SECRETION
•Salivary glands
•Gastric glands
•Small glands of esophagus and intestine
•Exocrine pancreas
•Liver
STIMULATION OF SECRETION
1. Neurocrine
2. Endocrine
3. Paracrine
• Lubrication of food
• Swallowing
• Mechanical protection of GIT
• Chemical protection of GIT
• Enzymes
• Immune function(s)
• Articulation
Common features of secretion:
water, ions, HCO3-, mucin
PRODUCTION OF SALIVA
•Mucinous vs. serose secretion
•Gl. parotis, gl. submandibularis, gl. sublingualis, small salivary glands in mouth
•1 litre / 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 stim. – Ach, VIP, VII. a IX.n., ; vasodilatation
ACINES
Serose secretion (H2O, ions;
isotonic)(gl.parotis)
Salivary amylase (zymogenic granules –
exocytosis)
Over pH 4!!!
PRIMARY SALIVA
Mucinose secretion (glykoproteins)
(gll.submandibularis and sublingualis)
Resembles exocrine pancreas
DUCTUS
Na+
Cl-
HCO3-
K+
SECONDARY SALIVA
(hypotonic, after stimulation – increased tonus)
pH ~ 8
Xerostomia
REGULATION OF SALIVA PRODUCTION
Transmitter 2. messenger Secretion
SYMPATHETIC NS
Only transient efect!!!
amylase
vasoconstriction
secretion of K+, HCO3-
Na+
ClH2O
volume
PARASYMPATHETIC NS
(dominant) - n.fac.,
glossoph.
amylase, mucin
vasodilatation
Trophic influence of PS
VIP cAMP
NOR
b
a
IP3Ach
Subst.P
K+
Na+
Na+
(antiport)
Ca2+
Ca2+
amylase
SECRETION OF GASTRIC JUICE
Mucin (pH 7-8)
Gastric pits (glands)
pH 2, high concentration of K+ (vomiting) a ClSurface
epithelia
Lamina propria
Mucose cells of neck
Parietal cells (HCl, intrinsic factor)
Main cells - zymogenic granula (pepsinogen)
G cells (gastrin)
Area:
•Subcardial (mucin)
•Fundus (HCl)
•Pyloric (mucin, G)
Gastric juice: water, salts, HCl, pepsin, intrinsic factor, mucin
Production increases after meal
Higher secretion – lower pH, lower secretion – more Na+, (always more K+ than in plasma)
pepsinogen pepsin
HCl
Gastric mucose barrier
Stimulation of a-receptors – decreased secretion of
HCO3
Gastric
ulcers
NSA – decreased secretion of HCO3
- and mucine
Ach, G, CCK, secretin
+
(individual number!!!)
HCl PRODUCTION IN PARIETAL CELL
AP
SP
SP
H2O+CO2=HCO3-+H+ (CA)
Cl-
Cl-
Na+
Na+
K+
K+
H+
K+
Cl-
HCl
INTRINSIC FACTOR: binding protein (glycoprotein) for vitamin B12 absorption (pernicious anemia)
Tubulovesicular system (rest, 10% – secretion)
Pepsinogen (together
with HCl)
Pepsin (protease)
Proton pump
Basolateral
membrane
Apical
membrane
blood
„alkaline tide“
(1 000 000 : 1 )
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 centr. reflexes; trypt., fenylalanin, 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
CONTROL OF PANCREATIC JUICE SECRETION
100 gr
1 l/day
exo-endo
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
1. Water phase (HCO3
-) - secretin
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 = trypt., fenylalanin, FA – CCK)
Pancreatitis acuta
Ach
CCK
Gastrin
Bombesin
Subst.P
Secretin
VIP (n.X.)
Cholera toxin
IP3
Ca2+
cAMP
REGULATION OF SECRETION IN ACINARY CELL
Depolarisation
Electr. uncoupling
cGMP
SECRETION OF
ENZYMES
LIVER FUNCTION
•Regulation of metabolism (saccharides – glycogenolysis,
glukoneogenesis; 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 – epinephrin, norepinephrin, steroids,
polypeptidic hormones)
•Inactivation and excretion (remedies, toxins) – detoxication by
conjugation with glucuronic acid, glycine and glutathion
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
ENTEROHEPATIC CIRCULATION
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
deconjugation of bile acids
SECRETION
FUNCTION OF GIT
AND ITS HUMORAL
CONTROL
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
(taste, smell…)
* GASTRIC
(Ach, H, S, G,
CCK stimulation
of
production
INTESTINAL PHASE OF
GASTRIC JUICE SECRETION
* mediated by gastrin