Anaemia Flashcards
What is anaemia?
- ‘Low Hb for a given volume of blood in comparison with healthy subject of same age and gender’
- An actual absolute reduction in Hb
What haematological values are changed in anaemia, and how?
- Hb - reduced
- RBC - reduced
- Hct - reduced
1) What else might cause a reduction in Hb which is not an absolute reduction in Hb, as in anaemia?
2) Why can the above pathophysiology not exist in healthy people?
1) Increase in plasma volume
2) Excess fluid is excreted by healthy people
List 4 fundamental mechanisms of anaemia - this is different to causes
- Reduced production in the bone marrow
- Haemorrhage
- Haemolytic problem - reduced survival of RBCs in circulation
- Pooling of RBCs in very large spleen
What are the 3 classifications of anaemia - and for each, are they usually hypo-, normo- or hyper- chromic?
- Microcytic - hypochromic
- Normocytic - normochromic
- Macrocytic - normochromic
List 2 classes of causes of microcytic anaemia and 2 examples for each
- Defect in HAEM synthesis
- Iron deficiency anaemia
- Anaemia of chronic disease
- Defect in GLOBIN synthesis (thalassaemia)
- Defect in alpha chain synthesis (alpha thalassaemia)
- Defect in beta chain synthesis (beta thalassaemia)
Describe the cause of macrocytic anaemia
Abnormal haematopoiesis - red cell precursors continue to synthesis haemoglobin and other cellular proteins but fail to divide normally - therefore RBCs end up larger than normal
List 5 causes of macrocytic anaemia
- Megaloblast erythropoiesis secondary to vitamin B12 deficiency
- Megaloblast erythropoiesis secondary to folic acid deficiency
- Use of drugs that interfere with DNA synthesis e.g. chemo
- Reticulocytosis secondary to haemorrhage with adequate iron stores
- Haemolytic anaemia (+secondary reticulocytosis)
1) What are megaloblasts and how are they formed?
2) Give 2 characteristic features of megaloblasts
3) How to detect megaloblasts
1)
- Megaloblasts are abnormal bone marrow erythroblasts
- Delay in nuclear maturation with normal cytoplasmic maturation - so misbalance between nuclear and cytoplasmic maturation in bone marrow erythropoiesis
2)
- Large
- Nucleo-cytoplasmic dissociation
3)
- Can suspect it from peripheral features but mainly you have to conduct bone marrow examination
What is reticulocytosis and how does it cause macrocytic anaemia?
- Premature release of cells from the bone marrow - immature rericulocytes which are 20% larger than mature RBCs increase in circulation - therefore higher MCV for given volume and thus macrocytic anaemia occurs
Give 2 causes of megaloblastic erythropoiesis
- Vitamin B12 deficiency
- Folic acid deficinecy
Give 2 causes of reticulocytosis
- Haemorrhage - due to premature reticulocyte release as bone marrow rushes to compensate for low RBC
- Haemolytic anaemia - due to premature reticulocyte release as bone marrow rushes to compensate for low RBC
What does the term normocytic normochromic anaemia suggest to you in terms of the haematological RBC parameters?
- Normocytic - normal MCV
- Normochromic - Normal MCH
What are the 3 mechanisms of normocytic normochromic anaemia?
- Haemorrhage
- Failure of RBC synthesis
- Pooling of RBCs in spleen - hypersplenism and splenomegaly
List 8 causes of normocytic normochromic anaemia, including one class of causes with 4 subsections
- Peptic ulcers
- Oesophageal varices
- Trauma
…..
Failure of RBC production
- Iron deficiency or anaemia of chronic disease
- Renal disease
- Bone marrow failure or suppression
- Bone marrow infiltration
…..
- Hypersplenism e.g. portal cirrhosis
List the 2 classifications from how you can get haemolytic anaemia and outline what usually causes them
- Inherited - defects of the RB cell
- 1 CSM defect e.g. hereditary spherocytosis
- 2 Hb defect e.g. sickle cell
- 3 Defect in glycolytic pathway e.g. pyruvate kinase deficiency
- 4 Defect in enzymes of pentose shunt e.g. G6PD deficiency
- Acquired - extrinsic factors
- 1 Damage to RBC membrane e.g. AIHA or snake bite
- 2 Damage to whole RBC e.g. Microangiopathic Haemolytic Anaemia (MAHA)
- 3 Oxidant exposure - damage to RBC and Hb - e.g. dapsone or primaquine
- 4 Oxidant exposure leading to precipitation of episodic haemolysis in individuals with enzyme deficiency
List the classifications of the mechanisms behind development of haemolytic anaemia and outline when they generally occur
- Intravascular - occurs if there is very acute damage to the RBC
- Extravascular - occurs when defective RBCs are removed by the spleen
Give 3 functions of G6PD in RBCs
- Involved in the pentose phosphate pathway that runs parallel to glycolysis and generates NADPH and pentoses
- G6PD pathway is the only source of reduced glutathione in RBCs
- G6PD confers protective effect against oxidative free radical damage
In what state are people with G6PD deficiency at particular risk of haemolytic anaemia and why?
In states of oxidative stress because G6PD normally protects against oxidative stress. Oxidative stress leads to haemolytic anaemia
What is the role of pyruvate kinase in the RBC and why would pyruvate kinase deficiency lead to haemolytic anaemia?
- Pyruvate kinase is involved in the last stage of glycolysis
- A deficiency of pyruvate kinase will result in a RBC with decreased energy and because RBCs cannot synthesise ATP, cellular death occurs
List 3 times when you might suspect haemolytic anaemia
- Evidence of morphologically abnormal RBCs - hereditary elliptocytosis, irregularly contracted cells fragments
- Evidence of increased red cell breakdown - fragments etc
- Evidence of increased bone marrow activity
What is microangiophathic haemolytic anaemia (MAHA) and what is an indication of it?
- Haemolytic breakdown of RBCs within small blood vessels
- The presence of fragments indicates MAHA because it indicates RBC breakdown within the circulation rather than by the spleen
Give 2 treatment methods for Microangiopathic Haemolytic Anaemia (MAHA)
- Removing the cause e.g. treating severe HTN or stopping a causative drug
- Plasma exchange when it is caused by an antibody in the plasma that is leading indirectly to fibrin deposition
Give 2 signs of haemolytic anaemia and why they occur
- Jaundice - due to high bilirubin from the breakdown of RBCs
- Black holes seen on gall bladder radiograph - if you have a high turnover of red cells and thus a build up of bilirubin, there is a greater chance of forminng bile pigment stones in the gall bladder. Particularly in reticulocytosis
The following are all sites of defect for inherited haemolytic anaemias, give an example cause for each…
1) Membrane
2) Haemoglobin
3) Glycolytic pathway
4) Pentose shunt
1) Herditary spherocytosis
2) Sickle cell anaemia
3) Pyruvate kinase deficiency
4) Glucose-6-phosphate dehydrogenase deficiency
The following are all sites of defect for acquired haemolytic anaemias, give an example cause for each…
1) Membrane - immune
2) Whole red cell - mechanical
3) Whole red cell - oxidant
4) Whole red cell - microbiological
1) Autoimmune haemolytic anaemia
2) Microangiopathic haemolytic anaemia
3) Drugs and chemicals
4) Malaria
What can be detected in a blood film with reticulocytosis?
Polychromasia - blue staining indicating juvenile RBCs (reticulocytes)
1) What is hereditary spherocytosis and why does it occur?
2) List 4 characteristic features of spherocytic RBCs
3) What type of haemolysis does it result in and why does it result in this haemolysis?
4) What is the treatment for hereditary spherocytosis?
1)
- Inherited intrinsic defect of the RBC CSM in which the CSM loses membrane and the cells become spherical
2)
- Larger
- Rounder
- Increased MCHC
- Less flexible
3)
- Extravascular haemolysis
- Normally the biconcave shape of RBCs allow them to escape the splenic sinusoids but spherocytes can’t so they are removed early by the spleen
4) Splenectomy
Why can you become vitamin deficient after haemolytic anaemia, and what vitamins will you be deficient in?
- Vitamin B12, folic acid, iron deficient
- Because all these are necessary for RBC synthesis and in haemolytic anaemia, there is increased RBC turnover resulting in depletion of these vitamins
List some extrinsic oxidants
- Food - e.g. broadbeans
- Chemicals - e.g. napthalene
- Drugs - e.g. dapsone, primaquine
Where is the gene for G6PD usually carried, and so in whom does G6PD deficiency occur?
- On the X chromosome
- Hemizygous males and occasionally homozygous females
G6PD deficiency usually causes ….., severe ….. haemolysis as a result of ….. or exposure to an ….. …..
G6PD deficiency usually causes intermittent, severe haemolysis as a result of infection or exposure to an exogenous oxidant
Episodes of intravascular haemolysis are associated with the appearance of considerable numbers of …..
…..irregularly contracted cells
1) What are heinz bodies and why do they occur?
2) How do they differ from Howell-Joly bodies?
1) Round inclusions that occur due to haemoglobin denaturing. They are removed by the spleen, leaving a defect in the cell
2) You can get more than one Heinz body in one cell, unlike Howell-Joly bodies
Give 2 causes of spherocytosis
- Hereditary Spherocytosis
- Autoimmune Haemolytic Anaemia
What is the pathophysiology of acute haemolytic anaemia?
- Production of antibodies against RBC antigens
- The immunoglobulin bound to the RBC is recognised by splenic macrophages, which removes parts of the CSM, leading to spherocytosis
- The combination of rigidity, antibody recognition and complement recognition on the RBC CSM by splenic macrophages by splenic receptors also leads to removal of the red cells from circulation by the spleen
3 ways to diagnose autoimmune haemolytic anaemia?
- Finding spherocytes and an increased reticulocyte count
- Detecting immunoglobulin on the RBC CSM
- Detecting antibodies to RBC antigens or other antibodies in the plasma
2 treatment methods for autoimmune haemolytic anaemia?
- Corticosteroid and other immunosuppressive agents
- Splenectomy for severe cases
