Flashcards in liver lecture Deck (102):
what are the functions of the liver?
glucose and fat metabolism
detoxification and excretion
defence against infection as part of the reticuloendothelial system
give examples of substances that the liver detoxifies the blood from and excretes
describe the normal histology of the liver
regular arrangement ie acinar and lobular
portal triad - hepatic artery, portal vein, bile duct
split into zones 1,2 and 3 receiving progressively less oxygenated blood
what type of epithelium lines the bile ducts?
what two paths can acute liver injury take?
What three paths can chronic liver injury take?
How does acute liver failure present generally?
liver pain (somatic nerves in the capsule of the liver)
how does chronic liver injury present generally?
oedema (eg in ankles)
haematemesis due to varices
which of the LFTs give SOME indication of liver function?
which of the LFTs give no indication of liver function?
the serum liver enzymes:
- cholestatic: ALP, gamma GT
- hepatocellular: the transaminases ie AST and ALT
what is the pother name for unconjugated jaundice?
what are the causes of pre-hepatic jaundice?
Give an example of post hepatic jaundice
bile duct obstruction
what are the cholestatic jaundice types?
hepatic and post-hepatic jaundice
what are the qualities of urine, stools, itching and liver tests in pre hepatic jaundice?
liver tests: normal (apart from bilirubin - isolated bilirubin rise)
what are the qualities of urine, stools, itching and liver tests in hepatic or post hepatic jaundice jaundice?
liver tests: abnormal
give examples of liver disease
congestion - due to CCF
Give examples of obstruction
give three causes of strictures
what is Mirizzi's syndrome?
gallstone becomes impacted in the cystic duct or neck of the gallbladder causing compression of the common bile duct (CBD) or common hepatic duct, resulting in obstruction and jaundice
List some causes of acute liver injury
viral A, B, EBV, hep E and CMV
what are the causes of chronic liver injury?
viral B, C
metabolic - iron and copper
What questions would you ask to a pt who presents with jaundice?
- dark urine, pale stools, itching?
- symptoms - biliary pain, rigors, abdomen swelling, weight loss
- PMH: biliary disease, biliary intervention, malignancy, heart failure, receiving blood products, autoimmune disease
- drug history - any started recently including herbs
- social history: alcohol, hepatitis contacts, IVDU, exotic travel, certain foods
- FH and system review
what would very high AST and ALT suggest?
liver disease - remember these are the transaminases that are present in the hepatocytes
what test would be done for biliary obstruction and what would this show?
dilated intrahepatic bile ducts
what other imaging tests are there available apart from ultrasound?
ERCP (endoscopic retrograde cholangiogram)
so overall, what tests should be done for sb with jaundice?
if further imaging needed:
where do most gallstones form?
what are the most common types of gallstone?
what are the risk factors for gallstones?
Forty - above the age of 40
Fertile -premenopausal- increased estrogen is thought to increase cholesterol levels in bile
also liver disease, ileal disease, total parenteral nutrition - ie IV nutrition
How do gallbladder stones present?
cholecystitis - inflammation of the gallbladder
obstructive jaundice - maybe if there is Mirizzi syndrome
no cholangitis - ie no infection of the bile duct
how do stones in the bile duct present?
no cholecytitis - no inflammation of the gall bladder (as the stone is not in the gallbladder)
obstructive jaundice present
cholangitis present - ie infection of the bile duct, as the stone is in the bile duct
How are gallbladder stones managed?
bile acid dissolution therapy
How are bile duct stones managed?
ERCP with sphincterotomy and stone removal, stone crushing, stent placement
surgery done for large stones
Is the alkaline phosphatase normal or abnormal with acute stone obstruction?
The ducts may not always be dilated on ultrasound in obstructive jaundice, T or F?
What happens to the ALT over time with obstructive gallstones?
rapidly falls over a period of days from being over 1000
What blood test LFT results would a person with drug induced liver injury get?
high ALT, high AST and raised bilirubin
ALP borderline raised
How might drug induced liver injury present?
recent onset of itching, nausea and vomiting
Name some drugs that can cause DILI
Does Atenolol cause DILI?
What are the different types of DILI?
What are the main points of abnormality in the LFT with hepatocellular DILI?
(ALP may also be raised)
think high liver enzymes due to liver cell damage
What is the main point of abnormality in cholestatic DILI?
How would you ask a pt about the drugs they take if you suspect DILI?
What drugs did you start recently, not what drugs are you on? - drugs taken in last 3 months are relevant
What is the duration of onset of symptoms from starting the drug to DILI?
What are the drugs that are the usual suspects for DILI?
Give examples of antibiotics that can cause DILI
Give an example of a GI drug that can cause DILI
which drugs do not tend to cause DILI?
low dose aspirin
NSAIDs other than diclofenac
calcium channel blockers
What changes would be seen in the LFT in paracetamol overdose?
ALT and AST are extremely high
PT time is increased (due to liver damage)
What is the antidote of paracetamol called?
How does paracetamol overdose cause liver damage?
CYP450 converts paracetamol into a reactive intermediate which causes hepatocyte necrosis
How is paracetamol induced fulminant hepatic failure managed?
give the antidote N acetylcysteine
supportive treatment to correct any coagulation defects, fluid electrolyte and acid base balance, renal failure, hypoglycaemia and encephalopathy
What are the poor prognosis indicators of paracetamol induced liver failure?
1. late presentation - after 24 hours, as NAC is not effective after then
3. PT >70 sec (n = 12-13 seconds)
4. serum creatinine >=300 µmol/L (normal is 45-90)
should a liver transplant be considered in paracetamol induced liver failure?
What are the signs of alcohol related liver injury?
What are the causes of ascites?
chronic liver disease
portal vein thrombosis
TB infection of the peritoneum
neoplasia eg of the ovary, uterus, pancreas
cardiac- eg constrictive pericarditis
explain the pathophysiology of ascites
1. increased intrahepatic resistance
2. leads to portal hypertension
3. this causes systemic vasodilatation sop that blood can be shunted into the systemic circulation
4. leads to activation of the RAAS, NA release and ADH release causing Na and water retention, leading to fluid retention
5. low serum albumin due to liver damage also leads to ascites
what may be seen in alcohol related liver injury in the LFTs?
raised serum bilirubin
What is the appearance of a liver with cirrhosis on ultrasound?
what are the histological features of acute alcohol related liver injury?
mediated by neutrophils
Mallory's hyaline/body - an accumulation of cytoskeletal protein (not specific to alcoholic liver disease)
fat - alcohol changes the way that the liver metabolises fat - so fat accumulates within hepatocytes = steatosis and can be associated with acute or chronic liver injury
which zone of the liver is most affected by alcohol?
zone 3 - the area with the lowest oxygen and blood supply
what are the two sequelae of fatty liver due to alcohol and which one is a more common sequelae? What do both of these lead to?
alcoholic hepattiis and cirrhosis
alcoholic hepatitis is the more common sequelae
they both lead to acute decompensation of the liver ie liver failure
What percentage of people who are heavy alcohol drinkers get ALD?
What drug can be given when there are bleeding varices?
Terlipressin - an analogue of vasopressin, causes vasoconstriction
What are the causes of portal hypertension?
portal vein thrombosis
what is the cause of varices?
portal hypertension results in collaterals forming, ie increased splanchnic blood flow
How is ascites managed?
fluid and salt restriction (as they are already overloaded with fluid)
diuretics - spirolonlactone and furosemide
large volume paracentesis plus albumin
What is TIPS?
a metal stent is passed over a guide wire in the internal jugular vein
the stent is then pushed into the liver substance under radiological guidance to create a shunt between the portal and hepatic veins, lowering portal pressure
What is the most commonly used benzodiazepine for alcohol withdrawal and what alternative is used in those at risk of drug accumulation ie pts with cirrhosis
Chlordiazepoxide is the drug of choice
Oxazepam and lorazepam are often used in patients at risk of drug accumulation
what are the complications that pts with liver disease can experience?
due to the effects of drugs they have been given
infection of the ascitic fluid, blood, skin, chest
hyponatraemia, hypokalaemia, hypoglycaemia aka heatorenal syndrome - renal failure due to chronic liver disease
other complications eg intracranial haemorrhage due to coagulopathies
If a pt with ascites has a high WBC count, low platelets, perhaps renal failure with low electrolytes, metabolic acidosis and high creatinine what could be the diagnosis?
spontaneous bacterial peritonitis
Why do pts with liver disease get pancytopenia?
in portal hypertension, you get splenomegaly due to congestion and this increases the breakdown of platelets, red cells and WBCs
Why are pts with liver disease vulnerable to infection?
impaired reticuloendothelial function (as the kupffer cells line the sinusoids)
reduced opsonic activity
impaired leukocyte function
permeability of gut wall increases - so greater translocation of bacteria into the blood
what are the types infection common in pts with liver disease?
spontaneous bacterial peritonitis
What is the diagnosis of SBP based on?
neutrophils in the ascitic fluid
What should pts be given after one episode of SBP?
liver transplantation should be considered
The symptoms of of SBP are very specific T or F?
False - they are vague!!
What is the diagnosis of SBP based on?
the number of neutrophils in the ascitic fluid
needs to be over 250
what are some of the causes of renal failure in liver disease?
drugs - overuse of diuretics, NSAIDs, ACEIs, aminoglycosides
renal tract obstruction
What is the cause of hepatic encephalopathy?
build up of ammonia
What factors may precipitate hepatic encephalopathy?
drugs eg sedatives and analgesics
what are the causes of coma in pts with chronic liver disease?
Why is hepatocellular carcinoma a risk in pts with long standing cirrhosis?
there is constant replication of hepatocytes due to the liver trying to repair itself from damage, and so it is more likely that mistakes will be made
what are some other consequences of liver dysfunction that have not already been mentioned?
Name three causes of coagulopathy that can be due to liver dysfunction
impaired coagulation factor synthesis
vit K deficiency due to cholestasis
what endocrine changes can occur in liver disease?
gynaecomastia impotence amenorrhoea
Which drugs should you be weary of in liver disease?
NSAIDs as they cause renal failure
short acting benzodiazepines use with care
look out for XS weight loss, hyponatraemia, hyperkalaemia nad renal failure with diuretics
avoid aminoglycosides (end in -mycin eg streptomycin and gentamycin)
How is malnutrition treated in liver disease?
how is variceal bleeding treated?
how is encephalopathy treated?
lactulose (remember constipation can cause encephalopathy)
how is ascites/ oedema treated?
What should you do when a liver pt experiences complications?
ABC - airway breathing circulation
look at the chart - to check vital signs, O2, sugars, check the drug chart
look at the pt - is there infection or bleeding?
order tests - FBC< U+E, blood cultures, ascitic fluid, clotting, LFTs
What are the causes of chronic liver disease?
non-alcoholic steatohepatitis (NASH)
viral hepatitis ie B and C
immune - autoimmune hepatitis, primary biliary cirrhosis, sclerosing cholangitis
metabolis - haemachromatosis, Wilson's, alpha 1 antitrypsin deficiency
vascular - Budd-Chiari
What investigations are done for investigations of chronic liver disease?
radiology - US (the standard radiological test), CT, MRI
What can we look for in viral serology?
hepatitis B surface antigen HBsAg
hepatitis C antibody
what antibodies can we look for in chronic liver disease?
1. AMA - antimitochondrial antibodies in primary biliary cholangitis
2. ANA - eg in autoimmune hepatitis, systemic lupus erythematosus, Sjögren's syndrome, scleroderma
3. AMSA - Anti-smooth muscle antibodies in autoimmune hepatitis
4. coeliac antibodies: Total immunoglobulin A (IgA)
IgA Tissue transglutaminase antibody (shortened to tTG)
If IgA tTG is weakly positive then IgA endomysial antibodies (shortened to EMA) should be used
immunoglobulins - can tell what type of autoimmune disease you have
What biochemistry studies should be done in chronic liver disease?
copper studies incl. Ceruloplasmin; the major copper-carrying protein in the blood and a 24hr urine copper
alpha 1 antitrypsin level
How can you differentiate hepatitis from obstruction by looking at the liver enzymes values?
if the liver enzymes are very very high, more likely to be hepatitis rather than obstruction
what are the differential diagnoses (different causes) of hepatitis?
viral A, B, C, CMV, EBV