The Liver in Health and Disease Flashcards
Which organs is the liver in close relationship with
The biliary tract and gallbladder
Describe the vascular relationships of the liver
Dual inflow of blood from hepatic artery and portal vein. Outflow of blood from hepatic vein
What does bile drainage follow
Hepatic artery and portal vein
What is the hepatic artery a branch from
The coeliac artery
What kind of epithelium is there in the liver
Glandular epithelium
Where does the gall bladder sit
On the under surface of the liver
Describe the biliary tree
Right and left hepatic duct form common hepatic duct. Common hepatic duct and cystic duct form common bile duct. Common bile duct and pancreatic duct enter the duodenum via the sphincter of Oddi
What does the epithelium in the gall bladder do
Acts to remove water and salts to concentrate bile
What are the functions of the liver
Vital organ capable of regenerating. Maintaining metabolic homeostasis. Cytoplasm of hepatocytes contain enzymes to enable homeostasis. Stores nutrients. Detoxifies harmful substances. Bile synthesis
What nutrients does the liver store
Glycogen, iron, copper and fat-soluble vitamins
The liver is responsible for the homeostasis of what
Carbohydrates, proteins and fats
Where does gluconeogenesis take place
In the liver
Describe acetoacetate
An energy source (fats) but dangerous if present for a long time
Describe the production of bile
RBC breakdown results in the formation of unconjugated bilirubin which binds to albumin in the blood and is transported to the liver. In the liver unconjugated bilirubin becomes conjugated to glucuronic acid in the hepatocytes, Glucuronic acid (conjugated bilirubin) is water soluble and is excreted in bile. Bile is stored and concentrated in the gall bladder before entering the gut
What does unconjugated bilirubin bind to in the blood
Albumin
What triggers bile release
The presence of fat in the small bowel (duodenum) triggers the release of cholecystokinin (CCK) from I cells of the duodenum and jejunum
What does CCK trigger
Production of more bile from the liver, contraction of the gallbladder and relaxation of the sphincter of Oddi
What are portal areas
Where blood feeds into the liver
What do terminal venules do
Drain blood from the liver
How can the functional unit of the liver be described
As a lobule or acnius
Describe a lobule
There is a central vein the in centre of each lobule
Describe an acinus
There is a portal triad at the centre of each acinus
What is contained in a portal triad
Portal vein, hepatic artery, bile duct
How many zones does an acinus have
3
Describe zone 1
Zone 1 is the very inner zone of an acinus. Zone 1 hepatocutes have better blood supply and are less vulnerable to ischaemia and toxins.
Describe zone 3
Zone 3 is the outermost zone of an acinus. Zone 3 hepatocytes are less well oxygenated and more vulnerable to poor perfusion and toxins
What can liver function tests check for
Hepatocyte damage and biliary obstructions
What does hepatocyte damage result in
Raised transaminases: alanine transferase (ALT), asparate transaminase (AST) and yGluatmyl transpeptidase (yGT)
What is there in chronic conditions
Low albumin
What does long term damage to hepatocytes do
Reduces capacity to synthesise proteins
What can biliary obstruction result in
Raised bilirubin and alkaline phosphatase
What do you get in biliary obstruction
Deranged clotting, impaired protein synthesis including clotting factors, lack of vitamin K which requires bile for absorption
When is conjugated bilirubin increased
In biliary obstruction
What is alkaline phosphatase produced by
Biliary canaliculi
Why is liver disease classified in different ways
Because of presentation/ appearance when you take a biopsy/ cause of disease (aetiological factors)
What does liver fibrosis result in
Function loss
What does acute liver disease result in
Cell death of hepatocytes
Why does acute liver failure lead to hyperbilirubinaemia
Acute liver failure results in cell death leading to an increase in enzymes (transaminases) and hepatic encephalopathy resulting in toxic effects on the brain and bilirubin not being conjugated properly. As a result you get conjugated hyperbilirubinaemia
How is chronic hepatitis divided
By grade/ stage
How is chronic hepatitis divided by grade
By the pattern and degree of inflammation and cell death
How is chronic hepatitis divided by stage
The degree of fibrosis
What is fibrosis
Permanent scarring
What causes fatty changes in the liver
Metabolic stresses, alcohol, pregnancy
What causes cholestasis
Obstruction, autoimmune disease, viral hepatitis, pregnancy, drugs
What is fatty changes in the liver
Accumulation of fat (no glycogen so cells don’t take up the stain)
What is cholestasis
When bile stays in the liver which damages the hepatocytes
Describe the natures of hepatocyte necrosis
Can be individual cells, zonal or massive
What is the end stage of fibrosis
Cirrhosis (permanent)
What can abnormal storage cause
Hemochromatosis
What substances can be stored abnormally in the liver
Iron, copper, glycogen, lipids
What are the most common causes of lipid disease
Alcohol, non-alcoholic fatty liver disease (obesity, pregnancy), viral hepatitis
What are less common causes of lipid disease
Extrahepatic obstruction- gallstones, autoimmune liver disease- primary biliary cirrhosis, drugs-paracetamol, tumours, heart failure, metabolic and storage disease
What is hepatitis A
Enterovirus
How is hepatitis A transfered
Faeco-oral transmission
What does an outbreak of hepatitis A lead to
Acute hepatitis: fever, malaise, jaundice
What causes damage to the liver in hepatitis A
Serum transaminase
What is hepatitis B
DNA virus
How is hepatitis B transferred
Via blood, semen, saliva, IV drug abuse, sexually transmitted, blood donations, mother to child
When can hepatitis D cause infection
Only in the presence of hepatitis B
What does hepatitis B cause in the liver
High rate of developing cirrhosis
What increases with age in relation to hepatitis B
Frequency of clinical disease
What decreases with age in relation to hepatitis B
Carriers
What is hepatitis B called when you are younger
A sub clinical infection
What is hepatitis B recognised as when you are older
A clinical disease
How many people with hepatitis B develop chronic hepatitis
20% of those with a chronic infection. 10% of those with acute hepatitis get chronic infection. 25% infected get acute hepatitis
What can chronic hepatitis cause
3% of people get cirrhosis leading to hepatocellular carcinoma
What does presence of HBeAg mean
High infectivity and severity of the disease
What does it mean if HBcAg is present
You have infection as cannot vaccinate against core
How many people infected with hepatitis C develop chronic hepatitis and chronic liver disease
85%
What does cirrhosis require
Transplantation as there is no cure
What is the most common cause of chronic liver disease in the UK
Alcohol
What happens in the liver if you drink too much alcohol
You develop fatty liver disease which results in reversible inflammation. If you continue to drink you get fibrosis then cirrhosis, both of which are irreversible
What two drugs can cause dose-dependent toxicity in the liver
Paracetamol and methotrexate
Describe idiosyncratic drug reactions
You inherit specific genes that control the transformation of a drug which leads to drug (and/or toxic metabolite) accumulation e.g. NSAIDs and antiretrovirals
Describe non-alcoholic fatty liver disease
Same pathological features as alcoholic liver disease
Describe autoimmune liver disease
Not that common. There are antibodies detected in serum
What is primary biliary cirrhosis
Destruction of bile ducts
What do gallstones result in
An obstruction which causes pale stools due to jaundice. As a result there is more bilirubin in the blood instead of in stools resulting in dark urine
What are the two types of gallstones
Cholesterol and pigment stones
Which type of gallstones are more common
Cholesterol- 80% (pigment- 20%)
What can cause cholesterol stones
Increased cholesterol or decreased bile salts
Who are at most risk of cholesterol stones
4 F’s: female, fair, forty, fat
Why are cholesterol stones more common in women
Cholesterol stones are more common in the presence of oestrogen. More common in women as oestrogen malabsorption causes a decrease in bile salts= cholesterol stones form
Who can pigment stones occur in
Increased red cell breakdown- children with sickle cell disease. Chronic biliary infection
How does increases red cell breakdown result in pigment stones
Increased red cell breakdown results in increased unconjugated bilirubin
How do chronic biliary infections result in the formation of pigment stones
Glucuronidase is released by injured hepatocytes and bacteria which hydrolyses bilirubin glucuronides, as a result the amount of unconjugated bilirubin increases- pigment stones form
What are liver tumours mostly due to
Metastatic disease making them a metastatic cancer
What are metastatic liver tumours causes by
Haematogenous (blood borne) metastases
What makes the liver vulnerable to its high level of metastases
Dual blood supply
What is primary liver cancer called
Hepatocellular carcinoma
What are the predisposing factors for hepatocellular carcinoma
Cirrhosis, hepatitis B and C infection, fungal toxins secondary to food contamination
What are causes of just chronic liver disease
Hepatitis C, alcohol, NAFLD
What are causes of just acute liver disease
Paracetamol, hepatitis A, drug reactions
What are causes of both acute and chronic liver disease
Hepatitis B, autoimmune, tumours
What does cytokine production in the liver result in
Scarring leading to cirrhosis
What happens when cirrhosis occurs in the liver
The liver can’t regenerate in the proper way resulting in nodules and therefore scarring. Micro/ macro nodular scarring.
What will affect whether someone gets a liver transplantation or not
If they are infectious or still drinking
What are the issues in end-stage liver cirrhosis
Splenomegaly, brusing, bleeding, can’t metabolise oestrogen, ascites, spider naevi, low albumin, portal hypertension, increased risk of sudden cardiac death (due to disturbance of Q-T interval)
