CH3 Flashcards
How long do red blood cells normally survive?
120 days
How long do red blood cells normally survive in a patient with haemolytic anaemia?
The red cell survival time is considerably shortened
Where does the breakdown of normal red cells occur?
In the macrophages of the bone marrow, liver & spleen
What can excessive destruction of red cells cause?
Haemolytic anaemias
Does the shortening of red cell lifespan always result in anaemia?
No, shortening of red cell survival does not always cause anaemia.
There is a compensatory increase in red cell production in the bone marrow
If red cell loss can be contained, a haemolytic state without anaemia can exist
- compensated haemolytic disease
What are the consequences of haemolysis?
Shortening of red cell lifespan
Marrow output increased 6-8x by
- increasing the proportion of cells committed to erythropoiesis (erythroid hyperplasia)
- expanding the volume of active marrow
Immature red cells (reticulocytes) are released prematurely
- larger than mature cells
- stain blue on peripheral blood film (polychromasia)
What are the two mechanisms whereby red blood cells are destroyed in haemolytic anaemia?
Extravascular haemolysis
Intravascular haemolysis
What is extravascular haemolysis?
Excessive removal of RBC from the circulation by the macrophages of the reticuloendothelial system (spleen)
What is intravascular haemolysis?
RBCs are broken down directly in the circulation .
• Haemoglobin is liberated. This is initially bound to plasma haptoglobins which become saturated
Name some of the causes of intravascular haemolysis
Mismatched blood transfusion G6PD deficiency with oxidant stress Red cell fragmentation syndromes Some autoimmune haemolytic anaemias Some drug- and infection- induced haemolytic anaemias Paroxysmal nocturnal haemoglobinuria March haemoglobinuria Unstable haemoglobin
When a red blood cell breaks down extravascularly, it breaks down into 3 components. What are they?
Globin
Haem
Protoporphyrin
When a red blood cell breaks down extravascularly, it breaks down into 3 components. What happens to the haem component?
The haem group breaks down into Fe3+ and biliverdin. The iron then binds to transferrin, which then recirculates.
The biliverdin is reduced to bilirubin, which is then released into the plasma, where it is bound to albumin, and then recirculated to the liver.
What happens to excess free plasma Hb?
It is filtered by the renal glomerulus.
It enters the urine and small amounts will be reabsorbed by renal tubules
Hb is broken down deposited in cells as haemosiderin
Some free plasma Hb is oxidised to methaemoglobin, which dissociates into ferrihaem & globin
Plasma haemopexin binds ferrihaem
If its binding capacity is exceeded ferrihaem becomes attached to albumin forming methaemalbumin
How can excess free plasma Hb be detected?
Detected in spun sediment of urine - Perls’ reaction
What organ removes Hb?
The liver removes Hb bound to haptoglobin, haemopexin and free Hb.
When the red blood cells break down, haemoglobin and haptoglobin complex forms, and will be removed by the liver.
When red blood cells break down, what happens to the globin chains?
Globin chains broken down to Amino acids, and reutilised for general protein synthesis
Haptoglobins bind to haemoglobin to form a Haptoglobin/ Haemoglobin complex, which is removed from plasma by reticuloendothelial system
What are laboratory findings of intravascular haemolysis?
Raised levels of plasma Hb
Very low or absent haptoglobins
Haemoglobinaemia, Haemoglobinuria
Haemosidinuria (Fe storage protein in the spun deposit of urine)
+ve Schumm’ test - shows methaemalbuminaemia detected spectrophotometrically
What evidence of haemolysis would be shown in a patient?
Increased red cell breakdown leads to:
- elevated serum bilirubin (unconjugated)
- excess urinary urobilinogen (bilirubin breakdown in intestine)
- reduced plasma haptoglobin
- raised serum lactic dehydrogenase (LDH)
Increased red cell production (compensatory mechanism) leads to
- Reticulocytosis
- Erythroid hyperplasia of the bone marrow
Abnormal red cells in some haemolytic anaemias:
- spherocytes
- sickle cells
- red cell fragments
What are the causes of haemolytic anaemias?
Inherited
- Red cells membrane defect
- Haemoglobin abnormalities
- Metabolic effects
Acquired
- Immune (autoimmune, alloimmune, drug induced)
- Non-immune
Miscellaneous
Describe the features of Autoimmune Haemolytic Anaemias
AIHAs are caused by antibody production by the body against its own red cells
They are characterised by a positive direct antiglobulin test (DAT) or Coombs’ test
AIHAs are divided into ‘warm’ and ‘cold’ types according to whether the antibody reacts more strongly with red cells at 37C or 4C
