The document outlines the pathophysiology of haemolysis, characterized by the accelerated destruction of red blood cells (RBCs), which can occur due to various conditions such as renal failure and sickle cell disease. It distinguishes between intra-vascular and extra-vascular haemolysis, detailing the mechanisms of RBC destruction, bilirubin production, and compensatory responses in the bone marrow. Additionally, it discusses specific types of extra-vascular haemolytic anemia and the clinical manifestations associated with haemoglobin breakdown.

1. PATHOPHYSIOLOGY OF
HAEMOLYSIS
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DR.HAMISI MKINDI,MD.
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2. Haemolysis
• Haemolysis is
– The accelerated destruction of red cells
• Can occur in many diseases
– Renal failure
– Cirrhosis of liver
– Megaloblastic anaemia
– Sickle cell disease
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3. Haemolysis
• Can be divided into
– Intra-vascular haemolysis
• RBC are destroyed in blood stream
– Extra-vascular haemolysis
• RBCs are destroyed by tissue macrophages
– Mainly in the spleen
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4. Extra-vascular Haemolysis
• Normal disposal of RBC
• RBC lifespan
– Four months (120 days)
– Then die of old age
– Disposal of old RBC
• Handled by spleen
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5. Extra-vascular Haemolysis
• In the spleen
– Blood flow is sluggish especially in splenic cords
– Hence there is a fall in
• Local O2 tension
• pH
• Glucose concentration
• Normal RBC
– Can resist these metabolic assaults
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6. Extra-vascular Hemolysis
• Senile or defective RBC
– Have impaired resistance
– They are destroyed by mononuclear phagocytes
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7. Extravascular Hemolysis
13-Jan-23 Jaundice 7
Hgb
Globin
Haeme
Biliverdin
RBC
Bilirubin
Bilirubin
+ albumin
Bilirubin +
Y, Z prot
Conjugated
Bilirubin
Conjugated
Bilirubin
Conj.Bil Urobilinogen Stercobilin
Urobilinogen
Urobilin
Urobilinogen
Faeces
Kidney
Liver
RES
Intestines
Plasma

8. Destruction of RBCs
• During extra-vascular haemolysis
– Some Hgb spill into circulation
• Free Hgb in plasma
– Handled by the liver
• It combines with haptoglobin
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9. Destruction of RBCs
• The Hgb-haptoglobin complex
– Taken up by the hepatocytes
– Hgb degradation occurs
• Protein is digested to amino acids
• Iron is deposited as ferritin
• Pophyrin ring is converted itno bilirubin
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10. Manifestation
• Increase in extra-vascular haemolysis leads to
– Hypertrophy of spleen
• Splenomegally
– To handle the RBC load
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11. Increase in Cell Production
• As a compensation to
–  Cell destruction
• Bone marrow activity increases
•  Release of young erythrocytes
– Reticulocytosis
– Some normoblasts may also occur
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12. Increase in Cell Production
• Normal marrow can
–  Red cell production by 8 times the normal
• Thus anaemia occurs only when
– Marrow’s ability to produce RBCs is
• Outstripped by the haemolytic process
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13. Increased Breakdown of Hgb
• Increased breakdown of Hgb leads to
–  Bilirubin production
• The serum bilirubin conc increases
– Jaundice
– Fall in serum haptoglobin level
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14. Increased Breakdown of Hgb
• Normally the increased bilirubin
– Is of the un-conjugated form
• In the presence of liver damage
– Haemolysis can cause accumulation of both
• Un-conjugated & conjugated bilirubin
• Due to leakage into blood stream
– From damaged liver cells
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15. Extra-vascular Haemolytic anaemia
• Extra-vascular haemolytic anaemia include:
• Auto-immune haemolytic anaemia
– Antibodies bind to aoutologous RBCs
– Mark them for destruction by phagocytes
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16. Extra-vascular Haemolytic anaemia
• Hereditary shperocytosis
– Inherited red cell disorder
– Results in abnormalities of cell membrane
– Extra-vascular haemolysis
• Sickle cell disease
– Abnormal Hgb
• Causes red cells to sickle
• They are destroyed by RES
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17. Extra-vascular Haemolytic anaemia
• Unstable Hgb
– Inherited as autosomal dominant trait
– Denatured by oxidative process
• Denature Hgb forms
– Intracellular precipitates
– Cause red cells to be held up & destroyed by
spleen, RES
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18. (II) Intra-vascular Haemolysis
• Intra-vascular haemolysis occurs when
– There is mechanical damage of normal RBC
• Presence of artificial cardiac valves
• Presence of thrombi within microcirculation
– Complement induced haemolysis
• Mismatched blood transfusion
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19. Intra-vascular haemolysis
• Can occur as a result of
– Deficiency of enzyme system
• Lead to damage to cell membrane
• Cells rupture during circulation
– Spilling Hgb into plasma
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20. Intra-vascular Haemolysis
• Disposal of plasma Hgb
• General mechanisms
– Haptoglobin-dependent mechanism
– Haptoglobin independent mechanisms
• Clearance by kidney
• Destruction in plasma
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21. Intra-vascular Haemolysis
• Haptoglobin mechanism
– Is an 2 - globulin
• Haptoglobin + Hgb complex
– Complex is then transported to liver
– Hgb is handled by the liver
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22. Intra-vascular Haemolysis
• Limitation
– Mechanism can only handle limited amount of
Hgb at a time
• Small amount of haptoglobin in blood
• Excess amount Hgb released
• Haptoglobin is consumed faster than it can be replaced
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23. Intra-vascular Haemolysis
• Haptoglobin indepented
mechanisms
• Clearance by the kidney
– Free haemoglobin
dissociates into -dimers
– These are small enough to
be filtered by glomerulus
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22
2
22 2
Globin AA
Haeme Bilirubin
Iron
Ferritin

24. Intra-vascular Haemolysis
• In the nephron
– Dimers are rapidily
reabsorbed
• Proximal tubular cells
– Degraded in the usual
way
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22
2
22 2
Globin AA
Haeme Bilirubin
Iron
Ferritin

25. Intra-vascular Haemolysis
• Proteins  AA
• Iron is deposited as
haemosiderin
• Haeme converted
into bilirubin
– Excreted in bile
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22
2
22 2
Globin AA
Haeme Bilirubin
Iron
Ferritin

26. Intra-vascular Haemolysis
• The proximal tubular
cells
– Have limited capacity
to take up Hgb dimers
• If capacity is
exceeded
– Hgb appears in urine
– Haemoglobinuria
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22
2
22 2
Globin AA
Haeme Bilirubin
Iron
Ferritin

27. Intra-vascular Haemolysis
• Proximal tubule cells
– Take up Hgb dimers
– Convert the iron into haemosiderin
– Cells are shed over the course of few weeks
• Presence of haemosiderin contain cells in urine
– Strong indication of intra-vascular haemolysis
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28. Intra-vascular Haemolysis
• After a bout of intravascular haemolysis
– Hgb can be detected in blood & urine
• For a few days only
– Haptoglobin is depressed for a couple of days
– Haemosiderin is detected in urine for few weeks
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29. Destruction of Hgb in Plasma
• Involve oxidation of iron of circulating Hgb
– Hgb-Fe++  Hgb-Fe+++ (methaemoglobin)
• This is a rapid reaction
– Take place before Hgb is lost though the kidney
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30. Destruction of Hgb in Plasma
• The formed methaemoglobin dissociate into
– Ferrihaeme
• Haeme in which is in the Fe+++
– Apoprotein
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31. Destruction of Hgb in Plasma
• The formed ferrihaeme is either bound to
– Albumin to form
• Methaemalbumin
– Haeme-binding protein
• Haemopexin
• Methaemalbumin & haemopexin
– Taken to liver where
• They are broken down to iron & bilirubin
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32. Signs of Haemoglobinaemia
• Fall in haptoglobin in plasma
– Most sensitive indicator of Hgb release in plasma
– In extra-vascular haemolysis
• Haptoglobin will vary from
– Near normal to zero depending on severity
– In intravascular haemolysis
• Haptoglobin disappears completely
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33. Signs of Haemoglobinaemia
• Evidence of intra-vascular haemolysis
– Presence of free Hgb in plasma or urine
• Haemoglobinuria
– Results in dark urine
– Give positive test for blood
• But myoglobin, RBC also give dark urine, test positive for blood
– Free Hgb give rise to haemosiderinuria
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34. Intra-vascular Haemolysis
• Manifestation
– Haemoglobinaemia
– Haemglobinuria
– Methaemalbuminaemia
– Jaundice (also in intravascular hemolysis)
– Haemosidenuria
– Decreased haptoglobin
• (also in intravascular hemolysis)
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