Liver Flashcards
What is hepatitis?
Inflammation of hepatocytes e.g. due to virus, alcohol, obesity
What are gallstones?
Stones that form in the gallbladder and stop the secretion of bile- blocking the bile duct.
What is cholangitis?
Inflammation of the bile duct that causes narrowing
What is haemochromatosis?
Inherited iron overload
What is Wilson’s disease?
Inherited copper overload
What is Gilbert’s disease?
Inability to metabolise bilirubin properly.
How do you classify acute vs chronic liver disease ?
Acute:
- Usually self-limiting- e.g. due to drugs or virus
- Causes hepatocyte inflammation/damage- but liver cells are good at repairing and regenerating
- occasionally can be severe and result in liver failure
Chronic:
- Inflammation persists for >6 months
- Results in permanent damage with structural changes
e.g. cirrhosis (fibrosis, scarring) = loss of hepatic function and death
- most common cause is alcohol abuse
Describe the progression of liver disease?
Normal liver
Then some kind of damage occurs e.g. alcohol, viral infection, Non-alcoholic fatty liver disease (NAFD), autoimmune disorder, cholestatic disorder
This leads to inflammation and potentially a fatty liver. This inflammatory damage leads to activation of pro-inflammatory cytokines, immune cells, matrix deposition, parenchymal cell death and angiogenesis.
This all leads to early fibrosis (note; at this stage id underlying cause can be removed or anti-fibrotic drugs can be used, the liver can be resolved to the normal liver phase above).
Early Fibrosis leads to late fibrosis and cirrhosis- this is irreversible.
Causes disrupted structure, loss of hepatocyte function.
Hepatocytes will be regenerated but to sub-standard function.
This can lead to liver failure and portal hypertension
at this stage, a liver transplant is required
This process usually takes from 5-50 years, dependent on co-factors such as obesity, alcohol, genetics and epigenetic markers.
What is a ‘Fatty liver’?
A reversible condition in which large vacuoles of triglyceride fats are deposited in the liver.
Has increased TGs, LFTs and liver fat
20-30% of adults have a fatty liver and 15-20% go on to have non-alcoholic fatty liver disease. This can lead to inflammation, fibrosis and steatosis (fat build up in liver cells). This may progress to cirrhotic liver and hepatocellular carcinoma.
What are the treatments for fatty liver?
There are no treatments available until the patient has cirrhosis and they become eligible for a liver transplant. This is not common though.
What are happening to different cell types during advanced fibrosis?
- Loss of hepatic stellate cells
- Immune cells e.g. lymphocytes are infiltrating
- Activated kupfer cells- try to phagocytose dead cells
- Hepatocytes are dying
- Sinusoid lumen has increased resistance to blood flow due to scarring and fibrosis
What are the potential causes of liver disease?
VIRUSES:
Can cause hepatitis of liver and inflammation
e.g.
Hepatitis A: faecal- oral transmission
causes acute inflammation that should usually resolve spontaneously
is a preventative vaccine available
Hep B: In Bodily fluids eg. blood (common in drug users)
can pass from mum to baby
acute but can progress to chronic inflammation
there is a vaccine and it is often given to healthcare workers
Hep C: bodily fluids
chronic inflammation
no vaccine
Hep D: body fluids
requires concomitant infection with hep B to survive
Hep E: Contaminated food and water
usually self-limited
Hep G: bodily fluids, chronic infection
DRUGS
- Some drugs require an over-dose in order to cause liver damage e.g. Paracetamol
- Some drugs can cause damage even when appropriately prescribed (Need LFTs) e.g.
Statins
Antibiotics e.g. amoxicillin, tetracycline
Methotrexate
- Some natural products can cause damage e.g. herbal remedies (kava kava), high dose vitamin A, wild mushrooms.
ALCOHOL
Most common cause
Is directly toxic to liver cells- inflammation progressing to fatty liver and fibrosis. fibrosis alters structure and blood flow = portal hypertension which causes back pressure back into the liver
- Damage tends to occur in >40g/day in men and >20g/day in women (1 unit = 9g)
What can cause cholestasis?
Cholestasis is the lack of bile entering the GI tract.
Can be due to hepatocytes:
- failure of bile production and secretion. Causes: hepatitis due to virus, alcohol, drugs, pregnancy
Can be due to problems with bile ducts e.g. obstruction in bile ducts via gall stones, carcinoma, cholangitis (progressive scarring).
What are the symptoms of acute liver disease?
May be asymptomatic!
- general malaise
- anorexia, appetite loss
- fever
- jaundice
What are the symptoms of chronic liver disease?
- fatigue, weakness
- weight loss, cachexia, muscle wasting
- N+V
- loss of apetite
- abdominal swelling
- right upper quadrant abdominal pain and tenderness
- jaundice
- bruising and bleeding- loss of coagulation factors
What are the symptoms of cirrhosis?
As disease progresses to cirrhosis, so does the symptoms:
- Inability to metabolise waste = bilirubin build up = jaundice
- failure ti produce proteins- hepatocytes stop = can’t clot blood, no albumin = swelling
- bruising (lack of clotting factors)
- Gynecomastia - increase in male breast size
- impotence- erectile dysfunction
- confusion
- Ascites- abdo swelling
- Portal hypertension
- oesophageal varices- enlarged veins in the oesophagus, can cause bleeding
What is jaundice?
Yellowing of skin & mucuos membranes (sclera-white of eye) due to build up of bilirubin.
What are the possible causes/types of jaundice?
- Haemolysis (haemolytic jaundice)- RBCs are breaking down but the liver isn’t removing the heme so bilirubin is building up in the skin
- Hepatocellular damage (Hepatic jaundice)- damage to hepatocytes
- Cholestasis (obstructive jaundice)- bile is being made but can’t reach the GI tract due to obstruction in bile duct.
What is portal hypertension- inc complications?
This is a back pressure caused by resistance of blood flow into liver as a result of fibrosis, causing back pressure in the portal vein (carries blood from GI tract and spleen to liver). This leads to blood being used into surrounding blood vessels inc thin walled veins in the oesophagus which can rupture and bleed. Uncontrolled bleeding can lead to shock and death.
Portal hypertension can lead to complications including ascites, GI bleeding, hepatic encephalopathy, splenomegaly.
What is ascites-inc causes?
A swelling of the abdomen due to abnormal accumulation of fluid in the peritoneal cavity due to a pressure imbalance between inside the circulation (blood vessels) (higher) and outside in the peritoneal cavity (lower).
Fluid moves from high pressure to low causing a build up in the peritoneal cavity that needs to be drained.
Causes:
Activation of the renin-angiotensin system due to decreased renal blood flow due to disordered liver anatomy= secondary hyperaldosteronism- fluid retention. This is exaggerated by aldosteone not being metabolised by the liver like normal.
Portal HTN- oedema localises in abdomen
Low plasma albumin- as not made in the liver like normal = decreased. osmotic pressure in plasma = oedema
retention of salt and water in kidneys e.g. secondary to renal problems e.g. hyperaldosteronism
What is hepatic encephalopathy- inc symptoms and causes?
Is caused by a build up of ammonia in the bloodstream which is normally converted to urea in the liver and excreted by the kidney.
- Ammonia build up is an issue as it can cross the BBB and lead to neurological abnormalities in the brain.
Symptoms:
altered mental state
fetor hepaticus- chronic bad breath- musty smell
Asterixis- hand tremor
drowsiness
confusion
coma
Causes/worsened by:
dehydration
hypovalemia
gi bleed
CNS drugs
alcohol
increased protein intake
constipation
What is wernicke’s encephalopathy/korsakoff syndrome?
Is a neurological abnormality due to deficiency of thiamine (Vit B).
This deficiency is often seen in chronic alcohol abuse as this decreases thiamine absorption and malnutrition. presents similarly to hepatic encephalopathy.
What causes anaemia in liver disease?
The effects on iron homeostasis due to splenomegaly caused by postural hypertension.
- alcohol is toxic to bone marrow
- can be due to decrease in clotting factor synthesis
- bruising and bleeding occurs
What circulatory and skin changes may occur as a result of liver disease/damage?
Circulatory:
- Palmer erythema: rash like dermatitis- red but NOT dry
- Spider naevi- clusters of blood vessels on skin surface- vascular lesion
- finger clubbing- due to changes inn interstitial fluid
skin
- pruritus- due to toxic substances being laid down in skin rather than being metabolised by the liver.
What tests are used in diagnosing liver disease?
- Medical history- signs and symptoms
- LFTs
- Electrolytes
- FBC- in end stake LF = bone marrow suppression causing decreased RBC, WBC, Platelets
- Viral screens
- Prothrombin time- blood clotting capability of liver
Imaging- assess function and structure of liver, gall bladder, bile ducts and look for cancer
- Ultrasound
- CT
- MRI
- liver biopsy
What LFTs are looked at in liver disease?
SERUM ENZYMES:
- Aspartate transaminase (AST)
- Alanine transaminase (ALT)
- Gamma glutamyl transferase (GGT)
- Alkaline phosphatase (ALP)
Others:
- Bilirubin
- plasma proteins and albumin
- prothrombin time
- urea and ammonia
Discuss use of AST in liver diagnosis?
Aspartate transaminase (AST) has a role in gluconeogenesis catalysing the reversible conversion of aspartate and alpha veto glutamate to oxaloacetate and glutamate.
Reference range 5-40 IU/L
- is found in liver, but also heart, brain, skeletal muscles = not used in isolation?
What is the normal AST levels?
Reference range 5-40 IU/L
Discuss use of ALT in liver diagnosis?
Alanine transaminase (ALT) also plays a role in gluconeogenesis to catalyse the reversible transfer of an amino group from L-alanine to alpha kept-glutarate = pyruvate and L-Glutamate
Reference range = 5-30 IU/L
Is more specific to liver than AST.
What is the normal ALT levels?
Reference range 5-30 IU/L
How are AST & ALT used in diagnosing liver disease?
- Very high levels of AST & ALT occur in acute viral/toxic hepatitis
- High (but not as as above) in cholestatic jaundice, cirrhosis
USE THE RATION OF AST/ALT IN DIAGANOSING DIFFERENT TYPE OF LIVER DISEASE:
AST/ALT: >2 could indicate possible alcohol injury
Most other liver injuries, AST:ALT is <1
Discuss use of GGT and ALP in liver diagnosis?
Gamma glutamyl transferase (GGT):
Catalyses the transfer of a gamma glutamyl moiety of glutathione to an AA, peptide or water.
Reference range: 5-45 IU/L
- is very high in biliary obstruction
- is elevated (but lower) inc chronic alcohol or drug toxicity, hepatitis, cirrhosis, cholestasis.
- can indicate alcohol consumption/abuse- levels will decrease in 3-6 weeks after abstinence.
Alkaline phosphate (ALP):
- Removes phosphate groups from nucleotides, proteins, alkaloids
Reference: 100-200 IU/L
- very high in billiard onstruction
What is the normal GGT levels?
5-45 IU/L
What is the normal ALP levels?
100-200 IU/L