Jaundice Flashcards
What is jaundice?
The result of accumulation of bilirubin in the bloodstream and subsequent deposition in the skin, sclera, and mucous membranes.
What are the 3 different sites in which bilirubin metabolism dysfunction can arise?
- Increased bilirubin production (prehepatic)
- Diseases that impair hepatocyte function (hepatocellular)
- Obstruction of the biliary system (cholestatic)
Briefly describe the pre-hepatic causes of jaundice
A rise in unconjugated (indirect) serum bilirubin indicates either increased bilirubin production from red blood cell destruction or a dysfunction in bilirubin conjugation. Referred to as prehepatic because the pathological process occurs before the bilirubin is metabolised by the liver.
Give examples of pre-hepatic causes of jaundice
- Haemolysis
- Hereditary haemolytic anaemias
- Acquired haemolytic anaemias
- Impaired bilirubin conjugation
- Gilbert’s syndrome
Briefly describe hereditary haemolytic anaemias
Haemolysis of red blood cells (RBCs) leads to elevation of serum unconjugated bilirubin levels.
Causes fall into three broad categories:
- RBC membrane defects (e.g. hereditary spherocytosis, elliptocytosis, pyropoikilocytosis)
- Enzyme deficiencies (e.g. glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency)
- Abnormal haemoglobin production (e.g. sickle cell anaemia, thalassaemia).
Briefly describe acquired haemolytic anaemias
Haemolysis of RBCs leads to elevation of serum unconjugated bilirubin levels.
Autoimmune haemolytic anaemia occurs when RBCs are attacked by autoantibodies and targeted for extravascular destruction. This usually occurs as part of other autoimmune conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, or scleroderma) or in relation to a lymphoproliferative disorder (usually non-Hodgkin’s lymphoma or chronic lymphocytic leukemia). Autoimmune haemolytic anaemia can be caused by transfusion reactions, usually due to ABO blood group incompatibility.
Briefly describe Gilbert’s syndrome (impaired bilirubin conjugation)
Characterised by intermittent jaundice due to unconjugated bilirubin in the absence of haemolysis or underlying liver disease.
Caused by a defect in the UGT1A1 gene, which encodes the hepatic conjugation enzyme uridine-diphosphoglucuronate glucuronosyltransferase.
Jaundice may be precipitated by dehydration, fasting, menstrual periods, or stress, such as an intercurrent illness or vigorous exercise.
Briefly describe the hepatic causes of jaundice
Conditions that damage the structure and/or function of hepatocytes give rise to hepatocellular jaundice. The liver loses the ability to conjugate bilirubin. This leads to both unconjugated and conjugated bilirubin in the blood, termed a ‘mixed picture’.
Such conditions include infections, toxin, cancer, autoimmune conditions, and genetic conditions.
Give examples of hepatic causes of jaundice
- Infections
- Toxins
- Neoplasia
- Autoimmune
- Genetic
Give examples of hepatic causes of jaundice: infection
- The viral hepatitides A, B, C, D and E
- HIV infection
- Leptospirosis
Give examples of hepatic causes of jaundice: toxins
- Alcohol
- Drug-induced liver injury
- Paracetamol-induced hepatotoxicity
- Antibiotics
- Antiepileptics
- Non-steroidal anti-inflammatory drugs (NSAIDs)
Give examples of hepatic causes of jaundice: neoplasia
- Hepatocellular carcinoma
- Lymphoma
- Liver metastases
Give examples of hepatic causes of jaundice: autoimmune
- Autoimmune hepatitis
- Primary biliary cholangitis
- Primary sclerosing cholangitis
Give examples of hepatic causes of jaundice: genetic
- Wilson’s disease
- Hereditary haemochromatosis
- Alpha-1 antitrypsin deficiency
Briefly describe the cholestatic causes of jaundice
Cholestatic jaundice (sometimes called post-hepatic jaundice) results from obstruction of bile drainage. The bilirubin that is not excreted will have been conjugated by the liver, hence the result is a conjugated hyperbilirubinaemia.
Causes may be benign or malignant.
