Liver disease pathophysiology Flashcards
What is the first impression of liver microanatomy?
A uniform mass of large glandular cells throughout the liver substance
How are liver cells arranged?
In perforated plates, one cell wide
What are the blood channels between liver cell plates called?
Sinusoids
What defines the classic hepatic lobules?
The distribution of blood vessels
What is the central vein in a liver lobule?
A very thin wall vessel that lies in the center of a lobule
What constitutes a portal triad in the liver?
- Branch of portal vein
- One or more small hepatic arteries/arterioles
- One or more bile ducts/ductules
What is the unique blood supply of the liver?
Immediate access to nutrient rich intestinal venous blood via portal vein
What are the main cell types in the liver and their functions?
- Hepatocytes - metabolism
- Kuppfer Cells - inflammatory response
- Stellate cells - responsible for fibrosis
What is drug metabolism also known as?
Xenobiotic metabolism
What is acute liver failure (ALF)?
Loss of liver function that occurs quickly in days or weeks in a person with NO pre-existing liver disease
What is the leading cause of acute liver failure in the UK?
Paracetamol
What are the early symptoms of acute liver failure?
- Malaise
- Nausea
- Vomiting
- Abdominal pains
- Dehydration
What can lead to multi-organ failure in acute liver failure?
Acidosis, profound hypoglycaemia, coagulopathy, and encephalopathy
What is bilirubin formed from?
The breakdown of haemoglobin
What makes unconjugated bilirubin not excreted in urine?
It is hydrophobic and strongly albumin-bound
What causes cholestasis?
Blockage of the bile ducts leading to increased conjugated bilirubin in blood
What is the pathophysiology of cirrhosis?
Fibrotic tissue disrupts hepatic architecture and leads to portal hypertension
What are oesophageal varices?
Enlarged veins in the esophagus due to portal hypertension
What characterizes fatty liver disease?
Excessive accumulation of triglycerides inside the liver cells
What are primary causes of fatty liver disease?
- MASLD associated with obesity and diabetes type II
- Alcohol (AFL)
- TPN
- Chemicals and drugs
- Malnutrition and rapid weight loss
- Pregnancy
What is the pathophysiology of alcoholic liver disease (ALD)?
Consumption of >60g alcohol per day leads to increased hepatic glycerol 3-phosphate and lipolysis
What is the diagnostic criterion for metabolic syndrome?
3 of the following: abdominal obesity, serum triglycerides >150mg/dl, HDL <40mg/dl for men, HDL <50mg/dl for women, BP >130/85, fasting blood glucose >110mg/dl
What is the prevalence of MASLD?
~ 20-23%
What is the significance of the HOMA-IR value?
HOMA-IR >3 indicates severe insulin resistance in non-diabetic patients
What is a recommended treatment for MASLD?
- Weight reduction
- Diet low in carbohydrates and saturated fat
- Exercise
- Anti-obesity agents
- Bariatric surgery
What is the role of ROS in metabolic dysfunction associated liver disease?
ROS can directly activate stellate cells leading to fibrosis
What are the clinical features of MASLD?
- Asymptomatic
- RUQ abdominal pain
- Fatigue
- Hepatomegaly
- Acanthosis nigricans (children)
What is the upper normal value of transaminases?
Usually < x3 upper limit
What is the diagnostic procedure for MASLD if there is doubt?
Liver biopsy
