Heamolytic anaemia: intrinsic anaemia

Question 1

Haemolytic anaemia refers to… & the changes that occurs overtime bc of this

Answer 1

• anaemia caused by increased & premature destrcution of RBC
  -initially normocytic & normochromic
  => inc. erythropoisis = inc retic.
  => spherocyte form = dec. MCV

Question 2

difference b/w extravascular & intravascular haemolysis *

Answer 2

• Extravascular: haemolyse after being removed from circulation (by macrophages in spleen/ BM/ liver) *No Hb released in plasma
• Intrav: haemolysed while cells in circulation

Question 3

What happens in intrav. haemolysis?

Answer 3

1. Free Hb binds to haptoglobin OR haemopexin (proteins)
2. blood -> liver
3. excess Hb oxidised to methaemoglobin (MetHb)
4. => haemin + globin
5. => globin broken down & AA recycled
   => Haemin binds to protein (haemopexin or Alb) -> degraded in liver

Question 4

What happens when there is excess fre Hb?

Answer 4

• Hb filtered through kidney & into urine (haemoglobinuria)

- Fe3+ filtered out -> urine (methaemoglobinuria)

Question 5

Mechanisms of Intravascular haemolysis (3)

Answer 5

• activate complement on RBC membrane
• Physical or mechanical trauma to RBC
• ‘Toxic’ plasma factors -> dircupt integrity of cell

Question 6

What happens in extrav.. haemolysis?

Answer 6

1. Hb degraded w/oin phagocyte => haem & globin
2. Haem degraded to Fe, biliverdin & CO
3. biliverdin converted to bilirubin -> + Alb -> liver to be degraded
4. degraded to urobilinogen & excreted in faeces

Question 7

primary causes that lead to extravascular haemolysis (3)

Answer 7

• inherited RBC defects
• Acquired RBC defects
• Autoimmune haemolytic anaemia

Question 8

How does the test osmotic fragility work?

Answer 8

• small amoun tof blood is added to excess buffered saline @ various [ ]
• the time/fraction for RBC to lyse at each saline solution is determined
• e.g. spherocyte take up less water in hypotonic solution before erupting

Question 9

WHat is hereditary spherocytosis?

Answer 9

• membrane defect in main structural protein (spectrin) = abnormal interactions w/ other proteins in membrane
  => microvesicles of membrane bud off
  = spherocytes

Question 10

WHat is hereditary elliptocytosis (caused by)?

Answer 10

• defect in glycophorin C

=> defect spectrin dimer-dimer association

Question 11

WHat is hereditary stomatocytosis (hyrocytes)?

Answer 11

• membrane abnormally permeable to Na & K+
• Gain Na+ > loss of K+
  => excess H2O enters cell = overhydrated = swell
• mild-moderate anaemia

Question 12

hereditary stomatocytosis can be classified in 2 forms

Answer 12

• syndromic form: show extrahematologi signs

- non-syndromic forms: selective involvement of erythroid sys.

Question 13

What is hereditary acanthocytosis (abetalipoproteinaemia)?

Answer 13

absence of: 
- serum beta-lipoprotein
=> low serum cholesterol
=> low triglyceride
=> inc ratioi of cholesterol to phopholipid
- mild haemolysis

Question 14

what can pyruvate kinase deficiency lead to in the body?

Answer 14

=> dec ATP levels
=> Na/K ATPase pump activity
=> K+ loss, cell dehydration
=> echinocyte formation
=> phagocytosed by macrophages in spleen