Liver Problems Flashcards
What are the functions of the liver?
- Factory for producing essential proteins including albumin
- Produces clotting factors
- Essential role in absorption and metabolism of fats and other food stuffs
- Storage of glycogen, minerals and other substrates
- Metabolism and excretion of toxic products in the body
What is included in LFTs?
-Bilirubin (total and split)
-ALT/AST (alanine aminotransferase/aspartate aminotransferase)
-Alkaline phosphatase
Gamma glutamyl transferase (GGT)
When is ALT/AST elevated?
In hepatocellular damage (hepatitis)
When are alkaline phosphatase and GGT elevated?
Biliary disease
What tests are used to assess the function of the liver?
- Coagualtion (prothrombin time (PT)/INR, APTT)
- Albumin
- Bilirubin
- Blood glucose
- Ammonia
How can paediatric liver disease manifest?
- JAUNDICE
- Incidental finding of abnormal blood test
- Symptoms/signs of chronic liver disease
What are the signs of chronic liver disease in children?
- Encephalopathy
- Jaundice
- Epistaxis
- Cholestasis
- Ascites
- Hypotonia
- Peripheral neuropathy
- Rickets secondary to vit D deficiency
- Varices with portal hypertension
- Spider naevi
- Muscle wasting
- Bruising and petechiae
- Spleomegaly
- Hypersplenism
- Hepatorenal failure
- Liver palms
- Clubbing
- Loss of fat stores
- Growth failure
What is jaundice?
- Yellow discolouration of skin and tissues due to accumulation of bilirubin
- Usually most obvious in sclera
When is jaundice usually visible?
Total bilirubin >40-50umol/l
What is diagnosis of infant jaundice dependent on?
- Bilirubin metabolism
- Age
How is bilirubin metabolised?
- Post mature RBC broken down in the reticuloendothelial system to bilveridan
- Converted to unconjugated bilirubin
- Bound to albumin and conjugated in the liver
- Mixes with bile in gallbladder and enters small intestine
- Coverted to urobilinogen and excreted by the kidneys as urine or in faeces
What is the solubility of conjugated bilirubin?
- Water soluble
- Fat insoluble
What is the solubility of unconjugated bilirubin?
- Fat soluble
- Water insoluble
When does pre-hepatic jaundice occur?
Excess of unconjugated birlirubin
When does intrahepatic jaundice occur?
-Excess of conjugated and unconjugated bilirubin jaundice due to issue within the liver
When does post-hepatic jaundice occur?
Excess of conjugated bilirubin normally due obstruction
What is early neonatal jaundice?
- <24 hours old
- ALWAYS PATHOLOGICAL
What can cause early neonatal jaundice?
- Haemolysis
- Sepsis
What is intermediate neonatal jaundice?
Occurs between 24hours and 2 weeks of age
What can cause intermediate neonatal jaundice?
- Physiological
- Breast milk
- Sepsis
- Haemolysis
What is prolonged neonatal jaundice?
Occurs after 2 weeks of age
What can cause prolonged neonatal jaundice?
- Extrahepatic obstruction
- Neonatal hepatitis
- Hypothyroidism
- Breast milk
Why does physiological jaundice occur?
- Shorter RBC life span in infants (80-90 days)
- Relative polycythaemia
- Relative immaturity of liver function
What type of jaundice is physiological jaundice?
Unconjugated
When does physiological jaundice occur?
After the 1st day of life as it takes time for RBC to break down
Why does jaundice occur with breast fed babies?
- Exact reason for prolongation of jaundice in breastfed infants unclear
- Inhibition of UDP by progesterone metabolite?
- Increased enterohepatic circulation?
What type of jaundice is breast milk jaundice?
Unconjugated
How long can breast milk jaundice persist?
Up to 12 weeks from birth
Apart from breast milk and physiological what other causes of unconjugated infant jaundice are there?
- Sepsis
- Haemolysis (excessive)
- Abnormal conjugation
Why might there be excessive haemolysis in a baby leading to jaundice?
- ABO incompatibility
- Rhesus disease
- Bruising/cephalhaematoma
- Red cell membrane defects (e.g. spherocytosis)
- Red cell enzyme defects (e.g. G6PD)
What causes of abnormal conjugation are there?
- Gilbert’s disease (common, mild)
- Crigler-Najjar syndrome (very rare but sever)
What investigation would you do for sepsis causing jaundice?
- Urine culture
- Blood culture
- TORCH screen
What investigation would you do for ABO incompatibility causing jaundice?
- Blood group
- DCT
What investigation would you do for Rhesus disease causing jaundice?
- Blood group
- DCT
What investigation would you do for bruising/cephalhaematoma causing jaundice?
Clinical examination
What investigation would you do for red cell membrane defects causing jaundice?
Blood film
What investigation would you do for red cell enzyme defects causing jaundice?
G6PD assay
What investigation would you do for Gilbert’s disease causing jaundice?
Genotype/phenotype
What investigation would you do for Crigler-Najjar syndorme causing jaundice?
Genotype/phenotype
What is a possible complication of unconjugated jaundice?
Kernicterus
Why does kernicterus occur?
- Unconjugated bilirubin is fat-soluble (water insoluble) so can cross blood-brain barrier
- It is neurotoxic and deposits in brain (particularly the basal ganglia)
What are the early signs of kernicterus?
- Encephalopathy
- Poor feeding
- Lethargy
- Seizures
What are the late signs of kernicterus?
- Severe choreoathetoid cerebral palsy
- Learning difficulties
- Sensorineural deafness
How is unconjugated jaundice treated?
Phototherapy
- Visible light (450nm wavelength) (not UV) converts bilirubin to water soluble isomer (photoisomerisation)
- Threshold for phototherapy in infants guided by charts
What is prolonged infant jaundice?
Jaundice persisting beyond 2 weeks of life or 3 weeks of life in preterms
What are the conjugated causes of prolonged infant jaundice?
- Anatomical (biliary obstruction)
- Neonatal hepatitis
What are the unconjugated causes of prolonged infant jaundice?
- Hypothyroidism
- Breast-milk jaundice
What causes of biliary obstruction can lead to prolonged jaundice?
- Biliary atresia
- Choledochal cyst
- Alagille syndrome
What is biliary atresia characterised by?
Conjugated jaundice with pale stools
What is choledochal cyst characterised by?
Conjugated jaundice with pale stools
What is Alagille syndrome characterised by?
- Intrahepatic cholestasis
- Dysmorphism
- Congenital cardiac disease
What is biliary atresia?
Congenital fibro-inflammatory disease of the bile ducts leading to destruction of extra-hepatic bile ducts
How does biliary atresia present?
- Prolonged conjugated jaundice
- Pale stools and dark urine
What can biliary atresia progress to?
Liver failure if not identified and treated (can occur within months of life)
What is the most common indication for liver transplant in children?
Biliary atresia
What is the treatment for biliary atresia?
Kasai portoenterostomy
- Success rate diminishes rapidly with age
- Best results if performed before 60 days (<9 weeks)
- Small bowel divided and extrahepatic ducts removed. Liver bile ducts plugged directly into the small bowel
What investigations are done for biliary atresia?
- Split bilirubin
- Stool colour
- Ultrasound
- liver biopsy
What investigations are done fro choledochal cyst?
- Split bilirubin
- Stool colour
- Ultrasound
What investigations are done for Alagille syndrome?
- Dysmorphism
- Genotype
What causes of neonatal hepatitis are there?
- Alpha-1-antitrypsin deficiency
- Galactosaemia
- Tyrosinaemia
- Urea cycle defects
- Haemochromatosis
- Glycogen storage disorders
- Hypothyroidism
- Viral hepatitis
- Parenteral nutrition
How is alpha-1 antitrypsin deficiency investigated?
Phenotype/level
How is galactosaemia investigated?
GAL-1-PUT
How is tyrosinaemia investigated?
Amino acid profile
How are urea cycle defects investigated?
Ammonia levels
How is haemochromotosis investigated?
- Iron studies
- Liver biopsy
How are glycogen storage disorders investigated?
Biopsy
How is hypothyroidism investigated?
TFTs
How is viral hepatitis investigated?
- Serology
- PCR
How is parenteral nutrition investigated?
History
What should you always ask about with prolonged infant jaundice?
Stool colour
What is the most important test fro prolonged infant jaundice?
Split bilirubin to determine if it is conjugated or unconjugated in nature
What is the main diagnosis to exclude with conjugate prolonged jaundice?
Biliary atresia
