Pathophysiology of jaundice
Pre-hepatic
o Increased breakdown of red cells leads to increased serum bilirubin. This unconjugated
bilirubin isn’t water-soluble so can’t be excreted in the urine. Intestinal bacteria convert
some of the extra bilirubin into urobilinogen, some of which is re-absorbed and IS excreted
by the kidneys – hence urinary urobilinogen is increased.
Hepatic
o Disorders of uptake, conjugation or secretion of bilirubin.
o Usually divided into conjugated or unconjugated bilirubinaemia.
The various causes of jaundice are traditionally classified into pre-hepatic, hepatic and post-hepatic
(or cholestatic) groups according to the mechanism of the jaundice.
Pre-hepatic causes of jaundice
Congenital red cell issues
o Cell shape
Sickle cell disease
Hereditary spherocytosis
Hereditary elliptocytosis
o Enzyme
G6PD deficiency
Pyruvate kinase deficiency
o Haemoglobin
Thalassemia
Autoimmune haemolytic anaemia
Drugs
o Penicillins
o Sulphasalazine
Infections
o Malaria
Mechanical
o Metallic valve prostheses
o DIC
Transfusion reactions
Paroxysmal nocturnal haemoglobinuria
Hepatic causes of jaundice
Conjugated causes:
o Cirrhosis (see chronic liver disease for further causes)
o Malignancy
Primary or metastases
o Viral hepatitis
o Drugs
Hepatitis
Isoniazid, rifampicin, atenolol, enalapril, verapamil, nifedipine, amiodarone,
ketoconazole, cytotoxics, halothane
Cholestasis
Ciclosporin, azathioprine, chlorpromazine, cimetidine, erythromycin, nitro,
ibuprofen, hypoglycaemics
o Enzymes
Dubin-Johnson syndrome (DJS)
Autosomal recessive (cMOAT gene) with excretion of conjugated bilirubin.
o Leads to pigmented liver.
Increase in conjugated bilirubin with no other enzyme changes
High coproporphyrin
Rotor syndrome
Similar to DJS
Liver not pigmented
Normal coproporphyrin
Unconjugated causes of jaundice (sometimes classified as pre-hepatic causes)
o Gilbert’s syndrome
Congenital hypo-activity of conjugation enzyme UGT-1. Benign and common (5%)
Normal LFTs except mildly elevated bilirubin, especially in times of physiological
stress/illness
Normal life expectancy
o Crigler-Najar syndrome
Autosomal recessive (type I) or dominant (type II). Severe unconjugated
hyperbilirubinaemia.
Congenital absence (I) or decrease (II) of glucoronyl transferase.
Normal liver histology.
Treatment is liver transplant (only type II survive to adulthood)
Post-hepatic causes of jaundice
Biliary tree obstruction
o Gallstones
o Compression e.g. pancreatitis, pancreatic tumour, lymph nodes, biliary atresia
o Cholangiocarcinoma
o Post-operative stricture
Primary biliary cirrhosis (see PBC section)
o M:F = 1:9
o ANA and Anti- mitochondrial antibodies
And anti-centromere for prognosis (though more association with CREST)
Primary sclerosing cholangitis (see PSC section)
o 80% of PSC have UC
o ANCA, anti-smooth muscle antibodies
o Association with cholangiocarcinoma
Pregnancy-associated jaundice
Obstetric cholestasis
o 0.1-0.2% of pregnancies
o Presentation
Itching – jaundice later
Raised liver markers, esp ALP
o Issues
Fetal mortality 3.5%
o Often recurs in further pregnancies
Treatment
Ursodeoxycholic acid
HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets)
o Occurs in 1-2 out of 1000 pregnancies and 10-20% of severe pre-eclampsia
o Leads to a variant of DIC
o Needs steroids and prompt delivery
o Maternal mortality 1-24%
Fatty liver of pregnancy
o All LFTs including synthetic function go off
Hyperemesis gravidum
Pre-eclampsia
o Associated with abnormal LFTs in 20% cases
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