Liver Failure Flashcards
A paracetomol-overdosed patient has come in to A and E with INR of 4.5, low blood glucose and flapping tremor. Explain why she has these symptoms
INR 4.5 shows bad clotting. The liver produces clotting factors
Low blood glucose. The liver is responsible for gluconeogenesis
Flapping tremor. The liver detoxifies ammonia to urea – accumulation of ammonia leads to encephalopathy
Basically her liver is messed up due to the paracetomol overdose
What is the difference between ALF and acute liver injury?
‘Acute’ or ‘Fulminant’ liver failure
Sudden onset of liver dysfunction
Absence of prior liver disease
Resulting in encephalopathy (brain dysfunction) within 8 weeks of onset
Acute Liver Injury
Increased liver enzymes
Not necessarily affecting synthetic function of liver
Not complicated by encephalopathy
What are the risk factors for ALF?
Hepatotoxic drugs taken
Contaminated food/water (enteric viruses – Hep A and E)
Blood borne virus risks (Hep B)
Recreational drugs
Threshold for liver injury reduced if hay underlying liver disease
What is the pathophysiology of ALF?
Caused by acute inflammation of the liver due to eg hepatitis, which damages hepatocytes
This increases aminotransferases (ALT and AST) bc these are released by death of hepatocytes
In some cases ongoing hepatocyte necrosis and loss of critical liver cell mass can lead to acute liver failure
How can hepatic encephalopathy arise from acute liver failure?
Sudden decrease in urea-cycle metabolism due to liver failure causes ammonia accumulation. NH3 crosses BBB
This is detoxified in astocytes to glutamine by glutamine synthase
Glutamine accumulation leads to influx of water and astrocyte swelling.
In ALF this can lead to raised intracranial pa
Grade III/IV encephalopathy associated with infection/SIRS, not ammonia
What is the clinical presentation of ALF?
Right upper quadrant pain
Nausea/Vomiting
A general sense of feeling unwell (malaise)
Abnormal blood clotting
Jaundice
Low glucose
Acidosis
Hyperammonaemia – lethargy, stupor, confusion, agitation, flapping tremor, coma
Infections (immune dysfunction)
RAJANILAH
Give some investigations you would do in suspected ALF
Standard blood tests: FBC, U&Es. LFTs, GGT, blood clotting. Glucose
In unwell/unstable patient: ABGs. Blood cultures
Massive transaminitis: ALT or AST >1000 should show in LFTs to show hepatocyte damage
What type of imaging investigations would you do in suspected ALF?
US Doppler scan of liver, spleen, biliary tree:
“Starry sky” appearance of acute hepatitis
Hepatic vein or portal vein patency
Gallstones
Spleen size
CT scan of the abdomen: Infiltrative pathology. Acute vs Chronic liver damage – signs of cirrhosis/portal hypertension
Draw and describe a flow diagram to show the metabolism of paracetamol
Paracetamol breakdown into NAPQI by CYP450 2E1. This is toxic, and is formed when the other two conjugation pathways become over-saturated.
The resultant toxic NAPQI byproduct is converted into nontoxic metabolites by glutathione, which is regenerated by N-acetylcysteine.
What is the initial management of ALF during paracetamol overdose?
Intravenous N-Acetyl Cysteine
Replenishes glutathione, detoxifies NAPQI
What is the difference between actute and chronic liver failure?
Describe the prognosis markers in end stage liver disease
Child-Pugh score: assesses surgical risk in cirrhosis patients
Model for End-stage Liver Disease (MELD) score: assesses mortality in those undergoing TIPSS
Serum creatinine, INR, bilirubin, sodium (newer addition)
UK model for End-stage Liver Disease (UKELD) score
Developed to allow risk stratification for purpose of listing for liver transplantation in UK
Serum creatinine, INR, bilirubin, sodium
