Anaemia Vit B12 And Folate Metabolism And Megaloblastic Anaemia Flashcards
What is anaemia?
Haemoglobin outside of the reference range for the normal
population
Haemoglobin carries oxygen
Symptoms: shortness of breath, tiredness, cardiac failure,
palpitations, headache
Signs: pallor, tachycardia, tachypnoea, hypotension
Other signs and symptoms specifically associated with
the cause of anaemia
What are specific signs of anaemia?
Iron deficiency
- koilonychia
- oesophageal webs
- angular stomatitis
Vit b12 deficiency
- glossitis
Thalassaemia
-abnormal facial bone development
What is the life of a red blood cell
Erythoropiesis and Hb synthesis in bone marrow
Cytoplasm goes blue to pink as it becomes more haemoglobinised
Peripheral RBCs circulate for ~120 days
Reticulo endothelial system removes RBCs - if not working properly the red cells not last the w120 days?
Why might anaemia develop?
Bone marrow
- reduced erythropoiesis
- dyserythropoiesis
- haemoglobin synthesis
Peripheral red blood cells
- structure (membrane) problems
- metabolism
-loss of red cells
Removal
- RE ssystem problems
Why might there be reduced erythropoiesis?
Lack of response to the haemostatic loop – eg in chronic kidney disease the kidney stops making EPO
- Empty bone marrow unable to respond to stimulus from EPO eg after chemotherapy or toxic insult such as parvovirus infection or in aplastic anaemia normal haemopoietic cells are reduced
- Marrow infiltrated by cancer cells or fibrous tissue (myelofibrosis) means the normal haemopoietic cells are reduced
Can be reduced for a number of reasons
Driven by erythropoeitin produced by kidney - low o2 levels
Stimulated bone marrow to produce more red dells
O2 levels increase
Chronic renal failure = anaemia
If bone marrow empty - wot produce enough
If by is infiltrated - may not be enough space for red cells to grow
What is dyserythropoiesis?
• Anaemia of Inflammation or anaemia of Chronic Disease
• Iron is not released for use in bone marrow
• reduced lifespan of red cells
• the marrow shows a lack of response to erythropoietin.
• Seen in: Renal disease, inflammatory conditions such as Rheumatoid arthritis, SLE, Inflammatory bowel disease (Ulcerative Colitis or Crohn’s), chronic infections
Cytokines lead to difficulty in released iron from macrophages so red cells don’t have enough
Myelodysplastic syndromes (MDS)
• Production of abnormal clones of marrow stem cells
Primary bone marrow disorders
Abnormal red cells - not allowed out into circulation
What are defects in Hb synthesis?
Deficiencies in essentials
Lack of iron: deficiency in Haem synthesis
◦ Iron deficiency
◦ Anaemia of chronic disease (functional lack of iron)
Lack of B12/folate: Deficiency in the building blocks for
DNA synthesis
◦ Megaloblastic anaemia Mutations in the proteins encoding the globin chains
◦ Thalassaemia
◦ Sickle cell disease
What are inherited defects in red cell membrane structure
Aren’t many structures in mature red cells - empty membrane - cytoplasm w/ Hb
Genetic changes in genes which code proteins for rbc memb which leads to structureal changes leading them to be taken out early
Hereditary spherocytosis - round
Hereditary eliptocytosis - eliptoid
Hereditary pyropoikilocytosis - change in shape and size, get stuck, some look abnormal and get taken out by reticuloendothelial system too quickly
Haemolytic anaemia
The cells are less legible and are damages more easily and break up or are removed more quickly from the circulation
What are acquired defects in red cell membrane structure
◦ Mechanical damage to red cells - cells taken out of circulation or break down in circulation
Heart valves - shared as they go through
Vasculitis
MAHA (microangiopathies) - blood clots form in small vessels - sheared ad they go through the clots
DIC – disseminated intravascular
coagulopathy
◦ Heat damage
Burns
◦ Osmotic change
Drowning
Do red cells make ATP?
Red cels make a bit of ATP to keep membrane working properly, 2 main pathways
Defects in these pathways can lead to problems in redox in he cells, abnormal oxidised problem leading to cells being taken out of circulation too quickly and lipid bilayer not being maintained properly
What are defects in red cel metabolism
Red cell enzyme defects can lead to anaemia
Best recognised are:
◦ Glucose-6-phosphate dehydrogenase
◦ Pyruvate kinase deficiency
How are excess red cells removed
The spleen removes damaged or defective red cells
In some conditions there’d cells dont look right
Cells in spleen and liver take them out and break them down
Excess of abnormal cels - taken out very quickly
It will do this in many of the causes of anaemia already covered eg membrane disorders, enzyme disorders, haemoglobin disorders
In Haemolytic anaemias (Session 5) red cells are destroyed more quickly as they are abnormal or damaged
This can occur within the blood vessels intravascular or outside
(within the RES macrophages in spleen. Liver, bone marrow)
extravascular
What is autoimmune haemolytic anaemia
In this condition autoantibodies (ie Immunoglobulin -Ig – protein
produced by own B lymphocytes) bind to the red cell membrane proteins
Cells in the RES recognise part of the antibody, attach to it and
remove it and the red cell from the circulation
Ab binds to red cells
Liver/spleen recognise this as abnormal
Removr rbc
Autoimmune
What is myelofibrosis?
Fibrotic marrow with little space for haemopoiesis Blood film shows red cells looking like tear drops
What is thalassaemia?
Hawmoglobinopathy Mutation in genes that code for globin chains Hb nabnormal Rbcs abnormal Cells removed very quickly Defect in Hb synthesis Body not able to make enough good red ells RE system problem
Erythropoiesis – expansion into other sites causes growth of liver and spleen, bone and sinus expansion