Levercirrhose, hand-out college

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Levercirrhose, hand-out college

• Jan F. Monkelbaan,
• Internist en MDL-arts
• Afdeling MDL UMCU

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Indeling

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

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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 fxning liver is needed for life.
• Liver accounts for 26 of our BMR!

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Diagrammatic representation of
a hepatic lobule
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Centrale vene
portaal gebied galgang portale vene arterietakje
Indeling Rappaport zone 1 periportaal zone 2
midden leverlobulus zone 3 pericentraal
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Veneuse bloedstroom(zuurstofrijk! lever heeft
dubbele voorziening zuurstofrijk bloed)) van
portaal via sinusoiden naar centraal Galstroom
van pericentraal naar portaal driehoekje
GAL
Bloed
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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.

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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 AAs
• ?-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

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Common Laboratory Tests for Liver Function

• 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

• Hepatic excretion
• Total serum bilirubin, urine bilirubin
• Cholestasis tests
• Serum alkaline phosphatase
• Hepatic enzymes
• ALT, AST

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

• Begrippen
• Hepatitis
• Steatose
• Fibrose
• Cirrose

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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.

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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

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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)

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Definition

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

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Etiology of Cirrhosis

• Alcoholic liver disease 60-70
• Viral hepatitis 10
• Biliary disease 5-10
• Primary hemochromatosis 5
• Cryptogenic cirrhosis 10-15
• Wilsons, ?1AT def rare

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Complications of Cirrhosis

• Portal hypertension
• Ascites
• Varices
• Coagulation defects
• Jaundice
• PSE (portal systemic encephalopathy)
• Hepatorenal syndrome

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Icterus

• Yellow discoloration of skin sclera due to
  excess serum bilirubin. gt40umol/l, (3mg/dl)
• Conjugated Unconjugated types
• Obstructive Non Obstructive (clinical)
• Pre-Hepatic, Hepatic Post Hepatic types
• Jaundice - Not necessarily liver disease

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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.

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Hepatic Failure/ESLD/ Hepatic Encephalopathy

• Stage Symptom
• I Mild confusion, agitation, irritability,
  sleep disturbance, decreased attention
• II Lethargy, disorientation, inappropriate
  behavior, drowsiness
• III Somnolence but arousable,
  incomprehensible speech, confusion,
  aggression when awake
• IV Coma

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T
ransjugular
I
ntrahepatic
orto-systemic

S
hunt
P
TIPS