FISIOLOGI SISTEM PENCERNAAN

Sekresi & Absorpsi

dr. Mustofa, M.Sc LAB. FISIOLOGI FKIK UNSOED

Learning Objective
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

Outline
1. AN OVERVIEW OF THE STRUCTURE AND FUNCTION 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

Heart
Liver Stomach
ABSORPTION Vitamin Karbonhidrat Protein C, D, B2, B12, dll enzim asam, dll Mineral Lipid SECRETION

Mouth

Hepatic Portal vein

Anus
Vitamin K Air, Elektrolit
FLATUS Pembentukan Gas CO2, Metana, dll

Rectum

Food and water

Salivary glands

FECES
Aktifitas BAKTERI

Small intestine

Digestion
MOTILITY

Large intestine

Adapted by:
Dr. Andreanyta Meliala, PhD.

Functions of the GI Tract (Continued)

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.

nutrients

GIT Regulation

GIT Regulation

Composition and function of saliva

Major salivary components

Histatins
Statherins Lysozyme

Proline-rich proteins Carbonic anhydrases

Amylases Peroxidases Lactoferrin Mucin 2 (MG2) sIgA Mucin 1 (MG1) 1 10 100 Size (kDa) 1000 10000

Multifunctionality
Cystatins, Histatins, Mucins, Peroxidases Carbonic anhydrases, Histatins AntiBacterial Buffering Amylases, Mucins, Lipase Digestion Salivary Families

Cystatins, Mucins

AntiViral

AntiFungal
Histatins Tissue Coating

Mineralization Lubrication &Viscoelasticity

Cystatins, Histatins, Prolinerich proteins, Statherins

Cystatins, Mucins, Proline-rich proteins, Statherins

Mucins, Statherins
adapted 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 (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

Amylases

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

glucose)

Lingual Lipase
Secreted by von Ebners 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

 Muramidase activity (lysis of peptidoglycan layer) Cationic-dependent activation of bacterial autolysins

disrupts membranes

Other anti-microbial activities of LZ

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

Major GIT hormone

CCK : Cholecytokinin GIP: Gluc-dep. InsulinoTropic peptide

Each hormone:
Feedback Multiple Targets

GIT Regulation
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.

Intestinal Phase
1. Chyme in the duodenum with
a pH less than 2 or containing fat digestion products (lipids) inhibits gastric secretions by three mechanisms. Medulla oblongata Vagus nerves

2. Sensory vagal action potentials

to the medulla oblongata (green arrow) inhibit motor action potentials from the medulla oblongata (pink arrow). Vagus nerves

Decreased gastric secretions

2 1
pH<2 or lipids

Local reflexes

3. Local reflexes inhibit gastric

secretion (orange arrows).

4. Secretin, gastric inhibitory

polypeptide, and cholecystokinin produced by the duodenum (brown arrows) inhibit gastric secretions in the stomach.

Secretin, gastric inhibitory peptide, cholecystokinin

4
Circulation

Stomach
Stomach
(continued)

Insert fig. 18.5

Gastric Glands
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.

HCl production
Parietal cells secrete H+ into gastric lumen by primary active transport, through H+/ K+ ATPase pump. Parietal cells basolateral membrane takes in Cl- against its electrochemical gradient, by coupling its transport with HC03-.

HCl Production
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 Function
Makes gastric juice very acidic.
Denatures ingested proteins (alter tertiary structure) so become more digestible.

Insert fig. 18.9

Activates pepsinogen to pepsin.

Pepsin is more active at pH of 2.0.

Digestion and Absorption in the Stomach

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.

Protective Mechanisms of 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.

Usus halus

Getah pencernaan di Usus halus

Getah Pankreas Getah Empedu Getah usus halus

Getah Usus halus

1,8 L /hari 1. 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 vili menghasilkan: amilase, enterokinase, lipase, peptidase, disakaridase, yang tidak dikeluarkan ke lumen namun akan memecah lemak, protein, karbohidrat begitu absorbsi dimulai

Getah Pankreas
1500 cc / hari Mengandung: bikarbonat, elektrolit: Na,K,Cl,enzim Mempunyai 2 fungsi:
1. Endokrin: sel endokrin sekresi insulin & glukagon

2. 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

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

Pengaturan sekresi

Enzim pankreatik
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

Aktifasi enzimatik

FOOD

Fase sekresi pankreas

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)

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

Absorbsi usus halus

Pengiriman nutrient dari saluran cerna ke sirkulasi, terutama tjd di usus halus permukaan yang luas. Absopsi efisien bila:
1. 2. 3. 4. Bentuk hasil pencernaan baik Permukaan absorpsi adekuat Kecepatan/ waktu transit nutrient di usus halus 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

Sirkulasi air

2000 g in, 150 g out

Absorbsi usus halus

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

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 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

4. 5.

inside cells resynthesis of triacylglycerols, cholesterol and phospholipids to chylomicrons 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
Carbohydrates Fru Glu/Gal

Absorption pathway
Facilitated diffusion Active Transport / Sodium

Protein

Amino Acids Proteins (except.)

Active transport / Sodium endo-exocytosis (infants mainly)

Diffusion Diffusion Diffusion (via micelles) Binds to Intrin. Factor. Endocytosis Active Transport then into ferritin

Fat

Free Fatty Acids Monoglyc. A, D, E, K

Vitamins (fat)

Vitamins (water) B-12

Iron

kolon

kolon
Sekresi:
mukus yang diproduksi oleh sel goblet untuk pelumas feses dan epitel HCO3- , untuk menyeimbangkan asam produksi bakteri

kolon
Absorbsi :
air Osmosis elektrolit vitamin yg dihasilkan kerja bakteri:
Vitamin K: larut lemak, untuk pembekuan darah Biotin: 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