17 - Liver Pathology

Question 1

How much does the liver weigh?

Answer 1

1400-1600 grams

Question 2

What is the anatomical division of the liver?

Answer 2

Hepatic Lobules

Question 3

What is the functional division of the liver?

Answer 3

Liver acini (relation to central vein, function and pathology)

Question 4

Zones and why are they important?

Answer 4

Within acinar structure - periportal/1, mid zonal/2, centrilobular (3)
Important in pathology. Different pathologies may affect different zones,

Question 5

What are the 5 general responses of the liver to injury/toxic insult?

Answer 5

1. Degeneration (loss of hepatocytes) and intra-cellular components - fat-steatosis - occurs with alcohol - and bilirubin-cholestasis - obstruction to biliary flow)
2. Necrosis and apoptosis
3. Inflammation - acute or chronic hepatitis causing damage to hepatocytes
   > especially viral but can be due to autoimmune, drug, alcohol
4. Fibrosis
   > scarring around the regenerating hepatocytes
   > progresses on to cirrhosis
5. Regeneration and proliferation of hepatocytes
   > trying to repair damage liver

Question 6

What is the most common cause of liver injury we will see?

Answer 6

Viral infection and drug/toxin affects especially alcohol

Question 7

What is hepatic failure?

Answer 7

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

Question 8

Where do you see liver failure most commonly?

Answer 8

Viral hepatitis - massive lost of hepatocytes and so liver function

Question 9

What is an example of chronic damage to the liver?

Answer 9

Chronic injury due to chronic alcohol intake - lost hepatic reserve and present with hepatic failure

Question 10

What dose it mean to say often in hepatic failure there is decompensation associated with increased demand?

Answer 10

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

Question 11

hepatic failure has a … mortality

Answer 11

high

Question 12

What are 3 clinical features of hepatic failure?

Answer 12

1. jaundice
2. hypoalbuminaemia (less albumin/clotting factor - loss of synthetic function)
3. elevated ammonia leading to neurological dysfunction (due to a decrease in protein breakdown/metabolic activity and detoxification by the liver)

Question 13

Describe hepatocellular necrosis

Answer 13

• may see in panadol overdose

- necrosis to hepatocytes near hepatic vein/portal triad i.e. periportal/zone 1

Question 14

What are some characteristics of cirrhosis?

Answer 14

• 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

Question 15

What is portal hypertension?

Answer 15

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

Question 16

What may cause increased pressure in the portal system/vein?

Answer 16

• 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

Question 17

Most common cause of portal hypertension?

Answer 17

Hepatic causes especially cirrhosis

Question 18

What are 4 consequences of portal hypertension?

Answer 18

1. Ascites
2. Porto-systemic shunts
3. Congestive splenomegaly
4. Hepatic encephalopathy

Question 19

Prehepatic causes of portal hypertension?

Answer 19

> obstruct before portal vein enters liver
obstructive thrombosis in the portal vein
often see in coagulation problems

Question 20

Post hepatic causes of portal hypertension

Answer 20

> obstruction after the liver

> SEVERE right side heart failure where there is increased pressure at the RA and so IVC and eventually portal vein

Question 21

Intra hepatic causes of portal hypertension

Answer 21

> within the liver
cirrhosis which causes a fibrosis and distortion of the vasculature causing and increasing the pressure of the hepatic vessels

Question 22

Congestive splenomegaly?

Answer 22

Pressure increase in portal vein so backflow into splenic vein = splenic congestion and enlargement of the spleen

Question 23

hepatic encephalopathy?

Answer 23

Shunting of hepatocytes so not normal metablic functions. Ammonia to brain.

Question 24

Causes of viral hepatitis?

Answer 24

Hepatitis A,B,C,D,E viruses
Cytomegalovirus (CMV)
Epstein-Barr virus
> i.e. many viruses will cause hepatic inflamation

Question 25

Tell me about hepatitis A?

Answer 25

• 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

Question 26

Does hepatisis A cause chronic hepatitis or cirrhosis?

Answer 26

NO (B and C do)

Question 27

What are some features about hepatitis B?

Answer 27

• 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

Question 28

How is hep B transmitted?

Answer 28

Blood and body fluid borne

Question 29

Features of hepatitis C?

Answer 29

• 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

Question 30

In which hep is it rare to have acute hepatitis?

Answer 30

Hep C - usually undetected and will present chronically with hep C antibodies

Question 31

What can cause hepatitis?

Answer 31

Anything that damages the liver and causes inflammation

Question 32

Autoimmune hepatitis?

Answer 32

• 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

Question 33

What are hepatotoxins that cause drug and toxin-induced liver injury classified into?

Answer 33

Predictable hepatotoxins that act in a dose dependent manner and unpredictable/idiosyncratic heptotoxins

Question 34

Hepatotoxins can act by …

Answer 34

Direct cell toxicity or the liver converts them to an active toxin or it activates immune mechanisms

Question 35

What is the leading cause of liver disease in most Western Countries?

Answer 35

Alcoholic Liver disease

Question 36

How does alcohol affect the liver?

Answer 36

> 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)

Question 37

What are the pathological consequences of alcohol of alcoholic liver disease/chronic alcohol consumption?

Answer 37

• 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)

Question 38

Can you have fatty change in the liver without excessive alcohol intake?

Answer 38

Yes - Non-alcoholic fatty liver disease (NAFLD)

Question 39

What is NAFLD?

Answer 39

• 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