Liver cirrhosis pathology Flashcards
What is the normal histology of the liver?
- Hexagonal in shape
- The hepatocytes are arranged concentrically around a central vein
- At the periphery of each lobule lies a portal triad, which consists of (hepatic artery, portal vein, and bile duct)
- The central region is the most susceptible to ischemic injury
What are the functions of the liver?
1) Immunity
- Phagocytes like kupffer cells destroys the pathogens like bacteria which enters the gut
2) Blood
- Creates blood clotting factors
- Filters the blood from the toxins
- Destroys old/damaged RBC
3) Metabolism
- Forms the bile
- Breaks down fats, proteins
- Involved in the regulation of blood glucose
4) Storage
- It stores fats, protein, glycogen, vitamins, copper and iron
- FYI: hEPATIC DISEASES CAN BE ATTRIBUTED to the dysfunction of any of these diverse liver functions
What are the different patterns of hepatic injury?
1) Degeneration and intracellular accumulation
- Pathological swelling of the liver cells (ballooning, with fat pigmentation)
2) Inflammation (influx of acute or chronic inflammatory cells into the portal tract/parenchyma)
3) Cell death (Could be coagulative necrosis due to ischemia or apoptosis due to toxic, viral, or immunological injury); the lesions might be focal, zonal, submissive, or massive
4) Regeneration
5) Fibrosis (can develop after inflammation or direct toxic insults; it divides the liver into nodule of regenerating hepatocytes surrounded by scar tissue)
6) Neoplasia (99% metastatic)
What is alcoholic liver disease?
- Alcohol is a well-known cause of fatty liver disease in adults, which histologically can manifest as steatosis, steatohepatitis, and cirrhosis
- Account to 40-50% of deaths due to cirrhosis
- Steatosis: Accumulation of fat within hepatocytes
- Steatohepatitis: Inflammation of the liver associated with fat accumulation, leading to liver damage
- Cirrhosis: Advanced liver fibrosis with nodular regeneration, resulting in irreversible liver dysfunction
What is meant by non-alcoholic fatty liver disease?
- Fatty liver disease due to non-alcoholic causes it can mimic the spectrum of hepatic changes that are associated with alcohol abuse
- It could be caused by insulin resistance, obesity, diabetes mellitus, hypertension and dyslipidemias
What are the different categories of liver alterations that are observed in fatty liver disease?
1) Hepatic steatosis (accumulation of fat within the hepatocytes) seen in 90-100% of heavy drinkers
2) Steatohepatitis + Fibrosis (fat + hepatocellular injury and inflammation)
3) Cirhosis (irreversible)
Describe the pathophysiology of alcoholic fatty liver disease
- Alcohol consumption causes the shunting of the normal substrates away from the catabolism and towards the biosynthesis of lipids due to:
1) Excess NADH generation from alcohol dehydrogenase and acetaldehyde dehydrogenase
2) Impaired assembly/secretion of lipoprotein
3) Increased peripheral fat catabolism
Describe the microscopic photos of hepatocellular steatosis
Hepatocellular fat accumulation typically begins in the centrilobular hepatocytes, and the lipid droplet could range from small (microvascular) to large (macrovascular “which completely replaces the cytoplasm of the hepatocyte) steatosis
What is steatohepatitis?
- More pronounced with alcohol than NAFLD
- Inflammation of the liver with fat accumulation, in alcoholic hepatitis it can be caused by:
1) Acetaldehyde (can bind to the hepatocellular proteins, disrupting the cytoskeleton and contributing to the damage of the hepatocytes)
2) Alcohol
3) Reactive oxygen species
4) Cytokine-Mediated inflammation and cell injury (as the ROS are generated during the metabolism of alcohol)
Describe the morphology of steatohepatitis
1) Hepatocyte ballooning (due to cell death it increases in size “balloon”
- Considered as a form of apoptosis
2) MALLORY-DENK bodies (intermediate filaments “keratin 8 and 18”), it is visible as eosinophilic cytoplasmic inclusions in the degenerating hepatocyte
3) Infiltration of neutrophils
What forms the MALLORY-DENK bodies?
Keratin 8 and 18 intermediate filaments
How does steatohepatitis with fibrosis occur?
- Fibrosis will appear first at the centrilobular region as central vein sclerosis
-Perisinusoidal scar appears after that in the centrilobular region and spreads outwards, encircling the individual or small clusters of the hepatocytes in a wire fence pattern
- These tendrils of fibrosis eventually link to the portal tracts and begin to condense, creating a central-portal fibrousa septa
So what are the characteristics in the appearance of the liver when fibrosis occurs?
The wire-fencing-like structure of he tendrils of fibrosis
What are the clinical features of hepatic steatosis?
1) Asymptomatic
2) Hepatomegaly with mild elevation in the serum bilirubin and alkaline phosphate
- At this stage, alcohol withdrawal and an adequate diet are sufficient as a treatment
3) Alcoholic hepatitis, which can occur after just weeks or
4) Alcoholic cirrhosis (15-20 years of drinking is required)
5) End-stage alcoholic liver disease, which could lead to death due to:
- Hepatic failure
- Massive GI hemorrhage
- Intercurrent infections
- Hepatocellular carcinoma
What are the complications of liver cirrhosis?
1) Liver failure (jaundice, coagulopathy, and encephalopathy)
2) Portal hypertension (varices, ascitis, bacterial perinotis)
3) Hepatocellular carcinoma
What is meant by NAFLD?
- A common condition where fatty liver disease develops in people who do not drink alcohol (steatosis, steatohepatitis, and cirrhosis)
- It is consistently associated with insulin resistance and the metabolic syndrome
- NAFLD is considered to be a significant contributor to the pathogenesis of cryptogenic cirrhosis
What are the main causes of NAFLD?
1) Insulin resistance
2) Metabolic syndromes
- Others might include:
1) Type-2 diabetes
2) Obesity
3) Dyslipidemia
4) Hypertension
How does Insulin resistance cause NAFLD?
Insulin resistance can result in the accumulation of TGs in hepatocytes via three mechanisms (at least)
1) Impaired oxidation of fatty acids
2) Increased synthesis and uptake of fatty acids
3) Decreased hepatic secretion of VLDL
What are the clinical features of NAFLD?
- It is the most common cause of incidental elevation of serum transaminases
1) Most people are asymptomatic
2) Some people might face (fatigue, malaise, RUQ discomfort, etc)
How to diagnose NAFLD?
Liver biopsy
- However, the progression of NAFLD from steatosis to active steatohepatitis and then to cirrhosis is low
