3. Anaemia and polycythaemia Flashcards
What is anaemia?
- Reduction in the amount of haemoglobin in a given volume of blood
- RBC and PCV/Hct usually also reduced
Why can’t anaemia resulting from an increase in plasma volume persist in a healthy person, but can in a sick patient?
- Excess fluid excreted when healthy
* Fluid retention possible in sick patients, which lowers the Hb
What are the mechanisms of anaemia?
- Reduced production of red cells/Hb in the bone marrow
- Loss of blood from the body
- Reduced survival in the circulation
- Pooling of red cells in a very large spleen
What can reduce the synthesis of haem?
- Iron deficiency
- Acute/chronic inflammation - delivery of iron from the bone marrow macrophage to the developing red cell is interfered with
Which inherited defect can lead to a reduced synthesis of globin?
Thalassaemia
What are the common causes of microcytic anaemia?
- Defect in haem synthesis
- Defect in globin synthesis
- Iron deficiency
What are the causes of macrocytic anaemia?
- Lack of vitamin B12 or folic acid
- Abnormal haemopoeisis
- RBC precursors continue to synthesise haemoglobin and other cellular proteins
- Red cells fail to divide normally - end up larger than normal
- Megaloblastic erythropoiesis - delay in maturation of the nucleus, while the cytoplasm continues to mature (nucleocytoplasmic dissociation)
- Premature release from bone marrow - reticulocytes are about 20% larger
- Drugs
- Liver disease and ethanol toxicity
- Major blood loss - reticulocytes increased
- Haemolytic anaemia - reticulocytes increased
What is a megaloblast?
- Abnormal bone marrow erythroblast
* Larger than normal and shows nucleocytoplasmic dissociation
How can you detect megaloblastic anaemia?
- Peripheral blood features
* Bone marrow examination more accurate
What are the causes of normochromic anaemia?
• Peptic ulcer, oesophageal varices, trauma
• Failure of production of red cells:
- iron deficiency
- renal failure
- bone marrow suppression/failure - cancer treatment
- bone marrow infiltration - cancer metastases
• Hypersplenism
What is haemolytic anaemia?
- Shortened survival of red cells
- Bone marrow cannot compensate
- Can result from intrinsic abnormality or extrinsic factors
- Can be inherited or acquired
What can inherited and acquired haemolytic anaemia result in?
- Inherited - abnormalities in the cell membrane, haemoglobin or enzymes
- Acquired - microorganisms, chemicals or drugs can damage the red cell membrane, or whole cell
What is the difference between intravascular and extravascular haemolysis?
- Intravascular - very acute damage to the red cell
* Extravascular - defective red cells are removed by the spleen
What happens to red cells if there is an abnormal cell membrane or haemoglobin or a defect in the glycolytic pathway
They can burst
How does Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency affect red cells?
- G6PD is an enzyme involved in the pentose phosphate pathway
- Metabolic parallel to glycolysis that generates NADPH and pentoses
- Only source of reduced glutathione in red cells
- G6PD offers protection to red cells from oxidising free radicals
- In people with G6PD deficiency, risk of haemolytic anaemia in states of oxidative stress
- Usually causes intermittent, severe intravascular haemolysis
- Haemoglobin is denatured and forms round inclusions - Heinz bodies (can get more than one Heinz body in a cell)
- Heinz bodies are removed by the spleen, leaving a defect in the cell
How does pyruvate kinase deficiency affect red cells?
- Pyruvate kinase is involved in the last stage of glycolysis
- Deficiency => cell with decreased energy
- Can’t synthesise ATP - cell dies
When should you suspect haemolytic anaemia?
- Unexplained (normochromic and either normocytic or macrocytic)
- Evidence of morphologically abnormal red cells
- Evidence of increased red cell breakdown (increased lactate DH, increased unconjugated bilirubin)
- Evidence of increased bone marrow activity
What does jaundice in sickle cell anaemia reflect?
Blood cell breakdown
What can increased bilirubin excretion in children with haemolytic anaemia lead to?
Gall stones
What is hereditary spherocytosis?
- Haemolytic anaemia or chronic compensated haemolysis
- Resulting from an inherited instrinsic defect of the red cell membrane
- Loss of membrane in the spleen
- Become more spherical - trapped in spleen - removed by splenic macrophages (extravascular haemolysis)
- Bone marrow responds - increased output - polychromasia + reticulocytosis
- Still have increased red cell breakdown - subject to jaundice and gall stones
How can hereditary spherocytosis be treated?
- Splenectomy in severe cases
- Good diet to avoid secondary folic acid deficiency
- Folic acid tablet daily
Who does G6PD deficiency usually affect?
- Gene is on the X chromosome
* So usually hemizygous males, but occasionally
What is autoimmune haemolytic anaemia?
- Production of autoantibodies directed at RBC antigens
- The immunoglobin bound to the red cell membrane is recognised by splenic macrophages
- These remove parts of the red cell membrane
- Spherocytosis
What is it about the spherocytes that lead to their removal by the spleen?
- Immunoglobin can also have complement components bound
- They are less flexible than normal red cells
- The combination of cell rigidity and recognition of antibody and complement on the surface leads to removal
How can you diagnose spherocytosis?
• Finding spherocytes and an increased reticulocyte count
• Detecting immunoglobin (with our without complement)
on the red cell surface
• Detecting antibodies to red cell antigens, or other autoantibodies in the plasma
How can spherocytosis be treated?
- Corticosteroids and other immunosuppressive agents
* Splenoctomy for severe cases
What are 2 of the causes of spherocytosis?
- Hereditary Spherocytosis
* Autoimmune haemolytic anaemia
How will haemolysis affect urine?
- Dark urine
* Lots of bilirubin
What is polycythaemia?
- Abnormally increased concentration of haemoglobin in the blood
- Reduction of plasma volume or increase in red cell numbers
A patient has polycythaemia and noticed blood in his urine, what is the likely cause?
Renal carcinoma
