1. Levercirrhose, hand-out college Jan F. Monkelbaan, Internist en MDL-arts Afdeling MDL UMCU

2. Indeling 1.Anatomie 2.Fysiology 3.Steatose 4.Fibrose 5.Cirrhose 6.Complicaties van cirrhose 7.Therapie 8.Leverfalen

3. Facts of the Liver largest gland in body 2 main lobes – R & L hepatic artery supplies oxygenated blood from aorta of (~ 1/3) portal vein supplies deoxygenated, nutrient rich blood from digestive tract (~ 2/3) bile exits through bile ducts Liver is able to regenerate itself, & only ~20% of fxn’ing liver is needed for life. Liver accounts for ~ 26% of our BMR!

4. Diagrammatic representation of a hepatic lobule

5. portaal gebied galgang portale vene arterietakje Centrale vene Indeling Rappaport zone 1: periportaal zone 2: midden leverlobulus zone 3: pericentraal

6. Veneuse bloedstroom(zuurstofrijk!: lever heeft dubbele voorziening zuurstofrijk bloed)): van portaal via sinusoiden naar centraal Galstroom: van pericentraal naar portaal driehoekje GAL Bloed

7. Liver ‘Functions’ Metabolism – Carbohydrate, Fat & Protein Secretory – bile, Bile acids, salts & pigments Excretory – Bilirubin, drugs, toxins Synthesis – Albumin, coagulation factors Storage – Vitamins, carbohydrates etc. Detoxification – toxins, ammonia, etc.

8. Physiology of the Liver produces ~ 1 quart of bile (water, bile acids, bile salts, cholesterol, lecithin & billirubin) toxins are stored or detoxified, & steroids hormones are metabolized carbohydrate metabolism –glycogenesis –glycogenolysis –gluconeogenesis (from AA and lactic acid) lipid metabolism –stores exogenous triglycerides –f.a. & TGA synthesis from glucose and AA’s –  -oxidation –ketogenesis –lipoprotein synthesis for transport of TAG & cholesterol –cholesterol synthesis (for production of bile salts) protein metabolism –deamination of AA –conversion of ammonia (NH3) into urea for excretion –synthesis of plasma proteins (albumin, prothrombin, fibrinogen, transferrin, etc.) –transamination (for synthesis of non-essential AA) storage –vitamin A –vitamin B12 –vitamin D –vitamin E –vitamin K –iron & copper –zinc & magnesium activation of Vitamin D, vitamin A, & folate phagocytosis – of worn-out rbs & wbc & some bacteria

9. Common Laboratory Tests for Liver Function Hepatic excretion —Total serum bilirubin, urine bilirubin Cholestasis tests —Serum alkaline phosphatase Hepatic enzymes —ALT, AST Serum proteins —PT, PTT, serum albumin Markers of specific liver diseases —Serum ferritin, ceruloplasmin Specific tests for viral hepatitis —IgM anti-HAV, anti- HBS, HCV-RNA

10. Galgang (canaliculus) Canaliculaire (apicale) membraanBasolaterale membraan (post)hepatische cholestase: verhoging canaliculaire membraan enzymen in bloed: alkalische fosfatase, gamma GT (bilirubine) levercelbeschadiging verhoging intracellulaire enzymen in bloed: ASAT ALAT LDH (bilirubine) Bloedafwijkingen bij leverziekten

11. Lever beschadiging Begrippen: Hepatitis Steatose Fibrose Cirrose

12. Fibrosis Response to inflammation or direct toxic insult Initially, may be portal, pericentral, or sinusoidal Eventually, fibrous tendrils link areas of the liver, called bridging Fibrosis is potential reversible; continuing injury and fibrosis lead to nodules of regenerating hepatocytes surrounded by fibrous bands, termed CIRRHOSIS. Cirrosis is irreversible.

13. Pathophysiology Fibrose Slow, insidious, progressive, chronic Fibrous bands replace normal liver structure Cell degeneration occurs Liver attempts to regenerate cells but cells are abnormal and disorganized Causes abnormal blood and lymph flow Results in more fibrous tissue formation

14. Levercirrose: is geen oorzaak maar een gevolg van diverse leverziekten Sterke verbindweefseling in de lever –door diverse oorzaken (meest hepatisch) –met vorming regeneratienoduli –waardoor portaal bloed niet goed meer door lever heen kan (portale hypertensie: ascites, slokdarmvarices) –en uiteindelijk ook de leverfunctie achteruitgaat (stollingsstoornis, laag albumine)

15. Definition: 1.Diffuse disorder of liver characterised by; 2.Complete loss of normal architecture, 3.Replaced by extensive fibrosis with, 4.Regenerating parenchymal nodules.

16. Etiology of Cirrhosis Alcoholic liver disease60-70% Viral hepatitis10% Biliary disease5-10% Primary hemochromatosis5% Cryptogenic cirrhosis10-15% Wilson’s,  1AT defrare

17. Complications of Cirrhosis Portal hypertension Ascites Varices Coagulation defects Jaundice PSE (portal systemic encephalopathy) Hepatorenal syndrome

18. Icterus Yellow discoloration of skin & sclera due to excess serum bilirubin. >40umol/l, (3mg/dl) Conjugated & Unconjugated types Obstructive & Non Obstructive (clinical) Pre-Hepatic, Hepatic & Post Hepatic types Jaundice - Not necessarily liver disease *

19. Portal Hypertension Increased pressure in the portal venous system. Normal portal pressure is 5 to 10 mm Hg (7 to 14 cm H2O), which exceeds inferior vena caval pressure by 4 to 5 mm Hg (the portal venous gradient). Higher values are defined as portal hypertension. Portal hypertension is asymptomatic; clinical findings result from its complications. The most important is acute variceal bleeding, usually from the distal esophagus, less often from the gastric fundus, and only rarely from other sites. Portal-systemic encephalopathy and ascites are the other major consequences of portal hypertension.

20. Hepatic Failure/ESLD/ Hepatic Encephalopathy StageSymptom IMild confusion, agitation, irritability, sleep disturbance, decreased attention IILethargy, disorientation, inappropriate behavior, drowsiness IIISomnolence but arousable, incomprehensible speech, confusion, aggression when awake IVComa

21. Transjugular Intrahepatic P orto-systemic Shunt TIPS