Liver and pancreas pathophysiology Flashcards
Patterns of alcohol-related damage to the liver (pathological names)
- fatty change -> steatosis
- steatohepatitis -> fatty liver disease, inflammation + fat accumulation in the liver
- fibrosis
- cirrhosis
What are Mallory Denk bodies?
When we drink alcohol -> hepatocytes are damaged -> accumulate fat -> if this is chronic * then filaments in hepatocytes break down -> Mallory Denk bodies will form
mallory denk bodies (red on the picture) + neutrophils (blue on the picture) = steatohepatitis (inflammation of the liver)
(hepatocytes may recover in 6-8 weeks of stopping drinking)
How long does it take for a) fat b) Mallory Denk bodies to disappear after alcohol cessation?
a) fat: 6-8 weeks
b) mallory denk: 3 months
*but if the alcohol drinking continue - end up with fibrosis
- What is the normal surface of the liver like?
- What is the surface of the liver in cirrhosis?
- Normal -> smooth
- Cirrhosis -> nodular
What pathological process is the nodule in the cirrhotic liver result of?
hepatocytes die -> nodules = residual hepatocytes that are stretched out and pulled apart by fibrosis
What is the pathologist assessing in the biopsy of the alcoholic liver (degrees of damage)?
- Steatosis
- Steatohepatitis (fat accumulation + inflammation)
- Degree of fibrosis
- Cirrhosis
- Hepatocellular Carcinoma
What else (apart from alcohol) can cause liver damage?
- non-alcoholic fatty liver disease (e.g.people with large BMI increased risk)
- non-alcoholic steatohepatitis
- viruses (hepatitis B, C etc)
- drugs/toxins
- other tumours (either hepato-cellular ca or metastases e.g. from the lung or colon)
Causes of liver cirrhosis in adults
- alcohol
- hepatitis B or C (chronic as inflammation and destruction of hepatocytes)
- non-alcoholic steatohepatitis
- immunological damage
- genetic problems
x2 examples of autoimmune liver problems leading to cirrhosis
a) autoimmune disease - antibody against and destruction of own hepatocytes
b) primary biliary cholangitis - inflamed bile ducts in the liver -> damage and destruction
x2 examples of genetic liver problems leading to cirrhosis
- hemochromatosis - excess of iron -> accumulation in the tissues -> damage to hepatocytes
- alpha-1 anti-trypsin deficiency -> damage to hepatocytes -> cirrhosis
Causes of liver cirrhosis in children
- CF
- chronic active hepatitis
- Wilson’s disease
- alpha-1 antitrypsin deficiency
- galactosaemia*
*galactosaemia - metabolic disease; body is unable to metabolise galactose -> galactose accumulates in the tissues
Complications of liver cirrhosis
- portal hypertension (ascites, enlarged spleen, varies)
- liver cell failure (jaundice, bleeding tendency)
- hepatocellular carcinoma
General categories of causes of jaundice
Elevated level of bilirubin:
A. Pre-Hepatic -> excess production
B. Hepatocellular -> #conjugation
C. Post-hepatic/ obstructive -> impaired bile flow
What are the possible causes of Pre-hepatic reasons for jaundice?
Pre-hepatic - an excess of bilirubin (e.g. broken RBCs)
Causes: haemolytic anaemia, thalassemia, major haemorrhage
Examples of the reasons for hepatocellular causes of jaundice?
Hepatocellular -> anything that will # liver’s ability to conjugate bilirubin
Examples of types of damage: reduced uptake, impaired conjugation, decreased hepatocellular excretion
Examples of conditions leading to hepatocellular damage: viruses, drugs, toxins, alcohol, circulatory disturbance, autoimmune disease, cirrhosis
Reasons of post-hepatic/obstructive causes of jaundice
Impaired bile flow:
A. Intrahepatic: biliary tree disease (primary biliary cirrhosis)
B. Extrahepatic: gallstones, BD stricture, Primary Sclerosing Cholangitis, pancreatic cancer
Simply, what RBCs break into
- RBC -> globin and heam
*globin recycled
*heam -> iron and bilirubin
*iron is reused
- Bilirubin bound to albumin -> travels to the liver -> conjugation -> excretion into bile
Patient presents with jaundice, what do we enquire about in the history ?
Try to determine if it`s chronic or acute
investigations in jaundice
What markers may be raised in case of bile duct (cholestasis) problems that lead to jaundice?
Alkaline Phosphatase (ALP) and GGT
What markers may be raised in case of hepatocytes damage/ problems that lead to jaundice?
AST and ALT
Stigmata of chronic liver disease/cirrhosis
- ascites
- spider naevi
- palmar erythema
What is Ishak score used for?
To assess the degree of inflammation and fibrosis in hepatitis C
Histological features of liver biopsy in Hepatitis C
inflammation and lymphocytes present
assessment of degree of scarring and fibrosis
What is the marker of Primary Biliary Cholangitis?
anti-mitochondrial antibodies (AMA)
Is Primary Biliary Cirrhosis same as Primary Biliary Cholangitis?
Yes. Primary biliary cholangitis is a new name for primary biliary cirrhosis
(as cirrhosis is generally thought/by public opinion/ to be associated with alcohol; when PBC is associated with autoimmune condition, it’s a bit unfair for the patients to be associated with alcohol damage to their liver)
Histology of PBC
Autoimmune hepatitis auto-antibodies markers
Autoantibodies:
- ANA
- anti-SMA
- anti-liver kidney microsomal (LKM)
medical treatment of autoimmune hepatitis
treatment of PBC
autoimmune hepatitis -> steroids
PBC -> urseodeoxyholic acid
Causes of intrinsic cholestatic injury (damage to bile ducts in the liver)
- Primary biliary cholangitis (PBC)
- Primary sclerosing cholangitis (PSC)
- Sarcoidosis
- Drugs
- Graft vs host disease (liver transplant)
- HIV
What process damages the bile ducts in sclerosing cholangitis?
Fibrosing process
Presentation of chronic pancreatitis
- chronic abdominal pain
- steatorrhoea (reduced enzyme activity)
- diabetes mellitus (loss of islet cells)
- obstructive jaundice
- ascending cholangitis
What do you see in the chronically damaged pancreas? (histology)
Red fibrosing tissue between the healthy tissue and then progressive destruction of a healthy pancreatic tissue
Causes of pancreatitis
I - idiopathic
G - gallstones
E - ethanol
T - trauma
S - steroids
M - mumps/ malignancy
A - autoimmune
S - scorpion bite
H - hypertriglycerides, hypercalcaemia
E - ERCP
D - drugs
What does ‘double duct’ sign mean?
Dilation of both: common bile duct and pancreatic duct
Suggestive of a problem around the ampulla of Vater
- How does ERCP work? (what structures does it go through)
Scope put down into the duodenum -> cannulated ampulla -> die injected = whole biliary tree and main pancreatic duct can be seen
*if the stricture, the die would not go through it
* while ERCP also brush cytology can be taken
Difference between Primary Sclerosing Cholangitis and Primary Biliary Cholangitis
- -* clinical features and population profile
- site of involvement
- cause of obstruction
- key microscopic feature
- diagnostic clue
- associations (other conditions)
- long term complications
How does Primary Sclerosing Cholangitis look like on ERCP?
