dr. Nuraiza Meutia,M.

Biomed

Departemen Fisiologi FK USU

Aktivitas saluran cerna untuk menjalankan proses percernaan diatur oleh sistem saraf dan endokrin. Saluran cerna memiliki kemandirian untuk kedua sistem tersebut. Terjadi aktivitas terintegrasi antara kedua sistem mengatur aktivitas motorik dan sekretorik

Pada akhir perkuliahan, anda harus dapat : 1. Menjelaskan anatomi fungsional dinding GIT 2. Menjelaskan aktivitas utama GIT 3. Menjelaskan persarafan otonom yang mengatur GIT 4. Menjelaskan letak dan fungsi pleksus saraf di GIT 5. Menyebutkan nama dan efek neurotransmitter yang bekerja di ENS 6. Menjelaskan peran hormon dalam kontrol GIT (nama hormon, sumber, target dan efek) 7. Menjelaskan proses integrasi sistem saraf dan endokrin di GIT 8. Menjelaskan perbedaan refleks lokal dan refleks sentral dalam regulasi kerja GIT 9. Menjelaskan aktivitas listrik pada otot polos GIT 10. Menjelaskan mekanisme kontraksi dan jenis motilitas GIT 11. Menjelaskan contoh-contoh refleks GI 12. Menjelaskan regulasi aktivitas lambung, usus halus, usus besar, pankreas dan kandung empedu.

Struktur Dinding GIT

Aktivitas GIT :

Motilitas Sekresi Digesti Absorbsi

Fungsi sistem regulasi di GIT :

Mengatur aktivitas motilitas dan sekresi Mengatur aliran darah ke GIT Menerima dan menyampaikan informasi melalui neuron sensori (aferen) , dari reseptor-reseptor yang menerima stimulus mekanikal, thermal, osmotik dan kimiawi.

GIT NEURAL CONTROL

Aktivitas GIT diatur oleh sistem Saraf Otonom

Terdiri dari : - Divisi parasimpatetik - Divisi simpatetik - Enteric Nervous System (ENS)

Parasimpatetik

N. Vagus & N.pelvik Neuron preganglionik panjang; postganglionik pendek, bersinaps dengan neuron ENS Stimulasi eksitasi aktivitas ENS Mengandung serat sensori aferen (80 %) N.Vagus bersinaps ke neuron ENS di esophagus, lambung,usus halus, sebagian kolon, kandung empedu, & pankreas N.Pelvik bersinaps dengan ENS di usus besar Neurotransmitter : Ach

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Parasympathetic Nervous System Craniosacral

 Simpatetik

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Serat simpatetik ke GIT berasal dari medula spinalis segmen T-5 sampai L2. Neurotransmitter : norepinefrin Aktivitas simpatetik inhibisi motilitas dan sekresi GIT, konstriksi sfinkter dan pembuluh darah.

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Sympathetic Nervous System Thoracolumbar

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Enteric Nervous System

Enteric Nervous System (ENS) terdapat di seluruh dinding GIT, mulai esophagus sampai anus. Terbentuk dari 100 juta neuron (mengimbangi spinal cord). Memiliki 3 jenis neuron : sensori, motorik, & interneuron ENS tersusun atas 2 pleksus utama : (1) Myenteric plexus atau Auerbach's Plexus: berada di antara lapisan otot sirkular dan longitudinal (outer plexus). Fungsi : mengontrol motilitas GIT (2) Submucosal Plexus atau Meissner's plexus : berada di lapisan submukosa (inner plexus). Fungsi : mengatur sekresi dan aliran darah lokal, sensing perubahan lumen, dan gerak pelipatan mukosa.

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ENS dapat berfungsi secara mandiri, terlepas dari pengaturan sistem simpatetik dan parasimpatetik. Meskipun, persarafan ekstrinsik dapat sangat mempengaruhi ENS, menyebabkan inhibisi atau eksitasi fungsi GIT. Ujung saraf sensori mengirimkan serat aferen ke kedua pleksus ENS, dan juga ke : (1) ganglia prevertebral sistem simpatetik, (2) spinal cord, dan (3) nervus vagus menuju batang otak. Informasi sensorik dapat menimbulkan refleks lokal dan sentral

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Figure 62-4; Guyton & Hall

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Neurotransmitters and Neuromodulators in the ENS

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GIT HORMONAL CONTROL

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GIT merupakan kelenjar endokrin terbesar Hormon dihasilkan oleh sel enteroendokrin yang tersebar di antara sel-sel epitel mukosa lambung dan usus Enteric Endocrine System.
Sekresi hormon terjadi akibat stimuli tertentu, dan berhenti bila stimuli lenyap. Sel-sel GIT menghasilkan regulator peptida, yang berfungsi secara parakrin atau sebagai Nts, untuk mempengaruhi motilitas, aliran darah, dan pertumbuhan mukosa GIT.

GIT Hormones
HORMONE

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ORIGIN
G cells of the stomach

STIMULUS

ACTIONS

Gastrin

Small peptides and Gastric H+ secretion amino acids Stimulates growth of gastric mucosa Distention of the stomach Vagal stimulation (GRP) Small peptides and amino acids Fatty acids Pancreatic enzyme secretion Pancreatic HCO3- secretion Stimulates contraction of the gallbladder and relaxation of the sphincter of Oddi Stimulates growth of the exocrine pancreas and gallbladder Inhibits gastric emptying Pancreatic HCO3- secretion Biliary HCO3- secretion Gastric H+ secretion Inhibits trophic effect of gastrin on gastric mucosa Insulin secretion from pancreatic cells Gastric H+ secretion Stimulates: Gastric motility Intestinal motility

I cells of the duodenum and jejunum

Cholecystokinin (CCK)

S cells of the duodenum

Secretin

H+ in the duodenum Fatty acids in the duodenum

Glucose-Dependent K cells of the Duodenum Insulinotropic Peptide and jejunum (GIP) Motilin
M cells of the duodenum and jejunum

Fatty acids Amino acids Oral glucose Fat Acid Nerve

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GIT NEURAL HORMONAL CONTROL INTEGRATION

Nervous and hormonal influences do not function independently - Neural activity release of hormones - Hormones neural activity - Simultaneous effects

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3 tipe refleks GI : 1. Refleks yang terintegrasi seluruhnya di dinding GIT (ENS): mengatur sekresi dan motilitas secara lokal. 2. Refleks dari GIT ke ganglia prevertebral simpatetik kembali ke GIT. Sehingga respon terjadi di bagian lain GIT. Misal : r.gastrokolik, r.enterogastrik, & r.kolonoileal. 3. Refleks dari GIT ke spinal cord atau batang otak kembali ke GIT. Misalnya : (1) refleks dari lambung & duodenum ke Bt.otak, kembali melalui N.Vagus untuk mengatur aktivitas sekresi dan motorik lambung. (2)refleks nyeri yang mengakibatkan inhibisi GIT.(3)refleks defekasi.

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Nerves Reflex or Hormone secretion

Regulasi Aliran Darah ke GIT

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Vasodilator : CCK, Secretin, Gastrin, VIP; kinin(kallidin & bradykinin) Penurunan konsentrasi oksigen peningkatan aliran darah 50-100 % Pengaruh persarafan otonom :

Stimulation of the Parasympathetic nerves going to the stomach and lower colon increases local blood flow at the same time that it increases glandular secretion. Sympathetic stimulation, by contrast, has a direct effect on essentially all the gastrointestinal tract to cause intense vasoconstriction of the arterioles with greatly decreased blood flow. But the local metabolic vasodilator mechanisms override the sympathetic vasoconstiction effects, returning the normal blood flow to GI muscle and glands...autoregulatory escape

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Stres atau cemas dapat menginduksi : inhibisi aktivitas saluran cerna bagian atas - dan stimulasi fungsi motorik saluran cerna bagian bawah
Disebabkan pengaruh corticotropin-releasing factor (CRF) endogen terhadap reseptor CRF di sistem saraf pusat. Interaksi CRF pada reseptor CRF-2 menyebabkan inhibisi pengosongan lambung . Sedangkan reseptor CRF-1 berperan dalam menghasilkan respon peningkatan motilitas kolon saat stres.

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Aktivitas Listrik pada Otot polos GIT

Di sepanjang otot polos GIT terjadi fluktuasi potensial membran sepanjang waktu. Perubahan potensial ini menyebabkan otot polos dapat berkontraksi. Aktivitas listrik ini 2 jenis : (a) slow waves (b) spikes.

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a. Slow Waves Bukan potensial aksi, fluktuasi depolarisasi dan repolarisasi . Amplitudo 5-15 mV Frekuensi berbeda di berbagai bagian GIT : lambung 3 x/mnt ; duodenum 12 x/mnt; ileum terminal 8-9 x/mnt. Berperan untuk mensinkronkan irama kontraksi di sepanjangOrigin GIT. of slow waves. They may originate in the interstitial cells of Cajal (the GI pacemaker), which are abundant in the myenteric plexues. These interstitial cells form a network with each other and are interposed between the smooth muscle layers, with synaptic-like contacts to smooth muscle cells.

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Source of Slow Waves in GIT Muscles

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b. Spike Potential

Apabila pada suatu tempat, potensial membran istirahat

meningkat, maka slow wave dapat mencetuskan potensial aksi (spike potential) kontraksi otot. Faktor yang dapat mendepolarisasi membran : Peregangan otot Ach Stimulasi parasimpatetik Stimulasi hormonal Faktor yang meng-hiperpolarisasi membran : Norepinephrine Stimulasi simpatetik

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Figure 62-3; Guyton & Hall

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Peristalsis Penjalaran gelombang mendorong bolus Segmentasi Gerakan mencampur dan mengaduk bolus.

Mass movements

Peristaltik haustra

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Relaxation Reflexes
Gastric Reservoir
The main functions of the upper part of the stomach (Reservoir part ):
To maintain a continuous compression To accommodate the received food without significant gastric wall distention or pressure (Storage of food)

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1. 2.

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Gastric secretion is controlled by both neural and hormonal mechanisms Under normal conditions the gastric mucosa creates as much as 3 liters of gastric juice every day Gastric juice is an acid solution that has the potential to dissolve nails

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Nervous control is regulated by long (vagus nerve mediated) and short (local enteric) nerve reflexes When the vagus nerves actively stimulate the stomach, secretory activity of virtually all of its glands increase The sympathetic nerves depress secretory activity

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Hormonal control of gastric secretion is largely from the presence of gastrin Gastrin stimulates the secretion of both enzymes and HCL in the stomach Hormones produced by the small intestine are largely gastrin antagonists

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Stimuli acting at three distinct sites, the head, stomach, and small intestine, provoke or inhibit gastric secretory activity Accordingly the three phases are called cephalic, gastric, and intestinal phases However, the effector site is the stomach in all cases and once initiated, one or all threephases may be occurring at the same time

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The cephalic reflex phase of gastric secretion occurs before food enters the stomach It is triggered by the aroma, taste, sight, or though of food During this phase the brain gets the stomach ready for food

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Inputs from activated olfactory receptors and taste buds are relayed to the hypothalamus which in turn stimulates the vagal nuclei of the medulla oblongata, causing motor impulses to be transmitted via the vagus nerves to the parasympathetic nerve ganglia Eneteric ganglionic neurons in turn stimulate the stomach glands

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The enhanced secretory activity that results when we see or think of food is a conditioned reflex and occurs only when we like or want the food If we are depressed or have no appetite, this part of the cephalic reflex is suppressed

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Once food reaches the stomach, local neural and hormonal mechanisms initiate the gastric phase This phase provides about two-thirds of the gastric juice released The most important stimuli are distension, peptids, and low acidity

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Stomach distension activates stretch receptors and initiates both local (myentertic) reflexes and the long vagovagal reflexes In vagovagal reflex, impulses travel to the medulla and then back to the stomach via vagal fibers Both types of reflexes lead to acetylcholine (ACH) release, which in turn stimulates the output of more gastric juice by cells

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Figure 24.15b

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Though neural influences initiated by stomach distension are important, the hormone gastrin probably plays a greater role in stimulating stomach gland secretion during the gastric phase Chemical stimuli provided by partially digested proteins (peptids)caffine (colas, coffee) and rising pH directly active gastrin secreting entoendocrine cells called G cells

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Although gastrin also stimulates the release of enzymes, its main target is the HCL secreting parietal cells, which it prods to spew out even more HCL Highly acidic (pH below 2) gastric contents inhibit gastrin secretion

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When protein foods are in the stomach, the pH of the gastric contents generally rises because proteins act as buffers to tie up H+ The rise in pH stimulates gastrin and subsequently HCL release, which in turn provides the acidic conditions needed for protein digestion

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The more protein in the meal, the greater the amount of gastrin and HCL released As proteins are digested, the gastric contents gradually become more acidic, which again inhibits the gastrin secreting cells This negative feedback mechanism helps maintain optimal pH and working conditions for the gastric enzymes

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G cells are also activated by the neural reflexes already described Emotional upsets, fear, anxiety, or anything that triggers the fight-or-flight response inhibits gastric secretion because (during such times) the sympathetic division overrides parasympathetic controls of digestion

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The control of the HCL secreting parietal cells is unique and multifaceted Basically, HCL secretion is stimulated by three chemicals, all of which work through second-messenger systems Ach released by parasympathetic nerve fibers and gastrin secreted by G cells

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Ach released by para-sympathetic nerve fibers and gastrin secreted by G cells bring about their effects by increasing intercellular Ca++ levels

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Histamine released by mucosal cells called histaminocyte s acts through cyclic AMP (cAMP)

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As hydrogen ions are secreted, chloride ions (Cl-) are also pumped into the lumen to maintain an electrical balance in the stomach The Cl- is obtained from blood plasma, while the H+ appears to come from a breakdown of carbonic acid formed by the combination of carbon dioxide and water and within the parietal cells

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CO2 + H2O H2CO3 H+ + HCO3As H+ is pumped from the cell and HCO3- is ejected through the basal cell membrane into the capillary blood

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The result of ejection of the bicarbonate ion into the capillary blood is that blood draining from the stomach is more alkaline than the blood serving it The phenomenon is called the alkaline tide

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The intestinal phase of gastric secretion has two components

One excitatory One inhibitory

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The excitatory aspect is set into motion as partially digested food begins to fill the initial part (duodenum) of the small intestine This stimulates intestinal mucosal cells to release a hormone that encourages the gastric glands to continue their secretory activity

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The effects of this hormone imitate those of gastrin, so it has been named intestinal (enteric) gastrin However, intestinal mechanisms stimulate gastrin secretion only briefly As the intestine distends with chyme containing large amounts of H+, fats, partially digested proteins, and irritating substances, the inhibitatory component is triggered in the form of the enterogastric reflex

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The enterogastric reflex is actually a trio of reflexes that

Inhibit the vagal nuclei in the medulla Inhibit local reflexes Activate sympathetic fibers that cause the pyloric sphincter to tighten and prevent further food entry into the small intestine

As a result, gastric secretory activity declines

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These inhibitions on gastric activity product the small intestine to harm due to excessive acidity and match the small intestines processing abilities to the amount of chyme entering it at a given time

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In addition, the factors just named trigger the release of several intestinal hormones collectively called enterogastrones which include Secretin Cholecystokinin (CCK) Vasoactive intestinal peptide (VIP) Gastric inhibitory peptide (GIP) All of these hormones inhibit gastric secretion when the stomach is very active

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Figure 24.15c

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Secretion of pancreatic juice is regulated both by local hormones and by the parasympathetic nervous system

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Both hormones act on the pancreas, but secretin targets the duct cells, prompting their release of watery bicarbonate-rich pancreatic juice, Whereas CCK stimulates the acini to release enzyme-rich pancreatic juice Vagal stimulation causes release of pancreatic juice primarily during the cephalic and gastric phases of gastric secretion

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Normally, the amount of HCL produced in the stomach is exactly balanced by the amount of bicarbonate (HCO3) actively secreted by the pancreas HCO3 is secreted into the pancreatic juice, and H+ enters the blood Consequently, the pH of venous blood returning to the heart remains relatively unchanged because alkaline blood draining from the stomach is neutralized by the acidic blood draining the pancreas

Regulation of Pancreatic Secretions

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Secretin

Acidity in intestines induces Secretin release Secretin releases pancreatic Sodium Bicarbonate (HCO3-) Fats and proteins induce CCK release CCK releases pancreatic digestive enzymes

CCK

GIP

Fatty acids and sugar causes induce GIP release GIP induces insulin release

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Although the liver makes bile continuously bile does not usually enter the small intestine until the gallbladder contract The major stimulus for gallbladder contraction is the intestinal hormone cholecystokinin (CCK) CCK is released to the blood when acidic, fatty chyme enters the duodenum

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Besides causing the gallbladder to contract, CCk has two other important effects It stimulates secreation of pancreatic juice It relaxes the hepatppancreatic sphincter so that bile and pancreatic juice can enter the duodenum Parasympathetic impulses delivered by the vagus nerves have a minor impact on stimulating gallbladder contraction

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The rectum is usually empty, but when feces are forced into it by mass movements, stretching of the rectal walls initiates the defecation reflex

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This is a spinal cord mediated reflex that causes the walls of the sigmoid colon and the rectum to contract and the anal sphincters to relax

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Distension or stretch of the rectal walls triggers a depolarization of sensory (afferent) fibers which synapse with the spinal cord

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Parasympathetic motor (efferent) fibers, in turn, stimulate contraction of the rectal walls and relaxation of the internal anal sphincter

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If it is convenient to defecate, voluntary signals stimulate the relaxation of the external anal sphincter

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As feces are forced into the anal canal, impulses reach the brain allowing us to decide whether the external(voluntary) anal sphincter should remain open or closed If defection is delayed, the reflex contractions end within a few seconds and the walls relax With the next mass movement, the reflex is initiated again and again until one chooses to defecate