Cirrhosis Flashcards
what is cirrhosis
the result of chronic inflammation and damage to liver cells
also known as end stage liver failure
damaged liver cells are replaced by scar tissue
what is portal hypertension
fibrosis affects the structure and blood flow through the liver which causes increased resistance in the vessels leading into the liver
causes of portal hypertension
prehepatic - portal vein thrombosis
Intrahepatic - schistosomiasis, cirrhosis.
Posthepatic - right sided heart failure
Describe the process of portal hypertension
- hepatocyte injury
- secretion of paracrine factors activate stellate cells
- stellate cells proliferate and release TGF-B
- produces collagen which is fibrotic
- extra fibrotic mass compresses sinusoids and central vein
- increases pressure which causes portal hypertension
What is the result of portal hypertension
collateral blood shunting to gastroesophageal veins or towards systemic circulation
Symptoms of portal hypertension
- mostly asymptomatic
- present when oesophageal varices rupture
complications of portal HTN
Ascites
bleeding varices
How does ascites lead to portal htn
fluid is more likely to get pushed into tissues and across into peritoneal cavity
most common causes of liver cirrhosis 4
alcoholic liver disease
non alcoholic fatty liver disease
hep B +D
hep c
What does chronic liver injury result in?
inflammation, matrix deposition, necrosis and angiogenesis all of which lead to FIBROSIS
What does liver injury cause
necrosis and apoptosis, releasing cell contents and reactive oxygen species (ROS)
This activates hepatic stellate cells and tissue macrophages (Kupffer cells)
What do hepatic stellate cells do?
release cytokines that attract neutrophils and macrophages to the liver which results in further inflammation and thus necrosis and eventual fibrosis
What do Kuppfer cells do? Macrophages
phagocytose necrotic and apoptotic cells and secrete pro- inflammatory mediators
What are the pr inflammatory mediators secreted by Kuppfer cells?
- Transforming growth factor-beta (TGF-beta) which leads to the transdifferentiation of stellate cells to myofibroblasts
- Platelet derived growth factor (PDGF) which stimulates myofibroblast proliferation
What does increased myofibroblasts do?
leads to progressive collagen matrix deposition resulting in fibrosis and scar accumulation in the liver
Characteristic features of cirrhosis
regenerating nodules separated by fibrous septa and loss of lobular architecture within the nodules