Jaundice and Liver function assessment Flashcards
What is the definintion of jaundice?
Yellowing of the skin, sclerae, and other tissues caused by excess circulating
At what bilirubin level does jaundice become clinically evident?
Serum levels exceed 51 micromol/L (3 mg/dL).
How are red blood cells broken down?
Macrophages breakdown haem into bilirubin
What is bilirubin conjugated with?
Glucouronic acid
What transports unconjugated bilirubin in the blood?
Albumin
Where is bilirubin secreted into after it has been conjugated with glucuronic acid?
Into bile and then the intestine
What happens to conjugated bilirubin when it enters the bowel?
Glucuronic acid is removed by intestinal bacteria
What happens to bilirubin once the glucuronic acid has been removed by bacteria?
Converted to urobilinogen
What happens to urobilinogen in the intestine?
- Absorbed from the gut -> to kidney
- Oxidised to stercobilinogen -> faeces
What is urobilinogen converted to in the kidneys?
Urobilin - characteristic colour of urine
What are causes of unconjugated hyperbilirubinaemia?
- Overproduction - Haemolysis, ineffective erythropoesis
- Impaired hepatic uptake - Drugs, ischaemic hepatitis
- Impaired conjugation - Gilbert’s syndrome, Crigler-Najjar
- Physiological neontala jaundice
What sort of hyperbilirubinaemia occurs in pre-hepatic jaundice?
Unconjugated hyperbilirubinaemia
What type of hyperbilirubinaemia occurs in gilbert’s syndrome?
Unconjugated hyperbilirubinaemia
What types of jaundice cause conjugated hyper bilirubinaemia?
- Hepatocellular dysfunction
- Post-hepatic/Cholestatic jaundice
What are causes of hepatocellular jaundice?
- Viral hepatitis
- CMV
- EBV
- Drugs
- Alcohol/Cirrhosis
- Liver mets
- Liver abscess
- Haemochromatosis
- Autoimmune hepatitis
- Septicaemia
- Leptospirosis
- Syphilis
- Alpha1-antitrypsin
- Budd chiari
- Wilson’s Disease
- Right heart failure
- Toxins
What are causes of post-hepatic jaundice?
- PBC, PSC
- Drugs
- CBD gallstones
- Pancreatic cancer
- Compression of the bile duct
- Cholangiocarcinoma
- Choledochal cyst
- Mirrizi’s syndrome
- Caroli’s syndrome
What blood tests are used to assess liver function?
- Alanine transaminase (ALT)
- Aspartate aminotransferase (AST)
- Alkaline phosphatase (ALP)
- Gamma-Glutamyltransferase (GGT)
- Bilirubin
- Albumin
- Prothrombin time (PT)
What tests are used to distinguish between hepatic and post-hepatic jaundice?
- ALT
- AST
- ALP
- GGT
What tests are used to assess livers synthetic function?
- Bilirubin
- Albumin
- PT
What is ALT a useful marker of?
Hepatocellular injury - found in high concentrations in hepatocytes and enters blood following hepatocellular injury
What is ALP a useful marker of?
Cholestasis (Indirect marker ) - particularly concentrated in the liver, bile duct and bone tissues. It is raised in liver pathology due to increased synthesis in response to cholestasis
What LFT results would indicate predominantly hepatocellular injury?
- ALT - > 10-fold increase
- ALP - <3-fold increase
What LFT results would indicate cholestasis?
- ALT - <10-fold increase
- ALP - >3-fold increase
- Raised GGT
What are causes of an isolated rise in ALP?
- Bony metastases / primary bone tumours (e.g. sarcoma)
- Vitamin D deficiency
- Recent bone fractures
- Renal osteodystrophy
- Paget’s Disease
How would you distinguish between hepatocellular jaundice and cholestatic jaundice?
Compare to what degree the ALT and ALP are raised. If ALT is raised markedly compared to the ALP, this is primarily a hepatocellular pattern of injury. If ALP is raised markedly compared to ALT, this is primarily a cholestatic pattern of injury.
What is a raised GGT indicative of?
Can be suggestive of biliary epithelial damage and bile flow obstruction.
It can also be raised in response to alcohol and drugs such as phenytoin.
A markedly raised ALP with a raised GGT is highly suggestive of cholestasis.
What would a raised ALP in the absence of raised GGT suggest?
Non-hepatobiliary cause - Alkaline phosphatase is also present in bone and therefore anything that leads to increased bone breakdown can elevate ALP.
What would jaundice with normal ALT/ALP levels suggest?
Pre-hepatic cause - Gilbert’s syndrome, haemolysis
What are the livers main synthetic functions?
- Conjugation and elimination of bilirubin
- Synthesis of albumin
- Synthesis of clotting factors
- Gluconeogenesis
What investigations can be used to test liver synthetic function?
- Serum bilirubin
- Serum albumin
- Prothrombin time (PT)
- Serum blood glucose
What happens to an individuals stool and urine if they have unconjugated hyperbilirubinaemia?
Normal urine and normal stool
What would the colour of someones stool be if they had hepatic jaundice?
Dark urine, normal stool
What colour is the stool and urine in someone with post-hepatic jaundice?
Pale stool, dark urine
What can cause albumin to fall?
- Liver disease resulting in a decreased production of albumin (e.g. cirrhosis)
- Inflammation triggering an acute phase response which temporarily decreases the liver’s production of albumin
- Excessive loss of albumin due to protein-losing enteropathies or nephrotic syndrome
What is PT, and what can it indicate in terms of liver disease?
Prothrombin time (PT) is a measure of the blood’s coagulation tendency, specifically assessing the extrinsic pathway.
In the absence of other secondary causes such as anticoagulant drug use and vitamin K deficiency, an increased PT can indicate liver disease and dysfunction.
What does an ALT > AST tend to indicate when looking as the ALT/AST ratio?
Chronic liver disease
What does an AST>ALT tend to indicate when looking as the ALT/AST ratio?
- Cirrhosis
- Acute alcoholic hepatitis
What LFT profile might be present in someone with acute hepatocellular damage?
- Markedly increased ALT
- Normal/increased ALP
- Normal/increased GGT
- Increased/Markedly increased Bilirubin
What LFT profile might you see in someone with Chronic hepatoceullular damage?
Normal or increase ALT, ALP, GGT and Bilirubin
What LFT profile might you see in someone with Cholestasis?
- Normal/increased ALT
- Mardkedly increased ALP
- Markedly Increased GGT
- Markedly increased Bilirubin
What are common causes of acute hepatoceullular damage?
- Poisoning (paracetamol overdose)
- Infection (Hepatitis A and B)
- Liver ischaemia
What are common causes of chronic hepatocellular injury?
- Alcoholic fatty liver disease
- Non-alcoholic fatty liver disease
- Chronic infection (Hepatitis B or C)
- Primary biliary cirrhosis
What are rare causes of chronic heptocellular injury?
- alpha-1 antitrypsin deficiency
- Wilson’s disease
- Haemochromatosis
What tests are included in a liver screen?
- LFTs
- Coagulation screen
- Hepatitis serology (A/B/C)
- Epstein-Barr Virus (EBV)
- Cytomegalovirus (CMV)
- Anti-mitochondrial antibody (AMA)
- Anti-smooth muscle antibody (ASMA)
- Anti-liver/kidney microsomal antibodies (Anti-LKM)
- Anti-nuclear antibody (ANA)
- p-ANCA
- Immunoglobulins – IgM/IgG
- Alpha-1 Antitrypsin – Alpha-1 Antitrypsin deficiency
- Serum Copper – Wilson’s disease
- Ceruloplasmin – Wilson’s disease
- Ferritin – Haemochromatosis
If someone presented with jaundice, what would you want to ask them in the histroy?
Ask about
- Blood transfusions
- IV drug use
- Body piercings/Tattoos
- Sexual activity
- Travel abroad
- Family history
- Contact with others with jaundice
- Alcohol use
- Fever/rigors
- Surgery/anaesthetic history
- Medications
What clinical signs may be present in someone with jaundice?
- Signs of chronic liver disease
- Hepatic encephalopathy
- Lymphadenopathy
- Hepatomegaly
- Splenomegaly
- Ascites
- Palpable gallbladder
- Pale stool, dark urine
What investigations would you consider doing in someone who presents with jaundice?
- Bloods - FBC; Clotting; Blood film; Haemolysis testing - retic count/coomb’s; U+E’s, LFTs, Total protein, Albumin, Paracetamol levels, gamma-GT, Liver screening tests
- Ultrasound - stones, bile ducts etc
- MRCP/ERCP - gallstones
- Liver biopsy
- CT/MRI - metastastatic disease
What are common causes of jaundice in someone with cirrhosis?
- Sepsis
- Malignancy - HCC
- Alcohol
- Drugs
- GI bleeding
What drugs can cause hepatocellular injury?
- Paracetamol overdose
- Isoniazid, rifampicin, pyrazinamide
- MOAI
- Sodium valproate
- Halothane
- Statins
What drugs can cause cholestatic jaundice?
- Fusidic acid, Co-amoxiclav, nitrofurantoin
- Steroids
- Flucloxacillin
- Sulphonylureas
- Prochlorperazine
- Chlorpromazine
What drugs can cause haemolytic jaundice?
Antimalarials
What might a AST/ALT ratio of >/=2.5:1 indicate as a cause of deranged LFTs?
Alcoholic hepatitis
What might an AST/ALT ratio = 1 indicate as the cause of deranged LFTs?
Associated with ischaemia (CCF and ischaemic necrosis and hepatitis)
