Liver Failure Flashcards
7 key functions of the liver
Synthesis of clotting factors (except factor 8)
Glucose homeostasis (gluconeogenesis, glycogen storage)
Albumin synthesis
Conjugation and clearance of bilirubin
NH3 metabolism (the urea cycle)
Drug metabolism and clearance
Immune (dealing with gut-derived bacteria and bacterial products)
Sequelae of liver failure by system
Brain: hepatic encephalopathy, cerebral oedema, intracranial HTN
Lungs: acute lung injury, ARDS
Heart: high output state, frequent subclinical myocardial injury
Pancreas: pancreatitis (particularly in acetaminophen-related disease)
Adrenal gland: inadequate glucocorticoid production contributing to hypotension
Kidney: frequent dysfunction or failure
Bone marrow: frequent suppression (esp in viral and seronegative disease)
Liver: loss of metabolic function (decreased gluconeogenesis causing hypoglycaemia, decreased lactate clearance causing lactic acidosis, decreased ammonia clearance causing hyperammonaemia, loss synthetic capacity causing coagulopathy), portal HTN
Systemic inflammatory response: high energy expenditure or rate of catabolism
What findings are seen on routine liver function tests (including coags) in liver failure?
Elevated bilirubin (mostly conjugated, as the liver has very high capacity for conjugation)
Liver enzyme patterns: hepatocellular injury or necrosis, intra- or extra-hepatic cholestasis, or mixed picture
Decreased albumin (but half life is 20 days so level can be normal in acute injury)
Clotting profile: INR affected more by liver disease than APTT
Why is INR affected more by liver disease than APTT?
Liver disease results in abnormal coagulation because of a loss of synthetic function (clotting factor production) AND vitamin K deficiency in cholestasis due to poor absorption of fat soluble vitamins
What pattern is seen on LFT in hepatocellular injury or necrosis, and in what pathological processes is this seen?
ALT and AST elevation (ALT predominantly from liver, AST from many sites)
Very high ALTs seen in acute viral hepatitis, acute drug toxicity, ischaemia
What pattern is seen on LFT in intra- or extra-hepatic cholestasis, and in what pathological processes is this seen?
Elevation of ALP (also produced in other tissues, esp bone), elevation of GGT
High ALP, GGT with minor elevation of transaminases typical of biliary obstruction, liver infiltration, cholestatic reactions to drugs
In what pathological processes is a mixed picture seen on LFTs?
Many forms of liver disease including alcoholic liver disease, fatty liver disease
Mrs EH, 45 year old non-smoker and mother of 4 children, employed full-time
PHx: menorrhagia and dysmenorrhoea from fibroids, treated with total abdominal hysterectomy (TAH)
Presented with intermittent abdominal pain post-surgery and admitted for suspected subacute bowel obstruction 4/52 post-TAH; settled with conservative Mx
Presents to ED again 7/52 post-TAH with increasing abdominal pain over 2 days, vomiting, obstipation, anorexia and LOW (10kg over 7/52)
Rx: paracetamol PRN, Mylanta PRN
Allergies: codeine
O/E: not unwell looking, BMI 22, haemodynamically stable, soft non-tender but distended abdomen
Ix: normal FBE, UEC shows K+ 3.3mmol/L, normal LFTs, AXR sows incomplete mid to distal SBO (Gastrografin follow-through requested)
Dx: recurrent subacute bowel obstruction secondary to adhesions from previous TAH
Mx: initially conservative (NGT, IVF and electrolyte replacement, NBM, analgesia in the form of paracetamol 1g QID strict)
Progress: day 1 - refused NGT and Gastrografin follow-through, day 2-4 - vomiting small quantities, accepted NGT, intermittent abdominal pain requiring PO and PR paracetamol, day 5 - laparoscopic division of adhesion, Pfannenstiel incision reopened for division of adhesion to free bowel, day 6-8 - NBM, ongoing post-op pain requiring tramadol and paracetamol 1g QID “strict”, day 9-10 0 haematuria and refused heparin, displaying odd behaviour, oliguria and CP, MET called, increasingly confused and drowsy, LOC, admitted to ICU unconscious and anuric (intubated, ventilated, CVC, CVVH, IDC, IV Abx)
O/E after day 10: jaundice, no signs of CLD, encephalopathic
Ix after day 10: elevated creatinine and lactate, acidotic, increased INR, CXR shows LLL connsolidatio but CTB normal
What do these findings suggest?
Further Ix?
What is the likely cause of Mrs EH’s illness?
Mx?
An acute liver injury
Further Ix: paracetamol levels (elevated), HAV/HBV/HCV (all negative except IgG anti-HAV and HBsAb) serology, liver U/S (normal)
Likely Dx: fulminant hepatic failure secondary to accidental paracetamol poisoning, with associated acute renal failure and HAP
Mx: n-acetylcysteine (NAC) loading dose, coagulation factors, continuous veno-venous haemofiltration (CVVH), IV Abx, sedated with morphine and midazolam, transfer to Austin ICU
What are the 7 most common causes of acute hepatitis?
Acute viral hepatitis
Drug-related
Ischaemic hepatitis
AI
Acute Budd Chiari
Wilson’s disease
Idiopathic
What is CVVH?
Continuous veno-venous haemofiltration is a temporary treatment for patients with acute renal failure who are unable to tolerate haemodialysis and are unstable
What are the criteria for transferring a patient to a liver transplant unit?
Avoid late referral and transfer of unstable patients
Criteria for transfer:
INR >1.5 and rising (except paracetamol overdose)
Any encephalopathy
Poor prognosis
Mrs EH’s progress:
Day 11 - transferred to Austin Hospital ICU for NAC infusion, correction of coagulopathy, paralysed and ventilated, mannitol infusion, CVVH (lactate free), hypernatraemia target (145-155mmol/L), develops hypothermia, referred to neurosurgery for intracranial pressure monitor insertion, urgently assessed and listed for liver transplantation
Day 12 - deterioration overnight (fixed dilated pupils, absent brainstem reflexes, ongoing sepsis with increasing NA requirements, persistent lactic acidosis), donor organ becomes available but patient assessed as too unstable for transplant, family meeting comes to decision to limit treatment and patient dies at 10:15
Post-mortem histology shows massive panlobular necrosis with relative preservation of portal tracts and hepatic necrosis with mild fatty changes; post-mortem findings include a) multi-system organ failure, b) fulminant hepatocellular necrosis and c) evidence of paracetamol toxicity
Pathologist comment: “ingestion of 10 or more standard tablets may result in fulminant hepatic failure resulting in death within 5-7/7 if unchecked”
When should the daily dose of paracetamol be reduced?
People who are fasting
Heavy EtOH users
Patients taking medications that induce cytochrome p450
Prolonged starvation (depleted hepatic glutathione stores)
Histopathology: describe the findings
Massive panlobular necrosis with relative preservation of portal tracts
Hepatic necrosis with mild fatty changes
What can increase susceptibility to paracetamol poisoning?
Prolonged starvation including fasting (depletes hepatic glutathione stores)
Heavy alcohol use
Patients taking medications that induce cytochrome p450
What is usually found on testing in the setting of paracetamol poisoning?
Large rises in serum transaminases
Define acute liver failure
Rapid deteriorating of liver function in previously normal liver
Jaundice to encephalopathy generally occurs within 8 weeks
What are the guidelines for acute liver failure?
INR >1.5
Any encephalopathy
Duration of illness (jaundice) up to 26 weeks
What % of liver transplants does acute liver failure account for?
5-8%
How common is ALF?
Rare
What is the prognosis of ALF?
>80% died in pre-transplant era
Survival now >70% in most leading centres
45% survival without transplant (probably reflects both availability of transplant as rescue therapy and improved medical Mx)
Outcome highly dependent on aetiology and rate of progression
Describe the common aetiologies of acute liver failure
Viral hepatitis
Paracetamol
Other drugs
Describe the interventions and their benefit in 6 common causes of acute liver failure
Describe normal paracetamol metabolism
Describe paracetamol metabolism in the setting of glutathione depletion
Describe the principles of Mx of paracetamol OD
Prevention of absorption: administer activated charcoal within 60 mins of ingestion
Symptomatic care: anti-emetics
Risk assessment: dose based/plasma paracetamol concentration
Specific care: NAC
Other activities: psychological assessment following deliberate self-poisoning, toxicovigilance, chronic/occupational poisonings, follow local and regional guidelines, ensure antidote is stocked, assay advice
Describe the acute Mx of paracetamol OD
Describe Mx of repeated supratherapeutic ingestion of paracetamol
