Haematology In Systemic Disease Flashcards
What could cause haemopoietic changes in systemic disease?
Often multifactorial. You need to look at the cause, complications and treatment.
What is anaemia of chronic disease?
Diserythropoiesis (Not enough red blood cells made).
What can cause anaemia of chronic disease?
- Iron dysregulation: iron not released for use in bone marrow
- The marrow shows a lack of response to erythropoietin
- Reduced lifespan of red cells.
What can cause reduced erythropoiesis?
- Empty bone marrow - unable to respond to stimulus from EPO e.g. after chemotherayp or toxic insult such as parvovirus or in aplastic anaemia.
- Marrow infiltrated by cancer cells or fibrous tissue (myelofibrosis) means the normal haemopoietic cells are reduced.
When is anaemia of chromic disease seen?
Renal disease, RA, SLE (lupus), IBD (Ulcerative colitis or crohn’s), Chronic infections.
What is a functional iron deficiency?
Sufficient iron in the body but not available to the developing erythrocytes cells.
What happens to iron?
Macrophages ‘eat’ old senescent RBCs and recycle iron.
Iron recycling is the main source of iron for new RBCs
Small amount of iron is absorbed from gut.
BUT, erythrocyte islands with ‘nursing’ macrophages. (Iron gets stuck in macrophages.
Why does iron get stuck in macrophages?
Hepcidin - Inhibit movement of iron from cells into blood by inhibiting ferroportin.
Hepcidin is produced by the liver and this degrades ferroportin so that iron can get in but not out of cells.
This means than iron cannot be released from macrophages or expected out into the blood.
Ferroportin diegredation also prevents iron absorbtion from the gut.
How is hepcidin regulated?
- By inflammatory cytokines.
- Transferrin receptor
- HFE (human haemochromatosis protein)
How does inflammation lead to anaemia?
Produce more cytokines (IL-6) so, this increases the amount of hepcidin produced which keeps iron in cells.
Degrades ferroportin.
Decreased iron released from RES and decreased absorbtion from the gut.
Inhibition of erythropoiesis in bone marrow.
(Cytokines also inhibit the kidney from responding to EPO).
Cytokines also effect RBCs produced so reduced lifecycle. So, anaemia.
Anaemia of chronic renal failure?
Reduced erythropoietin reduction due to damage to kidneys
Often associated with raised cytokines
Reduced clearance of hepcidin
Increased hepcidin production due to inflammatory cytokines.
Dialysis damage due to RBCs and loss due to bleeding.
Reduced lifespan of RBCs as a direct effect of uraemia - Also inhibit megakaryocytes leading to low platelet count.
What investigations would be done on people with chronic renal failure?
Ferritin is the best test of what iron stores are doing.
It is produced by the liver and is an inflammatory protein so, may not be the most accurate in chronic disease.
Now use CHr - if this is low there is not enough iron stores.
Elevated CRP as chronic disease / Inflammation.
Also often have normocytic normochromic or microcytic anaemia.
Treatment of anemia of chronic disease?
Treat the underlying condition
If associated renal failure - recombinant human erythropoietin (must have all bulding blocks e.g. Iron and Vit B12 / folate
Ensure Vit B12 folate and iron stores are adequate.
Transfuse - if all else fails and patient is symptomatic.
Management of anaemia of chromic renal failure?
Use reticulocyte Hb content (CHr) to assess functional iron deficiency.
Give iron if ferritin under 200um/L or CHr low then give Iron.
Iron given as IV as absorbtion is impaired (…Hepcidin)
Haematological changes in Renal disease?
Low Hb:
- ARF / ACD
- Blood loss
- Haematinic causes
High Hb:
- Post renal transplant
- Renal tumour
Low WBCs:
- Immunosuppression pops renal transplant drugs
- Marrow infiltration eg in myeloma
High WBCs:
- Inflammation
- Connective tissue disease
- Infection
- Drugs: steroids
Low platelet:
- Direct effect of uremia on platelet production
- Drugs
- haemolytic uraemic syndrome
High platelet:
- Reactive
- Bleeding
- Iron deficiency
