Anaemia Flashcards
What is macrocytic anaemia?
Red blood cells with a MCV that is greater than normal.
What are the two classification of macrocytic anaemia? What are the differences?
Megaloblastic: caused by VB12 and folate deficiency
Non-megaloblastic: caused by alcoholism, liver damage, myelodysplastic syndrome
How does VB12 deficiency affect folic acid?
VB12 binds to intrinsic factor secreted by gastric parietal cells and is absorbed in the terminal ileum.
VB12 also acts as a coenzyme for the production of folic acid.
Both are required for DNA synthesis, which becomes impaired.
How does VB12 and folate deficiency cause macrocytic anaemia?
Both are required for DNA synthesis, which becomes impaired. As RNA synthesis carries on as normal, there is an increase in cytoplasmic contents in the RBC –> macrocytic anaemia.
What is pernicious anaemia?
Pernicious anaemia is an autoimmune condition where antibodies attack intrinsic factor, impairing VB12 uptake thus causing VB12 deficiency.
What drugs can cause VB12 deficiency?
Metformin
Proton pump inhibitors
Nitrous oxide
How does metformin cause VB12 deficiency?
Metformin affects calcium-dependent membrane surface receptors. Calcium is required for VB12 uptake.
How do PPIs cause VB12 deficiency?
Gastric acid is involved in dissociating VB12 from food proteins. Drugs that lower gastric acid may lower VB12 deficiency.
How does nitrous oxide cause VB12 deficiency?
Inactivates VB12 synthesis and impairs its ability to act as a cofactor for methionine. Cobalamin (VB12) is a methionine synthase.
What drugs cause folic acid deficiency?
Methotrexate
Trimethoprim
Phenobarbitone
Phenytoin
How do methotrexate and trimethoprim cause folic acid deficiency?
Inhibits dihydrofolate reductase, which interferes with folic acid synthesis, and in turn interfering with DNA, RNA and protein synthesis
How do phenobarbitone and phenytoin cause folic acid deficiency?
Decrease mucosal uptake of folic acid
What tests should be done to confirm diagnosis of macrocytic anaemia?
Serum VB12 (<200pg/mL) Bilirubin: rules out haemolytic anaemia Reticulocyte: rules out acute blood loss TSH Liver function tests Copper levels Intrinsic factor
What is the treatment for VB12 deficiency?
PO: VB12 supplement
IM injection: Hydroxycobalamin (Neo-B12)
When is IM VB12 best?
Pernicious anaemia/altered GI anatomy: patients cannot absorb VB12 orally due to lack of intrinsic factor thus parenteral route is preferred.
What is the treatment of folate deficiency?
Oral folic acid
Why should VB12 be administered before folic acid?
Folic acid may reverse haematological abnormalities associated with VB12 deficiency, but does not treat the neurological symptoms of VB12 deficiency. Thus, may mask symptoms of VB12 deficiency and cause neurological damage.
What should be monitored in a patient with macrocytic anaemia?
Markers of haemolysis (lactate dehydrogenase, bilirubin) to exclude haemolytic origin of MA. Reticulocyte count Haemoglobin, haematocrit Serum folate and VB12 Neurological assessment
Lifestyle advice for patients with macrocytic anaemia?
Increase VB12 in the diet:
- meats, fish, eggs
- fortified cereals
- leafy green veg
What is the pathophysiology of anaemia of chronic disease?
Low iron: body limits available iron for invading microbes.
Hepcidin is produced in response to exposure to bacterial antigens. It causes iron to be retained within cells causing anaemia.
What is the pathophysiology of anaemia in CKD?
CKD causes damage to the kidneys and thus impairs EPO production, which causes anaemia. Additionally, CKD is inflammatory, and may bring about anaemia via ACD.
What lab tests are performed to confirm A-CKD?
Iron status
- Serum iron
- Total Iron Binding Capacity
- Serum Ferritin
- Transferrin saturation
What are the treatment options for A-CKD?
Iron supplementation
(oral, IV)
Erythropoiesis stimulating agents (oral, IV)
Erythropoiesis Stimulating Agents MOA?
Stimulates division and differentiation of erythroid progenitor cells to increase erythrocyte concentration.
