11. Liver & biliary system pathology Flashcards
What does the liver store?
Glycogen
Vitamins
Iron
Copper
What does the liver synthesise?
Glucose Protein Lipids & cholesterol Bile Coagulation factors Albumin
What does the liver metabolise/detoxify?
Bilirubin Ammonia Drugs Alcohol Carbohydrate/lipids
What are some general symptoms of liver disease?
◦ Nausea/vomiting
◦ Fatigue
◦ Anorexia
◦ Abdominal pain
Oedema/ascites is caused by what deranged liver function?
Synthetic function: Albumin production
albumin main protein that contributes to oncotic pressure and reduced albumin means reduced oncotic pressure so less ability to draw water into blood
Confusion is caused by what deranged liver function?
metabolic function :Impaired ammonia detoxification.
hyperammonemia affects the brain
Bleeding/easy bruising is caused by what deranged liver function?
synthetic function: Reduced or Abnormal synthesis of clotting factors
Jaundice is caused by what deranged liver function?
Metabolic function: impaired metabolism of bilirubin.
What is ascites?
flu8id within peritoneal cavity
What is acute liver failure?
Rapid onset reduced liver function, no previous liver disease
What can cause acute liver failure?`
◦ Paracetamol overdose
◦ Other medications e.g. tetracycline, aspirin in children
◦ Acute viral infections e.g. EBV, CMV, Hep A/B
◦ Acute excessive alcohol intake
What are 3 characteristics of chronic liver disease (cirrhosis)?
◦ Ongoing inflammation causes fibrosis
◦ Associated with hepatocyte necrosis
◦ Resulting architectural changes (nodules)
What is cirrhosis?
Cirrhosis is the ‘end result’ of a lot of conditions
Develops in response to any chronic liver injury
Are the changes to the liver in cirrhosis reversible?
No
What is the end result of liver cirrhosis>?
◦ Impairment of liver function
◦ Distortion of architecture
What are 5 general categories of causes of cirrhosis?
Drugs, infection, deposition, autoimmune, other
all cause inflammation
Give examples of hopw drugs can cause cirrhosis
- alcoholic liver disease
- iatrogenic - livers is site of drug metabolism and certain drugs for ling periods of time can damage liver and cause chronic inflammation
What are the 3 main mechanisms by which alcohol can affect the liver?
◦ Fatty change (weeks) - initially reversible
◦ Alcoholic Hepatitis (years) - initially reversible
◦ Cirrhosis (years) - end stage; irreversible damage
What is the damage to liver from alcoholic liver disease partly due to?
Build of acetaldehyde, an intermediate between conversion of ethanol to acetate
Why does alcohol cause fatty liver?
Alcohol oxidation leads to increased acetyl-CoA, which is converted to and stored as triglycerides
alcohol oxidation releases glucose and if in excess, can’t be put into storage by insulin so converted to triglycerides leading to fatty deposits in liver
What does fatty liver do to the size of the liver?
Increases, hepatomegaly
What are the symptoms of alcoholic hepatitis?
◦ Rapid onset jaundice, tender hepatomegaly (RUQ pain)
◦ Symptoms of more severe disease e.g. nausea, oedema and ascites, splenomegaly
What is alcohol hepatitis?
inflammation of liver
What is the treatment for alcohol liver disease?
Reduce alcohol intake
Which viral infections cause cirrhosis?
Chronic Hepatitis B or C
◦ Blood borne viruses
What are patients with viral chronic HepB/C at risk of developing?
Potential for chronic infection
Also poses risk for hepatocellular carcinoma
What is the treatment for Viral HepB/C, are vaccinations available?
B: no cure, life long anti-virals (vaccine available)
• May have symptoms during acute infection
C: cure, antiviral drug combo (no vaccine)
• Majority are asymptomatic during acute infection
How many patients with HepB/C experience symptoms and what symptoms?
Majority have no/vague symptoms in acute phase:
- Nausea, vomiting, anorexia, RUQ pain, fatigue
What 3 depositions can cause liver cirrhosis?
- fat
- iron
- copper
What is non-alcoholic fatty liver disease?
Accumulation of triglycerides and other lipids in hepatocytes, not due to alcohol
What is NAFLD called when inflammation is present?
Non-Alcoholic Steatohepatitis (‘NASH’)
What is the pathogenesis of NAFLD?
Similar pathogenesis to Alcoholic Liver Disease
◦ (But without the alcohol!!)
◦ Link to insulin resistance
What are risk factors for NAFLD?
◦ Obesity
◦ Diabetes
◦ Metabolic syndrome (dyslipidaemia)
◦ Familial hyperlipidaemia
How can NAFLD be prevented?
Reduce risk factors/lifestyle modification
◦ Oral hypoglycaemic agents
What is hereditary haemochromatosis?
Abnormal iron metabolism
Autosomal recessive, mutation in HFE gene.
- increases iron absorption from the small intestine -> excess deposition
- increases iron uptake into cells (ferritin store)
WHat are you at risk of developing with Hereditary haemochromatosis?
hepatocellular carcinoma
What is Wilson’s disease?
Abnormal copper metabolism ` Autosomal recessive ◦ Reduced secretion of copper from biliary system -> accumulation in tissues ◦ Low caeruloplasmin
What are 3 autoimmune causes of cirrhosis?
- autoimmune hepatitis
- Primary biliary cirrhosis (PBC)
- Primary sclerosing cirrhosis (PSC)
What is autoimmune hepatitis?
Autoantibodies cause damage/destruction of hepatocytes
hich antibodies are tested for in autoimmuine hepatitis?
Increases in Anti-smooth muscle antibody (ASMA) and anti-nuclear antibody (ANA)
What do PSC and PBC affect and what antibody can differentiate between them?
Affect bile ducts:
- PBC is anti-mitochondrial antibody positive
- PSC is AMA negative
What are some other causes of cirrhosis?
- alpha 1 antitrypsin
- glycogen storage diseases
- budd-chiari
What is portal hypertension and why does it occur in cirrhosis?
Build up of blood in the portal venous system
◦ Fibrotic liver is not very expansive
◦ Compresses veins entering the liver from the portal venous system
◦ This causes increased hydrostatic pressure in the portal venous system
Describe the portal system
splenic vein joins with IMV which both join with SMV to form the portal vein which enters livers and drain some of the liver as well and the form hepatic veins that drain into IVC
define systemic circulation
Any vein network that doesn’t go through liver and drain directly to IVC
What 3 things can portal hypertension cause?
◦ increased hydrostatic pressure in the portal venous system; ASCITES
◦ build up of pressure in the splenic circulation; SPLENOMEGALY
◦ VARICES
How do varices occur as a result of portal hypertension?
◦ Increased portal pressure causes blood to ‘shunt’ from the portal system to the systemic venous circulation via connections (anastomoses) that are not usually used.
◦ This increased blood flow and pressure leads to distension of the veins at the site of anastomoses; varices
What are 3 different type of varices of the portal system?
Oesophageal, umbilical and anorectal
where porto-sytemic anastomoses are present
What is the venous drainage of the oesophagus?
Upper 2/3rd drained by oesophageal veins into azygous vein which drain into SVC
Lower 1/3 drained by left gastric vein which drains into portal vein
What type of varices do oesophageal varices lead to and what occurs if these rupture?
◦ Can lead to mucosal varices
◦ If these rupture it can cause significant haematemesis
Between which veins does anorectal varices occur?
Between superior and middle / inferior rectal veins
Where do superior and middle/inferior rectal veins drain into?
superior - drain into IMV which drains into portal vein
middle/inferior - drain into internal iliac vein which drains into IVC
overlap of anastomoses is where they can distend
Are anorectal varices painful and do they bleed?
◦ Typically painless (above pectinate line)
◦ Rarely bleed
In which veins does umbilical varices occur and what is the appearance described as?
In ligamentum teres (normally no blood flow) (links liver to umbilicus)
- caput medusa
What is ligamentum teres a remnant of?
umbilical vein which supplied arterial blood to foetus in fetal life
- remnant remains a connection point between abdominal wall at umbilicus and circulation
What is hepatorenal syndrome?
Development of Acute Kidney Injury (AKI) in the presence of cirrhosis
What is the mechanism of hepatorenal syndrome?
Portal hypertension -> systemic arterial vasodilation -> RAAS activated - Renal artery vasocontriction (reduced blood flow to kidney)
Can kidney function be improved if liver failure reversed?
yes
Describe the pathway from hepatic duct to duodenum
right and left hepatic duct in liver join to form common hepatic duct which leaves liver and joins with cystic duct from gallbladder to form common bile duct which joins with pancreatic duct to form ampulla of vater and reaches sphincter of oddi
What are gall stones formed from?
Formed from bile contents:
◦ Cholesterol
◦ Bile pigments
◦ Mixed
Can gallstones be seen on xray
Not really as Most are radiolucent
◦ Comparison to renal calculi which can be seen on x-ray due to their calcium base
What are the risks for developing gall stones and what it the typical patient you see with them?
Diet & lifestyle Age Gender Pregnancy Pre-existing liver disease -Usually middle aged slightly overweight women
What are 4 complications of gallstones?
Biliary colic, Acute cholecystitis, Acute (ascending) cholangitis, acute pancreatitis
What is biliary colic?
RUQ pain (possibly spreading to back or right shoulder), typically few hours after eating fatty meal (CCK) - no features of inflammation
What causes biliary colic?
Temporary obstruction of a gallstone usually in the cystic duct
What is the management for biliary colic?
Analgesia, elective cholecystectomy
Describe the length of biliary colic pain
temporary pain that lasts for a while before easing
why does biliary colic come on after eating?
CCK released due to presence of food causes gallbladder to contract causing gallstone to be pushed against neck of gallbladder leading to temporary obstruction of cystic duct causing pain - gallstone comes back down when contraction eased
What is acute cholecystitis?
inflammation due to Impaction of a stone in the cystic duct - complete blockage
What are symptoms of acute cholecystitis?
- Severe pain in RUQ.
- Pain that spreads to your right shoulder or back.
- Tenderness over your abdomen when it’s touched.
- Nausea.
- Vomiting.
- Fever.
- Murphy’s sign positiive
Are there features of inflammation in acute cholecystitis?
Yes, seen on Ultrasound as thick wall of gallbladder
What is Murphy’s sign ?
Asking the patient to take in and hold a deep breath while palpating the right subcostal area. If pain occurs when the inflamed gallbladder comes into contact with the examiner’s hand, Murphy’s sign is positive, Occurs in acute cholecystitis. liver attached to diaphragm so pushes liver and gallbladder down when breathing in
What is the length of pain in acute chiolecystitis?
constant
What is the management for acute cholecystitis?
initially conservative, then cholecystectomy
What is acute cholangitis?
Bacterial infection of the biliary tract from obstruction, typically due to gallstone in common bile duct
What does acute cholangitis present with?
Charcot’s triad: RUQ pain, features of inflammation, and jaundice
What is management of acute cholangitis?
IV antibiotics, fluids, relieve obstruction
Compare symptoms of biliary colic, acute cholecystitis and acute cholangitis
biliary colic : RUQ pain
acute cholecystitis: RUQ pain, fever
acute cholangitis: RUQ pain, fever, jaundice
What occurs in acute pancreatitis?
◦ Acinar cell injury and necrosis
◦ Blockage of pancreatic duct (think causes)
◦ Evokes an inflammatory response
◦ ‘Autodigestion’ of pancreas
What does acute pancreatitis present with?
Epigastric pain
◦ Radiates to back
◦ Often associated with vomiting
◦ Cullen’s & Grey Turner’s sign (bruising in umbilical and flanks respectively)
What are the causes of acute pancreatitis?
(GET SMASHED) gallstones, ethanol, trauma, steroids, mumps, autoimmune, scorpion sting, hypercalcemia/hyperlipidaemia, ERCP, drugs
In acute pancreatitis due to gallstones, where would the gallstone be found?
in the common bile duct near to point where pancreatic duct joins
Levels of what are raised in blood in acute pancreatitis?
Amylase and lipase
What investigation can be done to rule out other causes in acute pancreatitis?
CT/MRI to identify any necrosis
What is the management for acute pancreatitis?
Management depends on severity
◦ Fluids
◦ Manage gallstones
◦ Organ support
