Acute Liver Failure ✅ Flashcards
What is acute liver failure defined as?
Development of hepatic necrosis in absence of pre-existing liver disease
How might acute liver failure present in infancy?
- Irritability
- Sleepiness
- Hypoglycaemia
- Bruising, petechiae, or bleeding/oozing from venepuncture sites/umbilical stump
- Jaundice
What are the categories of causes of acute live failure in neonates/infants up to 6 months?
- Infective
- Metabolic
- Poisoning
What are the infective causes of acute liver failure in neonates/infants up to 6 months?
- Septicaemia
- Hepatitis B
- Adenovirus
- Echovirus
- Coxsackie B
- Herpes simplex
What are the metabolic causes of acute liver failure in neonates/infants up to 6 months?
- Neonatal haemchromotosis
- Tyrosinaemia type 1
- Mitochondrial disease
- Fatty acid oxidation defects
What are the categories of causes of acute liver failure in children >6 months?
- Infection
- Autoimmune
- Drug
- Metabolic
What are the infectious causes of acute liver failure in over 6 month olds?
- Hepatitis A/B/E
- Epstein-Barr virus
- Parvovirus B19
What are the types of autoimmune disorders causing acute liver failure in children over 6 months?
Type I or II
What drugs can cause acute liver failure in children over 6 months?
- Paracetamol (in overdose)
- Anti-epileptics, e.g. sodium valproate, carbamazepine
- Isoniazid
- Halothane
What metabolic conditions can cause acute liver failure in over 6 months?
- Wilson’s disease
- Alper’s disease
What is neonatal haemochromotosis?
Iron storage disorder
In what form does iron exist in the body?
As transferrin
What is transferrin?
Iron bound to apotransferrin
Where is most of the iron used for haemoglobin production obtained from?
Haemoglobin breakdown of senescent red blood cells
How is haemoglobin released from RBCs?
They are phagocytosed by macrophages. Proteolytic enzymes in the macrophages degrade the ingested cells, and release haem and globin molecules as separate entities
Where are RBCs phagocytosed by macrophages?
- Spleen
- Liver
- Bone marrow
What happens to the globin molecules released from phagocytosed RBCs?
They are broken down into amino acids and used for protein production
What happens to the haem molecules released from phagocytosed RBCs?
Iron is released from haem, leaving a porphyrin ring, which is converted to bilirubin
What can lead to accumulation of iron in the liver?
Failure of processes of RBC breakdown
Excessive iron absorption
What are the clinical features of iron accumulation in the liver?
- Raised transaminases
- Conjugated jaundice
- Hypoalbuminaemia
- Severe coagulopathy
What kind of disorder is neonatal haemochromatosis considered to be?
Alloimmune disorder
What is the pathological process behind neonatal haemochromotosis?
Mothers develop an abnormal immune response to fetal liver protein, which results in liver damage and a direct or indirect effect on fetal iron storage
How does the number of pregnancies a mother has had affect the incidence of neonatal haemochromotosis?
It is rare in first pregnancies, but higher in subsequent
What will be found on iron studies in neonatal haemochromotosis?
- High serum iron
- Hypersaturation of iron-binding capacity
- Elevated ferritin
Describe the clinical course of neonatal haemochromotosis?
Progressive, with death from liver failure without transplantation
What is the diagnosis of neonatal haemochromotosis based on?
Demonstrating iron storage outside of the liver, e.g. salivary glands, pancreas, or brain on MRI
When does galactosaemia present?
Typically in early neonatal period
How does galactosaemia present?
- Sepsis
- Liver failure
- ‘Oil drop’ cataracts on opthalmoscopy
What is the inheritance of galactosaemia?
Autosomal recessive
What is the pathological process in galactosaemia?
Deficiency of galactose-1-phosphate uridyltransferase
How is a diagnosis of galactosaemia made?
- Suggested by detection of urinary reducing substances without glycosuria
- Confirmed by demonstrating reduced enzyme activity in blood (Gal-1-PUT)
When might misleading results be obtained when testing for galactosaemia?
In presence of recent blood transfusion
What organs are particularly affected by mitochondrial disease?
Those that need large amounts of energy;
- Brain
- Heart
- Liver
- Renal tubules
How might neonates with mitochondrial disease present?
- Acute liver failure
- Seizures
- Cardiomyopathy
- Renal failure
How might older children with mitochondrial disease present?
- Hepatic steatohepatitis
- Cholestasis
- Cirrhosis
What is a key feature of mitochondrial diseases?
Lactic acidaemia
Is liver transplasntation used in mitochondrial disease?
May be used if disease confined to liver, but contraindicated if multi-organ involvement
How might acute liver failure present in an older child?
- Jaundice
- Encephalopathy
- Coagulopathy
What complications may arise from acute liver failure?
- Cerebral oedema
- Coagulopathy
- Systemic inflammatory response syndrome
- Hyponatraemia
- Hypotension
What does cerebral oedema caused by liver failure lead to?
- Hepatic encephalopathy
- Coma
- Brain herniation
- Death
How severe is hepatic encephalopathy?
Varies from subtle deficit in higher brain function, e.g. mood, concentration in grade I encephalopathy, to deep coma in grade IV encephalopathy
Which patients are at highest risk of developing cerebral oedema and grade IV encephalopathy?
Patients presenting with acute and hyperacute liver failure
What causes cerebral oedema and encephalopathy in acute liver failure?
Exact pathogenesis unclear, but likely to be consequence of;
- Accumulation of toxins, e.g. ammonia, which affects neurotransmitter levels and neuroreceptor activation
- Impairment of autoregulation of cerebral blood flow, resulting in anaerobic glycolysis and oxidative stress
- Inflammatory mediatiators
Why do you get coagulopathy in acute liver failure?
Due to the livers role in production of coagulation factors
What measure of coagulation is used to monitor severity of hepatic injury?
PT time (prolonged in acute liver failure)
What happens to platelets in acute liver failure?
Platelet dysfunction, with loss of larger and more active platelets
In what % of patients with acute liver failure is systemic inflammatory response syndrome seen in?
Up to 60%
What does SIRS lead to?
Multi-organ failure
What causes SIRS in acute liver failure?
Impaired immune function, increasing the risk of sepsis
How is SIRS prevented in acute liver failure?
Patients are treated routinely with antibiotics and antifungals
How does acute liver failure cause hyponatraemia?
- Water retention in response to hypoalbuminaemia
- Shift in intracellular sodium transport from inhibition of Na/K-ATPase
What other electrolyte abnormalities are often seen in acute liver failure?
- Hypokalaemia
- Hypophosphataemia
- Metabolic alkalosis
Why is hypotension seen in acute liver failure?
- Peripheral vascular dilatation and reduced systemic vascular resistance
- Tissue hypoxia and lactic acidosis
How is hypotension in acute liver failure compensated for?
Cardiac output increases
What are the indications for transplant in acute liver failure?
- Worsening coagulopathy, which is unsupported by blood products and not responsive to vitamin K
- Worsening encephalopathy
What are the contraindications for transplant in acute liver failure?
- Multisystem disease
- Irreversible brain damage
- Pre-existing life-limiting disorders
What mutations have been identified as causing mitochondrial disease?
Mutations in nuclear genes such as SCO1, BCS1L, POLG, DGUOK, and MPV17, and deletion or rearrangement of mitochondrial DNA
