Basic Science D

151

Basic Science 4 IPD

Vani Marindani130112090058

BASIC SCIENCECARDIOLOGYHEART Location of the heart : bentuk cone# Besar : sebesar kepalan tangan, 12 cm x 9 cm x 6 cm , 250g pada wanita, 300g pada pria.# Terdapat di diafragma, dekat garis tengah thoracic cavity# Terletak di mediastinum : jaringan yg memanjang dari sternum ke vertebral column di antara paru2.# Sekitar 2/3 dari jantung terdapat di sebelah kiri dari midline# Titik akhir dari jantung : apex : directed anteriorly, inferiorly, & to the left# Broad Portion dari jantung : base : directed posteriorly, superiorly, & to the right. Berdasarkan Apex & Base, jantung memiliki beberapa surfaces dan borders# Surface :Anterior surface : deep to the sternum & ribsInferior surface : a. Part of the heart between the apex & right border b. Rest mostly on the diaphragm# Border : Right border : faces the right lung & extends from inferior surface to the baseLeft border : faces the left lung & extends from the base to the apex Pericardium : # Membran / selaput yg mengelilingi & melindungi jantung# Mempertahankan jantung di posisinya di mediastinum dengan tetap dapat bergerak untuk vigorous & kontraksi# Terdiri dari 2 bagian : 1. Superficial : fibrous pericardium : keras, tdk elastis, dense irreguler CTa. Menyerupai kantung yg menempel pada diafragmab. Its opening end berdifusi dgn CT dari pembuluh darah yg masuk & meninggalkan jantungc. Fungsi : mencegah overstreching jantung, untuk proteksi, mempertahankan jantung di mediastinum.2. Deeper : serous pericardium : tipis, membran yg lebih lembut, dan membentuk 2 lapisan mengelilingi jantunga. Parietal layer (outer) : berdifusi dgn fibrous pericardiumb. Visceral layer (inner) : melekat erat di permukaan jantung epicardiumc. Diantara parietal layer & viseral layer : Pericardial cavityd. Pericardial cavity mengandung pericardial fluid : slippery secretion of the pericardial cell that reduces friction between the membranes as the heart moves. Layers of The Heart Wall :Terdiri dari 3 lapisan : a. Epicardium (Visceral layer of the serous pericardium) : external layerComposed of mesothelium & delicate Cl- yg memberikan textur lembut, licin, thd permukaan paling luar dari jantung. b. Myocardium (middle layer) Cardiac muscle tissue Merupakan bagian terbesar dari jantung Untuk pumping actionc. Endocardium : selaput tipis endothelium yg terdapat di atas dari lapisan tipis CTFungsi : provides a smooth lining for the chambers of the heart, covers the valves (katup) of the heartBerkelanjutan dgn endothelium lining of the large blood vessel attached to the heart

Chambers of The Heart : 4 chambers2 Atria superior2 Ventricle : Inferior# Di permukaan anterior auricle (wrinkled pouchlike) Mirip telinga anjing Meningkatkan kapasitas dari atrium sehingga dapat menahan darah darah dalam volume yg besar# Sulci : Series og grooves Mengandung coronary blood vessels & variable amount of fat Setiap sulcus menandai external boundary di antara 2 ruangan di jantunga. Coronary Sulcus (deep) : 1. encircles most of the heart2. marks the boundary between superior atria & inferior ventriclesb. Anterior Interventricular Sulcus1. Shallow groove on the anterior surface of the heart2. Marks the boundary between the right & left ventriclesc. Posterior Interventricular Sulcus1. Marks the boundary between the ventricles on the posterior of the heart

RIGHT ATRIUM Menerima darah dari 5 vena 1. Vena Cava Superior2. Vena Cava Inferior3. Coronary Sinus4. Anterior cardiac vein5. Vena cordis minimae Posterior wall dari right atrium : smooth Anterior wall dari right atrium : rough adanya muscular ridges pectinate muscles extend from auricle Diantara right & left atrium interatrial septum : ada oval depression Fossa ovalis Fossa ovalis merupakan bekas / sisa dari Foramen Ovale : opening in the interatrial septum of the fetal heart that normally closes soon after birth Darah dari right atrium ke right ventricle melalui Tricuspid valuea. Consist of 3 leaflets or cuspsb. Composed of dense CT coveted by endocardium

RIGHT VENTRICLE Form most of the anterior surface of the heart Contain a series of ridges yg dibentuk oleh raised bundles of cardiac muscle fibers trabecuklae carnae untuk convey part of the conduction system Cusps of the tricuspid valve are connected to tendon like cords chordae tendinae connected to cone-shaped trabeculae carnae called papillary muscles Dipisahkan dengan left ventricle oleh interventricular septum Blood passes from the right ventricle through the polmunary valve ke pulmonary trunk : Right Pulmonary Arteries &Left Pulmonary Arteries

LEFT ATRIUM Form most of the base of the heart Menerima darah dari paru2 melalui Pulmonary Veinsa. Posterior wall : smoothb. Anterior wall : smooth, because pectinate muscle are confined to the auricle of the left atrium Blood passes from the left atrium into the left ventricle through bicuspid valve Mitral Refers to its resemblence (mirip) to the bishops miter, which is two shaped

LEFT VENTRICLE Forms apex of the heart Contain trabeculae carnae & chordae tendinae yg terikat pada cups di bicuspid valves to papillary muscles Blood passes from left ventricle through aortic valve ke ascending (largest artery in the body) aorta Beberapa bagian darah di aorta masuk ke coronary arteries (branch form the ascending aorta) & carry blood to the heart wall Remainder of the blood passes into the arch of the aorta & descending aorta sbgnya membawa darah ke seluruh tubuh ( Thoracic aorta & Abdominal aorta) During fetal life, ductus arteriousus shunts blood from the pulmonary trunk into aorta Ductus Arteriosus normally closes shortly after birth, leaving a remnant ligamentum arteriosum, which connects the arch of the aorta

Coronary Arteries a. Right & leftb. Bercabang dari ascending aorta & mensuplai darah O2 ke myocardium- Left Coronary Arterya. Passes inferior to the left auricleb. Divides into the anterior interventriculer & circlumflex branch- Right Coronary Arterya. Gives small atrial branches that the supply the right atriumb. Continues inferior to the right auriclec. Divides into the posterior interventricular & marginal branch - Anterior Interventricular Branch (Left Anterior descending)a. Memanjang di anterior interventricular sulcusb. Supplies oxygenated blood to the walls of both ventricles- Circlumflex Branch a. Terdapat di Coronary Sulcusb. Supplies oxygenated blood to the walls of the left ventricle & Left atrium- Posterior Interventricular Branch a. Posterior interventricular Sulcusb. Supplies the walls of the of the two ventricles with oxygenated- Right Marginal Brancha. In the Coronary Sulcusb. Carries oxygenated blood to the Myocardium of the right ventricle

CORONARY VEINS Great cardiac Veina. Anterior Interventricular Sulcusb. Drain the area of the heart supplied by the left coronary artery (Left & Right Ventricles and left atrium) Middle Cardiac Veina. Posterior interventricular sulcusb. Drain the area of the heart supplied by the posterior interventricular branch of the right coronary artery (left &right ventricles) Small Cardiac vein a. In the Coronary Sulcusb. Drain the right atrium & right ventricle Anterior Cardiac Veina. Drain the right ventricle & open directly into the right atrium

Action Potensial & Contraction Of Contractile Fibers Contactile Fibers have a stable resting membrane potensial ( -90 mV)1. ThresholdDepolarization

Voltage gated fast Na+ channels terbuka

Na+ masuk ke sitosol ( krn sitosol contractile fiber lebih (-) daripada interstitial fluid & Na- > di interstitial fluid)

Menghasilkan rapid depolarization

Dalam beberapa millisecond, Na+ channels tertutup, inflow Na+ menurun 2. Plateau maintain depolarization

Voltage gated slow Ca2+ channels di Sarcolemmaterbuka

Ca2+ masuk ke sitosol

Kenaikan konsentrasi Ca2+ merangsang kontraksi

Beberapa saat sebelum plateau phase, beberapa voltage gated K+ channel terbuka & K+ keluar dari kontractile fiber Plateau phase ditopang adanya balance antara Ca2+ dan K+ Plateau phase : 0,25 s Membran potensial contractile fiber close to 0 mV3. Voltage gated K+ channel terbukaRepolarization

K+ keluar, memperbaiki resting membran potensial ke 90 mV

Ca2+ channels di SR & Sarcolema tertutup

Cardiac Conduction System Source of rhytmical activity network of specialized cardiac muscle fibers (autorhyritmic fibers) Autorhyritmic fibers generate action potensial that triggers heart contraction mempunyai 2 fungsi : a. Pace maker mengatur rhythm dari electrical excitation yg mengakibatkan kontraksi jantungb. Membentuk conduction system jaringan dari specialized cardiac muscle fibers that provide a path for each cycle of cardiac excitation to progress through the heart

CONDUCTION SYSTEM 1. Jantung tereksitasi pada Sinoatrial Node (SA) yg berlokasi di dinding atrium kanan sebelah bawah dari opening vena cava superior, SA node tidak mempunyai resting potensial yg stabil. SA Node mengulang depolarisasi untuk mencapai threshold dengan spontan pacemaker potensial, jika mencapai threshold maka akan membangkitkan potensial aksi yang berpropagasi menuju kedua atrium melalui gap junction di intercalated discs di atrial muscle fiber atrium berkontraksi.2. Kemudian potensial aksi menacapai Atrioventricular (AV) node berlokasi di interatrial septum, bagian depan dari opening coronary sinus.3. Potensial aksi masuk ke atrioventricular bundle (bundle og His) tempat ini merupakan suatu tempat dimana potensial aksi dapat berkonduksi dari atria ke ventricle. 4. Potensial aksi kemudian masuk ke right & left bundle branches memanjang dari interventricular septum ke apex. 5. Large diameter purkinje fiber mengkonduksi potensial aksi dari apex naik ke remainder of the ventricular myocardium ventricle kontraksi darah masuk ke semilunar valves Autorhytmic fiber in the SA Node would initiate an action potensial about every 0,6 second 100 times / minute.

NERVOUS SYSTEM CONTROL of THE HEART Simpatis Dan ParasimpatisCompetitive situations heart rate may climb Proprioceptor ( monitor limb & muscle ) send nerve impulses at an increased frequency to cucera. Propioceptor input mayor stimulus for the quick rise in heart rate that occurs at onset of physical activity Chemoreceptor monitor chemical changes in the blood Baroreseptor monitor the stretching of mayor arteries & vein caused by pressure of the blood flowa. Baroreseptor yg berlokasi di arch of aorta & carotid arteries detect changes in blood pressure & provide input to cardiovasculer center when it change

Symphatetic Neuron extend from medula oblongata into the spinal cord Di Thoracic region dari spinal cord, cardiac accelerator nerve keluar menuju SA dan AV node & sebagian besar Myocardium.

Pumping Action of the heart (triggered by chest pain)Cardiac output : volume darah yang dikeluarkan ventrikel kiri (atau kanan) ke aorta (atau pulmonary trunk) setiap menitCardiac Output = Stroke Volume X Heart rateStroke Volume : volume darah yg dikeluarkan sekali kontraksiFaktor2 yg meregulasi stroke volume dan memastikan ventrikel kiri dan kanan memompa darah dgn jml yg sama:1. Preload : effect of stretchingBesarnya stretching dr otot jantung mempengaruhi besarnya kontraksi. Preload sebading dgn end-diastolic volume (EDV), shg smk besar EDV semakin kuat kontraksi berikutnya2. Contractility : kekuatan dari kontraksi setiap preload3. Afterload : tekanan sebelum katup semilunar terbukaMakin besar afterload makin kecil stroke volume

Normal Myocardial Contraction & RelaxationContractile cells : myocyte myofiber (group of myocytes), held by surrounding collagenMyocyte sarcolemma : plasma membrane invaginate to form T-tubule Sarcoplasmic reticulum ryanodine receptor & SERCA2 Mitochondria L-type calcium channelContractile protein : actin(thin filament), myosin(thick filament), titin(anchoring myosin to Z-lines), also there are troponin, tropomyosinMicroanatomy of Heart CellsCharacteristicVentricular MyocyteAtrial Myocyte

ShapeLong & narrowElliptical

Length, m60-140About 20

Diameter, mAbout 205-6

Volume, cubic m15.000-45.000About 500

T tubulesPlentifulRare or none

Intercalated discProminent end-to-end transmissionSide-to-side as well as end-to- end transmission

General AppearanceMitochondria & sacrcomere very abundant; rectangular branching bundles w/little interstitial collagenBundles of atrial tissue separated by wide area of collagen

Mechanism Cardiac Contraction-Relaxation Cycle

Depolarization waves causes opening of voltage-sensitive L-type Ca channelsCa entry & causes release Ca release from SR via Ca release channel (ryanodine receptor)Ca bind to troponin CChange formation of tropomyosin to uncover active site for myosin ATP HydrolysisMyosin head attaches to actinStrong binding statePower strokeActin filament displacedATP bindsHead detachesWeak binding states

Phospholamban inhibit SERCA2Phosphorylated (induced by -adrenergic)DeinhibitedActivates SERCA2Reuptake Ca into SRCardiac cycle1. LV contraction (isovolumic contraction & maximal ejection)2. LV relaxation (start of relax & reduced ejection ; isovolumic relaxation)3. LV filling ( LV filling, rapid phase; slow LV filling; Atrial systole or booster)

Contractile Performance of The Intact Heart3 determinants of myocardial performance1. loading condition (preload & afterload; Frank-Starling mechanism)Preload : load present before contraction has started, at the end of diastoleAfterload : systolic load on LV after it has started to contract or the wall stress during LV ejection

Frank-Starlings Law of heart interlinked preload & afterload in LV volume (preload) leads to contractile function in turn will systolic BP & hence afterload

Laplace law

Wall stress =Means : the larger the LV, the greate of its radius, the greater is wall stress At any given radius (LV size) the greater the pressure developed by LV, the greater the wall stress

2. contractile state inherent capacity of myocardium to contract independently of changes in preload or afterload interaction Ca & contractile proteinIncrease inotropic state, means a greater rate of contraction to reac a greater peak force Increase rates of relaxation

3. HRHeart rate & force-frequency relationship : HR progressively enhances the dorce off ventricular contraction, but too rapid will decrease forceCO = SV X HR

GASTRO-ENTEROHEPATOLOGY

STOMACHAnatomi J-shaped Terbagi menjadi 4 bagian : Cardia : superior opening of the stomach Fundus : rounded portion superior to & to the left of cardia Body : inferior dr fundus & central portion Pylorus : berhubungan dgn duodenum Pyloric antrum : terhubung dgn body of stomach Pyloric canal : terhubung dgn duodenum Concave medial border : lesser curvature Convex lateral border : greater curvature

Histologi Lapisan2 : Mucosa : simple columnar epithelium, lamina propria, muscularis mucosae Submucosa : areolar CT Muscularis : 3 lapisan otot polos (longitudinal, circular, oblique hanya terdapat di body of stomach) Serosa : simple squamous epithelium dan areolar CT Exocrine gland Mucous neck cells : mucus Parietal cells : menghasilkan factor intrinsic (utk penyerapan Vit B12) dan HCL Chief cells : mensekresi pepsinogen dan gastric lipase Enteroendocrine : G cells mensekresi hormone gastrin u/ stimulasi kerja lambung; terdapat di pyloric antrum

PhysiologyFungsi : serve as mixing chamber & holding reservoir

StructureActivityResult

MucosaChief cells

Parietal cells

Surface mucous cell & mucous neck cells

G cellsSecrete pepsinogen

Secrete gastric lipase

Secrete HCl

Secrete intrinsic factor

Secrete mucous

Absorption

Secrete gastrinPepsin, the activated form, breaks down protein into peptides

Split triglycerides into fatty acids & monoglycerides

Kills microbe in food, denature protein, convert pepsinogen into pepsin

Needed for absorption of Vit B12, which is used in RBC formation

Form a protective barrier that prevents digestion of stomach wallSmall quantity of water, ions, short-chain fatty acids, & some drug enter the bloodstream

Stimulate parietal cell to secrete HCl & chief cells to secrete pepsinogen; contract lower esophageal sphincter, increases motility of stomach & release pyloric sphincter

MuscularisMixing waves

PeristaltisMacerate food & mix it w/gastric juice, forming chyme

Forces chyme thru pyyloric sphincter

Pyloric sphincterOpens to permit passage of chyme into duodenumRegulate passage of chyme from stomach to duodenum, prevent breakflow of chyme from duodenum to stomach

SMALL INTESTINE

AnatomyA.Duodenum first & shortest (25cm) part of small intestine, also the widest part &most fixed part C-shaped, around head of pancreas Begin at pylorus & end @ duodenojejunal junction Partial retroperitoneal Divided into 4 parts Superior (1st part) : short (5cm) & lies anterolateral to the body of L1 vertebrae Descending (2nd part) : longer (7-10cm) & descends along the right sides of L1-L3 vertebrae Horizontal (3rd part) : (6-8 cm) long & crosses the L3 vertebrae Ascending (4th part) : short (5cm) & begins @ left of the L3 vertebrae & rises superiorly as for as the superior border of L3 vertebraeVascularizationArtery duodenal arteries, arise from celiac trunk & superior mesenteric arteryVein : follow the arteries & drain into portal vein some directly & others indirectly, thru superior mesenteric & splenic veinLymphatic follow the arteries Anterior lymphatic vessels : pancreaticoduodenal LN & pyloric LN Posterior lymphatic vessels : superior mesenteric LN & celiac LNNerve Vagus, Greater, & Lesser (abdominopelvic) splanchnic nerve

B. Jejunum & IleumTotal long : 6-7m jejunum 2/5 & ileum 3/5Jejunum begin @ duodenojejunal flexure in left upper quadrantsIleum ends @ iliocecal junction in right lower quadrants

VascularizationArtery Superior mesenteric artery Sending 15-18 branches to jejunum & ileum Arterial arches Vasa rectaVein superior mesenteric vein splenic vein portal veinLymphatic specialized @ intestinal villi lacteals (for absoprtion fat)lacteal Lymphatic plexuses @ wall of jejunum & ileum Lymph vessel @ layer of mesentery : into juxtaintestinal LN : close to intestinal wall mesenteric LN : scattered among arterial arcades superior central nodes : along the proximal part of SMAnote : from mesenteric LN drain into superior mesenteric LN from terminal ileum follow ileal branch to ileocolic LN

Nerve sympathetic : originate from T8-T10 segment of spinal cord presynapsis synapse w/postsynapstic neuron in celiac & superior mesenteric (prevertebra) ganglia parasympathetic : from posterior vagal trunks presynapsis synapse w/postsynaptic neuron in myenteric & submucosal plexus

Histology1. Mucuos membraneMacros : series of permanent fold/plicae circularis (terdiri atas mukosa dan submucosa, berbentuk semilunar, sirkular, spiral) ciri jejunumMicros : intestinal villi (p =0.5-1.5mm), duodenum leaf shaped; ileum fingers likeBetween the villi are small openings intestinal glands/glands of lieberkuhnIntestinal gland Stem cell Enterocyte (absorptive cell) : tall columnar cell (inti lonjong pd stengah bag basal); @ the apex striated (brush) border, merupakan microvilliMikrovili : Juluran silindris sitoplasma apikal Terdiri atas membran sel yg membungkus filamen2 aktin di pusat Ukuran : 1m x 0.1 m F(x) : memperluas permukaan kontak antara permukaan usus dengan makanan Goblet cell : less abundant in duodenum, makin banyak ke arah ileum; menghasilkan glikoprotein asam u/melindungi dan melapisi usus Paneths cell : in the basal portion; serosa eksokrin dgn granule sekresi di bag apeks sitoplasma; produce lysozyme (for killing bacteria) Sel M (lipatan mikro) Sel epitel khusus di atas folikel limpoid dari peyers patches Ditandai dengan banyak sekali sumur (pit) pada permukaan apikal dan invaginasi badan sel dan permukaan lateral o/limpoid intraepitel F(x) : fungsi immunologis Endocrine cells :Ciri sistem neuroendokrin difus2 kelompok : terbuka (apeks sel dgn mikrovili berkontak lumen organ) & tertutup (apeks sel ditutupi sel epitel lain) S cell secretin K cell gastric inhibitory polypeptide L cell glucagon-like peptide I I cell cholecystokinin (CCK) Mo cell motilin (for stimulate motility)Dikendalikan susunan saraf & hormonLamina Propria Loose CT w/blood & lymph vessels, nerve fiber Smooth muscle Peyers patches (aggregates of lymphoid nodules)Muscularis mucosa

2. Submucosa : duodenal/Brunners gland production alkaline (pH 8.1-9.3)3. Muscularis Internal : circular External : longitudinal4. Adventitia & serosa

Note :Lamina propria & submukosa peyers patches (kelompok limfonoduli; terdiri atas 10-200 nodul; terdapat 30 patches pd manusia)

Pembuluh darahMenembus muscularis externa Membentuk pleksus di submucosa Cabang2 melalui muscularis mucosaa & lamina propria ke dalam vili Menyusun kapiler tepat di bawah epitel Ujung vilus venul Vena pleksus submucosaPembuluh limfe Dimulai dari tabung buntu pada pusat vili Ke lamina propria diatas muscularis mucosa, dimana membentuk pleksus Submucosa Mengitari limfonoduliSaraf Dibentuk kelompok intrinsik & ekstrinsik Intrinsik: dibentuk kelompok neuron yg membentuk plexus Auerbach (terdapat di antara lapisan longitudinal luar dan circular dalam muskularis) dan pleksus submucous (Meissner) neuron kemoreseptor & mekanoreseptor efektor f(x) : bertanggung jawab atas kontraksi usus yg terjadi tanpa pengaruh saraf ekstrinsik ekstrinsik : parasimpatis (merangsang otot polos) & simpatis ( menekan otot polos)

Sel enteroendokrin utama dalam saluran cernaJenis sel & lokasiHormon yang dihasilkanFungsi Utama

A-lambungGlucagonGlikogenolisis hepatik

G-pilorusGastrinMerangsang sekresi asam lambung

S-usus kecilSekretinSekresi bikarbonat pankreas dan bilier serta air

K-usus kecilPolipeptide yg menghambat gastrik (GIP)Inhibisi sekresi asam lambung

L-usus kecilSubstansi mirip glucagon (glisentin)Glikogenolisis hepatik

I-usus kecilKolesistokininSekresi enzym pankreas, kontraksi kandung empedu

D-pilorus, duodenumSomatostatinHambatan setempat dari sel endokrin lain

Mo-usus kecilMotilinPenignkatan motilitas usus

EC-saluran cernaSerotonin, substansi PPeningkatan motilitas usus

D1-saluran cernaPolipeptida intestinal vasoaktif(VIP)Sekresi ion & air, peningkatan motilitas usus

D1-saluran cernaPolipeptida intestinal vasoaktif(VIP)Sekresi ion & air, peningkatan motilitas usus

PHYSIOLOGY OF SMALL INTESTINE

MovementI. Propulsive Movement - Peristaltis Causes the food to move forward along the tract at appropriate rate to accommodate digestion and absorption Process : a contractile ring appears around the gut then it moves forward sliding forward along the tube Stimulation : the usual stimulus for intestinal peristaltis is distension of the gut. Process : large amount of food collects at any point in the gut stretching the wall of the gut stimulate enteric nervous system to contract the gut wall 2-3 cm behind this point contractile ring appears initiates peristaltic movement. Other stimuli : chemical or physical irritation of the epithelial in the gut & parasympathetic nervous signal. Peristaltis is the inherent properties of many syncytial smooth muscle tube can also occur in the esophagus, bile duct, glandular ducts, ureters, etc. Effectual peristaltic reflex requires an active myenteric plexus.Peristaltic Reflex = Myenteric reflex Is a complex pattern of peristaltic movement. Direction : it normally dies out rapidly in the orad (arah mulut) direction while continuing for a considerable distance toward the anus. It is because the myenteric plexus is polarized in anal direction (Peristaltic Reflex) Mech: peritstaltis normally begins on the orad side of the distended segment moves toward the distended segment push the intestinal contents in the anal direction for 5-10 cm before dying out. At the same time, the gut sometimes relaxes several cm downward toward the anus (called receptive relaxation) allowing the food to be propelled more easily anally than orad. The peristaltic reflex plus the anal direction of movement of peristaltic is called the Law of the Gut

Propulsive Movements (Peristaltis) of Small Intestine Chyme is propelled through the small intestine by peristaltic waves occur at any part of the small intestine. Normally : Velocity: 0,5-2 cm/sec, faster in the proximal intestine & slower in terminal intestine. Very weak & usually die out after traveling only 3-5 cm, very rarely farther than 10cm Net forward movement of chyme along the small intestine 1cm/min 3-5 hours is required for passage of chyme from the pylorus to ileocecal valve. The function of peristaltic : to cause progression of chyme toward ileocecal valve to spread out the chyme along intestinal mucosa Propulsive movement of small intestine is also helped by the segmentation movement (lihat di bawah) Control of Peristaltis :(1) Neural control : Peristaltic activity after meal,due to Gastroenteric reflex initiated by distension of the stomach, conducted principally by myenteric plexus from the stomach along the wall of small intestine Stretching of the duodenal wall in the beginning of chyme enter the duodenum(2) Hormonal control Peristaltic activity : Gastrin, Cholecystokinin (CCK), Insulin, Motilin, and Serotonin. Peristaltic activity : Secretin & Glucagon

Peristaltic Rush intense irritation of the intestinal mucosa (e.g. severe infectious diarrhea) cause powerful & rapid peristaltsis (i.e. the Peristaltic Rush) sweeping the contents of the small intestine to the colon relieving the small intestine of irritating chyme & excessive distension. Initiated by : partly by nervous reflexes that involves the autonomic nervous system & brain stem partly by intrinsic enhancement of myenteric plexus reflexes within the gut itself. Movement caused by the muscularis mucosa & muscle fiber muscularis mucosa : cause short folds appear in intestinal mucosa surface area exposed to chyme absorption individual fiber of these muscle extend to intestinal villi cause them contract intermittently (shortening elongating - shortening) milk the chyme these mucosal & villous contraction are initiated mainly by local nervous reflexes in the submucosal nerve plexus initiated by chyme.

II.Mixing Movement Mixing movement differ in different part of the alimentary tract, i.e:(1) In some areas, the peristaltic contraction themselves cause most of the mixing especially when forward progression of the intestinal contents is blocked by a spinchter.(2) At the other times, local intermittent constrictive contractions occur every few cm in the gut wall usually last only 5-30 seconds at one segment then new constriction occur at the other point in the gut chopping & shearing the contents.

Mixing Contraction (Segmentation contractions) of Small Intestine Mixing movement in the small intestine = localized concentric contraction (segmentation contraction) Process: a portion of small intestine become distended with the chymestretching the intestinal wallelicits localized concentric contraction spaced at interval along the intestinecontraction cause segmentation of the small intestine (that is they divide the intestine into spaced segments that have the appearance of chain of sausage)as one set of segmentation relaxes, a new set often begins but the contraction this time occur mainly at the new points between the previous contractionThe segmentation contractions chop the chime 2-3 times per minute promoting progressive mixing of food with small intestine secretion

The maximum frequency of the segmentation contraction in small intestine is determined by the frequency of electrical slow waves in the intestinal wall. This frequency normally is not over 12 times of contraction per minute in the duodenum and proximal jejunum. In the terminal ileum frequency = 8-9/min The excitation stimulus mainly from the myenteric plexus.

Function of the Ileocecal Valve Principal function of the ileocecal valve is to prevent backflow of fecal content from the colon into the small intestine. The ileocecal valve itself protrudes into the lumen of the cecum and therefore is forcefully closed when excess pressure builds up in the cecum & tries to push cecal contents backward against the valve lips. The wall of the ileum for several cm immediately upstream from the ileocecal valve has thickened circular muscle called ileocecal spihincter. Normally : sphincter remains mildly constricted & slows emptying of ileal contents into the cecum Immediately after meal : gastroileal reflex intensifies peristaltis of the ileum emptying ileal content Resistance to emptying at the ileoecal valve prolongs the stay of chyme in the ileum fascilitates absorption.

SecretionI. Mucus Secretion by Bruners Gland in Duodenum Brunners gland is located in the wall of upper duodenum, mainly between pylorus of stomach & papilla of Vater where the pancreatic secretion & bile empty into duodenum. Brunner gland secretes large anount of alkanline mucus, in response to :1) Tactile or irritating stimuli on duodenal mucosa2) Vagal stimulation3) GI hormone, specially secretin. The function of the mucus : protect duodenal wall from digestion by highly acidic gastric juice contains >> bicarbonate ion add to the bicarbonate ion from pancreatic juice & liver bile neutralize HCl from gastric juice. Control of secretion :Inhibited by sympathetic n.s : very excitable person tend to have peptic ulcer in this area

II.Secretion of Intestinal Digestive Juices by Crypt of Lieberkuhn Crypt of Lieberkuhn are small pits located over the entire surface of small intestine, lies between intestinal villi. Surface of intestinal villi & crypts are covered by epithelium composed of 2 types of cell:1) moderate number of goblet cell secretes mucus lubricate & protect intestinal surface2) large number of enterocytes in the crypts : secretes >> water & electrolytes in villis surface : reabsorb water & electrolytes along with digested product. Intestinal secretions : 1800ml/day; pure extracelular fluid; slightly alkaline pH 7.5-8.0F(x) : watery vehicle for absorption of substances from chyme when it comes in contact w/villi The exact mechanism of secretion of water fluid by crypts is not known, but believed to involve :1. active secretion of chloride ion to the crypts2. active secretion of bicarbonate ion.All of the above cause drag of the sodium ion thru membrane into secreted fluid osmotic movement of water Digestive enzyme in the small intestine secretion : secreted by the enterocytes of the mucosa especially those that cover the villi contain digestive enzyme that digest specific food substace when they are being absorbed through the epithelium. The enzymes are :1) Several peptidase split small peptides into amino acids, i.e : aminopeptidase & dipeptidase2) Sucrase : split sucrose glucose & lactose3) Maltase : split maltose glucose4) Lactase : split lactose glucose & galactose5) -dextrinase : split -dextrin glucose6) Small amount of intestinal Lipase : split neutral fat glycerol & fatty acids7) Nucleosidase & Phosphatase : split nucleotides nitrogen bases, pentose & phosphate

Regulation of small intestine secretion : local enteric nervous reflexes, especially reflex initiated by tactile or irritative stimuli from the chyme in intestine.

Note:Epithelial cells deep in the crypts of lieberkuhn continually undergo mitosis & new cells migrate along the basement membrane upward out of the crypts toward tips of villi replacing villi epithelium & also forming new digestive enzyme

DigestionCarbohydrate By pancreatic amylase Digestion : occured within 15-30 min after the chyme empties from stomach into duodenum & mixed w/pancreatic juice Generally, CH are almost totally converted into maltose and/or other very small glucose polymers before passing beyond duodenum or upper jejunumBy intestinal epithelial enzyme Lactase, sucrase, maltase, -dextrinase : splitting lactose, sucrose, maltose into monosaccharides located in enterocytes covering intestinal microvilli brush border sucrose glucose & lactose maltose glucose lactose glucose & galactoseSo, final products are monosaccahrides water soluble & absorbed immediately into portal blood

ProteinBy pancreatic secretions most protein digestion occurs in upper small intestine in the duodenum & jejunum by pancreatic proteolytic enzymes enzymes : trypsin, chymotrypsin, carboxypolipeptidase, proelastasetrypsin & chymotrypsin : split protein molecules into small polypeptidescarboxypolypeptidase : cleaves individual amino acid from carboxyl ends of polypeptidesproelastase (convert into elastase) : digest elastin fibers that partially hold meat togetherOnly small percentage protein are digested all the way to their constituent amino acids by pancreatic juices, most remain as dipeptides & tripeptidesBy peptidases in enterocytes mainly in duodenum & jejunum @ villi of small intestine enzymes : aminopolypeptidase & dipeptidaseF(x) : splitting remaining larger polypeptides into tripeptides & dipeptides & a few into amino acidsBoth amino acid + dipeptides & tripeptides transported thru membrane into interior of enterocytesInside cytosol of enterocytes are multiple other peptidases that are specific for remaining types of linkages bween amino acidAll last dipeptides & tripeptides are digested into single AAPass on thru of underneath side of enterocyte into the blood

FatsIn stomach : by lingual lipase taht is secreted by lingual gland in mouth & swallowed w/ the saliva but, essentially all fat digestion occurs in the small intestine

Emulsification of fat by bile acids & lecithin emulsification of fat (by bile that containing bile salts & lecithin) : break the fat globules into small sizes so that the water soluble digestive enzymes can act on globule surfacebile salts & lecithinPolar part : soluble in water & remaining : soluble in fat (dissolve in surface layer of fat globules)Polar part projecting outwardSoluble in the surrounding watery fluidDecrease interfacial tension of fatBecomes nonmiscible fluidThat on agitation, can be broken up into many vary minute particles for more easily

F(x) of bile salts & lecithin : make the fat globules readily fragmentable by agitation of water in the small bowel so if agitation diameter fat globules decrease increase total surface area lipase easily to act

By pancreatic lipase digest within 1 minutes all triglycerides intestine also have enteric lipase unimportant

AbsorptionAbsorptive Surface of the Small intestine Mucosal Villi1. Valvulae Conniventes (or folds of Kerckring) It is folds on the mucosal surface surface area of absorptive mucosa 3 folds. Especially well developed in the duodenum and jejunum protrude 8 mm to the lumen.2. Million of small Villi Located on the epithelial suface of the small intestine all the way down to the ileocecal valve. The distribution less profuse in the distal small intestine. Projects 1mm from the surface of the mucosa total absorptive area another 10 folds3. Brush border Consist of as many as 1000 microvili 1m length & 0,1 m diameter protruding into chyme total absorptive area another 20 folds Extending from the epithelial cell bodies to each microvillus are multiple actin filament that contract rhythmically to cause continual movement of microvilli & constantly exposed to new quantities of intestinal fluid.The combination of the folds of Kerckring, villi, & microvilli increase the total absorptive area 1000 folds.

Absorption Capacity Absorption from the small intestine each day consist of : several hundreds of darbohydrate 100 grams fat - 50-100 grams ion 50-100 grams amino acids - 7-8 L of water Absorption capacity of normal intestine: several kg carbohydrate per day - 500 g fat per day 500 700 g protein per day 20L water per day

I.Absorption of Water Isosmotic Absorption Water is transported through the intestinal membrane entirely by diffusion this diffusion obeys the usual law of Osmosis. When the chyme is dilute enough, water is absorbed through the intestinal mucosa to the blood of the villi almost entirely by osmosis. When hyperosmotic solutions are discharged from the stomach to duodenum, water is transported from plasma to chyme chyme is isosmotic with plasma.II. Absorption of IonsActive transport of Na+ ion Na+ ion transported to the epithelial (absorptive) cell via diffusion & secondary active transport. Once inside the epithelial cell, the Na+ are actively transported out of the epithelial cells through the basal & side wall (basolateral) of these cells to paracellular space by Basolateral Sodium-Potassium pump (Na+/K+ ATPase). Part of the sodium ion is absorbed along with chloride ions. i.e. : the negatively charged chloride ions are mainly passively dragged by the positive electrical charges of Na.Transport of Other Ion Absorption of negatively charged ion such as : chloride, iodide, and nitrate ion in the duodenum & jejunum occur mainly by diffusion, that is passively follow the sodium ion or be actively transported. Absorption of calcium, iron, potassium, magnesium & phosphate ion active transport mechanism.Absorption of Bicarbonate The bicarbonate ion in an indirect way as follow:Na+ is absorbed moderate amount of H+ is secreted to the lumen of gut in exchange for Na+ H+ + HCO3- H2CO3 H2O + CO2, the water remains as a part of chyme in intestine, CO2 is readily absorbed into blood & subsequently expired through the lung. This is so called : Active absorption of Bicarbonate ion. The epithelial surfaces of villi in the ileum as well as on all surface of large intestine have special capability to bicarbonate ion in exchange of chloride ion.III.Absorption of NutrientsA.Absorption of carbohydrate Essentially, all the carbohydrate absorbed in the food are in the form of monosaccharide, only a small fraction & almost none as larger carbohydrate compound. Glucose : 80% because it is the final digestion product of our most abundant carbohydrate food, i.e. the starches. Galactose & Fructose : 20% Virtually, all the monosaccharides pass from the lumen through the apical membrane via facilitated diffusion or secondary active transport.(1) Absorption of Glucose & Galactose : Sodium co-transport Mechanism (secondary active transport) The transport protein for transport of Na+ has 3 binding sites : 1 for glucose, 2 for Na+ unless all three sites are filled, neither substance is transported, so when 2Na+ is transported to the absorptive cell, 1 molecule of glucose is also transported to the cell with the same direction (therefore, it is a symporter) . Galactose compete the glucose to ride the same symporter. Once inside the epithelial cell, other transport proteins & enzymes cause facilitated diffusion of glucose through cells basolateral membrane paracellular space into the blood(2)Absorption of Fructose Fructose transport does not occur by the sodium co-transport mechanism Fructose is transported by facilitated diffusion all the way through intestinal epithelium but not coupled with sodium transport. Much of fructose on entering the epithelial cell becomes phosphorylated converted to glucose transported in the form of glucose.BAbsorption of Protein Proteins after digestion are absorbed through the luminal membranes of the intestinal epithelial cells in the form of dipeptide, tripeptide, & a few amino acids. Mechanism of transport : (1)Absorption of Amino Acids Most proteins are absorbed as amino acid in duodenum & jejunum Amino acids are transported by secondary active transport with Na+ (in the same way as glucose)(2)Absorption of Dipeptides & Tripeptides Absorption of dipeptide & tripeptide occur by the H+ symporter Peptides then hydrolyzes inside the cell amino acids Amino acids move out the absorptive cells via diffusion enter capillary of the villus Both the monosaccharides & amino acid transported in the blood to the liver by hepatic portal system.

CAbsorption of Fat When fat is digested to form monoglycerides & FFA, they become dissolved in the central lipid portions of bile micelles. All dietary lipid are absorbed via simple diffusion.(1)Absorption of Micelles the micelles perform a ferrying function in fat absorption In the presence of the abundance micelles, about 97% of fat is absorbed, in the absence of bile micelles, only 40 50% is absorbed Mech :In the form of micelles, monoglycerides & free fatty acid (esp.LCFA) are carried to the surface of the microvilli of intestinal cell brush borderpenetrate to the recess among the moving, agitating microvillimonoglycerides & FFA diffuse immediately out of micelles diffuse into the interior of epithelial cell.After entering the epithelial cell, the fatty acids & monoglycerides are taken up by the cell SERIn SER, they are mainly used to form new triglyceridesTriglycerides aggregates into globules along with phospholipid & cholesterol & coated with protein chylomicronchylomicrons leave the epithelial cell through the base of epithelial cell by exocytosisChylomicrons flow upward through lymphatic system empty into circulating blood(2)Absorption of short chain fatty acid : direct diffusion without converting into micelles. Small quantities of short & medium chain fatty acids are absorbed directly into the portal blood rather than being converted into triglycerides & absorbed by way of lymphatic system This is because : the short chain fatty acid are more water soluble than long chain fatty acids this allow direct diffusion of short chain fatty acid from intestinal epithelial cell directly into the capillary blood of intestinal villi.D.Absorption of Vitamin Fat soluble vitamin (A,D,E,K) are included with ingested dietary lipid in micelles & are absorbed via simple diffusion Most water soluble vitamin (B & C), also absorbed via simple diffusion Vit.B12 combined with intrinsic factor produce by stomach the combination is absorbed in the ileum via active transport mechanism.

LARGE INTESTINEConsists of1. Cecum2. Appendix3. Ascending, transverse, descending & sigmoid colon4. Rectum5. Anal canalFeatures*Omental appendices : small, fatty, omentum like projections*Three teniae coli (thickened band of SM representing most of longitudinal coat) Mesocolic : which transverse & sigmoid mesocolons attachOmental : which omental appendices attachFree : which neither mesocolons nor omental appendices are attached*Haustra : sacculation of the wall of the colon bween teniae*A much greater caliber

Cecum & AppendixCecum : *Blind intestinal pouch, 7.5 in length & breadth* Located in right lower quadrants, lies in the iliac fossa inferior to the junction of terminal ileum & cecumAppendix Blind intestinal diverticulum (6-10cm in length) Contain masses of lymphoid tissue Vascularization*Artery :Cecum : Ileocolic arteryAppendix : appendicular artery* Vein : ileocolic vein *Lymphatic : LN in mesoappendix to ileocolic LN *Nerve : Sympathetic : originate from lower thoracic of spinal cord Parasympathetic : from vagus nerveColonAscending colon Passes superiorly on right side of abdominal cavity from cecum to right lobe of liver turn to lef @ right colic flexure Covered by peritoneum anteriorlyVascularization Arteries : ileocolic & right colic arteries Veins : ileocolic & right colic veins Lymphatic : epicolic & paracolic LN Nerve : from superior mesenteric plexusTransverse colon 45 cm in long Third, longest, most mobile part of large intestine from right colic flexure to left colic flexure & bends inferiorly to bcomes descending colonVascularization arteries : middle colic artery veins : SMV lymphatic : middle colic LN nerve : superior mesenteric nerve plexus Descending Colon secondarily retroperitoneal position bween left colic flexure & left iliac fossa peritoneum covers the colon anteriorly & laterally & bind it to posterior abdominal wallSigmoid Colon S-shaped loop of variable length (40 cm) Extend from iliac fossa to S3 segments, where it join w/rectum Termination of teniae coli (15 cm from anus) rectosigmoid junctionVascularization of Descending & Sigmoid colon Arteries : Left colic & sigmoid arteries Veins : inferior mesenteric vein Lymphatic vessel : pass to epicolic & paracolic LN Nerve Sympathetic : from lumbar splanchnic nerves, superior mesenteric plexus, periarterial plexus Parasympathetic : from pelvic splancnic nerve via inferior hypogastric (pelvic) plexus & nervesRectum Fixed (primarily retroperitoneal & subperitoneal) terminal part of large intestine Continuos w/sigmoid colon @ level S3 vertebrae Continuos inferiorly w/anal canal 3 sharp lateral flexures of the rectum (superior, intermediate, inferior) 3 internal folding (transverse rectal folds): 2 on left & 1 on right Ampulla of the rectum : dilated terminal part of the rectum, lying directly superior to & supported by the pelvic diaphragm (levator ani) & anococcygeal ligament Peritoneum covers : the anterior & lateral surfaces of the superior third of the rectum only anterior surface of the middle third no surface of inferior third Vascularizationarteries superior rectal artery supplies proximal part of rectum right & left middle rectal arteries supplies middle & inferior parts of the rectum inferior rectal arteries supply anorectal junction & anal canal Veins Superior rectal veins : drain into portal venous vein Middle & inferior rectal veins : drain into systemic vein Rectal venous plexus : Internal rectal venous plexus : deep to mucosa of anorectal junction External rectal venous plexus : external to muscular wall of rectumLymphatic Superior half into lumbar (caval/aortic) LN Inferior half sacral LN From distal ampulla internal iliac LNNerve Sympathetic : from lumbar spinal cord, via lumbar splanchnic nerves & hypogastric/pelvic plexuses Parasympathetic : from S2-4 spinal cord level, via pelvic splanchnic nerves & left & right inferior hypogastriv plesux

Anal Canal Extend from superior aspect of pelvic diaphragm to the anus 2.5-3.5 cm long Internal anal sphincter Involuntary sphincter, superior 2/3 of anal canal Thickening of circular muscle layer External anal sphincter voluntary ; inferior 2/3 of anal canal Supplied mainly by S4 thru inferior rectal nerve Superior half longitudinal ridges, called anal columns (contain terminal branches of superior rectal artery & vein) Inferior ends of anal column are joined by anal valves Superior of valve anal sinuses Pectinate line divide anal canal Superior : visceral, derived from hindgut Inferior : somatic, from embryonic proctodeumVascularizationArteries : Superior rectal artery : supply anal canal superior to pectinate muscle 2 inferior rectal artery : supply inferior part of anal canal Middle rectal artery Veins Internal rectal venous plexus drain in both direction from the lvel of the pectinate muscle Superior rectal vein & portal vein from superior to the pectinate line Inferior rectal vein inferior pectinate line Middle rectal vein drain muscularis externa of ampulla & form anastomoses w/superior & inferior rectal veinLymphatic Superior to pectinate line into internal iliac LN common iliac & lumbar LN Inferior to pectinate line into superficially inguinal LN Nerve Superior pectinate line inferior hypogastric plexus (sympathetic, parasympathetic, visceral afferent fiber) Inferior pectinate line inferior anal (rectal) nerve, branches of pudendal nerve

HistologyKelenjar usus panjang2, banyak sel goblet, sel2 absorptif, sedikit sel enteroendokrinMucosa Epitel pelapis silindris, mikrovili pendek, tidak teratur Lamina propria : kaya akan limfosit dan limfonoduli meluas ke submucosaSubmucosaMuscularis Longitudinal & circular Serat2 lapisan longitudinal tergabung dalam 3 pita tebal memanjang tenia koliSerosa appendiks epiploika ( tonjol2 kecil bertangkai terdiri atas jaringan lemak)2 cm di atas muara anus:-epitel berlapis gepeng-lamina propria : terdapat pleksus vena2 besar bisa hemorrhoid

Physiology1. Movement of ColonMixing movement (Haustration)Propulsive movements-Mass movement : Modified peristaltic take over propulsive role ffrom transverse colon sigmoid ( usually occur 1-3 x/day, most abundant for 15 min during the first hour after eating breakfast)Defecation reflexIntrinsic reflex(weak) mediated by local eneteric nervous system in rectal wall when feces in rectumDistention of wallAfferent signalsMyenteric plexusInitiate peristaltic waves in descending colon, sigmoid, rectumForcing feces toward anusInternal anal sphincter relaxIf external anal aphincter also consciously (voluntary relax)defecation

Parasympathetic reflexNerve endings in rectum is stimulatedInvolve a sacral segment in spinal cordParasympathetic nerve fiber in pelvic nerveDescending colon, sigmoid, rectum & anus Greatly intensify peristaltic wave Relaxed internal anal sphincter Convert intrinsic reflex from weak to powerful

taking a deep breathclosure of glottiscontraction of abdominal wallIncrease pressure in abdominal cavityForcing fecal content in rectum to cause a new reflex

2. Secretion only mucus (+ small bicarbonate from few nonmucuos secreting cells between mucus cell)3. Absorption : water & electrolytes

PERITONEUM Is the largest serous membrane of the body Consist of simple squamous epithelium + areolar CT Divided into1. Parietal peritoneum : lines the wall of abdominopelvic cavity2. Visceral peritoneum : covers some organs in the cavity & is their serosa Space bween them : peritoneal cavity Retropertinoeal covered by peritoneum only on their anterior surfaces; kidney & pancreas 5 major peritoneal foldsa. Greater omentum Drapes over transverse colon & coil small intestine like fatty apron Double sheet total 4 layer Contain adipose tissue & lymph nodesb. Falciform ligament Attaches liver to anterior abdominal wall & diaphragmc. Lesser omentum Suspends stomach & duodenum from liver Contain some lymph nodesd. Mesentery Binds small intestine to posterior abdominal walle. Mesocolon Binds large intestine to posterior abdominal wall Carries blood & lymph vessel to intestines

LIVERAnatomy Largest organ after skin Weight : 1500 g; 2.5% body weight Occupy almost Right Hypochondrium & epigastrium Extents into Left hypochondrium, inferior to the diaphragmSurface, Peritoneal Reflections, & Relationship of the LiverDiaphragmatic surface anterior, superior, some posterior convex, smooth, dome-shaped related to concavity of inferior surface of diaphragm subphrenic recesses bween diaphragm & anterior & superior aspect of diaphragmatic surface of the liver separated into R & L by falciform ligament subhepatic space : portion of supracolic compartment of peritoneal cavity immediately inferior to the liver hepatorenal recess (hepatorenal pouch; Morison pouch) posterosuperior extension of subhepatic space, lying bween R part of visceral surface of liver & R kidney & suprarenal gland Gravity dependent; fluid from omental bursa flow into this recess Communicates anteriorly w/right subphrenic recess Covered w/visceral peritoneum, except bare area of liver Demarcated by the reflection of peritoneum from diaphragm to as its anterior & posterior layer of coronary ligament Meet on the right to form right triangular ligament Near apex of wedge shaped liver : meet to form left triangular ligamentVisceral surface Concave, posteroinferior Covered w/peritoneum, except @ fossa for gallbladder & porta hepatis Bears multiple fissure & impression Right sagital fissure : formed anteriorly by fossa for the gallbladder & posteriorly by groove for vena cava Left sagital fissure : formed anteriorly by fissure for ligamentum teres (round ligament) & posteriorly by fissure for ligamentum venosumLinked centrally by porta hepatis & form letter H Impressions Right side of anterior aspect of the stomach (gastric & pyloric area) Superior part of duodenum (duodenal area) Lesser omentum (extends into the fissures for the ligamentum venosum) Gallbladder Right colic flexure & Right transverse colon Right kidney & suprarenal gland Round ligament fibrous remnant of umbilical vein Ligamentum venosum fibrous remnant of fetal ductus venosus Lesser omentum enclose portal triad Hepatoduodenal ligament : passes from liver to the lesser curvature w/stomach & the first 2 cm of superior part of duodenum Hepatogastric ligament :Anatomical Lobes of the Liver Divide into 2 anatomically lobes & 2 accessory lobes 2 anatomical : right lobe & left lobe Separated by falciform ligament & left sagital fissure 2 accessory lobe : caudate (posterosuperior) & quadrate ligament(anteroinferior) Separated by R & L sagital fissures

Functional subdivisions of the liver Right & left liver right liver larger Each part receives its own primary branch of hepatic artery & portal v ein & is drained by its own hepatic duct Caudate lobe Considered a third liver Vascularization is independent of bifurcation of portal triad (it receives vessels from both bundles) Drained by one or two small hepatic vein directly into IVC Liver can be further divided into 4 division & then 8 surgically resectable hepatic segment each served by a secondary or tertiary branch of portal triadVascularization Dual blood supply dominant venous & lesser arterial one Portal vein : 75-80% of blood to liver Containing >40% oxygen than blood returning to heart Carries all nutrient absorbed by GIT (except lipid) to sinusoid of liver Short, wide vein formed by superior mesenteric & splenic vein posterior to the neck of pancreas & ascend anterior to IVC arterial blood from Hepatic Artery(branch from celiac trunk)Branches into common hepatic artery & hepatic artery properNote :@ or close to porta hepatis, hepatic artery & portal vein divide into Right & Left Branches supply R & L liverEach, branches into secondary branches supply medial & lateral division of R & L liverTertiary branching supply 7-8 hepatic segments

Vein : Collecting vein Central vein IVC

Lymphatic1. superficial : in subperitoneal fibrous capsule of liver2. deep : in CT, which accompany ramifications of portal triad & hepatic veinmost of lymph is formed in the perisinusoidal spaces (of Disse)Drains into deep lymphatic in the surrounding intralobular portal triad

Superficial in anterior aspect of diaphragmatic & visceral surface of liver & deep lymphatic vessel accompanying portal triad converge toward porta hepatisHepatic lymph nodesCeliac lymph nodesChyle cistern(dilated sac @ inferior end of thoracic duct)

Superficial lymphatic from posterior aspect of diaphragmatic & visceral surface drain toward bare area of liverPhrenic lymph nodesOrJoin deep lymph that accompanying hepatic vein converging on IVCPosterior mediastinal lymph nodesRight lymphatic & thoracic duct

Another route from posterior surface of the left lobe toward esophageal hiatus left gastric lymph nodes from anterior central diaphragmatic surfaces along the falciform ligament parasternal lymph nodes along the round ligament og the liver to the umbilicus & lymphatic of the anterior abdominal wallnerve derived from hepatic plexus consist of symphatetic from celiac plexus & parasympathetic from the anterior & posterior vagal nerve

Histology

Stroma dibungkus simpai tipis CT (kapsula Glisson) yg menebal di hilum jalinan serat retikular halus menunjang hepatosit & sel endotel sinusoid dari lobulus hatiLobulus hati komponen utama : sel hati atau hepatosit epitel ini berkelompok membentuk lempeng2 satuan struktural lobulus hati lobulus hati poligonal; 0.7 x 2 mm berkontak, pd beberapa daerah dibatasi CT ygmengandung duktus biliaris, lymph, saraf, & pembuluh darah celah portal, dihuni triad portal triad portal 3-6 buah per lobulus Venul : darah asal vena mesenterika superior + inferior & vena lienalis arteriol : dari trunkus seliakus & aorta abdominalis duktus : dilapisi epitel kuboid, membawa cairan empedu lymph Hepatosit Radier, membentuk lapisan setebal 1-2 sel seperti batu bata Eosinophilic, byk mitochondria & retikulum endoplasma Byk mikrovili; 1-2 inti bulat dgn 1-2 nucleoli Lisosom & badan golgi Lempeng sel mengarah dari tepian lobulus ke pusat & beranastomosis scr bebas, membentuk sperti labirin dan busa Celah antara lempeng : kapiler sinusoid Sinusoid Celah di anata lempeng hepatosit mengandung kapiler Endotel membentuk lapisan tidak utuh Sel endotel dipisahkan dari hepatosit o/celah Disse, mengandung mikrovili dari hepatosit, memudahkan untuk pertukaran makromolekul Dikelilingi serat retikular Sel kupffer Sel penimbun lemak (Ito)/stellate cell mengumpulkan vitamin A yg msk dr luar sbg ester retinil dlm tetes lipid Bermuara ke vena sentralisLobulus hati klasik Darah mengalir dr tepi ke pusat terjadi perbedaan kejadian di sel2 perilobular dan sel2 sentrolobularLobulus portal Portal triad sentral Mencurahkan empedu ke pusatnya Mengandung bagian dari 3 lobulus dati yg berdekatan Pada setiap ujung terdapat central veinAsinus hati (rappaport) Terletak pada daerah 2 lobulus Pusat cabang2 terminal dari portal vein, cabang asteri & sebuah duktus biliarisPembagian berdasarkan kedekatan dgn vena distribusi Zona I : plg dkt dgn pembuluh; plg pertama dipengaruhi oleh atau mengubah darah yg masuk Zona II Zona IIIAliran darah 80% dr vena porta : rendah oksigen, kaya nutrien 20% dr arteri hepatika : kaya oksigen Sistem vena portaVena porta Venul porta (cbg interlobular) Vena distribusi Vena ceruk SinusoidVena sentralis (sentrolobular) Vena sublobularis Vena hepatika IVC Sistem arteriArteri hepatika Arteri interlobularSinusoidAliran empeduBile canaliculi Bile ductules Bile duct Right and left hepatic ductCommon hepatic duct + cystic duct Common bile ductPANCREAS

Anatomy Elongated, accessory digestive gland Lies retroperitoneally & transverse across the posterior abdominal wall, posterior to the stomach bween the duodenum on the right & spleen on the left Produces : Exocrine secretion (pancreatic juice) : enter the duodenum thru main & accessory pancreatic duct Endocrine secretion (glucagon, insulin from pancreatic islet) : enter the blood Divided into : Head of the pancreas Expanded part of the gland that is embraced by the C-shaped curved of duodenum to the right of SM vessels Attaches to medial aspect of descending & horizontal part of duodenum Uncinate process projection from inferior part of pancreatic head, extends medially to the left, posterior to SMA Rests posteriorly on the IVC, right renal artery & vein, left renal vein Neck of the pancreas Short (1.5-2 cm) & overlies the superior mesenteric vessel Anterior surface of the neck,covered w/peritoneum SMV joins splenic vein posterior to the neck to form portal vein Body of pancreas Lies to the left of SM vessels, passing over the aorta & L2 vertebra, posterior to the omental bursa Anterior surface is covered by peritoneum and lies in the floor of omental bursa & forms part of the stomach bed Posterior surface is devoid of peritoneum & contact w/aorta, SMA, left suprarenal gland, left kidney & renal vessels Tail of the pancreas Lies anterior to left kidney Relatuvely mobile & passes between the layers of splenorenal ligament w/splenic vessels Tip of the tail is usually blunted & turned superiorly Main pancreatic duct Begin in the tail of pancreas Runs thru parenchyma of gland to the pancreatic head turn inferiorly & closely related to bile duct Main pancreatic duct + bile duct hepatopancreatic ampulla (of Vater), open into duodenum @ major duodenal papilla Sphinter of pancreatic duct, bile duct, hepatopancreatic sphincter (of Oddi) smooth muscle sphincter Accessory pancreatic duct Open into duodenum @ minor duodenal papilla Usually, (60%) communicates w/ main pancreatic ductVascularization Arteries Splenic artery supply body & tail Anterior & posterior superior pancreaticoduodenal arteries (branch of gastroduodenal artery) and anterior & posterior inferior pancreaticoduodenal arteries (branch of SMA) supply head Vein : pancreatic vein splenic & SMV (most to splenic) Lymphatic : Most end in pancreaticosplenic LN Pyloric LNEfferent vessel drain into Superior mesenteric LN or celiac LN via hepatic LN Nerve : derived from vagus & abdominopelvic splanchnic nerve Parasympathetic & sympathetic : from celiac plexus & superior mesenteric plexus Parasympathetic fiber are secretomotor, but pancreatic secretion is mainly mediated by secretin & cholecystokininHistology Adlh campuran kelenjar eksokrin dan endokrin yg memproduksi enzyme dan hormon pencernaan Enzym dari sel eksokrin Hormon pulau2 langerhans Ditutpi simpai tipis jaringan ikat yg mencabangkan septa ke bagian dalamnya memisahkan lobuli pankreas Asinus dikelilingi lamina basal + serat2 retikular halus Memiliki jalinen kapiler luasEksokrin Kelenjar asinar kompleks serupa kel parotis Bagian awal duktus interkalaris menjulur ke dalam lumen asini Inti dikelilingi sitoplasma pucat bagian sel centroacinar, yg merupakan bagian intraasinar dr duktus interkalaris Duktus interkalaris berubah menjadi dektus interlobularis (dilapis epitel silindris) Tidak ada duktus striata Terdiri dari beberapa sel serosa yg mengelilingi lumen terpolarisasi, inti bulat, merupakan sel2 penghasil protein; jmlh granul zymogen bervariasi Produce air, ion, tripsinogen, kimotripsinogen, karboksipeptidase, ribonuklease, deoksiribonuklease, triasilgliserol lipase, fosfolipase A2, elastase, amilase Sekresi dikendalikan : Sekretin : merangsang sekresi yg banyak cairan, kurang enzym, kaya bicarbonat; disekresi oleh sel duktus bukan asinarF(x) : menetralisir asam Kolesistokinin : merangsang sekret yg tidak begitu banyak tetapi kaya enzim terutama mempengaruhi proses pengeluaran granul zymogen vagus

BILIARY DUCT & GALLBLADDER

Bile Duct

Anatomy Forms in the free edge of the lesser omentum by the unio of cystic duct & common hepatic duct Length 5-15cm Descend posterior to the superior part of duodenum & lies in the groove on posterior surface of the head of pancreas On the left side of descending part of the duodenum contact w/main pancreatic duct hepatopancreatic ampulla major duodenal papilla Circular muscle around distal end of the bile duct is thickened to form the spinchter of the bile ductVascularization Arteries Cystic artery : supply proximal part of duct Right hepatic artery : supply middle part of duct Posterior superior pancreaticoduodenal artery & gastroduodenal artery : supply retroduodenal part of duct Vein Proximal part of bile duct & hepatic duct directly enter liver Posterior superior pancreaticoduodenal vein drain distal part of duct into portal vein Lymphatic Cystic LN Node of omental foramen Hepatic LNHistologyHepatic duct, cystic duct, common bile duct1. Mucosa Simple columnar epithelium Lamina propria : thin, surrounding w/smooth muscleMakin ke duodenum, makin menebalDi bagian intramural membentuk sphincter of OddiGallbladder

Anatomy 7-10 cm long, lies in the fossa for gallbladder on visceral surfaces of liver Body of gallbladder lies anterior to duodenum Neck & cystic duct are immediately superior to duodenum Peritoneum completely surround fundus gallbladder & binds its body & neck to the liver Hepatic surface of gallbladder attaches to liver by CT of fibrous capsule of liver Has 3 parts : Fundus : wide end of organ, projects from inferior border of the liver & is usually located at the tip of the right 9th costal cartilage in MCL Body : contacts the visceral surface of the liver, transverse colon, & superior part of duodenum Neck : narrow & tapered; directed toward the porta hepatis; it makes S-shaped bend & joins the cystic duct Cystic duct (3-4 cm in long) connect neck of gallbladder to common hepatic duct Mucosa of the neck spiral into spiral fold helps keep cystic duct openVascularization Arteries Cystic artery, arises from right hepatic artery Veins cystic vein : draining the neck gallbladder & cystic ductenter liver directly or thru portal vein vein from fundus & body of gallbladder directly into visceral surface of liver hepatic sinusoid Lymphatic : hepatic LN & cystic LN celial LN Nerve Celiac plexus : sympathetic & visceral afferent (pain) fiber Vagus nerve : parasympathetic Right phrenic nerve : somatic afferent fiberHistology Berbentuk avokad, melekat di bwh permukaan hati Menampung 30-50 ml empedu Berhubungan dengan hati dengan cystic ductDinding kantung empedu Simple columnar epithelium Lamina propria Selapis otot polos Selapis jaringan ikat perimuscular yg berkembang baik Membran serosaMucosa Berlipat2 jelas saat kosong Epitel : mengandung byk mitochondria, inti si 1/3 bagian basal sel; apikal banyak mikrovili Dekat duktus sistikus : epitel berlekuk ke lamina propria membentuk kelenjar tubuloasinar dengan lumen lebar penghasil mukusMuscular Tipis, kebanyakan otot polos tersusun di sekitar lingkaran kandung empeduAdventitia & serosa Jaringan ikat mengikat permukaan superior Serosa permukaan berlawanan

Fungsi kantung empedu : menyimpan & memekatinya dengan menyerap airnya melepaskan ke saluran cerna bergantung transpor aktif natrium dalam epitel

Kontraksi diinduksi o/kolesistokinin dirangsang adanya lemak

PHYSIOLOGY OF LIVER & GALLBLADDERThe main function of the liver & hepatocytesFunctionprocesses involve

Protein metabolismsynthesis &secretion of albuminSynthesis of plasma proteinFormation of urea from ammoniaDeamination of amino acidsSynthesis coagulation factors e.g factors V,VII,IX,X & protrombhinmetabolism of polypeptide hormone

fat metabolismformation of lipoprotein & fatty acidssynthesis cholesterolconversion of cholesterol to bile saltsconversion of carbohydrate & protein to fatketogenesiscarbohydrate metabolismgluconeogenesissynthesis & breakdown of glycogen

bile secretionproduction of bile saltselimination of bilirubin

storageglycogenvitamin (A & B12)

biotransformation andof drugs & exogenous substance detoxificationgonadal hormonealdosteroneglucocorticoidnitrogrnous gut toxins

protectionfiltration of portal bloodremoval of bacteria/antigens by kupfer cells

haematopoiesisthe fetal liver is the majorsource of blood cells

BILE PRODUCTION Hati mengeluarkan empedu (bile) sebanyak 600-1200 ml/hari Function of bile acid1. Cholesterol metabolisma. reduction in excess cholesterol through degradation of cholesterol to bile acids by solubilization of cholesterol in the bileb. regulation of cholesterol synthesis in the liver and intestinec. regulation of cholesterol output into the bile 3-,7-bile acids inhibit secretion 3-,12-bile acids increase secretion2. Digestion and resorption of dietary fatsa. by formation of micellesb. by stabilization and activation of enzymes(e. g. pancreatic lipase, phospholipase A2,pancreatic cholesterol esterase)3. Effects on the bile flow due to osmotic water movement4. Effects on bile secretiona. monohydroxy bile acids function cholestaticallyb. dihydroxy and trihydroxy bile acids have a choleretical effect5. Emulsification of fat-soluble vitamins6. Stimulation of intestinal motility

BileBile components. electrolytes, bile salts (bile acids), cholesterol, lecithin (phosphatidylcholine), bilirubin diglucuronide, steroid hormones, medications etc.pathway(1.) Bile acid uptake at the sinusoidal membrane surface is achieved Actively by several Na+-dependent (NTCP) as well as Na+-independent (OATP) carrier proteins passively by facilitated biological diffusion or free physical diffusion processes.(2.) Bile acid release occurs at the biliary membrane surface in the canaliculi either actively, facilitated by ATP-driven carrier glycoproteins such as MRP2 (also called cMRP or MOAT) and hBSEP (human bile salt export pump ), identical to cBAT (canalicular bile acid transporter). by exocytosis of intracellularly derived mixed vesicles, with the help of a potential-dependent membrane carrier.(3.) Bile acid uptake at the mucosal surface of the enterocytes proceeds actively either through Na+-dependent carrier systems in the ileum or by free diffusion in the ileum and colon. The gall bladder and upper small intestine serve as mechanical stores with the ability to drive the circulation of the bile pool by peristaltic action. The bile acids become bound chiefly to albumin or HDL for transport in the blood. Incorporation into HDL is effected by apolipoproteins A1 and A2. Uptake into the hepatocytes is mediated by a membrane-specific transport system This influx process is predominantly an active transport mechanism against an electrochemical gradient. Energy is supplied by Na+/K+-ATPase. Intracellular transport of bile acids to the biliary pole of the hepatocytes follows after their binding to cytosolic proteins: free bile acids would be damaging to subcellular structures because of their amphiphilic nature and detergent activity. Control of bile secretion and release1. Secretin : produced by duodenum, stimulate bile secretion by the liver2. Cholecystokinin: produced by duodenum, stimulate gall bladder to contract, thereby releasing bile into duodenum3. Vagal nerve stimulation : causes gallbladder to contract, thereb releasing bile into duodenum.

The gallbladder stores & concentrate bile Bile continually secreted by the liver & flows to gallbladder, where 40-70 ml of bile can be stored While bile in the gallbladder, water & electrolyte are absorbed

Bile salts & pigments become as much as 5-10 times more concentrated

PHYSIOLOGY OF BILE Bile : fluid secreted by the liver, concentrated in gallbladder, and poured to the small intestine via bile duct. Chief constituent : conjugated bile salt, cholesterol, phospholipid, bilirubin, & electrolytes Function : helps in emulsification, absorption, digestion of fats alkalinize the intestinal content Bile Acid : any of the steroid acid derived from the cholesterol Bile salt : glycine or taurine conjugate of bile acids formed in the liver & secreted in the bile.

Bile Acids Metabolism1) Formation of bile acids from cholesterol Occurs in the hepatocytes : mostly pericentral hepatocytes This process convert the highly insoluble cholesterol to the water soluble bile acid. Steps :1. hydroxylation of cholesterol by the enzyme 7-hydroxylase2. epimerization : conversion of -orientation to - orientation 3 hydroxyl group the process yields primary bile acids :1. chenodoxycholic acid2. cholic acid when these primary bile acid enter the distal small intestine or the colon, they can be acted by the bacterial enzymes to yield secondary bile acids :1. lithocholic acid from chenodoxycholic acid2. deoxycholic acid from cholic acid3. ursodeocholic acid. The most important conversion is litocholic acid & deoxycholic acid Lithocholic acid is cytotoxic in high concentration very little ursodeoxycholic acid is formed in humans . It is formed by epimerization of the 7 hydroxyl group.

2) Bile acid conjugation Following hepatic synthesis : Primary bile acid secondary bile acidReturned toglycine & taurineliver

conjugated bile salt

Primary Bile Acid The primary bile acids are formed in the hepatocytes as liver-specific degradation products of cholesterol due to the action of microsomal, peroxisomal and mitochondrial enzymes; they are linked to cytosolic proteins The two primary bile acids represent 60-90% of the total bile acid production:

Biosynthesis of the two primary bile acids is followed by conjugation of their carboxylic group with the amino group of either glycine or taurine, mediated by a cytoplasmic enzyme. By means of this conjugation, the primary bile acids, which initially are barely water-soluble, become anions and are thus rendered hydrophilic. In this way four conjugated bile acids are formed:

Secondary Bile Acid The secondary bile acids result from the activity of anaerobic intestinal microorganisms in the ileum, caecum and colon. bacteria can deconjugate both primary and secondary bile acids, making them more lipophilic This is followed by 7-dehydroxylation of : cholic acid deoxycholic acid chenodeoxycholic acid lithocholic acid, 7-dehydrogenation and oxidation of chenodeoxycholic acid also yield ketolithocholic acid Unconjugated bile acids can be considered "damaged" and can be passively absorbed across the wall of the intestine Secondary bile acid :

The secondary bile acids become partially (30-50%) absorbed in the intestine,They then travel through the portal vein back to the liver, where they are reconjugated in the hepatocyte following reconjugation with glycine or taurine in the liver, they excreted into the canaliculi.

The bile thus contains a mixture of primary and secondary bile acids & therefore, all bile acids secreted by the hepatocyte are in their conjugated forms. The conjugated bile salt are more water soluble and structurally can be actively transported across the canalicular membrane Deoxycholic acid as a secondary bile acid is likewise an end-product; it enters the enterohepatic circulation without further modification. (re) Conjugation of the secondary bile acids in the liver yields the following four conjugated bile acids:

Tertiary Bile Acids The tertiary bile acids are formed in the liver as well as in the gut. Intestinally absorbed lithocholic acid is enzymatically converted to sulpholithocholic acid in the liver. Ketolithocholic acid is transformed to (hypercholeretic) ursodeoxycholic acid in both the intestine and the liver. When passing through the canaliculi, UDC is partly reabsorbed by epithelial cells and returned to the liver via the blood circulation (cholehepatic shunt). The tertiary bile acids:

The bile acids may be further modified by enzymatic reactions. The enzymes involved have been found in the liver, intestine and kidney. By their action, conjugated and unconjugated primary or secondary bile acids may become bound to sulphuric acid, glucuronic acid or glucose. A further improvement in water-solubility can be obtained by sulphation or glucuronidation. lithocholic acid can be sulfated, particularly if present in abnormally high concentrations This increases the hydrophilicity of the molecule and is therefore believed to reduce its cytotoxic effects

Regulation of bile biosynthesis of bile acid Regulation of the biosynthesis of bile acids : through feedback by the respective daily loss quota (predominantly) by HMGCoA reductase and 7-hydroxylase, which are themselves chiefly adjusted by ursodeoxycholic acid. Bile acids exert feedback inhibition on cholesterol 7 -hydroxylase, such that when return of bile acids from the intestine is high, the synthesis of new primary bile acids is reduced. With advancing age, bile acid synthesis in the liver decreases and excretion of cholesterol in the bile increases. The terms bile acids and bile salts are interchangeable.

Bile Acids Composition1.Canalicular bile The secretion of bile begins when bile acids are actively secreted across the canalicular membrane. Canalicular bile is transiently hyperosmotic However, the tight junctions that delineate the canaliculus are relatively permeable, and so water is drawn into the canaliculus to balance this, along with plasma cations to maintain electrical neutrality. The composition of canalicular bile is also modified by the active secretion of additional substrates from the hepatocyte itself. The composition are : Conjugated bilirubin -Gluthathione Cholesterol -Phosphatidylcholine Glucose, amino acids, urea -Xenobiotics Cations : e.g. Calcium

2.Ductular bile The bile ductules (canal of hering) are lined by cholangiocytes, which are columnar epithelial cells specialized to modify bile composition. The tight junctions linking the cholangiocytes are much less permeable than those linking hepatocytes. They are freely permeable to water, but are only selectively permeable to electrolytes and impermeant to larger solutes bile rapidly becomes isotonic

Modification : glucose is actively reabsorbed and returned to the bloodstream. glutathione is hydrolyzed to its constituent amino acids by the apically-fixed enzyme, gamma glutamyltranspeptidase (GGT) The reuptake of glucose and amino acids is likely important in preventing bacterial overgrowth in the biliary tree, by limiting nutrient availability. Overgrowth of bacteria in the bile ductules has potentially serious consequences because bacterial enzymes can deconjugate bilirubin, yielding a product that can form a highly insoluble salt with calcium that is present in the bile pigment stone. the cholangiocytes secrete bicarbonate in response to secretin Sodium ions follow paracellularly to maintain electrical neutrality, in turn drawing additional water into the bile and increasing its volume and flow. Thus, bile becomes slightly alkaline. the ductules secrete IgA molecules into the bile The composition of ductular bile :

3. Hepatic bile Hepatic bile refers to the bile that emerges from the liver in the common hepatic duct, prior to further modification by gallbladder storage The large bile ducts are thought to have little ability to modify bile composition, other than by adding mucus that presumably serves a protective and lubricating role. Thus, the composition of hepatic bile reflects that which emerges from the ductules liver synthesizes 200400 mg of bile acids per day

Enterohepatic Circulation of Bile AcidIntestinal Uptake MechanismsBile acids secreted into the gut lumen are initially entirely in conjugated form. Because these conjugated bile acids are ionized, they cannot cross the wall of the intestine passively. The reabsorption of conjugated bilirubin via the process of secondary active transport. The transporter : 1) sodium-coupled transporter,i.e. the apical sodium-dependent bile salt transporter or ASBT. ASBT expression in the intestine is limited to epithelial cells in the terminal ileum. Thus, conjugated bile acids remain with the meal in the lumen until the nutrients are absorbed.2) OST is present at the basolateral domain of ileal epithelial cells Only a minor portion of the bile acid pool spills over into the colon in health.

Hepatocyte transport mechanism Bile acids returned to the liver, either in conjugated or unconjugated form, leave the portal circulation in the sinusoids bound to albumin and then are specifically taken up across the basolateral membrane of the periportal hepatocytes. The transporter are :Table 111. Hepatocyte Transporters

NameLocationSubstrate/function

Sodium taurocholate cotransporting polypeptide (NTCP) Basolateral membrane Uptake of conjugated bile acids from blood

Organic anion transporting protein (OATP) Basolateral membrane Uptake of bile acids and xenobiotics from blood

Bile salt export pump (BSEP) Canalicular membrane Secretion of conjugated bile acids into bile

Multidrug resistance protein 3 (MDR3) Canalicular membrane "Flippase" that adds phosphatidylcholine to bile

Multidrug resistance protein 1 (MDR1) Canalicular membrane Secretion of hydrophobic cationic drugs into bile

ABC5/ABC8 Canalicular membrane Secretion of cholesterol into bile

Multiple organic anion transport protein (cMOAT, MRP2) Canalicular membrane Secretion of sulfated lithocholic acid and conjugated bilirubin into bile

Regulation of bile secretion motor function of gallbladder & biliary system1. determinants of gallbladder pressure & filling whether hepatic bile will enter the gallbladder, or be secreted directly to the intestine, depends on interrelationship between 3 pressures :(a) hepatic secretion pressure (b) sphincter of Oddi pressure(c) receptive relaxation of gallbladdergallbladder contraction & sphincter of Oddi contraction

BILIRUBIN METABOLISM ( liat bagan)

DRUGS & HORMONE METABOLISM The liver metabolized drugs & hormone via biotransformation in 3 stages :phase 1 : oxidation major reaction involved is hydroxylation, catalyzed by members of a class of enzymes referred to as monooxygenases or cytochrome P450s. Hydroxylation may terminate the action of drug, In addition to hydroxylation, these enzymes catalyze a wide range of reactions, including those involving deamination, dehalogenation, desulfuration, epoxidation, peroxygenation, and reduction. phase 2 : conjugation the hydroxylated or other compounds produced in phase 1 are converted by specific enzymes to various polar metabolites by conjugation with glucuronic acid, sulfate, acetate, glutathione, or certain amino acids, or by methylation.Phase 3 : elimination The overall purpose of the two phases metabolism of xenobiotics is to increase their water solubility (polarity) and thus excretion from the body. Very hydrophobic xenobiotics would persist in adipose tissue In certain cases, phase 1 metabolic reactions convert xenobiotics from inactive to biologically active compounds. convert the active compounds to less active or inactive forms prior to conjugation.

PHASE 1The reaction catalyzed by a monooxygenase (cytochrome P450) is as follows:RH (drugs) + O2 + NADPH + H+ R-OH + H2O +NADPORReduced cytochrome P450 oxidized cytochrome P450

RH + O2 R-OH + H2OPHASE IIFive Types of Phase 2 Reactions Are Described Here1. Glucuronidation UDP-glucuronic acid is the glucuronyl donor, variety of glucuronosyltransferases, present in both the endoplasmic reticulum and cytosol, are the catalysts. Molecules such as 2-acetylaminofluorene (a carcinogen), aniline, benzoic acid, meprobamate (a tranquilizer), phenol, and many steroids are excreted as glucuronides. the most frequent conjugation reaction.2. Sulfation Some alcohols, arylamines, and phenols are sulfated. the sulfate donor in these and other biologic sulfation reactions (eg, sulfation of steroids, glycosaminoglycans, glycolipids, and glycoproteins) is adenosine 3'-phosphate-5'-phosphosulfate (PAPS) 3. Conjugation with Glutathione (gsh) Glutathione (-glutamyl-cysteinylglycine) is a tripeptide consisting of glutamic acid, cysteine, and glycine A number of potentially toxic electrophilic xenobiotics (such as certain carcinogens) are conjugated to the nucleophilic GSH in reactions that can be represented as follows:R (electrolic xenobiotic)+ GSH R-S-G Enzim untuk katalisisnya : glutathione S-transferases found in liver cytosol and in lower amounts in other tissues. If the potentially toxic xenobiotics were not conjugated to GSH, they would be free to combine covalently with DNA, RNA, or cell protein and could thus lead to serious cell damage. GSH defense mechanism

Other reactionAcetylationAcetylation is represented byX + Acetyl-CoA Acetyl-X + CoA catalyzed by acetyltransferases present in the cytosol of various tissues, particularly liver Slow acetylators are more subject to certain toxic effects.MethylationA few xenobiotics are subject to methylation by methyltransferases, employing S-adenosylmethionine as the methyl donor.

PHYSIOLOGY OF PANCREASPancreatic Secretion Product of pancreatic secretion = Pancreatic Juice Pancreatic juice is a mixture of : Pancreatic enzymes secreted by pancreatic acini Large volume of sodium bicarbonate solution secreted by small ductule & larger ducts leading from the acini. Pancreatic juice is secreted most abundantly in response to the presence of chyme in the upper portion of small intestine.

I.Pancreatic Digestive EnzymesEnzyme for digestion of protein The most important of the pancreatic enzymes for digesting proteins are : Trypsin, Chymotrypsin & Carboxypolypeptidase.1) Trypsin & Chymotrypsin : split whole & partially digested protein various sizes of polypeptide (but not cause release of individual amino acids)2) Carboxypolypeptidase : split some peptides individual amino acids (completing digestion of some proteins all the way to amino acids state) The proteolytic enzymes are in the inactive forms when first synthesized in the pancreatic cells, i.e. Trypsinogen, chymotrypsinogen, & procarboxypolypeptidase become activated only after they are secreted into intestinal tract. Trypsinogen is activated by enterokinase (secreted by intestinal mucosa) or autocatalytically activated by trypsin that has already been formed from previously secreted trypsinogen. Chymotrypsinogen, Procarboxypolypeptidase is activated by trypsinEnzyme for digestion of carbohydrate Pancreatic enzyme for digesting carbohydrates is : pancreatic amylase : hydrolyzes starches, glycogen, & most other carbohydrate (except cellulose) form mostly disaccharides (maltose) & a few trisaccharides (maltotriose) & -dextrin.Enzyme for digestion of fat The main enzymes for fat digestion are : 2. Pancreatic Lipase : hydrolyzing neutral fat fatty acids & monoglycerides3. Cholesterol Esterase : hydrolysis of cholesterol esters4. Phospholipase : splits fatty acids from phospholipidsEnzyme for digestion of Nucleic Acids (Nuclease)1. Ribonuclease : split RNA nucleotide2. Deoxyribonuclease : split DNA nucleotideSecretion of Trypsin Inhibitor IMPORTANT: proteolytic enzyme of the pancreatic juice must not become activated until after they have been secreted to intestine because : trypsin & other enzymes would digest the pancreatic itself. Fortunately the same cell that secretes proteolytic enzymes into the acini of pancreas secrete simultaneously another substance called Trypsin Inhibitor prevents activation of trypsin directly & other enzymes indirectly.II.Secretion of Bicarbonate Ion Bicarbonate ion & water are secreted mainly by the epithelial cells of ductules & duct that lead from acini. Basic steps in secretion of bicarbonate ion :1) CO2 diffuse to the interior of the cell from blood, then : CO2 + H2O H2CO3 HCO3- + H+2) Bicarbonate ion (HCO3-) are actively transported in association with Na+ through the luminal border of the cell into the lumen of the duct.3) H+ are exchanged for Na+ through the blood border of the cell by secondary active transport process supplies Na+4) The overall movement of H+ & Na+ ions from the blood into the duct lumen creates osmotic pressure gradient osmosis of water to the pancreatic duct forming an almost isosmotic bicarbonate solution.

Regulation Of Pancreatic Secretion3 Basic stimuli are important in causing pancreatic secretion :1. Acetylcholine : release from parasympathetic n.s.2. Cholecystokinin : secreted by duodenal & upper jejunal mucosa3. Secretin : secreted by duodenal & upper jejunal mucosa when theres highly acid food enters small intestine. Acetylcholine & Cholecystokinin stimulate the acinar cell to produce large quantity of digestive enzyme but relatively small quantities of water & electrolytes without the water, most of the enzyme remain temporarily stored in the acini & ducts until more fluid secretion comes to wash them into the duodenum. Secretin : >>water & electrolytes (sodium bicarbonate)Pancreatic secretion normally results from the combined effects of the multiple basic stimuli, not from one alone.

Phases of Pancreatic SecretionOccurs in 3 phases :1) Cephalic phase nervous signal acetylcholine release by vagus nerve moderate amounts of enzymes secreted into the pancreatic acini (20% after meal) little of the pancreatic secretion flows immediately through the pancreatic duct to the intestine because only small amount of water & electrolyte are secreted.2) Gastric phase continuation of nervous stimulation secretion of pancreatic juice (5-10% after meal) only small amount of the juice reach the duodenum3) Intestinal phase after chyme leaves the stomach & enters the small intestine, pancreatic secretion becomes copious, mainly in response to hormone secretin. Secretin simulates secretion of copious quantities of Bicarbonate ion neutralize acidic stomach chyme. Cholecystokinin (CCK) Release of CCK especially caused by presence of proteoses & peptone (product of partial protein digestion) & Long chain Fatty Acid (LCFA)