L11: Heamatological changes in systemic disease Flashcards
What can cause the blood to change in systemic disease?
Multifactorial
- Underlying physiological or external cause
- Complications of disease
- Treatment- adverse effects
How can erythropoietin result in anaemias?
Reduced or dysfunctional erythropoiesis
- -> lack of response in haemostatic loop
- -> Bone marrow unable to respond to EPO
- -> Other factors not present
What is the role of erythropoietin?
Hormonal control of erythropoiesis
Low blood O2–> Kidney hypoxia–> ↑ EPO production–> Bone marrow–> ↑RBC production–> high blood O2
What are the three contributors in anaemia of chronic disease?
Caused by inflammatory cytokines-
- Iron dysregulation-> available iron not released for bone marrow use
- Lack of response to EPO in bone marrow
- Reduced lifespan of RBC
What is meant by functional iron deficiency?
Sufficient iron in the body but not available to the developing erythroid cells
What is the main source of iron in the body?
Recycled iron from old RBC
Require ferroportin
What is Hepcidin? What does it do? How is it regulated?
Peptide hormone released from the liver Degrade ferroportin -->Prevents absorbtion from gut -->Prevents release from macrophages HFE (homeostatic iron regulator), Transferrin receptors and inflammatory cytokines
How do chronic inflammatory conditions cause anaemia?
- Increased cytokines (IL-6), chemokines etc… released by immune cells
- Increase production of hepcidin by liver
- Inhibits ferroportin
- Decreased iron released from reticuloendothelial cells and absorption from gut
- Plasma iron reduced
- Inhibition of erythropoiesis in bone marrow
What are the causes of anaemia in chronic kidney disease (CKD)?
1- Reduced EPO –> due to kidney damage
2- Raised cytokines
3- Reduced clearance of hepcidin, increased hepcidin production due to inflammatory cytokines
4- Dialysis–> damage to RBC due to shear stress
5- Reduced lifespan of RBC–> uraemia (raised urea) (also inhibits megakaryocytes, low platelet count)
How is anaemia of chronic disease treated?
- Treat underlying condition
- If renal failure–> Recombinant human erythropoietin
- Ensure Vit B12 and Folate stores adequate
- Transfusion RBC if all else fails and patient symptomatic
What are the NICE guidelines on management of chronic kidney disease?
Reticulocyte Haemoglobin Content (CHr) to assess functional iron deficiency
Give iron if ferritin <200ug/L or CHr low
Iron given intravenously as problem with absorption
What are the haematological abnormalities in kidney disease?
Red blood cells
–> Anaemia (CKD, Blood loss, dietary, cancer)
–> Secondary polycythaemia (renal transplant, tumour, polycystic kidneys)
Neutrophils
–> Neutropenia (low) (Immunosuppression, post renal transplant, autoimmune kidney)
–> Neutrophilia (high) (inflammation, infection, drugs (steroid))
Platelets
–> Thrombocytopenia (low) (Uraemia inhibits production, drugs, haemolytic uraemic syndrome
–> High platelets (thrombocythemia) (inflammation, bleeding, iron deficiency)
What is Rheumatoid Arthritis?
Chronic immune mediated inflammatory condition
How is Rheumatoid Arthritis treated?
Pain relief usually NSAID
Disease Modifying Agents (DMARDs): corticosteroids, chemotherapy, monoclonal antibodies against cytokines (reduce inflammation)
How does Rheumatoid Arthritis cause anaemia?
Multifactorial
1- Anaemia of chronic disease
2- GI blood loss from NSAIDs and steroids
3- Autoimmune haemolytic anaemias