Liver Disorders Flashcards
what are the basic functions of the liver? (7)
protein metabolism
- produces circulating proteins - clotting factors and albumin
nitrogen excretion
- amino acids break down into ammonia
- pass out into urine
carbohydrate metabolism
- glucose homeostasis
lipid metabolism
bile production
bilirubin metabolism
- breakdown product of RBC
hormone/drug inactivation
- broken down by the liver
immunological functions
- manages bacteria from the GIT
what is the function of albumin
maintaining osmotic pressure
what percent of innate immune proteins are produced by the liver?
80-90%
where is the liver?
upper right quadrant of abdominal cavity
what is the weight of the liver?
usually 1.5kg in adults
what are liver cells called?
hepatocytes
describe the blood supply of the liver.
70% comes from portal vein - from intestines and spleen
30% from hepatic arteries from branch of aorta called coeliac axis
- blood enters via portal tracts, travels through liver through the sinusoids (gaps between hepatocytes)
- blood leaves via hepatic vein in the centre of the lobule
describe bile in the liver
produced by the liver
- leaves the liver via bile duct out of the portal tract
- travels against the blood flow
describe the organisation of the liver.
comprised mostly of hepatocytes
- arranged in rows
what are the potential implications if the liver fails?
protein metabolism
- impaired clotting
- reduced albumin - leads to oedema and ascites
nitrogen exretion
- excess ammonia in blood
- mimic neurotransmitters
= impaire cognitive function
what is ascites?
when fluid collects in spaces within the abdomen
what is bilirubin?
a breakdown product of red blood cells
describe the pathway of bilirubin from the blood and being passed out.
- not water soluble
- must be bound with albumin to travel in the blood = unconjugated
- becomes conjugated in the liver = water soluble
- bilirubin travel via bile duct into gut
in the gut
- bilirubin converted into:
- urobilinogen - travel out in urine or enterohepatic circulation - back through the liver
- or stercobilinogen - travel out in faeces
- some absorbed back into the blood
what is jaundice?
excess bilirubin in the blood
what are the 3 types of Jaundice? describe them.
- Pre-Hepatic
- the liver is fine
- too much bilirubin is produced
- seen in haemolytic anaemia - Hepatic
- acute diffuse liver cell injury from end stage chronic liver disease or metabolic disorders
- = too few functioning liver cells
- unable to process bilirubin normally - Post-Hepatic
- the liver is fine
- bile duct obstruction
- stones, strictures, tumours
how much bilirubin accumulates in the blood to become visible for jaundice?
more than 40 micromol/litre
how can liver disease be detected? (5)
- detect liver enzymes
- albumin levels
- clotting
- ultra-sounds
- biopsies
what two places can liver enzymes leak from, showing indications for liver disease?
- from damaged hepatocytes
- from damaged bile duct cells
which 2 liver enzymes leaking from damaged hepatocytes can indicate liver disease?
ALT - alanine aminotransferase
AST - aspartate aminotransferase
- mild, slow, progressive increase = chronic liver disease
- rapid, large increase = severe acute liver disease
which liver enzyme leaking from damaged bile duct cells can indicate liver disease?
ALP - alkaline phosphatase
how can albumin levels indicate liver disease?
- synthesised by the liver
- have a long half life
- if the levels drop = chronic liver disease
how can clotting indicate liver disease?
- look at how well the blood is clotting
- clotting factors produced by the liver
= short half life - can indicate acute and chronic
how can ultrasounds be used to detect liver disease?
- check for dilated bile ducts
- if dilation = obstruction
when would biopsies be taken to investigate liver disease? what is the most common case found when undergoing this investigation
after ultrasound
- if bile ducts aren’t dilated = no obstruction
- best to visualise the abnormalities within the liver
= most cases are due to acute hepatitis
what is hepatitis? what are the 2 types
inflammation of the liver, defined by raised liver enzymes
- describes any liver disease which isnt neoplastic
acute and chronic
what are the causes of acute and chronic hepatitis?
viral
alcohol
obesity
drugs
inherited conditions
autoimmune conditions
describe acute hepatitis
- caused by something that goes away
- short-lived
- resolves by itself
- no signs
- often only noticed by blood tests
give 6 conditions arising from acute hepatitis, in increasing order of rarity and severity
- asymptomatic
- malaise - general feeling of discomfort
- jaundice - high bilirubin levels
- coagulopathy - affected blood clotting
- encephalopathy - brain function affected
- death
give 3 inherited disorders which can cause hepatitis.
Haemochromatosis - iron accumulation
Wilson’s disease - copper accumulation
Alpha-1-antrypsin deficiency
describe chronic hepatitis
- caused by persistent liver injury
- persistent cycle of damage and repair
= long term liver damage
what does chronic hepatitis progress to?
cirrhosis
what is a big cause of chronic hepatitis?
non alcoholic fatty liver disease
NAFLD
what 2 things does the severity of acute hepatitis depend on?
- how many hepatocytes are damaged as a result
- how well the liver is able to regenerate the lost cells
what is cirrhosis?
a irreversible change in the liver due to chronic liver disease
describe the pathology of chronic liver disease/cirrhosis
- hepatocytes injured and repaired continuously
- causes scarring
- scar tissue links vascular structures - portal tract and hepatic vein = bridging fibrosis
- liver tissue becomes into separated nodules
- end stage = cirrhosis
cirrhosis is clinically silent, what does this in turn mean?
means that you find out when the liver function fails (decompensation) and leading to liver failure and portal hypertension
what are the 4 complications of cirrhosis?
liver failure
portal hypertension
infection
hepatocellular carcinoma
is cirrhosis a disease?
NO
cirrhosis is the end point of all chronic liver diseases
what effect can alcohol gradually have on the liver?
fatty changes
alcohol induced liver inflammation
= alcoholic steatohepatitis
cirrhosis
what does alcohol liver injury depend on?
dosage and susceptibility
how does steatohepatits appear under the microscope?
fatty changes
ballooned hepatocytes with mallory body - pink things
inflammatory cells
what condition is regarded as the most common cause of liver disease?
non alcoholic fatty liver disease
describe the pathogenesis of NAFLD.
- fat accumulation = steatosis
- steatohepatitis
- cirrhosis
- hepatocellular carcinoma
how is NAFLD treated?
need to address the metabolic syndrome
- obesity
- diabetes
- hyperlipidaemia
what are the 5 hepatitis virus’ and which other 3 viruses can cause hepatitis?
A
B
C
D - only found in people with B
E - faecal-oral transmission via infected water
EBV - epstein-barr virus
CMV - cytomegaloblastic virus
HSV - herpes
define hepatotoxic
toxins which cause injury to the liver
what are the two types of hepatotoxic drugs? describe them.
intrinsic
- when excessive doses are administered
- liver injury is predictable
idiosyncratic
- liver injury is rare and unpredictable
- happens from metabolic and immunological response variability
can drug-induced liver injury be reversed?
yes can stop taking the drugs
time of onset for injury is variable and can be months
what is the most common symptom of drug induced liver injury?
jaundice
describe paracetamol overdose
- 2-3 days massive hepatocellular necrosis - liver looks all pink
- no inflammation - just around the central vein
- death if no transplant
describe Haemochromatosis - the pathogenesis and treatment
- inherited disorder of iron metabolism
of the HFE gene - increase iron absorption in the gut
- iron deposited in various organs
- pancreas - can cause diabetes
- skin - pigmentation
- heart - cardiomyopathy
- liver - chronic hepatocellular injury - cirrhosis
- increase risk of HCC hepatocellular carcinoma
treatment
- venesection - reduce 1 unit of RBC per week
describe a Haemochromatosis biopsy
use Perl’s Stain
- highlights iron in the tissues = blue
describe Wilson’s Disease and the treatment
- rare
- autosomal recessive
- mutation of ATP7B gene
- impairs the excretion of copper
- copper accumulates
- in liver - chronic liver injury - cirrhosis
- in eye - Kaiser-Fleisher ring
- in brain - psychiatric
treated by removing the copper
- using penicillamine
describe Alpha-1-Antitrypsin deficiency and another condition which it causes, relating to the lungs.
A-1-A = protein in blood
- inactivates neutrophil elastases
= digestive enzyme produced by neutrophils in the liver
- deficiency
- process impaired
- A-1-A not secreted
- accumulates in blood
- lots of PAS+ globules in liver
- chronic liver injury - cirrhosis
also causes emphysema in the lungs
- neutrophil elastase damages lung tissues
- lose ability to recoil
- traps air in lungs
= emphysema
describe how liver diseases can occur from autoimmunity.
- normal immune regulation disturbed
- self-antigens are recognised
- manifest destruction of hepatocytes = autoimmune hepatitis
or - damage to bile ducts = autoimmune biliary diseases
- primary sclerosing cholangitis
- primary biliary cirrhosis
autoimmune hepatitis - describe the diagnosis, biopsy and treatment.
diagnosis
- autoantibodies
- raised IgG, ALT
biopsy
- interface hepatitis
- lots of plasma cells
treatment
- immunosuppression to avoid progression to cirrhosis
what are the 2 autoimmune biliary diseases? describe them
primary biliary cholangitis
- anti-mitochrondial antibodies
- increased IgM, ALP
- bile duct granulomas
- progresses to cirrhosis
primary scelorising cholangitis
- associated with ulcerative colitis
- pANCA antibodies
- diagnose with imaging
- periductal onion skin fibrosis around bile duct
- progresses to cirrhosis
what is acute liver failure?
when there is sudden and severe liver damage
why would some people with cirrhosis not know they have it?
the liver can compensate
- have some residual function
what is decompensated liver?
liver loses all function
= liver failure
give 4 features related to impaired liver function due to cirrhosis
hypoalbuminemia/clotting factor deficiencies
- bruising and bleeding
ascites
- low albumin
- aldosterone disturbances
encephalopathy
- due to impaired breakdown of nitrogen substances
gynaecomastia
- due to impaired oestrogen breakdown
describe portal hypertension as a result of cirrhosis, what does it cause? (3)
- liver is structurally abnormal
- blood flow is impaired
- pressure build up
- back pressure build up in portal vein
- blood can’t get through the liver
- causes ascites and splenomegaly
- due to pressures
- porto-systemic shunts
what are porto-systemic shunts? (cirrhosis portal hypertension), how does this happen (3) and what do they lead to (2)?
blood attempts to bypass the liver
- oesophageal varices
- haemorrhoids
- caput medusae
- patient becomes prone to bleeding and ruptures - due to weak vessels and paths
- bypasses the liver function
what cells in the liver act to fight infection?
Kuppfer cells
what is a malignant tumour of hepatocytes called?
Hepatocellular Carcinoma
give 4 other benign liver tumours
haemangioma
bile duct adenoma
focal nodular hyperplasia
hepatocellular adenoma
give 3 malignant liver tumours
hepatocellular carncoma
cholangiocarcinoma
metastatic tumours
what other tumour is metastasis of the liver observed?
colorectal cancer
how does liver disease affect dental treatment?
- coagulopathies
- may be carrying infections - hepatitis
- drug-toxicity can be different due to lower metabolisms
