49. Jaundice, distinct effects on bilirubin metabolism within each group to form diagnosis Flashcards
Outline the mechanism causing pre-hepatic jaundice
Increase RBC breakdown (haemolysis)
Increased haemoglobin breakdown
Increased production of bilirubin (UCB)
List some of the causes of prehepatic jaundice
Tropical diseases e.g. yellow fever
Side effect of quinine based anti-malarial drugs
Genetic disorders associated with increased haemolysis (sickle cell anaemia)
Describe physiological jaundice of the newborn and how does it arise?
After birth, newborns need to destroy foetal haemoglobin and replace with adult haemoglobin - RBCs have a short lifespan
Undeveloped liver has insufficient capacity to cope with elevated haemolysis due to lack of glucuronyl transferase
Breast milk also contains inhibitors of conjugation
Peaks at 3-5 days and lasts for over 14 days
How is physiological jaundice of the newborn treated?
Phototherapy
- blue light changes unconjugated bilirubin into conjugated bilirubin (water soluble) so it can be excreted
Describe how haemolytic disease of the newborn arises
Rh incompatibility between the mother and foetus can cause increased haemolysis
Rh- of mother is sensitised by Rh+ foetus of previous pregnancy or a Rh+ blood transfusion
Can cause very high bilirubin concentrations
Babies with haemolytic disease of the newborn are at risk of kernicterus. What is this?
Bilirubin crosses the immature blood brain barrier and is deposited in basal ganglia and brainstem nuclei - can lead to brain damage if untreated
How is haemolytic disease of the newborn treated?
High dose phototherapy and blood transfusion
What are the three main issues which cause hepatic jaundice?
- Impaired UCB uptake
- Impaired conjugation of bilirubin (e.g. Gilbert’s syndrome)
- Impaired transport of conjugated bilirubin into bile canaliculi (e.g. primary biliary colangitis - autoimmune destruction of small bile ducts)
What are some of the causes of hepatic jaundice?
Viral hepatitis
Cirrhosis
Hepatotoxic drugs
Define post-hepatic jaundice
Obstruction of the cystic, hepatic, or common bile ducts preventing bile from entering the small intestine
What are the three main causes of post-hepatic jaundice?
- Gallstones - small pebbles made of cholesterol that move from gallbladder and block bile ducts
- Pancreatitis
- Pancreatic tumours
What causes the formation of gallstones?
When the capacity for bile salts and phospholipids to solubilise cholesterol is exceeded
What are the effects of a cystic duct blockage?
Painful contractions
What are the effects of a common bile duct blockage?
No bile secretion into gut
Steatorrhoea (fatty faeces with no bile salts)
Grey faeces (no bile pigments)
Post-hepatic jaundice (as no excretion of bilirubin)
What are the effects of a blockage of the duodenal papilla?
No bile or pancreatic secretions into the intestines
Malnutrition (no digestion of contents)
Acute pancreatitis
Why is it important that vitamin K is injected into patients with post-hepatic jaundice prior to surgery?
Bile salts are required for the absorption of fat soluble vitamins and for the digestion and absorption of lipids
Vit K is important in efficiency of coagulation cofactor gamma-glutamyl carboxylase (GGCX) in the liver
GGCX required for the production of many activated coagulation factors (II, VII, IX, X)
Vit K administration therefore prevents haemorrhage
What reagent is used to test for serum C-bilirubin?
Diazo reagent (turns C-bilirubin blue - azobilirubin)
What reagent(s) is used to test for total bilirubin in serum?
Diazo reagent AND caffeine
Caffeine displaces unconjugated bilirubin, unbinding it from albumin and making it water soluble to react with diazo
What are the reference ranges for total bilirubin and conjugated bilirubin in adults?
Total bilirubin <21 micro mol/L
Conjugated bilirubin <7 micro mol/L
How are bile pigments measured in urine?
Multistix urinalysis
Tests for urobilinogen and bilirubin (not UCB)
What does it mean if there is conjugated bilirubin detected in the urine?
At low concentrations - normal
Otherwise, always a pathological finding as it means conjugated bilirubin has leaked back into the bloodstream (hepatic or post-hepatic jaundice)
What does absence of urobilinogen in the urine indicate when there is a jaundiced patient?
Biliary obstruction
What do high urobilinogen levels indicate in the urine?
Increased haemolysis or liver disease
What does absence of stercobilin in faeces indicate?
Post-hepatic jaundice (can tell just by looking)
What are blood gas analysers used for in some neonatal care units?
Allows early detection of jaundice and monitors severity/treatment
Based on absorbance of whole blood sample
What are transcutaneous measurements used for?
Measure yellowness of skin due to bilirubin
Measures at various wavelengths to correct for variations in haemoglobin, melanin, and skin thickness
Not to be used as a substitute for lab measurements but can minimise the requirement for blood samples for monitoring
