20 - Liver Disease Case Studies Flashcards
What are the 2 transaminase liver enzymes?
AST - Aspartate transaminase
ALT - Alanine Transaminase
What does an increase in ALT and AST indicate?
Hepatic inflammation or damage to hepatocytes (hepatocellular injury) as these enzymes are found in the middle of the liver cells
What are the 2 biliary/cholestatic enzymes?
GGT - Gamma - glutamyl transferase
ALP - Alkaline phosphatase
What does an increase in GGT and ALP indicate?
Cholestasis - bile stasis obstruction to bile/impaired or obstructed blood flow
What are 3 measures of liver function?
Bilirubin
Albumin
Clotting factors (IRN ratio)
What can cause bilirubin increase?
Both hepatocellular injury and biliary obstruction
What does abnormal albumin and INR suggest?
Chronic liver damage leading to impaired function of the liver (liver synthesises)
What is INR a measure of?
Clotting factors and so how long it takes the blood to clot
What patterns do you look for in abnormal liver tests?
Is the pattern of abnormality mostly hepatocelullar, cholestatic or mixed?
If there is jaundice this suggest
increased bilirubin suggesting it is a more serious abnormality/injury as involves liver function (metabolism not synthesis)
How do you know if liver synthetic function is impaired?
Function can still be normal with hepatitis or cholestasis
- serious injury when function is impaired
What is anorexia?
Loss of apatite
How do you clinically see jaundice?
Yellow sclera and skin - very high levels of BR if clinically present
What can hepatitis B and C cause?
Both acute and chronic viral hepatitis
How do you define acute and chronic infection?
Acute - first 6 months
Chronic - still infected after 6 months
How are hep B and C transmitted?
Blood
When was hep C discovered and what does this mean?
1989 - anyone how received a blood transfusion before this is at risk of having hep C as it wasn’t screened or tested for
What can hep B and C cause?
Can cause chronic liver disease and cirrhosis
Is there a vaccine for hep B and C?
Only hep B
HCV is a …. … virus
Single stranded RNA virus
HCV exists as … called … this is significant because
Strains called genotypes - significant because means making a vaccine is difficult and some genotypes are easier to treat than others
Are people with Hep C likely to clear it?
No they are unlikely to clear the virus - 85% of people with acute hep C infection end up with chronic infection
What are some risk factors for hep C?
- injecting drug users make up 2/3 of hepc patients
- unscreened blood products (pre 1992 and other countries)
- sexual (low but ^ with HIV)
- vertical
- occupational
- poor sterile practice in medical procedures i.e. re-using needles and not sterilsing
- tatooing and piercing
What was initial treatment for Hep C?
- interferon
- cytokine released from lympocytes
- exogenous interferon given to increase the immune response to the virus
- side effects similar to flu i.e. lethargic, aches, fever, fatigue)
- given as a subcutaneous injection
- only a 50% cure rate
How has interferon treatment evolved?
- monotherapy (interferon alone)
- interferon with ribavirin as a tablet
- pegylation of interferon with ribavirin
What is pegylation of interferon?
Addition of large PEG molecule to interferon to increase its half life so it stays in the body for longer
What were the problems with interferon?
- sub-optimal cure rates (50-80% depending on the genotype)
- side effects
- long duration 6 -12 months depending on genotype
What was the breakthrough in HCV treatment?
- direct acting antiviral agents
- increased cure rate (90%)
- tablets
- no interferon so less side effects
- shorter course (3 months compared to 6-12)
What is melaena?
Black bowel motions
What causes black bowel motions and what can it indicate?
Malaena - when there is a bleed in the stomach and this is digested and becomes black. Can indicate oesophageal varices that has burst causing bleeding into the stomach
What is cirrhosis and what is 1 complication?
Complication of chronic liver disease. Permanent scarring of the liver due to chronic disease. A complication is portal hypertension
What is the portal circulation?
Portal vein conducts nutrient rich venous blood from the GI tract to the liver (organ to organ bypass heart)
Where can varices occur in the foregut?
Oesophageal and gastric varices (along fundus) and at OG junction and IOS
How do you treat varices?
Via an endoscopy, suck up the bleeding vein and attach a rubber band at the end of the varix to stop circulation and bleeding
What is the most common cause of hypertension?
Cirrhosis (liver becomes fibrotic and stiff and vascular architecture re-arranges so resistance to blood flow increases)
Causes of portal hypertension?
Pre hepatic - portal vein thrombosis
Intra hepatic - cirrhosis
Post hepatic - hepatic vein thrombosis, R heart failure (if severe)
How does blood return from the portal circulation back tot the systemic circulation?
Via hepatic veins to IVC
Immediate consequence of portal hypertension?
Shunts/porto-systemic collaterals to BYPASS liver so blood isn’t receiving nutrient rich blood so majority isn’t filtered or detoxified
Describe liver cirrhosis?
- irreversible liver scarring and fibrosis
- occurs in advanced liver disease as a result of scarring from chronic inflammation
- liver is initially swollen but shrinks
- surface becomes irregular and nodular
Is fibrosis the same thing as cirrhosis?
No. Fibrosis due to prolonged or repeated injury is initially reversible if the liver is given enough time to regenerate by removing the injurious stimulus. Cirrhosis occurs where the fibrosis is irreversible
Does cirrhosis cause liver function failure?
Initially during mild cirrhosis the liver can function normally, but eventually it will progress and the liver can no longer function normally = liver failure
What is hepatic encephalopathy?
Hepatic encephalopathy is a result of chronic failure. It is due to the decrease in function of metabolising and detoxifing ammonia as well as the shunting of unfiltered blood away from the liver. There is a build up of ammonia in the blood and is able to cross the blood brain barrier to affect the brain function
Side effects of HE?
- early side effects are non-specific; mood and personality change, inverted sleep pattern
- late symptoms include confusion and bizzare behaviour, drowsiness and coma
What is the treatment of HE and how does it work?
Lactulose
- lactulose is a non-absorbed disacch used as a laxative to cause osmotic diarrhoea. In HE it
1. Decreases the ammount of ammonia made by bacteria
2. Converts ammonia to a NON absorbable molecule
3. Increases bowel transit
Lactulose helps to manage HE symptoms but isnt a definitive treatment
What is ascites?
Abdominal distension due to the accumulation peritoneal fluid (also occurs in cancer and heart failure as well as chronic liver disease) where the oncotic pressure in vessels increases so fluid leaks out of vessels
What are 2 causes of ascites?
- An elevated HYDROSTATIC pressure in the portal vein causing a fluid shift out of the vessels
- LOW ONCOTIC pressure in the portal vein due to low serum albumin (decreased liver synthetic function) so is less able to hold onto fluid in the circulation
What is the difference between the 2 causes of ascites?
One is due to a fluid shift while the other is due to a shift in protein levels in the portal vein
What is hepatic encephalopathy an indication of?
Advanced cirrhosis with liver failure
When does hepatocellular carcinoma occur?
Only occurs as a consequence of cirrhosis or chronic hep B
Budd Chiari syndrome?
Acute thrombosis/clot in hepatic vein > liver congested > less outflow from liver > increase pressure > portal hypertension > ascites and hepatocellular damage
Budd Chiari syndrome causes?
75% unknown cause others include - external compression - genetic disorders - contraception pill - pregnancy - ^ RBCs (polycythemia) - clotting disorderes
Treatment of Budd Chiari syndrome?
- diuretics
- anti-coagulation
- shunting to other hep vein to divert blood flow from obstructed vessel
