Viva - Acute Liver Failure / Paracetamol Flashcards
Definition of acute liver failure
New liver injury <26 weeks old
Impaired synthetic function (INR>1.5)
Triad of jaundice, encephalopathy and coagulopathy
Progresses to MOF / Death in half of cases
Classified by the O Grady system
Describe the O Grady System
Categorises ALF on the basis of interval between onset of jaundice to the development of encephalopathy
Hyper acute <1week
Acute 1-4 weeks
Subacute 4-12 weeks
Causes of ALF
Infection - Hepatitis’ A-E, HSV, CMV, VZV, EBV
Drugs - Paracetamol, epileptics (phenytoin), TB (isoniazid), Chemo, St Johns Wort, recreational (ecstasy, amphetamines)
Pregnancy- HELLP, fatty liver
Malignancy - primary or secondary
Vascular - budd chiari - hep vein thrombosis,
Ischaemic hep -
Toxins - mushrooms
Autoimmune,
Describe the Kings college criteria for paracetamol overdose
PH<7.30
OR
All 3 of INR>6.5 (PT>100)
Creatinine > 300
Grade 3 or 4 encephalopathy
Changes in lactate >3 after resus
Kings College criteria for non-paracetamol ALF
INR > 6.5 (PT>100 secs)
OR
Any three of: Age<11 or >40 Aetiology is non A, non B hep. Time from jaundice to encephalopathy > 7 days (eg not hyper acute) INR>3.5 (PT>50 sec) Serum Bilirubin >300 umol
How does ALF present
Malaise, nausea, jaundice
Encephalopathy develops over time
High cardiac output, with reduced SVR (differential for sepsis)
Liver necrosis -> inflammatory cascade, vasoplegic collapse, AKI, cerebral oedema
Grading of Encephalopathy
West Haven Criteria
Grade 4 - coma unresponsive to stimuli
Grade 3 - Somnolence, semi-stupour, confusion, remains to verbal stimulation
Grade 2 - Lethargy, apathy, disorientated in time, persona change, inappropriate
Grade 1 - Trivial lack of awareness, anxiety, short attention span, impaired addition
What happens in the later stages of encephalopathy
Elevated ICP
Due to cerebral oedema (present in 80% of grade 4)
25% die
How does renal failure happen in ALF
1 - Acute tubular necrosis —> hypovolaemia, hypotension, perfusion
—> nephrotoxins eg paracetamol
2 - Underlying disease process - glomerular nephritis in Hep B/C
3 - Intra abdomnial hypertension from ascites
4 - Hepatorenal syndrome
ICU management of ALF - respiratory
Grade III, IV encephalopathy —I&V.
Excessive PEEP with increase hepatic venous pressure and ICP
ICU management cardiovascular
Reduced SVR with high CO.
Hepatic hypoperfusion.
Needs fluid resus, taking care not to overload and worsen cerebral oedema.
Vasopressin to maintain MAP 60-65, CPP60-80
ICU management - Neuro
Elevate head to improve CPP Sedate MAP 75, CPP 60-80 Avoid hypoxia and hypercapnoea Sugars 4-10 Avoid fever
Mannitol, hypertonic saline for ICP
?therapeutic hypothermia, barbiturates, indamethacin
ICU management - renal and coag
Renal - RRT when there is fluid overload, acidosis or worsenign failure
Coag - Liver makes all factors except VIII.
Abnormal synthesis and antithrombin III deficiency —> coagulaopathy and DIC
Product replacement in active bleeding. But leave alone otherwise as PT is marker of severity/prognostic marker.
Liver transplant is only effective tx when high likelihood of death.
Mechanism of paracetamol overdose
N-acetyl p benzoquinone (NAPQI) is responsible for the hepatotoxicity.
Normal - paracetamol is metabolised by glucoronidiation and sulphation.
Small amount metabolised by cP450 system into NAPQI.
In overdose - glucoronidation and sulphation is saturated, cp450 takes over.
More NAPQI made
Glutathoine stores deplete
NAPQI causes widespread hepatocyte damage —> acute hepatic necrosis.
Treatment of paracetamol toxicity
N-acetylcysteine, (NAC)
Glutathione precursor, replenishes hepatic stores
Effective within 8 hours, but also improves prognosis after 8 hours
Treat when above the nomogragm
