5. Liver disease and intestinal failure Flashcards
Causes of Acute liver disease
acute insult:
viruses (Hep A, B, C, E, CMV, EBV)
drugs - termed DILI, paracetamol, herbal remedies, ecstasy
Immune - autoimmune hepatitis
Alcohol rarely
Symptoms of acute liver disease
jaundice
increased serum bilirubin
dark urine
pale stools
bile duct obstruction or biliary obstruction
feeling unwell
nausea
occasionally fever
confusion due to hepatic encephalopathy and liver failure
Cirrhosis and platelet count
Cirrhosis causes decrease in platelets
increased shear stress causing platelet aggregation
Thrombocytopenia:
Thrombopoietin is predominantly produced by the liver and is reduced when liver cell mass is severely damaged
diagnose jaundice and severe itching
gall stone obstruction
diagnose an increase in alkaline phosphotase and gamma GT
bile duct disease
Bilirubin
breakdown product of heme proteins - hemoglobin&myoglobin
excreted in bile
conjugated with glucuronic acid
unconjugated fraction binds to serum albumin
unconjugated hyperbilirubinemia: haemolysis, gilberts (mild)
urinalysis is negatice for bilirubin
increased serum bilirubin indicates jaundice caused by hemolysis, liver disease (impairment of bilirubin handling) and biliary obstruction
albumin
major circulating protein
synthesised in liver
half life 21 days, decreases during intercurrent infection
low serum albumin in infection eg pneumonia
low in renal loss - nephrotic syndrome
low in impaired synthesis - severe liver disease
low in severe malnutrition
ALT or SGPT
alanine transaminase
cytosolic enzyme
liver enzyme»_space;muscle
increases during liver injuries
AST or SGOT
aspartate transaminase
muscle>liver
found in cytsols and mitochondria
alcohol is mitochondrial poison, so AST increases when alcohol increases
transaminases
very high signifies liver cell injury with release of enzymes into circulation
very very very high = paracetamol overdose of ischemic hepatitis
moderately elevated = fatty liver, cholangitis
ALT > AST for liver injuries
AST>ALT w severe fibrosis or cirrhosis, alcohol excess or muscle injury
alkaline phosphotase
in liver, bone, biliary, placenta and intestine
increased in pregnancy and bone disease (Pagets disease)
more cholestatic than hepatitic (involving bile duct/secretion)
increase in biliary obstruction or primary biliary cholangitis
gamma glutamyl transpeptidase
Gamma GT is membrane-bound enzyme present in liver, kidney and pancreas
plays a role in the metabolism of glutathione (antioxygenase) and facilitates amino-acid transport.
Serum gamma-GT activity is induced by alcohol and certain drugs such as phenytoin and cholestasis or biliary obstruction.
Very sensitive: Modest increases common in most liver diseases
Very high levels suggest biliary obstruction or cholestasis or alcohol.
FIB4 Score
An indirect biomarker of liver fibrosis
noninvasive test
Calculated from ALT, AST, Platelet count and age.
A score of <1.45 and >3.25 enables the correct identification of patients who have moderate or significant fibrosis, respectively
chronic liver disease and causes
Chronic Liver disease
Repetitive liver injury
Finger prick analogy
Chronic inflammation leads to cell death and regeneration and fibrosis
Alcohol
Chronic viral hepatitis
Fatty liver disease
Autoimmune liver disease
Other causes – iron overload, biliary disease, inherited diseases
alcoholic liver disease
Alcohol is metabolised to acetaldehyde and fat
Excess alcohol causes fatty liver
Need to drink >50-100 units alcohol per week for >10 years to developed alcohol related cirrhosis
Only 20% of patients who drink to excess develop alcohol related cirrhosis
The pathology is very similar to fatty liver disease – hence why sometimes called non-alcoholic fatty liver disease
fatty liver disease
how its diagnosed
Diagnosed by ultrasound scan examination or other imaging
Of 100 patients with fatty liver disease only50% have abnormal liver function tests.
The critical determinate of fatty liver disease is whether or not a patient has NASH or simple steatosis.
85% have simple steatosis and 15% have NASH.
You can only tell by liver biopsy or if the patient has significant fibrosis on fibroscan.
Abnormal liver function tests do not predict whether a patient has NASH or simple steatosis.
FIB4 calculation enhances predictability.
fibroscan
Determines liver stiffness and CAP score
Works by measuring the speed of ultrasound waves as they move through liver tissue. This measurement can tell us about the state of the liver. For example, ultrasound waves move faster through fibrotic/scarred livers.
Liver stiffness is measured in kPa and is an assessment of how wobbly the liver is. (Normal <6.0kPa)
CAP score measures fat content (normal <220dBM)
chronic viral hepatitis
Only hepatitis B and C cause chronic liver disease.
300 million people worldwide have chronic hepatitis B – it is transmitted vertically, through sex, IVDU and IV products not screened.
60 million people worldwide have chronic hepatitis C – it is transmitted through IV drug use (IVDU) and IV products not screened.
Both can cause chronic inflammation of the liver and the development of cirrhosis.
Chronic hepatitis B and C both cause liver cancer with a risk of 2-4% per year in those with underlying cirrhosis.
Important to diagnose as current treatments are nearly 100% effective
primary biliary cholangitis
Primary biliary cholangitis once a rare disease now affects neary 1: 1000 women over the age of 40 years in the UK. Men are less commonly affected (<10%).
Associated with anti-mitochondrial antibody and so is considered an autoimmune disease – but immunosuppression relatively ineffective.
It is treated with ursodeoxcholic acid.
primary sclerosing cholangitis
Primary Sclerosing cholangitis (PSC) causes stricturing of the small and large bile ducts.
Associated with ulcerative colitis (80%) and yet only 5% of patients with ulcerative colitis develop PSC.
Some develop cirrhosis, and 10% develop cholangiocarcinoma over ten years.
Both may develop xanthalasma of the eyes or hands but most common is PBC and due to acumulatin of lipoprtien X
Complications of cirrhosis
Portal Hypertension
Ascites
Varices
Hepatorenal syndrome
Hepatic encephalopathy
Immune paresis
Patients with cirrhosis are immunocompromised
20-40% develop infections when admitted to hospital
diagnose severe abdominal pain and distension
and absolute constipation
bile obstruction
vitamin D surgical sieve
vascular
infection/inflammation
trauma/toxic
autoimmune
metabolic
idiopathic
nutritional/neoplastic
degenerative
how to assess someone’s nutritional status
bedside tests:
urine, blood glucose, ecg, rectal scan, history, temp, height/weight
blood tests:
cardiac screening, check for malnutrition, electrolyte abnormalities, inflammation, full blood test, haemoglobin
microbiology:
infection
plain xrays:
CT
specialist tests:
endoscopy
