the phosphorylated myosin
(myosin P) interacts with actin. Ca2+ levels fall, myosin is dephosphorylated, and relaxation occurs. In tonically
active muscles, contraction can be maintained at low levels of phosphorylation and ATP utilization.
Periodic membrane depolarizations and repolarizations, called slow waves, are major determinants of the phasic
nature of contraction. Slow wave activity results from ionic currents initiated through the interactions of the ICCs
with the smooth muscle cells.
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University56
The functions of the GI tract are regulated by mediators acting as hormones (endocrine), paracrine, or
neurocrine substances.
Two chemically related families of peptides are responsible for much of the regulation of GI function.
These are gastrin/CCK peptides and a second group containing secretin, VIP, GIP, and glucagon.
The GI hormones are located in endocrine cells scattered throughout the mucosa and released by
chemicals in food, neural activity, or mechanical distention.
The GI peptides have many pharmacologic actions, but only a few of these are physiologically
significant.
Gastrin, CCK, secretin, GIP, and motilin are important GI hormones.
Somatostatin and histamine have important functions as paracrine agents.
Neurocrines VIP, bombesin (or GRP), and the enkephalins are released from nerves and mediate
many important functions of the digestive tract.
Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University57
• Both active and passive mechanisms participate in GIT absorption
• Both paracellular and transcellular movements are involved
• Absorption area is enlarged by folds, villi and microvilli (mostly in small intestine)
• Absorption of water and electrolytes occurs in both small and large intestine,
absorption of nutrients occurs only in small intestine
• Small intestine absorbs water and electrolytes and secretes HCO3
-, large intestine
absorbs water and electrolytes and secretes potassium and HCO3
•
Water „follows“ electrolytes, eventually is „drafted“ by osmotically active substances
• Numerous absorption mechanisms depend on sodium gradient
THM