Flashcards in MEH - Anaemia And Polycythemia Deck (23):
How are red blood cells removed from the circulation?
Filtered out by reticule-endothelial system in spleen
Give some reasons why reduced erythropoiesis may occur
- chronic kidney disease may stop kidney producing erythropoietin
- bone marrow may be 'empty' due to chemotherapy, toxic insult (eg parvovirus) or aplastic anaemia
- marrow infiltrated by cancer cells or fibrous tissue means normal haematopoietic cells are reduced in number
What may cause 'anaemia of chronic disease'?
- inflammatory conditions eg. Rheumatoid arthritis, ulcerative colitis, Crohns
- chronic infection eg. TB
What are the features of anaemia of chronic disease?
- iron stored in macrophages not released into bone marrow
- circulating red cells have reduced lifespan
- marrow shows lack of response to erythropoietin
- raised CRP and ferritin levels
How could a chromosomal abnormality lead to progressive anaemia?
Abnormal clones of marrow stem cells mean that red cells are defective and large, so macrocytic anaemia develops. As the cells are defective, they are prematurely destroyed by the RES and progressive anaemia develops.
How does vitamin B12 travel from the stomach to bone marrow?
- humans eat food of animal origin which contains B12
- B12 combined with glycoproteins intrinsic factor (IF) produced by parietal cells in stomach
- IF-B12 complex binds in the ileum, leading to absorption of B12 and destruction of IF
- in portal blood, B12 is bound to plasma protein transcobalamin which delivers it to bone marrow and other tissues
Vitamin B12, IF, transcobalamin and ileum binding space can all be deficient
Where is folate absorbed in the intestine?
Duodenum and jejunum
What happens to dietary folates once they are absorbed?
They are converted into one compound, methyltetrahydrofolate, which circulates in the plasma and is needed throughout the body for DNA synthesis.
Give some causes of folate deficiency
- dietary deficiency
- proximal small bowel disease
- drugs which inhibit dihydrofolate reductase
Why are the symptoms of anaemia usually fairly mild in sickle cell disease?
HbS readily gives up oxygen in comparison to HbA
What can trigger a worsening of sickle cell symptoms?
- if people get cold
How does thalassemia cause anaemia?
Relative excess of insoluble aggregates of alpha chains contributes to defective nature of red cell. This means many maturing erythroblastosis are destroyed within the bone marrow and there is excessive destruction of mature red cells in the spleen
Why do patients with thalassaemia have enlarged spleens?
Extramedullary haemopoiesis occurs in an attempt to compensate for reduced red cells, but results in enlarged spleen, liver and expansion of haemopoiesis into the bone cortex (causing skeletal abnormalities)
Why do many thalassaemia patients die of iron overload?
- excessive absorption of dietary iron due to ineffective haematopoiesis
- repeated blood transfusions are required to treat anaemia and cause excess iron build up
Give some examples of ways that red blood cells can become damaged
- mechanical damage (heart valves, vasculitis, 'MAHA', disseminated intravascular coagulopathy
- burns (heat damage)
- drowning (osmotic damage)
Give some examples of red cell enzyme defects which can lead to anaemia
- G6P dehydrogenase deficiency
- pyruvate kinase deficiency
Why may anaemia due to blood loss not be immediately obvious?
May be due to chronic blood loss which occurs slowly over time, eg gastric ulceration, gastric cancer, colon cancer, excessive menstruation, bladder cancer
What is autoimmune haemolytic anaemia?
Antibodies bind to the red cell membrane proteins
Give some examples of myeloproliferative disorders
- essential thrombocythaemia
- polycythaemia vera
What is polycythaemia?
A group of varied disorders with an increase in circulating red cells, typified by a persistently raised haematocrit
What is erythrocytosis?
Increase in the concentration of red blood cells (can be relative to plasma volume, or absolute)
Why may erythrocytosis be 'physiologically appropriate'?
In response to tissue hypoxia