5.20
Zirrhose II: Pathophysiologie
Leberzirrhose ist eine fortschreitende chronische Leberschädigung, die durch anhaltende Entzündungen, übermäßige fibrotische Remodellierung und beeint…
Zirrhose beginnt mit wiederholten Leberschädigungen, die drei Hauptprozesse auslösen: Entzündung, Aktivierung des Immunsystems und Zelltod.
Gemeinsam führen diese Prozesse zu fortschreitenden Leberschäden.
Entzündungen ziehen Immunzellen zur Leber und lösen so entzündliche Zytokine wie Tumornekrosefaktor-alpha und Interleukin-1 aus.
Diese Zytokine stimulieren die Freisetzung des transformierenden Wachstumsfaktor-Beta, dem Haupttreiber der Fibrose.
Die Aktivierung des Immunsystems bewirkt, dass hepatische stellate Zellen aktiviert werden und überschüssiges Kollagen sowie extrazelluläre Matrixproteine produzieren.
Kontinuierliche Aktivierung führt zur Ansammlung dichter faseröser Bänder im Lebergewebe, was dessen normale Architektur verzerrt und den Blutfluss behindert.
Hepatozytenapoptose und -nekrose treten parallel zu diesen Veränderungen auf und lösen eine desorganisierte Regeneration aus, während die Fibrose fortschreitet.
Diese gestörte Regeneration führt zu Knoten der Leberzellen, die von dichtem fibrotischem Gewebe umgeben sind.
Die daraus resultierende Verzerrung erhöht den Widerstand gegen den Portalblutfluss und verursacht portale Hypertonie.
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Q1: What three main processes drive cirrhosis development?
Cirrhosis develops through inflammation, immune system activation, and hepatocyte death. Inflammation recruits immune cells that release cytokines like tumor necrosis factor-alpha and interleukin-1, triggering transforming growth factor-beta production. These processes activate hepatic stellate cells, stimulate collagen production, and cause liver cell death, collectively driving progressive liver damage and fibrosis.
Q2: How do hepatic stellate cells contribute to cirrhosis?
Hepatic stellate cells normally store vitamin A in a quiescent state. When activated by inflammatory signals, they transform into myofibroblasts and produce excess collagen and extracellular matrix proteins. Continuous activation leads to dense fibrous tissue accumulation that replaces normal liver tissue, distorting the liver's architecture and impairing its function.
Q3: What happens to the liver's structure as fibrosis progresses?
As fibrosis progresses, dense fibrous bands accumulate within liver tissue, distorting normal architecture. Hepatocyte death triggers disorganized regeneration, creating regenerative nodules—clusters of liver cells surrounded by fibrous tissue. These nodules further distort vascular and biliary structures, increasing resistance to portal blood flow and leading to portal hypertension.
Q4: How does cirrhosis lead to portal hypertension?
Fibrosis and regenerative nodules in the liver distort normal vascular architecture, increasing resistance to portal blood flow. This elevated pressure in the portal vein causes portal hypertension, which can trigger serious complications including ascites, splenomegaly, and bleeding from esophageal or gastric varices.
Q5: What role does inflammation play in cirrhosis pathophysiology?
Chronic liver injury triggers inflammation that recruits immune cells and promotes oxidative stress and reactive oxygen species production. Inflammatory cytokines damage liver tissue, disrupt cellular balance, and initiate fibrogenesis. This sustained inflammation accelerates hepatocyte injury and perpetuates the cycle of liver damage and fibrotic remodeling.
Q6: How does impaired liver regeneration affect cirrhosis progression?
Hepatocyte apoptosis and necrosis accelerate liver damage, prompting regeneration attempts. However, surrounding fibrosis disrupts this regenerative process, resulting in disorganized regeneration and regenerative nodules rather than normal tissue repair. This impaired regeneration perpetuates structural distortion and progressive functional decline in the liver.
Q7: What metabolic complications can result from advanced cirrhosis?
Advanced cirrhosis reduces the liver's ability to detoxify substances, allowing toxins like ammonia to accumulate and cause hepatic encephalopathy. The liver's diminished metabolic capacity also leads to kidney dysfunction, hormonal problems, and potential multi-organ failure in severe cases of decompensated cirrhosis.