Anaemia Flashcards
What is anaemia?
inability of body to deliver enough oxygen to tissues?
can be due to no of red cells, or carrying capacity of red cells
When is reduced erythropoiesis seen? give examples
Chronic kidney disease- EPO not produced in response to hypoxia
Empty bone marrow- e.g after chemotherapy, parvovirus
Marrow infiltrated by cancer cells or fibrous tissue so normal haemopoietic cells reduced
What is dyserythropoiesis? When is it seen and what are its features?
‘anaemia of chronic disease’
seen in:
- inflammatory conditions e.g UC, Crohn’s
- chronic infection e.g. tb
- bronchiectasis
features;
iron stored in macrophages not released for use in bore marrow, marrow shows lower response to EPO, can lead to any kind of anaemia
clinical clues are raised CRP and ferritin
What are myelodysplastic syndromes?
- normally seen in elderly
- production of abnormal clones of marrow stem cells
- defective, large red cells produced (macrocytic anaemia)
RES destroys prematurely so progressive anaemia develops and there is acute leukaemia in a high proportion of cases.
treated by chronic transfusion of red cells in a lot of patients
What are some potential causes for haemoglobin abnormalities?
- lack of iron (functional deficiency in AoCD)
- vit B12/folate deficiency (DNA synthesis)
- gene mutations (thallasemia/scd)
How does folate/b12 deficiency cause anaemia?
Both B12 and folate necessary for nuclear divisions and nuclear maturation. When deficient, nuclear maturation and cell divisions lag behind cytoplasm development. This leads to large red cell precursors with inappropriately large nuclei and open chromatin. The mature red cells are also large leading to a macrocytic anaemia
How is b12 delivered to tissues?
Vitamin B12 is synthesised by microorganisms; humans acquire B12 by eating foods of animal origin, leading to a large excess of B12 in the diet of meat eaters. B12 is combined with the glycoprotein intrinsic factor (IF) produced by parietal cells in the stomach. IF-B12 complex then binds in the ileum, leading to absorption of B12 and
destruction of IF. In the portal blood B12 is bound to the plasma protein transcobalamin which delivers B12 to the bone marrow and other tissues.
How can b12 deficiency arise?
dietary deficiency- Vegan diet; poor diet
Pernicious anaemia – an autoimmune disease affecting gastric parietal cells causing lack of intrinsic factor; gastrectomy
disease of the terminal ileum- e.g. Crohn’s disease; ileal resection; tropical sprue (as this is where it is absorbed)
Transcobalamin- congenital deficiency
How is folate absorbed?
Folate present in most foods, yeast, liver and leafy greens especially rich source. Absorption occurs in the duodenum and jejunum. Dietary folates are all converted to one compound, methyltetrahydrofolate, methylTHF. MethylTHF circulates in plasma and is needed throughout the body for DNA synthesis.
How can folate deficiency arise?
-Dietary deficiency
-increased use as seen in pregnancy,
-increased erythropoiesis eg haemolytic anaemia, severe
skin disease – psoriasis, exfoliative dermatitis
-problems with duodenum and jejunum: proximal small bowel disease eg coeliac disease, Crohn’s disease
-methylTHF : drugs which inhibit dihydrofolate reductase enzyme (eg Methotrexate)
-Others: alcoholism (multifactorial); urinary loss of folate in liver disease and heart failure; other drugs eg anticonvulsants
Aside from macrocytic anaemia, what are the issues associated with folate/b12 deficiency?
As deficiency progresses a pancytopenia can develop ie low platelets and neutrophils too
Vitamin B12 (not folate) deficiency is also associated with
neurological disease – focal demyelination affecting the spinal cord, peripheral nerves and optic nerves. Depression and dementia can also develop.
What are the clinical problems seen in Sickle Cell disease?
- aplastic, haemolytic anemia
- organ damage due to vaso occlusive sickle cell crises (cold, infection, stress triggers)
What kind of anaemia does thalassemia present with?
-hypochromic, microcytic red cells
What are compensatory mechanisms seen in thalassemia?
- extramedullary haemopoiesis- splenomegaly, hepatomegaly, skeletal abnormalities
- EPO stimulation
- iron overload (excessive absorption and deposition)
treatment is by transfusions, iron chelation, folic acid, stem cells in some.
How may chronic blood loss lead to anaemia?
e.g= cancer
may present as microcytic anaemia from iron deficient state. unexplained microcytic anaemia requires investigation.
