Aetiologies and Pathophysiology of Chronic Liver Disease

Question 1

What is chronic liver disease?

Answer 1

Duration is greater than 6 months although the disease can present acutely; it progresses to cirrhosis

Question 2

Pathology of chronic liver disease?

Answer 2

Recurrent inflammation and repair with fibrosis and regeneration of hepatocytes

Question 3

Flow of chronic liver disease?

Answer 3

Causes of chronic liver disease lead to recurrent inflammation and fibrosis (the causal disease causes signs and symptoms)

There is compensated cirrhosis (there is enough liver to function) and then stigmata of cirrhosis appears (clinical signs)

Cirrhosis becomes decompensated and there is chronic liver failure (may be acute onset)

Question 4

Appearance of liver cirrhosis?

Answer 4

Bumps - regenerating nodules

Dips - scarring liver

Question 5

4 types of cells in the liver?

Answer 5

Hepatocytes
Endothelial cells
Kupffer cells (macrophages of liver)
Hepatic stellate cells (HSC) - cells that respond to aggravation by laying down scar tissue

Question 6

Stimulation of HSC response?

Answer 6

Apoptosis of hepatocytes
Kupffer cell response to disease
Products of damaged cells

Quiescent HSC activates and they:
Increase in number
Increase their production of, for example, metalloproteinase

TIMPs (Tissue Inhibitors of Metalloproteinase) cause apoptosis of the HSC and this allows resolution

Question 7

Causes of chronic liver disease?

Answer 7

Alcohol
Non-Alcoholic Fatty Liver Disease
Hepatitis C
Primary biliary cirrhosis
Autoimmune hepatitis
Hepatitis B
Haemochromatosis
Primary sclerosing cholangitis
Wilson's disease
α1-antitrypsin
Budd-Chiari
Methotrexate

Question 8

Pathogenesis of non-alcoholic fatty liver disease?

Answer 8

2 hit paradigm:
1st hit - excess fat accumulation

2nd hit - intra-hepatic oxidative stress caused by:
Lipid peroxidation, pro-flammatory cytokine release (TNFα), LPS, ischaemia-reperfusion injury, etc
This activates NF-κB and leads to progression of NASH

Question 9

How is fat stored in the liver?

Answer 9

Stored in the liver but this is saturable and eventually there is not enough space, so triglycerides are not longer stored

Fatty acids are the dangerous component

Question 10

What is the metabolic syndrome?

Answer 10

Type II diabetes (fasting glucose > or equal to 110 mg/dL)
Triglycerides (> or equal to 150 mg/dL)
NAFLD/NASH
Obesity
HDL cholesterol (