17-02-23 - Hepatobiliary and pancreatic disease Flashcards
Learning outcomes
- Classify the types and causes of jaundice
- Describe the causes and effects of acute liver injury
- Describe the causes and effects of chronic liver injury
- Describe common tumours of the liver and biliary tree
- Describe the causes and effects of gallstones
- Describe the main features of pancreatitis
- Describe the main features of pancreatic carcinoma
Biliary tree structure.
What is the common hepatic duct formed from?
What is the common bile duct formed from?
How large is the common bile duct?
What structure does it run in?
What structures join at the hepatopancreatic ampulla (of Vater)?
Where does this occur?
Where is the sphincter of Oddi located?
- Biliary tree structure
- The right and left hepatic ducts join to form common hepatic duct
- The cystic duct joins with the common hepatic duct and forms the common bile duct
- The common bile duct is 4-6 mm diameter and runs in hepatoduodenal ligament
- The common bile duct joins with the main pancreatic duct at the hepatopancreatic ampulla (of Vater) before entering into the 2nd (descending) part of the duodenum at major duodenal papilla
- The Sphincter of Oddi is around the around the final part of common bile duct
What do hepatic lobules consist of?
What do they form around?
What 3 structures do interlobular triads consist of?
Where does blood from interlobular triads flow to?
Where does bile from interlobular triads flow to?
What are the 2 roles of hepatocytes?
- Hepatic lobules consist of parenchymal cells (hepatocytes)
- Hepatocytes form lobules around a central vein that drains back to the hepatic vein
- 3 structures Interlobular triads consist of:
1) A branch of the hepatic artery proper
2) A venule from the portal vein
3) A bile duct to the hepatic duct (bile goes in opposite direction to blood and goes into common bile duct) - Blood from the interlobular triads flows to the sinusoids (between sheets of hepatocytes), which then flow into the ventral vein of the lobules
- Bile from interlobular triads flows in the canaliculi between the hepatocytes towards biliary ducts
- 2 roles of hepatocytes:
1) Produce bile
2) Detoxify blood
What are the different zones of liver lobules?
What are they each near?
- Different zones of liver lobules:
1) Zone 1 – Closest to blood supply from hepatic artery proper
2) Zone 2
3) Zone 3 - Near the central vein, furthest from blood source from proper hepatic artery
What 6 substances does the liver synthesise?
What 3 substances does the liver break down?
What is the role of Kupffer cells in the liver?
- 6 substances the liver synthesises:
1) Albumin
2) Clotting factors
3) Complement
4) α-1-antitrypsin
5) Thrombopoietin
6) Bile through conjugation of bilirubin - 3 substances the liver breaks down:
1) Drugs
2) Insulin
3) Ammonia - Kupffer cells in the liver phagocytose old blood cells, bacteria and foreign materials from the bloodstream/gut
What is jaundice?
At what bilirubin level will we see jaundice?
What symptom can jaundice cause?
Is jaundice always present in liver disease?
Is liver disease the only cause of jaundice?
- Jaundice is yellowing of skin and mucosal surfaces
- We will see jaundice at a bilirubin level of >40μmol/L
- Jaundice can cause intense itch
- Jaundice is not always present in liver disease, even when severe
- Liver disease is not the only cause
What are the 2 forms bilirubin can exist in?
- 2 forms bilirubin can exist in:
1) Unconjugated
* Water insoluble
* Travels in blood stream attached to other plasma proteins e.g albumin
2) Conjugated
* Water soluble (can be excreted in the urine, leading to dark urine)
* Has been processed by the liver
What are the 3 different types of jaundice?
- 3 different types of jaundice:
1) Prehepatic
* Haemolysis leads to the release of bilirubin from RBCs
2) Intrahepatic
* Normally coupled with intrinsic liver disease
* Some bilirubin may be conjugated while some is left unconjugated
* Leads to excess bilirubin in the liver and blood stream
3) Post-hepatic (obstructive)
* Obstruction of bile outflow
* Results in dark urine and pale stools
What are the 4 main causes of acute liver disease?
What are 3 common symptoms of acute liver injury?
What are 3 differences in serum can we see from acute liver injury?
What are 4 signs of liver failure?
- 4 main causes of acute liver injury:
1) Viral Infections
2) Alcohol
3) Adverse drug reactions
4) Biliary obstruction (gallstones) - 3 common symptoms of acute liver injury:
1) Jaundice
2) Malaise
3) Liver failure (can lead to) - 3 differences in serum can we see from acute liver injury:
1) Raised serum bilirubin
2) Raised transaminases (ALT and AST)
3) If caused biliary obstruction, can see raised ALK too - 4 signs of liver failure:
1) ↓albumin
2) Ascites
3) Bruising
4) Encephalopathy
What are 4 different patterns of hepatocyte injury?
What zones do they affect?
What conditions can they be seen in?
- 4 different patterns of hepatocyte injury:
1) Zonal
* Zone 3 affected first
* Seen in Toxic (e.g alcoholic) or haemodynamic causes
2) Bridging
* All 3 zones can be affected
* Seen in severe viral hepatitis
3) Interface hepatitis
* Zone 1 affected first
* Seen in autoimmune hepatitis
4) Apoptotic
* Spots
* Seen in acute viral hepatitis
Alcoholic liver injury.
How can alcohol cause steatosis?
How can steatosis lead to Acute hepatitis with Mallory’s hyaline?
How can this lead to cirrhosis?
- Alcoholic liver injury
- All of these are potential outcomes from alcoholic liver injury, but patients may not go through all of these stages
- When hepatocytes try to metabolise alcohol as it comes in, the metabolism of other substances are put on hold, including fat
- If fat metabolism is stopped, it will build up in hepatocytes, causing steatosis (alcoholic fatty liver)
- Steatosis can lead to an inflammatory process, which can lead to Acute hepatitis with Mallory’s hyaline
- If this condition becomes chronic, there can be recruitment of fibroblasts and myofibroblasts
Describe the histology of steatosis
Is alcohol itself toxic to the liver?
What does acetaldehyde bind to?
What does this cause?
What is recruited to the area?
What does inflammation lead to?
- Alcohol itself is not toxic to the liver, but rather the breakdown product acetaldehyde
- Acetaldehyde binds to hepatocytes causing damage and leading to an inflammatory reaction
- This results in the recruitment of leukocytes (neutrophils, lymphocytes) and other inflammatory cells
- This inflammation leads to the recruitment of fibroblasts, which start to produce collagen, which isn’t good for organs, as it scar tissues (fibrosis) and not functional tissue
What % of drug reactions involve the liver?
What are the 2 types of drug-induced liver injury?
What should we always do with patients with deranged LFTs?
- 10% of all drug reactions involve the liver
- 2 types of drug-induced liver injury:
1) Hepatocellular
* Damage to liver cells
* Caused by paracetamol overdose
2) Cholestatic
* Injury to bile production/secretion cells
* Caused by – methyl testosterone
- Always take a full drug history from a patient with deranged LFTs
What can acute biliary obstruction cause?
What is it usually due to?
How can gallstones cause injury to the liver?
What kind of pain do gallstones in the biliary tree cause?
How can acute biliary obstruction be complicated?
- Acute biliary obstruction can cause acute liver injury
- Acute biliary obstructions is usually due to gallstones
- When gallstones build up in the gallbladder, they can come down and block the common bile duct, leading to the backing up of bile into the liver biliary tree, which can become toxic to the liver
- Gallstones in the biliary tree can cause colicky pain and obstruction jaundice, resulting in dark urine and pale stools
- Acute biliary obstruction can be complicated by infection of the blocked common bile duct, leading to infective cholangitis
What is the difference between Non-alcoholic steatohepatitis (NASH) and Nonalcoholic fatty liver disease (NAFLD)?
What syndrome is NASH/NAFLD associated with?
How are hepatocytes affected in NASH/NAFLD)?
How can this lead to cirrhosis?
- If you just have fat but no damage to your liver, the disease is called nonalcoholic fatty liver disease (NAFLD).
- If you have fat in your liver plus signs of inflammation and liver cell damage, the disease is called nonalcoholic steatohepatitis (NASH)
- NASH/NAFLD is associated with metabolic syndrome
- Metabolic syndrome is the medical term for a combination of diabetes, high blood pressure (hypertension) and obesity (Low HDL good cholesterol and high triglycerides)
- In NASH/NAFLD, there is fat deposition in hepatocytes (white parts of cells in histology)
- The fat build-up in the liver can lead to inflammatory responses, which can trigger cytokine release and the recruitment of fibroblasts, leading to liver cirrhosis
20) Comparison between Primary Biliary Cholangitis (PBC) and Primary Sclerosing Cholangitis (PSC):
* Age/gender
* Disease associations
* Serum immunoglobulins
* Autoantibodies
* Cholangiography
* Bild duct injury
* Portal inflammation
* Obliterative fibrosis of larger ducts
* Periportal copper
What is hemochromatosis?
What are 3 stages of hemochromatosis?
What are the 2 types of hemochromatosis?
How do we treat hemochromatosis?
- Hemochromatosis is Iron deposition in the liver around the portal tract, which will damage hepatocytes and lead to fibrosis
- 3 stages of hemochromatosis:
1) Alteration of architecture
2) Fibrosis
3) Cirrhosis - 2 types of hemochromatosis:
1) Primary
* Autosomal recessive disorder
* Caused by mutation in the HFE gene
* Results in liver not being able to process iron properly
2) Secondary
* Generally caused by repeated drug transfusions
- Haemochromatosis is treated through regular venesection (bloodletting), then testing the iron and ferritin levels of the blood
- Patients who have a condition where they require regular blood transfusions should have their iron and ferritin levels checked regularly
What type of disorder is α-1-antitrypsin deficiency?
What is α-1-antitrypsin?
What is the role of α-1-antitrypsin?
How does α-1-antitrypsin deficiency affect α-1-antitrypsin?
What can this lead to?
What condition is α-1-antitrypsin associated with?
- α-1-antitrypsin Deficiency is an autosomal recessive disorder
- Alpha-1-antitrypsin (AAT) is a protein produced in the liver that protects the body’s tissues from being damaged by infection-fighting agents released by its immune system through acting as a protease inhibitor
- α-1-antitrypsin deficiency can lead to the liver not producing α-1-antitrypsin, producing an abnormal form of α-1-antitrypsin that can’t be release and can build up and damage hepatocytes, or is released and isn’t effective
- This can lead to liver cirrhosis
- α-1-antitrypsin is associated with emphysema, as without α-1-antitrypsin, proteases can break down the alveolar walls
What kind of disorder is Wilson’s disease?
How does it affect the liver?
How does Wilson’s disease affect the brain?
What is a common symptom of Wilson’s disease?
What is seen in the blood test of Wilson’s Disease?
- Wilson’s disease is an autosomal recessive disorder
- Wilson’s disease results in the failure of the liver to excrete copper in bile, which results in the build up of copper in the liver, which can lead to fibrosis and cirrhosis
- Wilson’s disease can result in Copper deposits in the brain tissue, which leads to neurological dysfunction
- A common symptom of Wilson’s disease is Kayser-Fleischer rings around the iris
- In the blood test of Wilson’s Disease we see low caeruloplasmin levels
What causes cirrhosis?
Why is fibrosis useless in organs?
Why does regeneration in the liver occur with fibrosis?
Describe the appearance of cirrhosis (in picture)
- Fibrosis (collagen) + regeneration leads to cirrhosis
- Collagen is useless in organs, and results in contraction of the liver tissue, which makes it difficult for the liver to function (more fibrosis, less liver function)
- Cellular regeneration amongst fibrosed areas try to build up the number of hepatocytes available for function
- Appearance of cirrhosis (in picture)
What are 2 ways cirrhosis can be classified?
- 2 ways cirrhosis can be classified:
1) Morphological
* Micronodular – nodules ≤ 3mm
* Macronodular – nodules > 3mm
* Mixed (most common)
2) Aetiological (causes)
* Alcohol
* Hepatitis B and C viruses
* Iron overload
* Gallstones
* Autoimmune liver disease
What types of tumours are hepatocellular carcinomas?
What are 3 causes of hepatocellular carcinoma?
- Hepatocellular carcinomas are often multifocal (multiple tumours happening at the same time) – breaks rules
- 3 causes of hepatocellular carcinoma:
1) Aflatoxins – fungal origin
2) Hepatitis B + C viruses
3) Cirrhosis (any cause)
What are the 5 risk factors for gallstones (5Fs)?
What can gallstones be formed from?
What 5 conditions can gallstones cause?
- 5 risk factors for gallstones (5Fs)?
1) Female
2) Fair
3) Fat
4) Forty
5) Fertile - Chile-bearing age or those who have had children
- Gallstones can be formed from cholesterol, bile pigment or mixed (most common)
- 5 conditions gallstones can cause:
1) Cholecystitis
2) Obstructive jaundice – gallstones getting stuck in the common bile duct
3) Cholangitis
4) Pancreatitis (if they get stuck in the ampulla of vater – causes back up of pancreatic amylase)
5) Cholangiocarcinoma
Where does annular pancreas occur?
What does it occur?
What are 3 signs of annular pancreas?
- Annular pancreas occurs around the 2nd part of the duodenum
- It causes obstruction
- 3 signs of annular pancreas:
1) Polyhydramnios
2) Low birth weight
3) Poor feeding
