17 - Liver Pathology Flashcards
How much does the liver weigh?
1400-1600 grams
What is the anatomical division of the liver?
Hepatic Lobules
What is the functional division of the liver?
Liver acini (relation to central vein, function and pathology)
Zones and why are they important?
Within acinar structure - periportal/1, mid zonal/2, centrilobular (3)
Important in pathology. Different pathologies may affect different zones,
What are the 5 general responses of the liver to injury/toxic insult?
- Degeneration (loss of hepatocytes) and intra-cellular components - fat-steatosis - occurs with alcohol - and bilirubin-cholestasis - obstruction to biliary flow)
- Necrosis and apoptosis
- Inflammation - acute or chronic hepatitis causing damage to hepatocytes
> especially viral but can be due to autoimmune, drug, alcohol - Fibrosis
> scarring around the regenerating hepatocytes
> progresses on to cirrhosis - Regeneration and proliferation of hepatocytes
> trying to repair damage liver
What is the most common cause of liver injury we will see?
Viral infection and drug/toxin affects especially alcohol
What is hepatic failure?
When there is sudden and massive damage to the liver or is the end point of chronic damage resulting in 80-90% loss of liver capacity/function. The threshold for liver failure to present is so high because of the large hepatic reserve/regenerative capacity
Where do you see liver failure most commonly?
Viral hepatitis - massive lost of hepatocytes and so liver function
What is an example of chronic damage to the liver?
Chronic injury due to chronic alcohol intake - lost hepatic reserve and present with hepatic failure
What dose it mean to say often in hepatic failure there is decompensation associated with increased demand?
Often patients are on the boderline of hepatic function/don’t have any hepatic reserve but cope fine. If an injury or event occurs such as bleeding, or infection, that requires an increase demand/function, this can tip the patient into over into hepatic failure as they have no hepatic reserve
hepatic failure has a … mortality
high
What are 3 clinical features of hepatic failure?
- jaundice
- hypoalbuminaemia (less albumin/clotting factor - loss of synthetic function)
- elevated ammonia leading to neurological dysfunction (due to a decrease in protein breakdown/metabolic activity and detoxification by the liver)
Describe hepatocellular necrosis
- may see in panadol overdose
- necrosis to hepatocytes near hepatic vein/portal triad i.e. periportal/zone 1
What are some characteristics of cirrhosis?
- there is bridging of fibrous septa that often links portal tracts
- parenchymal nodules (micro and macronodules) of proliferating hepatocytes encircled by fibrosis
- disruption of liver and vasculature architecture disrupting function
> vasculature interupted and increased pressure causes formation of shunts and reversal of blood flow from hepatocytes and portal vein
What is portal hypertension?
Where there is increased resistance to portal blood flow i.e. fibrosis/cirrhosis and interuption of vasculature resulting in increased pressure and backflow/shunting of the portal system to the systemic system
What may cause increased pressure in the portal system/vein?
- prehepatic
> obstruct before portal vein enters liver
> obstructive thrombosis in the portal vein
> often see in coagulation problems - post hepatic
> obstruction after the liver
> SEVERE right side heart failure where there is increased pressure at the RA and so IVC and eventually portal vein - intrahepatic (most common)
> within the liver
> cirrhosis which causes a fibrosis and distortion of the vasculature causing and increasing the pressure of the hepatic vessels
Most common cause of portal hypertension?
Hepatic causes especially cirrhosis
What are 4 consequences of portal hypertension?
- Ascites
- Porto-systemic shunts
- Congestive splenomegaly
- Hepatic encephalopathy
Prehepatic causes of portal hypertension?
> obstruct before portal vein enters liver
obstructive thrombosis in the portal vein
often see in coagulation problems
Post hepatic causes of portal hypertension
> obstruction after the liver
> SEVERE right side heart failure where there is increased pressure at the RA and so IVC and eventually portal vein
Intra hepatic causes of portal hypertension
> within the liver
cirrhosis which causes a fibrosis and distortion of the vasculature causing and increasing the pressure of the hepatic vessels
Congestive splenomegaly?
Pressure increase in portal vein so backflow into splenic vein = splenic congestion and enlargement of the spleen
hepatic encephalopathy?
Shunting of hepatocytes so not normal metablic functions. Ammonia to brain.
Causes of viral hepatitis?
Hepatitis A,B,C,D,E viruses
Cytomegalovirus (CMV)
Epstein-Barr virus
> i.e. many viruses will cause hepatic inflamation
Tell me about hepatitis A?
- person to person, faecal-oral transmission
- usually benign self-limiting infection/hepatitis
- patients can be asymptomatic or flu-like symptoms/mild-febrile and jaundice
- does NOT cause chronic hepatitis or cirrhosis as people clear the virus
- no intervention only supportive care
- incubation period 2-6 weeks
Does hepatisis A cause chronic hepatitis or cirrhosis?
NO (B and C do)
What are some features about hepatitis B?
- is a significant problem globally
- can occur as acute hepatitis and may resolve
- or can can present as chronic hepatitis which may lead to cirrhosis, compicated by hypertension and hepatic failure
- can lead to massive necrosis due to the damage of the virus infecting hepatocytes as well as the damage from the immune response to viral antigen on infected hepatocytes > fibrosis and cirrhosis
- blood and body fluid borne
- 350 million carriers worldwide
How is hep B transmitted?
Blood and body fluid borne
Features of hepatitis C?
- hepatitis C is a major cause of liver failure
- like hep B is also transmitted by inoculations and blood transfusions i.e. body fluids)
- acute infection is usually undetected and present with antibodies to Hep C (chronic hep C carriers)
- chronic hepatitis occurs in MOST people with hep C, causing chronic damage, cirrhosis and increased risk of carcinoma
- more than 20% of people with hep C develop cirrhosis 5 - 20 years after infection
- now new successful drugs
In which hep is it rare to have acute hepatitis?
Hep C - usually undetected and will present chronically with hep C antibodies
What can cause hepatitis?
Anything that damages the liver and causes inflammation
Autoimmune hepatitis?
- IS attacks hepatocytes
- exclude viral cause first
- infiltration around hepatocytes of lymphocyte cells and plasma cells
- therapy is immunosuppression
- genetic predisposition
- often have other autoimmune diseases
What are hepatotoxins that cause drug and toxin-induced liver injury classified into?
Predictable hepatotoxins that act in a dose dependent manner and unpredictable/idiosyncratic heptotoxins
Hepatotoxins can act by …
Direct cell toxicity or the liver converts them to an active toxin or it activates immune mechanisms
What is the leading cause of liver disease in most Western Countries?
Alcoholic Liver disease
How does alcohol affect the liver?
> the alcohol has multiple effects on the liver not just a single toxic effect
- changes in lipid metabolism
- decreased export of lipoproteins
- cell injury caused by ROS and CYTOKINES
Consequences
- hepatic steatosis (fat accumulation causing damage and cirrhosis)
- alcoholic hepatitis (acute and see an increase in hepatic enzymes)
- cirrhosis (if exposure is ongoing and chronic)
What are the pathological consequences of alcohol of alcoholic liver disease/chronic alcohol consumption?
- hepatic steatosis (fat accumulation causing damage and cirrhosis
- alcoholic hepatitis (acute and see an increase in hepatic enzymes)
- cirrhosis (if exposure is ongoing and chronic and large loss of hepatocytes)
Can you have fatty change in the liver without excessive alcohol intake?
Yes - Non-alcoholic fatty liver disease (NAFLD)
What is NAFLD?
- often see associated with other metabolic diseases and lifestyle diseases, obesity, type 3 diabetes, hypertension
- often see in males 40-60, overweight, higher alcohol, hypertension
- may present with mild liver dysfunction and mild liver steatosis and inflammation but CAN progress to cirrhosis so suggests is NOT just a benign fatty change in the liver
