There’s nothing wrong with the liver… yet.
When you see a jaundiced patient, most people (students included!) immediately point to the liver and say, “Aha! That’s the trouble.”
But sometimes… the liver is innocent.
In pre-hepatic jaundice, the liver is like a frantic worker at a conveyor belt, bilirubin is arriving faster than it can conjugate and clear. The real trouble is upstream, where red blood cells (RBCs) are being destroyed at a rate the liver simply can’t handle.
The result?
Unconjugated bilirubin rises
Scleral icterus appears
Urine stays normal colour (because unconjugated bilirubin isn’t water-soluble)
The yellow is real, but the liver is merely the messenger.
So why are RBCs being destroyed?
Haemolysis is the villain. But it’s not one villain, it’s an entire rogues’ gallery, each with a different motive. Let’s break them into categories medical students remember well for exams
Intrinsic causes, RBCs built with a flaw
These are problems inside the red cells themselves. The spleen looks at them and says,
“Nope. Not acceptable.”
… and starts destroying them.
Common culprits:
| Type | Example | Why it happens |
| Membrane defects | Hereditary spherocytosis | Misshapen cells → removed by spleen |
| Enzyme defects | G6PD deficiency, Pyruvate kinase deficiency | Cells can’t handle oxidative stress |
| Haemoglobin defects | Sickle cell disease, Thalassemia | Abnormal Hb → fragile RBCs |
These conditions are often genetic, chronic, and present early in life.
Pearls for exams:
- Spherocytes? Think hereditary spherocytosis
- Bite cells? Think G6PD deficiency
- Target cells? Think thalassemia
Extrinsic causes, RBCs facing outside attack
Here, the RBCs are perfectly fine, until something in the environment goes wrong.
| Mechanism | Examples | Where destruction happens |
| Immune-mediated haemolysis | Autoimmune haemolytic anaemia, transfusion reactions | Spleen + circulation |
| Mechanical destruction | Prosthetic heart valves, marching haemoglobinuria | Blood vessels |
| Microangiopathic haemolytic anaemia (MAHA) | DIC, HUS, TTP | Small vessels, schistocytes! |
| Infections | Malaria, sepsis | Direct RBC destruction |
| Drugs/toxins | Antimalarials, sulfonamides, snake venom | Depends on cause |
Schistocytes on a blood film = microangiopathic process
That’s a gold-standard buzzword for viva exams
What do the labs look like?
A beautiful pattern emerges:
| Test | Result | Why |
| ↑ Unconjugated bilirubin | Yes | Excess haem breakdown |
| ↑ LDH | Yes | Released from destroyed RBCs |
| ↓ Haptoglobin | Yes | Used up binding free Hb |
| Reticulocytes ↑ | Yes | Bone marrow response |
Urine remains normal colour
(you can’t pee out unconjugated bilirubin, insoluble!)
How to think fast on wards
If a jaundiced patient has:
Normal-coloured urine
Anaemia
Raised reticulocytes
→ Think haemolysis until proven otherwise
Add malaria travel history or transfusion mistakes to the differential and you’ll make your consultant very happy.
If they also have splenomegaly, the spleen is clearly involved in the cleanup operation.
Treatment: Fix the cause, not the bilirubin
Depending on the root issue:
- Autoimmune → corticosteroids, IVIG, sometimes splenectomy
- G6PD deficiency → avoid triggers (e.g., fava beans, certain drugs)
- Infections → treat the pathogen
- Inherited conditions → folate, transfusion support, specialist care
The bilirubin level will calm down once the haemolysis does.
One last pearl
If the urine is yellow-brown, think liver or obstruction.
If the urine is normal, think haemolysis every time.
It’s one of the fastest bedside clues to the “Kingdom” of jaundice you’re dealing with.
