Fisiologi Sekresi&Absopsi-blok Digest13 Edit
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Transcript of Fisiologi Sekresi&Absopsi-blok Digest13 Edit
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dr. Mustofa, M.ScLAB. FISIOLOGI FKIK UNSOED
FISIOLOGI SISTEM PENCERNAANSekresi & Absorpsi
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1. Describe the secretion of the oral cavity juice.2. Describe the secretion of gastric juice and the roles
of stomach in absorption. 3. Explain the functions of the intestinal secretions,
and discuss the regulation of secretory activities.4. Describe the secretion and regulation of the
accessory digestive organs.5. Describe the intestinal absorptive processes
Learning Objective
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1. AN OVERVIEW OF THE STRUCTURE AND FUNCTION OF THE DIGESTIVE TRACT
2. ORAL CAVITY AND ASSOCIATED GLANDULAR ORGANS3. THE STOMACH4. THE SMALL INTESTINE AND ASSOCIATED GLANDULAR
ORGANS5. THE LARGE INTESTINE
Outline
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HeartLiver
ABSORPTION
SECRETION
Large intestine
RectumAnusMouth
Food andwater
StomachHepatic
Portal vein
Small intestineSalivary glands
MOTILITY
FECES
enzim asam, dllVitamin
C, D, B2, B12, dllProteinMineral
KarbonhidratLipid
Adapted by:Dr. Andreanyta Meliala, PhD.
Vitamin KAir, Elektrolit
AktifitasBAKTERI
Pembentukan Gas CO2, Metana, dll
FLATUS
Digestion
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• Movement of Food Through the System
• The large, hollow organs of the digestive system contain muscle that enables their walls to move. The movement of organ walls can propel food and liquid and also can mix the contents within each organ. Typical movement of the esophagus, stomach, and intestine is called peristalsis. The action of peristalsis looks like an ocean wave moving through the muscle. The muscle of the organ produces a narrowing and then propels the narrowed portion slowly down the length of the organ. These waves of narrowing push the food and fluid in front of them through each hollow organ.
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• Secretion:– Includes both exocrine and endocrine secretions.
• Exocrine:– HCl, H20, HC03
-, bile, lipase, pepsin, amylase, trypsin, elastase, and histamine are secreted into the lumen of the GI tract.
• Endocrine:– Stomach and small intestine secrete hormones to help regulate
the GI system.» Gastrin, secretin, CCK, GIP, GLP-1, guanylin, VIP, and
somatostatin.
Functions of the GI Tract (Continued)
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• Absorption:– Process of the passage of digestion (chemical
subunits) into the blood or lymph.
Functions of the GI Tract (Continued)
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nutrients
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• The gut wall has a layered organization, with the absorptive cells lining the lumen and neural and muscular components below. Blood and lymph vasculature is abundant to transport absorbed nutrients.
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GIT Regulation
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• The enteric nervous system coordinates digestion, secretion, and motility to optimize nutrient absorption. Its activity is modified by information from the CNS and from local chemical and mechanical sensors.
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GIT Regulation
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Johnson Chap. 34-35Johnson Chap. 34-35
Apical MembraneApical Membrane
Johnson Chap. 34-35Johnson Chap. 34-35
(Gut lumen)(Gut lumen) (interstitial (interstitial space)space)
PP
OutsideOutside InsideInside
ApicalApical BasolateralBasolateral
NaNa++
KK++
ClCl--
ChannelsChannels
NaNa++
glucoseglucose
NaNa++ coupled coupledorganicorganic
ClCl--
HCOHCO33-- AntiporterAntiporter
NaNa++
KK++
2Cl2Cl--
SymporterSymporter
Apical SurfaceApical Surface
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Johnson Chap. 34-35Johnson Chap. 34-35Johnson Chap. 34-35Johnson Chap. 34-35
Basolateral MembraneBasolateral Membrane
Johnson Chap. 34-35Johnson Chap. 34-35
NaNa++
HH++
AntiporterAntiporter
NaNa++
KK++
2Cl2Cl--
SymporterSymporter
KK++
ActiveActiveTransporterTransporter
NaNa++
ATPATP
(Gut lumen)(Gut lumen)
OutsideOutside
ApicalApical BasolateralBasolateral
PP
(interstitial (interstitial space)space)
InsideInside
Basolateral SurfaceBasolateral Surface
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Johnson Chap. 34-35Johnson Chap. 34-35
55 1010 1515 2020
1010
2020
3030
4040
NaNa++ (mM) (mM) (Intracellular)(Intracellular)
Tran
spor
t Rat
eTr
ansp
ort R
ate
Na Pump Transport RateNa Pump Transport Rate
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Johnson Chap. 34-35Johnson Chap. 34-35
Gut lumenGut lumenGut lumenGut lumen interstitial interstitial spacespace
ClCl--
NaNa++KK++ClCl--
NaNa++
KK++
KK++
NaNa++
Salt SecretionSalt Secretioninterstitial interstitial spacespace
Salt AbsorptionSalt Absorption
NaNa++
KK++
KK++
ClCl--
NaNa++
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Johnson Chap. 34-35Johnson Chap. 34-35
11 22 33 4400
2020
4040
6060
8080
100100
Ion
conc
entra
tion
Ion
conc
entra
tion
(mM
)(m
M)
Flow Flow (ml/min)(ml/min)
NaNa
HCOHCO33
ClCl
KK2020
4040
6060
8080
100100
120120
140140
00
Ion
conc
entra
tion
Ion
conc
entra
tion
(mM
)(m
M)
NaNa
ClCl
HCOHCO33
KK
SalivaSaliva PlasmaPlasmaSalivary Duct CellSalivary Duct Cell
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Secretion of NaSecretion of Na++, K, K++, and Cl, and Cl--
Salivary Acinar CellSalivary Acinar Cell
Johnson Chap. 34-35Johnson Chap. 34-35
NaNa NaNaNaNa++KK++ClCl-- KK++
ATPATP
NaNa++
KK++ClCl--
KK++
LumenLumen
Serosal surfaceSerosal surface stimulistimuli
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Johnson Chap. 34-35Johnson Chap. 34-35Johnson Chap. 34-35Johnson Chap. 34-35
NaNa++NaNa++
KK++
ClCl--
COCO22
KK++
ATPATP
NaNa++
ClCl--
KK++
LumenLumen
Serosal surfaceSerosal surface NaNa++
HH++
COCO22
HH22COCO33
HCOHCO33--
NaNa++
KK++
ClCl--
HCOHCO33--
Salivary Duct CellSalivary Duct Cell
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Johnson Chap. 34-35Johnson Chap. 34-35
11 22 33 4400
2020
4040
6060
8080
100100
Ion
conc
entra
tion
Ion
conc
entra
tion
(mM
)(m
M)
Flow Flow (ml/min)(ml/min)
NaNa
HCOHCO33
ClCl
KK2020
4040
6060
8080
100100
120120
140140
00
Ion
conc
entra
tion
Ion
conc
entra
tion
(mM
)(m
M)
NaNa
ClCl
HCOHCO33
KK
SalivaSaliva PlasmaPlasmaSalivary Duct CellSalivary Duct Cell
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Johnson Chap. 34-35Johnson Chap. 34-35
100100 300300 50050000
Secretion rate (ml/hr)Secretion rate (ml/hr)
00
160160
120120
8080
4040
Ion
Con
cent
ratio
n Io
n C
once
ntra
tion
(mM
)(m
M)
7.87.8
7.47.4
8.28.2pHpH 300300
260260
340340
Osm
olal
ityO
smol
ality
OsmOsm
pHpH
NaNa++
HCOHCO33--
ClCl--
KK++
Pancreatic SecretionPancreatic Secretion
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Johnson Chap. 34-35Johnson Chap. 34-35
Intestinal Absorbing CellIntestinal Absorbing Cell
NaNa++KK++ClCl--ClCl ClCl
KK++
ATPATP
NaNa++
NaNa++
KK++
LumenLumen
Serosal surfaceSerosal surface
glucoseglucoseNaNa++ ClCl--
HCOHCO33--
KK++
ATP
ATP
NaNa++
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Intestinal Secretory CellIntestinal Secretory Cell
Johnson Chap. 34-35Johnson Chap. 34-35
NaNa NaNaNaNa++KK++ClCl-- KK++
ATPATP
NaNa++
ClCl--ClCl--
KK++
LumenLumen
Serosal surfaceSerosal surface
stimulistimuliKK++
ATP
ATP
NaNa++
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Composition and function of saliva
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Major salivary components
Mucin 1 (MG1)Mucin 1 (MG1)
sIgAsIgAMucin 2 (MG2)Mucin 2 (MG2)
LactoferrinLactoferrin
PeroxidasesPeroxidases
AmylasesAmylasesCarbonic anhydrasesCarbonic anhydrases
Proline-rich proteinsProline-rich proteinsLysozymeLysozyme
StatherinsStatherins
HistatinsHistatins
11 1010 100100 10001000 1000010000
Size (kDa)Size (kDa)
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Multifunctionality
SalivarySalivaryFamiliesFamilies
Anti-Anti-BacterialBacterial
BufferingBuffering
DigestionDigestion
Mineral-Mineral-izationization
Lubricat-Lubricat-ion &Visco-ion &Visco-elasticityelasticity
TissueTissueCoatingCoating
Anti-Anti-FungalFungal
Anti-Anti-ViralViral
Carbonic anhydrases,Carbonic anhydrases,HistatinsHistatins
Amylases,Amylases,Mucins, LipaseMucins, Lipase
Cystatins,Cystatins,Histatins, Proline-Histatins, Proline-rich proteins,rich proteins,StatherinsStatherins
Mucins, StatherinsMucins, Statherins
Cystatins, Mucins, Cystatins, Mucins, Proline-rich proteins, StatherinsProline-rich proteins, Statherins
HistatinsHistatins
Cystatins,Cystatins,MucinsMucins
Cystatins,Cystatins,Histatins, Mucins,Histatins, Mucins,PeroxidasesPeroxidases
adapted from M.J. Levine, 1993adapted from M.J. Levine, 1993
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Mucin Functions• Tissue Coating
– Protective coating about hard and soft tissues– Concentrates anti-microbial molecules at mucosal
interface• Lubrication
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Mucin Functions (cont’d)
• Aggregation of bacterial cells– Bacterial adhere to mucins may result in surface
attachment, or– Mucin-coated bacteria may be unable to attach to
surface• Bacterial adhesion
– Mucin oligosaccharides mimic those on mucosal cell surface
– React with bacterial adhesins, thereby blocking them
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Amylases
• Hydrolyzes (1-4) bonds of starches• Maltose is the major end-product (20% is
glucose)
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Lingual Lipase• Secreted by von Ebner’s glands of tongue• Involved in first phase of fat digestion• Hydrolyzes medium- to long-chain
triglycerides• Important in digestion of milk fat in new-
born• Unlike other mammalian lipases, it is highly
hydrophobic and readily enters fat globules
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Statherins• Calcium phosphate salts of dental enamel are
soluble• Supersaturation of calcium phosphates
maintain enamel integrity• Statherins prevent precipitation or
crystallization of supersaturated calcium phosphate in ductal saliva and oral fluid
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Proline-rich Proteins (PRPs)
Inhibit calcium phosphate crystal growth
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Calculus formation
• Calculus forms in plaque despite inhibitory action of statherin and PRPs in saliva
• Proteolytic enzymes of oral bacteria or lysed leukocytes may destroy inhibitory proteins
• Plaque bacteria may produce their own inhibitors
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Lactoferrin
• Nutritional immunity• Some microorganisms (e.g., E. coli) have adapted
to this mechanism by producing enterochelins.– bind iron more effectively than lactoferrin– iron-rich enterochelins are then reabsorbed by
bacteria• Lactoferrin, with or without iron, can be
degraded by some bacterial proteases.• In unbound state, a direct bactericidal effect
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Lysozyme• Present in numerous organs and most body fluids• Sources of oral LZ:
– major and minor salivary glands, phagocytic cells
• Biological function– Classic concept of anti-microbial activity of LZ is based on its
muramidase activity (hydrolysis of (1-4) bond between N-acetylmuramic acid and N-acetylglucosamine in the peptidoglycan layer.
– Gram negative bacteria generally more resistant than gram positive because of outer LPS layer
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Other anti-microbial activities of LZ• Muramidase activity (lysis of peptidoglycan
layer)• Cationic-dependent activation of bacterial
autolysins– disrupts membranes
• Aggregation of bacteria• Inhibition of glucose uptake and acid production• De-chaining of streptococci
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Histatins
• A group of small histidine-rich proteins• Potent inhibitors of Candida albicans
growth
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Cystatins• Are inhibitors of cysteine-proteases• Are ubiquitous in many body fluids• Considered to be protective against unwanted
proteolysis– bacterial proteases– lysed leukocytes
• May play inhibit proteases in periodontal tissues• Also have an effect on calcium phosphate
precipitation
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Mekanisme lokal:• Prostaglandin, histamin, dan bahan kimia lain yg
dilepaskan ke cairan interstitial dapat berpengaruh pada sel sekitar
• Mesenger lokal ini penting dalam kordinasi tanggap terhadap perubahan pH lokal, rangsang fisik atau kimia lain.
GIT Regulation
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Stomach (continued)
Insert fig. 18.5
Stomach
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• 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.– oxintic: ghrelin.
Gastric Glands
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Gastric Secretion
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HCl Production• Parietal cells
secrete H+ into gastric lumen by primary active transport, through H+/ K+ ATPase pump.
• Parietal cell’s basolateral membrane takes in Cl- against its electrochemical gradient, by coupling its transport with HC03
-.
Insert fig. 18.8
HCl production
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• HCl production is stimulated:– Indirectly by gastrin.– Indirectly by ACh.
• ACh and gastrin stimulate release of histamine.– Histamine:
• Stimulates parietal cells to secrete HCl.
HCl production
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• Makes gastric juice very acidic.– Denatures ingested
proteins (alter tertiary structure) so become more digestible.
• Activates pepsinogen to pepsin.– Pepsin is more
active at pH of 2.0.
Insert fig. 18.9
HCl Function
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• 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.
Digestion and Absorption in the Stomach
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• 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.
Protective Mechanisms of Stomach
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Usus halus
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• Getah Pankreas• Getah Empedu • Getah usus halus
Getah pencernaan di Usus halus
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1,8 L /hari1. Kelenjar Brunner: di mukosa duodenum,
merangsang sekresi:– Mukus: melindungi mukosa duodenum dari iritasi HCl &
pepsin– Buffer :me pH (khime dlm duodenum pH: 1-2 sp 7-8)
2. Kripte Lieberkuhn Produksi enzim, cairan isotonik dan alkalin
Getah Usus halus
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3. Enterosit vilimenghasilkan: amilase, enterokinase, lipase, peptidase, disakaridase, yang tidak dikeluarkan ke lumen namun akan memecah lemak, protein, karbohidrat begitu absorbsi dimulai
Getah Usus halus
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• 1500 cc / hari• Mengandung: bikarbonat, elektrolit: Na,K,Cl,enzim • Mempunyai 2 fungsi:
1. Endokrin: sel endokrin sekresi insulin & glukagon2. Eksokrin: berasal dari sel asinus dan epitel: keduanya
menghasilkan cairan disebut cairan pankreas (pancreatic juice) yg dikeluarkan ke usus halus.• enzim yang dikeluarkan sel asinus berguna untuk memecah khime
menjadi molekul kecil yang mudah diabsorbsi.• Sel epitel mengeluarkan air & ion untuk mengencerkan khime &
sebagai buffer
Getah Pankreas
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• Pengaturan sekresi melalui pengendalian hormon.
Bila khime masuk duodenum, maka duodenum mengeluarkan hormon :
1. sekretin: memacu pankreas sekresi buffer air dengan pH 7,5-8,8 dan buffer bicarbonat serta fosfat
2. kolesistokinin: rangsang produksi dan sekresi enzim pankreas
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Pengaturan sekresi
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• Secretin secretion from the duodenum is triggered by the arrival of acidic chyme from the stomach.
• Secretin is a hormone: • its receptors are found in the pancreas,
which responds with additional bicarbonate delivery, and its receptors are also associated with the stomach; this enterogastrone inhibits gastric motility and secretion.
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Pengaturan sekresi
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• Cholecystokinin secretion from the small intestine is triggered by the arrival of amino acids and fatty acids in the chyme.
• Cholecystokinin is a hormone: its receptors are in the pancreas, which responds with additional enzyme delivery, and
• in the gall bladder, which contracts to deliver more bile, and in the sphincter of Oddi, which relaxes to facilitate delivery of the enzymes and bile salts (it is also an enterogastrone).
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• digestive enzymes secreted as inactive precursors (zymogens) to prevent autodigestion
• important proteolytic enzymes are trypsin, chymotrypsin and carboxypeptidases
other enzymes are-• pancreatic lipase• pancreatic amylase• trypsinogen is activated by enteropeptidase which is
secreted by intestinal mucosa in response to chyme• trypsin then activates the other proenzymes• trypsin inhibitor secreted to delay activation of
trypsinogen
Enzim pankreatik
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F O O D
Aktifasi enzimatik
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• 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,
which activates many other precursors) only after they are transported to
the appropriate place.
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• cephalic phase ~15% mainly causes secretion of enzymes into the acini - vagus mediated
• gastric phase ~15% gastric distension by means of vago-vagal reflex evokes enzyme secretion
• gastrin release by antral lumen causing more enzyme release
• intestinal phase ~70% -pancreatic HCO3 secretion strongly stimulated when duodenal pH is acid - S cells secrete secretin into the blood and this stimluates pancreatic duct cells
• chyme also causes I cells to release CCK which causes pancreatic enzymes to be secreted (mainly due to peptones and fatty acids)
Fase sekresi pankreas
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Stimuli of Pancreatic Secretion
• ACh - parasympathic vagus nerves as well as myenteric cholinergics
• Gastrin - liberated during gastric phase of stomach secretion
• CCK (cholecystokinin) - secreted by duodenal and upper jejunal mucosa when food enters small intestine
• these 3 all stimulate production of digestive enzymes by the acini and act via IP3 to release intracellular Ca
• Secretin - same duodenal and upper jejunal mucosa but secretin acts via cAMP on the ductal cells to increase HCO3 secretion
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Pengiriman nutrient dari saluran cerna ke sirkulasi, terutama tjd di usus halus permukaan yang luas.
Absopsi efisien bila:1. Bentuk hasil pencernaan baik2. Permukaan absorpsi adekuat3. Kecepatan/ waktu transit nutrient di usus halus4. Kofaktor dan atau karier spesifik
Absorbsi usus halus
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1. Absorbsi air dan elektrolit– membran intestinal sangat permeabel terhadap
air– Air diserap menggunakan osmotic gradient– Sebagian besar nutrient diserap oleh yeyunum
Absorbsi usus halus
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– brush border ↑ permukaan absorbsi
– Na via Na channel dan Na-nutrient cotransporter
– Na dipompa ke darah oleh Na-K ATPase
Absorbsi usus halus
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2000 g in, 150 g out
Sirkulasi air
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• Digestive secretions are mostly water, with the average amounts indicated here. Note that only 100 ml are excreted in feces, so the mechanisms for water absorption are efficient (recall the kidneys’ primary role in water and osmotic homeostasis).
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2. Pencernaan & absorpsi karbohidrat ± 300g / hari – Polisakarida kompleks: 64% pati, 0.5%
glikogen– Disakarida: 26% sukrosa, 6.5% laktosa, 3%
MALTOSA– Hidrolisis lengkap 80% glucosa, 14%
fruktosa, 5% galaktosa kapiler
Absorbsi usus halus
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Carbohydrate absorption
• pancreatic juices cannot further hydrolyse oligosaccharides
• brush border oligosaccharidases• brush border lactase, sucrase-isomaltase and maltase
release monosaccharides (glucose, galactose and fructose)
• glucose and galactose taken up by SGLT1• fructose by GLUT5• all three transported via GLUT2 out into the portal
vein and to the liver
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In a normal diet, bulk is Carbs, 250-800 g (ex. Atkins)+ 125 g protein, +25-160 g fat.
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Fat absorption
• lipids- mainly triacylglycerols1 - large oil droplets (shearing forces in gut)2 - emulsified oil drops with bile salts
pancreatic lipase at oil-water interface3 - formation of micelles
micelles come to the absorptive surface of gut monoglycerides and free fatty acids are then absorbed
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4. inside cells resynthesis of triacylglycerols, cholesterol and phospholipids to chylomicrons
5. secreted into lacteal and to systemic circulation to adipose tissue where the chylomicron is stripped of its triacylglycerols and chylomicron remnant goes to liver - dietary cholesterol to liver. free fatty acids are also synthesised to prostaglandins (can act as local gut hormones)
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Product Absorption pathway
Carbohydrates Fru Facilitated diffusionGlu/Gal Active Transport / Sodium
Protein Amino Acids Active transport / SodiumProteins (except.) endo-exocytosis
(infants mainly)
Fat Free Fatty Acids DiffusionMonoglyc. Diffusion
Vitamins (fat) A, D, E, K Diffusion (via micelles)
Vitamins (water) B-12 Binds to Intrin. Factor. Endocytosis
Iron Active Transport then into ferritin
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kolon
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Sekresi:mukus yang diproduksi oleh sel goblet untuk
“pelumas” feses dan epitelHCO3
- , untuk menyeimbangkan asam produksi bakteri
kolon
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Absorbsi : air Osmosiselektrolitvitamin yg dihasilkan kerja bakteri:
Vitamin K: larut lemak, untuk pembekuan darahBiotin: larut air, penting untuk metabolisne glukosaVitamin B5: asam pantotenat: larut air, untuk
membuat hormon steroid & beberapa neurotransmiter• Bakteri mengubah bilirubin menjadi urobilinogen (diabsorpsi ke
sirkulasi, dibuang melalui urin) dan sterkobilinIn the large intestine, active transport of sodium, coupled with osmotic absorption of water, are the primary activities. Microbes here are active in the production of vitamin K.
kolon