Diseases of the Biliary Tract and Liver Flashcards
What is liver cirrhosis?
- parenchyme tissue is replaced by scar tissue
- liver becomes smaller
What is the histological definition of liver cirrhosis?
- fibrous collagenous bands between nodules of hepatocytes
- collagen should only be in liver capsule not in parenchyme tissue
What are the 3 most common causes of liver cirrhosis?
1 - alcohol
2 - obesity
3 - hepatitis B and C
If a patient presents with jaundice, but no other symptoms, is this likley to be acute or chronic?
- acute
What 2 places are most affected by jaundice most common in the body?
1 - skin
2 - eyes
Where does biliruben come from?
- yellow pigment formed during catabolism of old RBCs
What cells breakdown old RBCs in the blood to form biliruben?
- macrophages
Once a macrophage has phagocytosed old RBCs, the RBCs are broken down into what?
- globulin = amino acids
- heme = iron (Fe) and Protoporphyrin
Once a macrophage has phagocytosed old RBCs, the RBCs are broken down into their main compounds globulin which creates amino acids and heme, which is then broken down into iron (Fe) and protoporphyrin. What is protoporphyrin then converted into and what happens to this?
- unconjugated biliruben (insoluble in H2O)
- binds to albumin and is transferred to the liver
Once unconjugated biliruben (insoluble in H2O) has bound to albumin and trravels to the liver, what do hepatocytes do with it?
- converted into conjugated biliruben
- pumped into canaliculi and to the gall bladder as bile
What enzyme is responsible for the conjugation of unconjugated bilirubin in the liver?
- uridine 5 diphospho glucuronosyltransferase (UGT)
Once unconjugated biliruben (insoluble in H2O) has been converted into conjugated biliruben in the liver and pumped into canaliculi and to the gall bladder as bile, what happens to it then?
- pumped into GIT with bile
- converted into urobilinogen
- some urobilinogen is converted into stercobilin (makes stool brown)
Once the conjucgated biliruben in the bile has been converted into urobilinogen in the GIT, then some has been converted into stercobilin (makes stool brown). What happens to the rest of the urobilinogen?
- reabsorbed by body and oxidised into urobilin
- transported to liver and kidneys
- gives urine its yellow colour
What are some physical presentations of chronic liver disease, like liver cirrhosis?
- palmer erythema
- spider nevi
- ascites
- hepatolmegly
What are the 5 main things to do when trying to diagnose a patient with liver disease
1 - patients history
2 - clinical examination
3 -blood tests
4 -radiology
5 - gastroscopy
How can chronic liver disease cause low platelets?
- chronic liver disease causes portal hypertension (PH)
- PH push more blood to the spleen
- spleen traps and removes platelets reducing their numbers
Why is it important to understand if a liver disease is acute or chronic?
- different pathologies
What are the 4 basic steps of liver cirrhosis?
1 - normal liver
2 - fatty liver
3 - liver fibrosis
4 - liver cirrhosis
What is liver failure?
- when the liver is unable to function
In liver failure, jaundice can occur, what is this?
- increased concentrations of biliruben in the blood
- yellow pigment in biliruben changes skin colour
In liver failure, there will be a reduction in clotting factors used in the clotting cascade. What clotting factors does the liver produce?
- 2, 7, 9, 10
- remember 2+7=9 then 10
In liver failure, there is a reduction in albumin, what can this cause?
- hypoalbuminaemia
- result in odema
- leukonychia in nails
Liver failure can fresult in encephalopathy, what is this?
- failure to remove toxins from the body
- ammonia builds up
- asterixis flap due to toxins in the brain
In liver failure, patients can have ascites, what is this?
- fluid collects in spaces within the abdomen
- portal hypertension causes increased pressure on veins
- fluid leaks into abdomen
What is portal hypertension?
- liver becomes inflammed, cirrhotic or damaged
- blood can not enter and backs up into the portal mesenteric system
- also causes increased fluid leakage into the abdomen
How can portal hypertension affect the spleen?
- blood backs up into the portal mesenteric system
- increased blood and pressure causes splenomegaly
- decreases platelet count
Portal hypertension can cause hepatorenal failure, what is this?
- acute kidney failure caused by liver failure
- caused by reduced blood flow to kidneys
- patients tend to have low BP
In patients with liver cirrhosis, they can also have portal hypertension. This can cause an increased pressure in veins draining the stomach. What can this then go on to cause?
- oesophageal and/or gastric varices
- varices are large and swollen veins
In patients with liver cirrhosis, they can also have portal hypertension. This can cause an increased pressure in veins draining the stomach. This can then go onto cause oesophageal and/or gastric varices, which are large and swollen veins. How can patients present sometimes with these?
- varices may bleed or rupture
- can cause haematemesis (vomitting of blood)
- can cause melaena (blood in stool)
How can we treat oesophageal or gastric varices, that is secondary due to portal hypertension?
- endoscopy used to suck up blood vessels and place rubber bands around them
The causes of jaundice can be divided into 3 area where the liver can be causing it, which helps identify the cause of the jaundice. What are these 3 areas?
1 - pre-hepatic
2 - intrahepatic
3 - post-hepatic
The causes of jaundice can be divided into 3 area where the liver can be causing it, which helps identify the cause of the jaundice. Pre-hepatic causes of jaundice, also called unconjugated causes include what?
- haemolysis – excessive breakdown of red blood cells e.g sickle cells disease or neonatal jaundice
- Gilberts - uridine 5 diphospho glucuronosyltransferase deficiency
- liver is generally ok though
The causes of jaundice can be divided into 3 area where the liver can be causing it, which helps identify the cause of the jaundice. intrahepatic causes of jaundice, what happens here?
- intrahepatic means due to inside the liver
- hepatic cells unable to conjugate bilirubin, so biliruben cannot be removed
The causes of jaundice can be divided into 3 area where the liver can be causing it, which helps identify the cause of the jaundice. post-hepatic causes of jaundice, what happens here?
- biliruben has ben conjugated but cannot be removed
- biule ducts may be blocked, potentially due to gallstones
Intrahepatic jaundice is when the liver cannot clear bile can be divided into Hepatocellular and Cholestatic. What is Hepatocellular?
- inflammation of hepatocytes called hepatitis
- liver enzymes ALT/AST will be raised
Intrahepatic jaundice is when the liver cannot clear bile can be divided into Hepatocellular and Cholestatic. Hepatocellular is inflammation of hepatocytes called hepatitis and will raise liver enzymes ALT/AST. What are some of the most common causes of this?
- viruses
- fat
- alcohol
- drugs
- ischaemia
- inherited conditions
Intrahepatic jaundice is when the liver cannot clear bile can be divided into Hepatocellular and Cholestatic. What is Cholestatic?
- inflammation of cholangiocytes
- cholangiocytes are epithelial cells of the biliary tree
Intrahepatic jaundice is when the liver cannot clear bile can be divided into Hepatocellular and Cholestatic. Cholestatic is inflammation of cholangiocytes, which are the epithelial cells of the biliary tree. What can this cause to liver enzymes and some of the most common causes?
- liver enzymes ALP/GGT will be raised
- primary biliary cirrhosis
- primary sclerosing cholangitis
- drugs e.g flucoxacillin
- sarcoidosis
In hepatocellular, which is inflammation of hepatocytes, why are liver enzymes ALT/AST transaminases raised?
- hepatocytes create ALT/AST
- hepatocytes are damaged and leak ALT/AST into blood
In Cholestatic, which is inflammation of cholangiocytes, which are the epithelial cells of the biliary tree causes, causes liver enzymes ALP/GGT transaminases raised, why is this?
- cholangiocytes produce ALP/GGT
- inflammation of cholangiocytes = raised ALP/GGT
Post hepatic jaundice is a blockage in the drainage of biliruben from the liver. In this case the liver could be normal, but biliary tree is blocked. What are some of the most common causes of this?
- gallstones
- strictures (narrowing of biliary trees)
- worms (in developing countries)
- pancreatic cancer (tumour at head of pancreas blocks ducts)
- gall bladder cancer tumour/mass can blocks ducts)
- cholangiocarcinomas
What is Primary Sclerosing Cholangitis?
- progressive course of cholestasis with inflammation and fibrosis of the intrahepatic and extrahepatic bile ducts
- causes narrowing of the ducts
In Primary Sclerosing Cholangitis (PSC) 80% of the patients also have an GIT disease, what is this disease?
- ulcerative colitis
- BUT only 5% of patients with UC have PSC
In patients with Primary Sclerosing Cholangitis (PSC), why should they be screened for ulcerative colitis (UC)?
- 80% or patients with PSC have UC
- having PSG abd UC increases risk of colon cancer
Patients with Primary Sclerosing Cholangitis are at an increased risk of what 2 types of cancer?
1 - bowel cancer due to ulcerative colitis
2 - cholangiocarcinoma
What 2 transaminase (enzymes) do hepatocytes create?
- alanine transaminase (ALT)
- aspartate transaminases (AST)
Hepatocytes produce transaminases (enzymes) alanine transaminase (ALT) and aspartate transaminases (AST). What does AST do?
- transfer of an amino group to oxaloacetate to make asperate or alanine
- this reaction is reversible
Hepatocytes produce transaminases (enzymes) alanine transaminase (ALT) and aspartate transaminases (AST). What does ALT do in the liver?
- alanine is produced in muscle and transported to the liver following glycolysis
- ALT then convert alanione into pyruvate using 6 ATP
- pyruvate through gluconeogenesis is converted into glucose
- glucose travels to muscle and process repeats
Hepatocytes produce transaminases (enzymes) alanine transaminase (ALT) and aspartate transaminases (AST). What does AST do in the liver?
- converts asparatate into oxaloacetate in cytosol
- oxaloacetate is reduced (electrons and H+ added) creating malate
- malate can transfer across intermembrane space
- above process is reversed releasing electrons and H+
- oxaloacetate is converted into asparatate in matrix and asparatate travels back to cytosol
What is alkaline phosphate (ALP)?
- responsible for removing phosphates
In Hepatocellular and Cholestatics liver enzymes ALT, AST, ALP and GGT can all be raised at the same time. But which of these enzymes is raised more in Hepatocellular and Cholestatic?
- Hepatocellular (or hepatitis) = ALT and AST
- Cholestatic = ALP and GGT
When looking at liver enzymes, if AST, ALT and GGT are normal but ALP is high, what can this be suggestive of?
- bone problem
- pregnancy
If the upper limit of normal (ULN) of ALT is significantly raised, what can this be suggestive of?
- viral, drug or ischaemia
If AST and ALT are raised, but ALT is higher, what may this suggest?
- alcohol
If biliruben is raised but all other enzymes are normal, would could this be indicitive of?
- Gilbert’s syndrome
What is included in a full liver screen?
- check for viruses- Hep A,B,C, E serology
- autoimmune function
- inherited causes
- ultrasound of the liver
When looking at a patients liver enzymes when should a patient be referred to see a gastroenterologist?
- liver enzymes are x2 above upper limit of normal levels
In a full liver screen viruses (Hep A,B,C, E serology), autoimmune function, inherited causes and an ultrasound of the liver are performed if patient has liver symptoms. If any of these are abnormal, who should the patient be referred to?
- gastroenterologist
What’s the disease progression that leads to cirrhosis (fff)
Inflammation, fatty liver, fibrosis, cirrhosis
What is a budd chiari
Hepatic vein thrombosis (vascular acute liver disease)
What is liver failure?
Jaundice Coagulopathy (raised INR) Hypoalhuminaemia Encephalopathy Ascites
What are the following signs Jaundice Coagulopathy (raised INR) Hypoalhuminaemia Encephalopathy Ascites
Jaundice - failure to clear bilirubin Coagulopathy (raised INR)- failure to reduce clotting factors (liver cause) Hypoalhuminaemia - liver fails to produce protein Encephalopathy - liver fails to clear toxins eg ammonia Ascites - leakage of fluid from portal blood vessels into peritoneal cavity
What’s portal hypertension? What can it cause
Back pressure on portal vein Can cause hepatorenal failure Can cause oesophageal and gastric varices Can cause ascites
What is a TIPSS procedure
Trans intrahepatic portosystemic shunt
Varices - presentation and how to treat
Oesophageal or gastric Presents - haematenesis/melaena Secondary to portal hypertension & venous collaterals Treatments Endoscopic banding Beta blockers TIPSS surgery (venous shunts)
Where does unconjugated bilirubin come from
Heme RBCs
What conjugates bilirubin. How is it transported
UDP glucaronyl transferase To bilirubin glucuronide Transported bound to albumin
How is bilirubin glucuronide excreted
Bacteria in bowel - converted to excrete in faeces as stercobilin Or Reabsorbed into blood and urine excrete as urobilin
Causes of jaundice (categories)
Prehepatic - raised unconj bilirubin (haemolysis or Gilbert’s UDP glcuronyl transferase deficiency ) Intrahepatic Post hepatic
Examples of haemolysis disease causing jaundice prehepatic
Sickle cell Neonatal jaundice
Post hepatic jaundice causes
Stones Strictures (PSC) Worms Pancreatic cancer Gall bladder cancer Cholangeocarcinomas
How many PSC patients have UC
80%
How many UC patients have PSC
5%
What do hepatocytes produce
ALT AST
What do cholangiocytes produce
ALP GGT
What does ALT mean?
Alanine transaminase Elevaation Suggests hepatocellular
What does ALP mean
Alkaline phosphatase Elevaation Suggests cholangiostatic
What is FIB4?
Fibrosis-4 (FIB-4) Index for Liver Fibrosis Noninvasive estimate of liver scarring in HCV and HBV patients, to assess need for biopsy.
