Fisiologi Sekresi&Absopsi-blok Digest12

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    dr. Mustofa, M.ScLAB. FISIOLOGI FKIK UNSOED

    FISIOLOGI SISTEMPENCERNAAN

    Sekresi & 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 intestinalsecretions, and discuss the regulation of

    secretory activities.

    4. Describe the secretion and regulation of theaccessory digestive organs.

    5. Describe the intestinal absorptive processes

    Learning Objective

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    1. AN OVERVIEW OF THE STRUCTURE ANDFUNCTION OF THE DIGESTIVE TRACT

    2. ORAL CAVITY AND ASSOCIATED GLANDULAR

    ORGANS

    3. THE STOMACH

    4. THE SMALL INTESTINE AND ASSOCIATED

    GLANDULAR ORGANS

    5. THE LARGE INTESTINE

    Outline

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    Heart

    Liver

    ABSORPTION

    SECRETION

    Large intestine

    Rectum

    AnusMouth

    Food andwater

    StomachHepatic

    Portal vein

    Small intestineSalivary glands

    MOTILIT

    Y

    FECES

    enzim asam, dll

    VitaminC, D, B2, B12, dll

    ProteinMineral

    Karbonhidrat

    Lipid

    Adapted by:Dr. Andreanyta Meliala, PhD.

    Vitamin KAir, Elektrolit

    AktifitasBAKTERI

    PembentukanGas CO2, Metana, dll

    FLATUS

    Digestion

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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 theGI tract.

    Endocrine: Stomach and small intestine secrete hormones to help

    regulate the GI system.

    Gastrin, secretin, CCK, GIP, GLP-1, guanylin, VIP, andsomatostatin.

    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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    GIT Regulation

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    GIT Regulation

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    Composition and function of

    saliva

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    Major salivary components

    Mucin 1 (MG1)

    sIgA

    Mucin 2 (MG2)

    Lactoferrin

    Peroxidases

    AmylasesCarbonic anhydrases

    Proline-rich proteins

    Lysozyme

    StatherinsHistatins

    1 10 100 1000 10000

    Size (kDa)

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    Multifunctionality

    Salivary

    Families

    Anti-

    BacterialBuffering

    Digestion

    Mineral-

    ization

    Lubricat-

    ion &Visco-

    elasticity

    Tissue

    Coating

    Anti-

    Fungal

    Anti-

    Viral

    Carbonic anhydrases,

    Histatins

    Amylases,

    Mucins, Lipase

    Cystatins,

    Histatins, Proline-

    rich proteins,

    Statherins

    Mucins, Statherins

    Cystatins, Mucins,

    Proline-rich proteins, Statherins

    Histatins

    Cystatins,

    Mucins

    Cystatins,

    Histatins, Mucins,

    Peroxidases

    adapted 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 (contd)

    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 Ebners glands oftongue

    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 enamelare 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 producingenterochelins.

    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) bondbetween N-acetylmuramic acid and N-acetylglucosamine

    in the peptidoglycan layer.

    Gram negative bacteria generally more resistant thangram 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 acidproduction

    De-chaining of streptococci

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    Histatins

    A group of small histidine-rich proteins

    Potent inhibitors ofCandida 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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    CCK :

    Cholecytokinin

    GIP:

    Gluc-dep. Insulino-

    Tropic peptide

    Each hormone:

    Feedback

    Multiple Targets

    Major GIT hormone

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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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    1.Chyme in the duodenum witha pH less than 2 or containingfat digestion products (lipids)

    inhibits gastric secretions by

    three mechanisms.

    2.Sensory vagal action potentials

    to the medulla oblongata(green arrow) inhibit motor

    action potentials from the

    medulla oblongata (pink arrow).

    3.Local reflexes inhibit gastricsecretion (orange arrow s).

    4.Secretin, gastric inhibitorypolypeptide, and cholecystokinin

    produced by the duodenum

    (brown arrows) inhibit gastric

    secretions in the stomach.

    Intestinal Phase

    Secretin, gastric inhibitory

    peptide, cholecystokininCirculation

    pH

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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.

    Stomach: ghrelin.

    Gastric Glands

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    HCl Production Parietal cells

    secrete H+ intogastric lumen byprimary activetransport, throughH+/ K+ATPasepump.

    Parietal cellsbasolateralmembrane takes

    in Cl-

    against itselectrochemicalgradient, bycoupling itstransport withHC03

    -.

    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 gastricjuice very acidic. Denatures

    ingested proteins

    (alter tertiarystructure) sobecome moredigestible.

    Activates

    pepsinogen topepsin. Pepsin is more

    active at pH of 2.0.

    Insert fig. 18.9

    HCl Function

    Digestion and Absorption in the

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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 (entireepithelium replaced in 3 days).

    Prostaglandins inhibit gastric secretions.

    Protective Mechanisms of Stomach

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    Usus halus

    Getah pencernaan di Usus

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    Getah Pankreas

    Getah Empedu

    Getah usus halus

    Getah pencernaan di Usushalus

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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 sp7-8)

    2. Kripte Lieberkuhn

    Produksi enzim, cairan isotonik dan alkalin

    Getah Usus halus

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    3. Enterosit vili

    menghasilkan: 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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    Pengaturan sekresi

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    digestive enzymes secreted as inactive precursors(zymogens) to prevent autodigestion

    important proteolytic enzymes are t ryps in,chymotryps inandcarboxypept idases

    other enzymes are-

    panc reatic l ipase panc reatic amylase

    t ryps inogenis activated byenteropeptidasewhichis secreted by intestinal mucosa in response to

    chyme trypsin then activates the other proenzymes

    t ryps ininh ib i torsecreted to delay activation oftrypsinogen

    Enzim pankreatik

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    F O O D

    Aktifasi enzimatik

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    cephal ic phase~15% mainly causes secretion ofenzymes into the acini - vagus mediated

    gastr ic phase~15% gastric distension by means of

    vago-vagal reflex evokes enzyme secretion

    gastrin release by antral lumen causing more enzymerelease

    intest inal phase~70% -pancreatic HCO3 secretion

    strongly stimulated when duodenal pH is acid - S

    cellssecrete secretin into the blood and thisstimluates pancreatic duct cells

    chyme also causes I cellsto release CCKwhich

    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 ofstomach secretion

    CCK (cholecystokinin) - secreted by duodenaland upper jejunal mucosa when food enters

    small intestine these 3 all stimulate production of digestive

    enzymes by the acini and act via IP3 to releaseintracellular Ca

    Secretin - same duodenal and upper jejunalmucosa but secretin acts via cAMP on the ductalcells to increase HCO3 secretion

    Ab b i h l

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    Pengiriman nutrientdari saluran cerna ke

    sirkulasi, terutama tjd di usus halus

    permukaan yang luas.

    Absopsi efisien bila:

    1. Bentuk hasil pencernaan baik

    2. Permukaan absorpsi adekuat

    3. Kecepatan/ waktu transit nutrientdi usus halus

    4. Kofaktor dan atau karier spesifik

    Absorbsi usus halus

    Ab b i h l

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    1. Absorbsi air dan elektrolit

    membranintestinalsangat permeabel

    terhadap air

    Air diserap menggunakan osmot ic gradient

    Sebagian besarnutrientdiserap oleh

    yeyunum

    Absorbsi usus halus

    Ab b i h l

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    brush border

    permukaan absorbsi Na via Na channeldan Na-nutrient

    cotransporter

    Na dipompa ke darah oleh Na-K ATPase

    Absorbsi usus halus

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    Ab b i h l

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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

    C b h d t b ti

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    Carbohydrate absorption

    pancreatic juices cannot further hydrolyse

    oligosaccharides brush borderoligosaccharidases

    brush border lactase, sucrase-isomaltase andmaltase release monosaccharides (glucose,galactose and fructose)

    glucose and galactose taken up by SGLT1 fructose by GLUT5

    all three transported via GLUT2 out into theportal 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 triacylglycerols

    1 - large oil droplets (shearing forces in gut)

    2 - emulsified oil drops with bile salts

    pancreatic lipase at oil-water interface

    3 - 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 diffusion

    Glu/Gal Active Transport / Sodium

    Protein Amino Acids Active transport / Sodium

    Proteins (except.) endo-exocytosis

    (infants mainly)

    Fat Free Fatty Acids Diffusion

    Monoglyc. 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

    kolon

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    kolon

    kolon

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    Sekresi:mukus yang diproduksi oleh sel goblet untuk

    pelumas feses dan epitel

    HCO3- , untuk menyeimbangkan asam produksi

    bakteri

    kolon

    kolon

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    Absorbsi :

    airOsmosis

    elektrolit

    vitamin yg dihasilkan kerja bakteri:

    Vitamin K: larut lemak, untuk pembekuan darahBiotin: larut air, penting untuk metabolisne glukosa

    Vitamin B5: asam pantotenat: larut air, untuk membuat

    hormon steroid & beberapa neurotransmiter

    Bakteri mengubah bilirubin menjadi urobilinogen

    (diabsorpsi ke sirkulasi, dibuang melalui urin) dan

    sterkobilin

    kolon