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Clinical Science Session Sirosis Hati Mazley Dini

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  • Clinical Science Session

    Sirosis HatiMazleyDini

  • Sirosis HatiDefinisi :Kerusakan parenkim hepar yang terjadi secara kronik dan irreversibel berupa fibrosis dan regenerasi noduler

  • Patofisiologi FibrosisMengubah sel2 penyimpan lemak menjadi myofibroblastMengubah monosit menjadi makrofagMemacu proliferasi dari fibroblastKeluarnya enzim lisosom Pelepasan sitokin Aktivasi sel kupffer(di sinusoid) Growth factordan sitokin pembentukan matriks ektraselulerNekrosis sel-sel hepar Regenerasinoduler

  • Manifestasi klinik

    Merupakan komplikasi dari gangguan fungsi hepar dan hipertensi porta yang disebabkan oleh fibrosis dan gangguan vaskularisasiTidak berdasarkan etiologi

  • Nekrosis hepar Terganggunya fungsi heparFungsi metabolismeKarbohidrat, protein dan lipid Hipoglikemi protein plasma asites dan edema detoksikasi amonia encephalopathy hepatik

  • Fungsi detoksifikasiobat, taksin, sisa metabolisme dan hormon androgen dan estrogenGinekomastia bulu tubuhVirilizasi dan Gangguan menstruasiSpider neviPalmar eritem ADH dan aldosteronEdema

  • Fungsi hemostasis dan hematologiSintesis faktor pembekuan darahResiko perdarahanPT memanjangFungsi sintesis dan eksresi empedu absorpsi lemak dan vitamin larut lemakBAB berwarna seperti dempulMetabolisme bilirubinHiperbilirubinemia jaundice urobilinogen urin berwarna seperti teh

  • Perubahan biokimiawi AST dan ALT Bilirubin Albumin Alkaline phosphatase

  • Jaundice

  • Ginekomastia

  • Palmar eritem

  • Spider Nevi

  • Liver Nail

  • Dupuytren contracture

  • Fibrosis Hipertensi portaVena porta membawa darah dari GI tract, spleen, pankreas, dan vesika felea ke sinusoid dalam hepar V. hepatika V. cava inferiorTekanan St. porta normal 5 10 mmHgPada SirosisFibrosis pada sinusoid obstruksi tek. V. porta (> 10 mmHg)

  • Portal systemic collateralsVena PortalSirosis heparSplenomegalyFibrosis pd sinusoid resistensi vaskular

  • Hipertensi portaPembuluh darah Kolateral V. sistemik Gastroesophaeal junction Dinding anterior abdomen RectumVarices Varices esophagus Caput medussae Hemorroid tekanan V. lienalis Congestive Splenomegaly Anemia Trombositopenia Leukopenia

  • Varises kecilVarises besarTidak ada varisesVarises Esophagus

  • Hipertensi portaGangguan fungsihepar Asites Hepatik Ensefalopatik

  • Cirrhosis Hepatis

    Albumin Intra hepatic Vasc. Resistance

    Plasma oncotic press Portal venous press

    Ascites

    Na. Retention Effective intravas. vol

    Aldosteron Renal perfusion

    Plasma Renin activity

  • Asites

  • Patogenesis Hepatik EnsefalopatiBacterial actionProtein loadFailure to metabolize NH3NH3 ShuntingGABA-BD receptorsToxins

  • Hepatic Encephalopathy PrecipitantsGI bleeding

    Excess proteinSedatives / hypnoticsTIPSDiureticsSerum K+Plasma volume

    AzotemiaTempInfectionsHEPATIC ENCEPHALOPATHY PRECIPITANTS

  • StageMental stateNeurologic signs1Mild confusion: limited attention Incoordination, tremor,span, irritability, inverted sleep impaired handwritingpattern2Drowsiness, personality changes,Asterixis, ataxia, dysarthriaintermittent disorientation3Somnolent, gross disorientation,Hyperreflexia, musclemarked confusion, slurred speechrigidity, Babinski sign4ComaNo response to pain, decerebrate postureStadium Hepatik EnsefalopatiSTAGES OF HEPATIC ENCEPHALOPATHY

  • Komplikasi lainSpontaneous bacterial peritonitis72 % disebabkan batang gram (-) : E. coli, klebsiellaKriteria diagnostik : PMN > 250 pada cairan ascitesSindroma hepatorenal

  • sirosis(Advanced)Bacteremia TransientProlonged BacteremiaColonization AscitesSpontaneous Bacterial PeritonitisImunitas menurunTranslokasi Bacteriintestine RES ComplementSumber lain* RES Reticulo-endothelial system

  • AscitesSirosis

  • KlasifikasiBerdasarkan etiologi dan morfologiAlkoholikPosthepatitis dan KriptogenikBiliarisKardiakMetabolik, herediter , drug-related

  • Sirosis alkoholik (Laennecs)DefinisiSalah satu kerusakan hepar yang disebabkan karena konsumsi alkohol secara kronik. Perjalanan penyakit bergantung dari durasi dan kuantitas alkohol yang dikonsumsi

  • KarakteristikPatologi : Skar halus difus, dengan kerusakan sel hepar seragam dan regenerasi mikronodularPerjalan penyakit lambat, 10 thn setelah konsumsi alkohol yang berlebihanKenaikan AST yang tidak proporsional terhadap AST (ratio AST/ALT > 2)Hepar biasanya membesar, namun dapat normal atau mengecil

  • Patogenesis

  • Sirosis Posthepatitis & KriptogenikDefinisiStadium akhir dari sebagian besar penyakit hati kronikEtiologiHepatitis kronis e.c HBV atau HCVKriptogenik (tidak diketahui)KarakteristikPatologi : Nodular kasar dan multilobularHepar biasanya mengecil

  • Patogenesis

  • Sirosis BiliarisDefinisiSirosis yang diakibatkan oleh kerusakan atau obstruksi dari sistem biliaris baik intrahepatik maupun ekstrahepati

    Dibagi menjadi :Sirosis biliaris primerSirosis biliaris sekunder

  • Sirosis Biliaris PrimerEtiologiTidak diketahui??Berhubungan dengan penyakit autoimun >

  • KarakteristikAdanya inflamasi, destruksi, fibrosis dan obstruksi dari duktus biliaris intrahepatikdibagi dalam 4 stadium :Kolangitis destruktif non-supuratif infiltrat inflamasi dan jumlah duktus biliaris proliferasi duktus biliaris kecil duktus interlobularis, hepatosit dan fibrosis periportal (dalam beberapa bulan tahun)Sirosis (mikro/makronoduler)Adanya antimitokondrial antibody IgG (AMA) pada > 90% pasien

  • Lanjutan karakteristikSebagian besar asimptomatikGejala awal berupa pruritus, steatorea, malabsorpsi vitamin larut lemakKadar enzim alkali phospatase meningkat dengan bilirubin normal (tahap awal)

  • Sirosis Biliaris SekunderEtiologiObstruksi parsial atau komplit pada duktus biliaris komunis dan cabang2nya.Penyebab obstruksi :Batu empedu (Biasanya + cholangitis)Striktur postoperative atau karena pankreatitis kronisTumor Atresia biliaris Cystic fibrosispada anak

  • Karakteristik Hampir sama dengan S.B. primerDemam dan nyeri abdomen kuadran kanan atas KolangitisPatogenesisobstruksi dukt. Biliaris ekstrahepatik akumulasi empedu centrilobular space nekrotik area Proliferasi dan dilatasi duktus biliaris edema dan fibrosis regenerasi noduler halusJika saluran portal ruptur di sekililing nekroti area Pool of bile

  • Sirosis kardiakDefinisiSirosis yang disebabkan karena gagal jantung kongestif kananKarakteristik AST yang sangat tinggi dan bersifat sementara (shock liver)Hepar membesar dan keras

  • Patogenesisgagal jantung kanan aliran balik dari V.Cava Inferior ke V. hepatika kongesti hepar dilatasi sinusoid (hepar oedem) terjadi terus menerus + iskemi karena perfusi ( cardiac output) nekrosis fibrosis

  • Sirosis metabolik, Drug-related, herediter

  • DiagnosisAnamnesa Gejala sirosis : lelah, lemah badan, anoreksia, kuning, pruritusEtiologi : alkohol, infeksi HBV atau HCV, dllPerjalanan penyakitPemeriksaan fisikJaundice (kulit dan mukosa) rambut tubuhAscitesLiver nail, spider nevi, ginekomastia, atrofi testis, palmar eritemOedema

  • LaboratoriumBilirubinAST dan ALTAlkali phosphataseAlbuminPTUSGBiopsi hepar

  • Penilaian beratnya sirosis hatiModified Child-Plugh Classification of the severity of liver disease

    Poin total : Grade A (1-6), Grade B (7-9), Grade C (10-15)

  • TerapiEtiologi alkohol hentikan konsumsiIstirahatDiet : protein min 1 gr/hari, vitamin dan hepatoprotektorPerdarahan karena ruptur varisesSubtitusi cairan (i.v line)Vasokonstriktor i.v (somastatin/vasopresin)Ballon tamponadeTerapi endoskopik : ligasi, skleroterapiTerapi shunt : TIPS (Transjugular intrahepatic portosystemic shunt)Pencegahan perdarahan : -blocker (propanolol, nadolol)

  • AsitesDiet rendah garam (
  • Spontaneous bakterial peritonitisCefotaksim i.vMinimal 5 hari

  • *Slide 48ARCHITECTURAL LIVER DISRUPTION IS THE MAIN MECHANISM THAT LEADS TO AN INCREASED INTRAHEPATIC RESISTANCEThe deposition of fibrous tissue and the formation of nodules, disrupts the architecture of the liver, leading to an increased resistance to flow and to portal hypertension. Vessels that normally drain into the portal system, such as the coronary vein, reverse their flow and become porto-systemic collaterals. Additionally, with portal hypertension, the spleen increases in size and sequesters platelets and other formed blood cells leading to hypersplenism.*Slide 82VARICES INCREASE IN DIAMETER PROGRESSIVELYBoth development of varices and growth of small varices occurs at a rate of 7-8% per year. Although there are no identified clinical predictors for the development of varices, factors associated with variceal growth are Child B/C cirrhosis, alcoholic etiology and presence of red wale marks on initial endoscopy.

    Merli et al., J Hepatol 2003; 38: 266

    *Slide 350PATHOPHYSIOLOGY OF HEPATIC ENCEPHALOPATHY This slide demonstrates how ammonia bypasses the liver, either through porto-systemic collaterals or through a created shunt (transjugular intrahepatic porto-systemic shunt) and ultimately reaches the brain.*Slide 362HEPATIC ENCEPHALOPATHY PRECIPITANTSPrecipitating factors for hepatic encephalopathy include a high protein load, gastrointestinal bleeding or constipation, as well as infection and overdiuresis (leading to azotemia and hypokalemia). Narcotics and sedatives by directly depressing brain function further contribute to hepatic encephalopathy. A commonly seen cause of chronic encephalopathy is the placement of the transjugular intrahepatic porto-systemic shunt (TIPS).*Slide 352STAGES OF HEPATIC ENCEPHALOPATHYThese clinical stages of hepatic encephalopathy depend on the mental state and neurological signs.*Slide 273PATHOGENESIS OF SPONTANEOUS BACTERIAL PERITONITIS (SBP) AND SPONTANEOUS BACTEREMIA IN CIRRHOSISIn cirrhosis, particularly in the presence of ascites, there is an increase in bacterial translocation (BT). A failure of local and systemic immune defenses, more evident with greater severity of liver disease, is a major element in promoting a clinically significant bacterial translocation. Cirrhosis is accompanied by a decrease in bactericidal activity by phagocytic cells and an impaired reticuloendothelial system (RES) activity. The RES is the main defensive system against bacteremia and other infections acquired through a hematogenous route. Most of the RES activity is located in the liver where Kupffer cells (tissue macrophages) are the major components. In cirrhosis, RES activity is impaired because of porto-systemic shunting that bypasses the liver (thereby escaping the action of the RES) and because of an impaired phagocytic activity of Kupffer cells. Impaired RES allows a transient bacteremia (bacteria arising from the gut or from other sources) to become prolonged and, in the presence of ascites, bacterial colonization occurs. In patients with reduced local defense mechanisms (e.g. low ascites complement levels), an overt ascites infection will develop (i.e. spontaneous bacterial peritonitis).*Slide 218WORSENING OF CIRRHOSIS LEADS TO WORSENING OF ASCITES AND HEPATORENAL SYNDROMECirrhosis leads to increased intrahepatic resistance and thereby to an increased sinusoidal pressure. In addition, portal hypertension leads to splanchnic and systemic arteriolar vasodilation, decreased effective arterial blood volume, upregulation of sodium-retaining hormones, sodium and water retention and consequently, plasma volume expansion. With progression of cirrhosis and portal hypertension, the systemic arteriolar resistance is more pronounced, leading to further activation of the renin-angiotensin-aldosterone and sympathetic nervous systems. The resulting increase in water and sodium retention can lead to refractory ascites while the increase in renal vasoconstriction can lead to a functional renal failure, the hepatorenal syndrome.