Anaemia Flashcards
What are the cells that form in the process of erythropoiesis?
Multipotent haemopoietic stem cell
Common myeloid progenitor cell
Early normoblast
Intermediate normoblast
Late normoblast
Reticulocyte
Erythrocyte
Where does erythropoiesis take place?
Bone marrow
What process occurs within in intermediate and late normoblast?
Haemoglobin accumulation
What process occurs as a late normoblast becomes a reticulocyte?
Ejection of the nucleus
How many red blood cells are produced daily by bone marrow?
10^12
What hormone regulates erythropoiesis?
Erythropoietin
Where is 90% of erythropoietin produced?
Kidneys
Erythropoietin production is stimulated by what?
Hypoxia
What initial effect does erythropoietin have?
Increases the number of erythroid progenitor cells
What happens to the erythroid progenitor cells?
They proliferate, differentiate and produce Hb
What is another name for erythropoietin?
EPO
What sort of feedback does red blood cell production as a result of EPO production have on the kidneys?
Negative feedback
What is the effect of the negative feedback exerted on the kidneys by increase RBC production?
Decreased EPO production
What chronic condition can cause decreased EPO production?
CKD
As a result of decreased EPO production, CKD can lead to what presentation?
Anaemia
What sort of molecule is haemoglobin?
Tetrameric
How many pairs of globin chains make up haemoglobin?
2 pairs of identical chains
What does each globin chain have?
Its own harm group
How many configurations can haemoglobin exist in?
2
What are the two configurations of haemoglobin?
High affinity structure
Low affinity structure
What peptide chains make up adult haemoglobin?
2 x α-chains + 2 x β-chains
What peptide chains make up foetal haemoglobin?
(2 x α-chains) + (2 x γ-chains)
What are the functions of haemoglobin?
Carriage of O₂ form lungs to tissues
Carriage of CO₂ from tissues to lungs
Iron is essential for the formation of which molecules?
Hb
Myoglobin
Cytochromes
What is the role of myoglobin?
Facilitates oxygen use and storage in muscles
Problems with what aspects of the RBC lifecycle can lead to anaemia?
Erythropoiesis
Haemoglobin synthesis
Membrane structure
Metabolism
Intravascular haemolysis
Blood loss
Removal
What types of problems can lead to problems creating Hb?
Mutations in the genes encoding Hb proteins
Lack of iron
Deficiency in molecules required for DNA synthesis
What type of anaemia can mutations in the genes encoding globin proteins lead to?
Haemolytic anaemia
Which conditions can occur as a result of mutation of proteins encoding globin proteins?
Thalassaemia
Sickle cell disease
Deficiency in which molecules required for DNA synthesis can lead to anaemia?
Vitamin B12
Folate
What shape is a regular red blood cell?
Biconcave
What is the average diameter of a red blood cell?
8 µm
What property of red blood cells is required for them to be able to fit through blood vessels?
Flexibility
What type of anaemia can occur as a result of abnormal red blood cell membrane structure?
Haemolytic anaemia
What can lead to abnormal red blood cell membrane structure?
Abnormalities of membrane proteins
What conditions result in abnormal red blood cell membrane structure?
Hereditary spherocytosis
Hereditary eliptocytosis
What are the 2 main metabolic pathways in red blood cells?
Embden Meyerhof Pathway:
- Glucose metabolised to lactate and ATP generated
Hexose Monophosphate Pathway:
- Glucose-6-phosphate metabolised and NADPH generated
What type of anaemia do abnormalities of metabolism lead to?
Haemolytic anaemia
Which metabolic abnormalities can lead to anaemia?
G6PD deficiency
Pyruvate kinase deficiency
What system is responsible for the removal of damaged or antibody coated red blood cells?
The reticuloendothelial system
What organ makes up the majority of the reticuloendothelial system?
Spleen
Enlargement of which organ can lead to anaemia?
Spleen
What can cause an enlarged spleen?
Liver disease
Malaria
Malignancy
How does an enlarged spleen lead to anaemia?
Increased removal of red blood cells
Are abnormal FBC results always indicative of an underlying haematological disorder?
No
How should abnormal FBC results be interpreted?
In light of clinical context and any previous FBC results (if known)
How is anaemia defined on the basis of an FBC?
Reduced haemoglobin concentration in the blood
What is a low haemoglobin count in an adult male?
<130g/L
What is a low haemoglobin count in an adult female?
<115g/L
What is a low haemoglobin count in a child?
<110g/L
What is a low haemoglobin count in a newborn?
<150g/L
What cardiovascular adaptations occur as a result of anaemia?
Increased cardiac output
Increased stroke volume
Tachycardia
What other physiological adaptations occur as a result of anaemia?
Shift in the Hb-oxygen dissociation curve
Increased erythropoiesis (EPO stimulated)
The extent to which physiological adaptations occur as a result of anaemia depends upon what?
Speed of onset
Severity
Age
What are the symptoms of anaemia?
SoB
Weakness/lethargy
Palpitations
Headaches
Angina, hearty failure, clarification, confusion
What are the signs of anaemia?
Pallor
Tachycardia
Systolic flow murmur
Heart failure
What are some specific signs of anaemia?
Koilonychia
Glossitis
Leg ulceration
Angular stomatitis
When evaluating anaemia, which factors should be considered?
Reticulocyte count
Mean cell volume
Mean cell haemoglobin
White cell and platelet count
What is a normal reticulocyte count?
0.5-1.5% of total red cells
What does an absence of an appropriate number of reticulocytes suggest in the setting of anaemia?
RBC are not being produced appropriately
When evaluating anaemia, which count should be considered first (after Hb concentration)?
Reticulocyte count
If there is an appropriate number of reticulocytes, what should be considered next?
Evidence of haemolysis
If there is evidence of haemolysis, what should be done?
Look for the cause of the haemolysis
If there is no evidence of haemolysis, what should be looked for?
Evidence of bleeding
Other that bleeding and haemolysis, what else can cause anaemia with reticulocytosis?
Splenic sequestration
What are some hereditary causes of haemolysis?
Abnormalities of cell membrane
Red cell enzymopathies
Abnormal haemoglobin
What are the types of acquired haemolysis?
Alloimmune
Autoimmune
Non-immune
When screening for haemolysis, what should be looked for on a blood film?
Spherocytes
Red cell fragments
Polychromasia
What else should be looked for during a haemolysis screen?
DCT
Bilirubin
LDH
Haptoglobin
Reticulocyte count
Urinary haemosiderin
What should be assessed next if there is an inappropriate number of reticulocytes?
Mean cell volumn
What can microcytic anaemia?
Thalassaemia Anaemia of chronic disease Iron deficiency Lead poisoning Sideroblastic anaemia
What tests should be conducted to investigate iron deficiency?
Ferritin
Low serum iron
What can cause iron deficiency?
Inadequate intake
Increased loss from gut
Excessive use
How can iron deficiency be treated?
Dietary advice
Oral iron supplements
Intramuscular iron injections
Intravenous iron
Transfusion (if cardiac compromise is imminent)
How much of dietary iron is absorbed?
10-20%
Where are iron supplements absorbed?
Duodenum and jejunum
What can inhibit iron absorption?
H2 blockers, PPIs, tetracyclines
What should happen in iron deficiency anaemia once a oral iron is administered?
Increase in Hb by 2g/dL in 3 weeks
Increased MCV
Increased serum ferritin
What can cause macrocytosis with hypersegmented neutrophils?
B12 deficiency
Folate deficiency
Myelodysplasia
How long does it take to become B12 deficient?
Many years
Who is prone to B12 deficiency?
Vegans/vegetarians
What is a gastric cause of B12 deficiency?
Pernicious anaemia
What is pernicious anaemia?
Autoantibodies to intrinsic factor required to absorb B12
How long does it take to become folate deficient?
Months
What can cause folate deficiency?
Diet
Malabsorption
Sickle cell disease
Co-trimoxazole
What should be investigated in microcytic anaemia?
B12/folate
TFT/LFT
Immunoglobulins
What can cause normocytic anaemia?
Anaemia of chronic disease
Mixed iron and B12/folate deficiency
Bone marrow failure
What is anaemia of chronic disease associated with?
Chronic inflammation/infection
Describe the pathophysiology of anaemia of chronic disease
Cytokines driven reduction in serum iron
Reduction in EPO production
Reduction in RBC life span
What MCV does anaemia of chronic disease cause?
Normocytic/microcytic
In anaemia of chronic disease, what are ferritin levels?
Normal or raised
In anaemia of chronic disease, what are serum iron levels?
Reduced
