Anaemia Flashcards
What is anaemia?
Reduced total cell mass
What are the normal Hb values?
Male <130g/L
Female <120g/L
How is Hb concentration measured?
Burst the red cells and stabilise. Measure the optical density - the more red, the more absorbed, more Hb
Other than Hb what else can be measured to determine red cell count?
Haematocrit
When are Hb and Hct not useful?
Rapid blood loss
Haemodilution
Define reticulocytosis
Normal response to anaemia is to produce more red cells
Describe reticulocytes
- red cells that have just left the bone marrow
- remnants of RNA, stain purple
- blood film appears polychromatic
- up regulation takes a few days
- marker of bone marrow function
Name the two key causes of anaemia
- decreased production
- increased loss/destruction
What can cause decreased production of red blood cells?
Hypoproliferation - reduced erythropoiesis
Maturation abnormality - erythropoiesis present but ineffective
Name the two subtypes of maturation abnormality
Cytoplasmic defect (impaired haemoglobinisation) Nuclear defect (impaired cell division)
What causes increased loss/destruction of red blood cells?
Bleeding/Haemolysis
How can anaemia be described in terms of mean cell volume?
Microcytic
Macrocytic
How is haemoglobin synthesised?
Iron from blood enters mitochondria
Fe3+ moves out of mitochondria and binds to protophorphyrin to form haem
Haem binds to globin subunits
How does microcytic anaemia arise?
Hb is synthesised in the cytoplasm and requires specific building blocks. If one is missing the cells will continue to divide but will lack certain substances - small
What do microcytic anaemia red blood cells look like?
Hypochromic due to little Hb
State the causes of microcytic anaemia
Thalassemia - globulin subunits Anaemia of chronic disease Iron deficiency Lead poisoning - porphyrin synthesis Sideroblastic - porphyrin synthesis
How can you calculate the average Hb content in a solution?
Litres/2
What transports iron?
Transferrin
What stores iron?
Ferritin
What should the saturation of transferrin be?
30-40%
What is the best measure of iron?
Ferritin
What can cause a rise in ferritin?
Inflammatory disease
Name the causes of iron deficiency
Diet
Loss of iron - blood loss
Malabsorption (coeliac, achlorhydria)
Where is iron absorbed?
Proximal small bowel (jejunum and duodenum)
Define macrocytosis
Reduction in red cells that have a larger volume
What are the two key types of macrocytic anaemia?
Genuine
Spurious
Name the two types of genuine macrocytosis
Megaloblastic
Non-megaloblastic
What is a megaloblastic cell?
An abnormally large nucleated red cell precursor with an immature nucleus
Describe megaloblastic anaemia
Lack of red cells due to defects in DNA synthesis and nuclear maturation in developing precursor cells in the marrow.
Reduced division, more apoptosis
Why do megaloblastic cells still increase in size?
There is normal cytoplasmic development and Hb accumulation
State the causes of megaloblastic anaemia
B12 deficiency
Folate deficiency
Drugs
Inherited disorders
How is B12 handled by the body?
Binds to rapid binder proteins in stomach
Secretion of intrinsic factor
Binds to IF to form a complex and travels to small bowel
Absorbed in ileum and enters blood
Binds to transcobalamin
How long will B12 stores last?
2-4 years
State the causes of B12 deficiency
Dietary
Stomach acid/intrinsic factor
Small bowel - bacteria overgrowth, coeliac, resection, IBD
Inherited disorder
What is pernicious anaemia?
Autoimmune condition with resulting destruction of gastric parietal cells and inability to secrete IF
How is pernicious anaemia treated?
IM B12 3 monthly
Where is folate absorbed in the body?
Jejunum
How long do folate supplies last?
4 months
What causes folate deficiency?
Diet
Malabsorption
Excess ultilisation - haemolysis, pregnancy, malignancy, drugs, exfoliating dermatitis
Name the clinical features of B12/folate deficiency
Anaemia, weight loss, diarrhoea, infertility, sore tongue, jaundice, developmental problems
What serious symptom can B12 deficiency cause?
Neurological - subacute combined degeneration of the cord
Name two auto-antibodies that can be measured in suspected pernicious anaemia
Anti-gastric parietal cell
Anti- intrinsic factor
How is anaemia treated?
B12 injection
Folic acid tablets
Red cell transfusion if life threatening
State the causes of non-megaloblastic anaemia
Alcohol
Liver disease
Hypothyroidism
Marrow failure
What is supious macrocytosis?
Volume is normal but MCV is measured as high
What can cause supious macrocytosis?
Reticulocytosis
Cold Agglutinins
What is meant by cold agglutinins?
Abnormal protein causes clumping of RBC in infections and cancers. Usually extraordinarily high MCV and accurate sample obtained by warming blood
Why does jaundice occur in anaemia?
Ineffective erythropoiesis due to intramedullary haemolysis - breakdown occurs in the bone marrow and bilirubin is released
State the causes of normocytic anaemia
Marrow failure Hypometabolic Marrow infiltration Renal impairment Chronic disease
How does inflammation lead to anaemia?
Activates monocytes and T cells causing release of cytokines
What are the effects of cytokine release leading to anaemia?
Increase hepcidin
Inhibition of erythropoietin release
Inhibition of erythroid proliferation
Increased red cell destruction
When will anaemia of chronic disease be microcytic?
If the predominant mechanism is through hepcidin leading to reduced release of iron
What is the key difference between iron deficiency anaemia and anaemia of chronic disease?
Ferritin will be normal/raised in anaemia of chronic disease
