Fisiologi Sekresi&Absopsi-blok Digest13 Edit

dr. Mustofa, M.ScLAB. FISIOLOGI FKIK UNSOED

FISIOLOGI SISTEM PENCERNAANSekresi & Absorpsi

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

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

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

• 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.

• 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)

• Absorption:– Process of the passage of digestion (chemical

subunits) into the blood or lymph.

Functions of the GI Tract (Continued)

nutrients

• 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.

GIT Regulation

• 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.

GIT Regulation

Johnson Chap. 34-35Johnson Chap. 34-35

Apical MembraneApical Membrane


(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

Johnson Chap. 34-35Johnson Chap. 34-35Johnson Chap. 34-35Johnson Chap. 34-35

Basolateral MembraneBasolateral Membrane


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


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


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++


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

Secretion of NaSecretion of Na++, K, K++, and Cl, and Cl--

Salivary Acinar CellSalivary Acinar Cell


NaNa NaNaNaNa++KK++ClCl-- KK++

ATPATP

NaNa++

KK++ClCl--

KK++

LumenLumen

Serosal surfaceSerosal surface stimulistimuli

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


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


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


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++

Intestinal Secretory CellIntestinal Secretory Cell


NaNa NaNaNaNa++KK++ClCl-- KK++

ATPATP

NaNa++

ClCl--ClCl--

KK++

LumenLumen

Serosal surfaceSerosal surface

stimulistimuliKK++

ATP

ATP

NaNa++

Composition and function of saliva

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)

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

Mucin Functions• Tissue Coating

– Protective coating about hard and soft tissues– Concentrates anti-microbial molecules at mucosal

interface• Lubrication

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

Amylases

• Hydrolyzes (1-4) bonds of starches• Maltose is the major end-product (20% is

glucose)

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

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

Proline-rich Proteins (PRPs)

Inhibit calcium phosphate crystal growth

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

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

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

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

Histatins

• A group of small histidine-rich proteins• Potent inhibitors of Candida albicans

growth

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

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

Stomach (continued)

Insert fig. 18.5

Stomach

• 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

Gastric Secretion

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

• 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

• 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

• 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

• 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

Usus halus

• Getah Pankreas• Getah Empedu • Getah usus halus

Getah pencernaan di Usus halus

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

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

• 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

• 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

Pengaturan sekresi

• 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.

Pengaturan sekresi

• 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).

• 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

F O O D

Aktifasi enzimatik

• 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.

• 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

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

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

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

– brush border ↑ permukaan absorbsi

– Na via Na channel dan Na-nutrient cotransporter

– Na dipompa ke darah oleh Na-K ATPase

Absorbsi usus halus

2000 g in, 150 g out

Sirkulasi air

• 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).

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

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

In a normal diet, bulk is Carbs, 250-800 g (ex. Atkins)+ 125 g protein, +25-160 g fat.

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

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)

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

kolon

Sekresi:mukus yang diproduksi oleh sel goblet untuk

“pelumas” feses dan epitelHCO3

- , untuk menyeimbangkan asam produksi bakteri

kolon

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

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Fisiologi Sekresi&Absopsi-blok Digest13 Edit