Pathophysiology of Anaemia Flashcards
1
Q
What are the requirements for normal RBC production?
A
- Drive (EPO)
- Recipe (genes)
- Ingredients (iron, B12, folate and minerals)
- Functional bone marrow
2
Q
What is transferrin (Tf)?
A
- Glycoprotein synthesised in hepatocytes that has 2 iron binding domains and delivers iron to all tissues
3
Q
What is Hepcidin?
A
- The ‘low iron’ hormone and reduces levels of iron in the plasma by binding to ferroportin and degrading it
- This reduces iron absorption and decreases iron release from the RES
- It is synthesised in the liver and requires HFE for its production
4
Q
What are the signs and symptoms of anaemia?
A
- General
- Pale skin
- Conjunctival pallor
- Tachycardia
- Raised RR
- Specific7
- IDA
- Kolionychia (spoon shaped nails)
- Atrophic glossitis (smooth tongue)
- Angular chelitis/stomatitis (red patches at corners of mouth)
- Brittle hair and nails
- Oesophageal web (Plummer Vinson Syndrome)
- Haemolytic anaemia
- Jaundice
- Splenomegaly
- Red urine in the morning (PNH)
- Pernicious anaemia (B12 deficiency)
- Peripheral neuropathy with numbness and parasthesia
- Loss of vibration sense or proprioception
- Visual changes
- Mood or cognitive changes
- IDA
5
Q
What are the causes of IDA?
A
- Insufficient dietary iron
- Increased requirement (i.e. pregnancy)
- Iron being lost (most common cause in adults, i.e. menstruation, slow bleeding from CRC)
- Inadequate iron absorption (mainly absorbed in the duodenum and jejunum, requries acid from the stomach to keep it in the soluble form - Fe2+, medications such as PPIs interfere, conditions like coeliac and Crohn’s also affect absoprtion)
6
Q
How is IDA diagnosed and treated?
A
- Transferring saturation = Serum iron/TIBC
- In IDA:
- Low serum ferritin (ferritin is the form that iron takes when it is deposited and stored in cells, released in inflammation)
- Hypochromic microcytic RBCs on blood film
- Treat is replacement with ferrous sulphate, ferrous gluconate and IV iron, Hb should rise by around 10g/l/week - remember to discover cause
7
Q
What is the pathophysiology of ACD?
A
- RES iron blockage/iron trapped in macrophages, reduced EPO response and depressed marrow activity/cytokine marrow depression
8
Q
How is ACD diagnosed?
A
- N/↓ MCV/MCH
- ↓ Iron
- ↓ TIBC
- ↑ ESR
- ↑/N Ferritin
- Hypochromic mycrocytic or normochromic normocytic RBCs on blood film
9
Q
Why does B12/folate deficiency cause anaemia?
A
- Disparity in rate of synthesis or precursors of DNA
- Ineffective erythropoiesis (death of mature cells whilst still in marrow)
10
Q
How is B12/folate deficiency diagnosed and treated?
A
- Diagnosis:
- Intrinsic factor antibody
- Gastric parietal cell antibody
- Megaloblastic anaemia on blood film
- Raised bilirubin
- Raised LDH
- Management:
- Dietary deficiency with oral replacement with cyanocobalamin unless deficiency is severe.
- In pernicious anaemia IM hydroxycobalamin is required.
- If folate deficiency must treat B12 deficiency first and then treat with folic acid.
11
Q
What is the pathophysiology of B12 deficiency?
A
- Parietal cells produce a protein called intrinsic factor which is essential for the absorption of vitamin B12 in the terminal ileum.
- Pernicious anaemia is an autoimmune condition where antibodies form against parietal cells or intrinsic factor leading to reduced B12 absorption.
12
Q
What is the most common cause of folate deficiency?
A
- Lack of dietary intake
13
Q
What are haemoglobinopathies?
A
- Normal Hb consists of 2 alpha and 2 beta globin chains
- Inherited conditions causing a relative lack of normal globin chains due to absent genes (thalassaemias) or variants (abnormal) globin chains (i.e. sickle cell disease)
14
Q
What are problems with alpha globin chains?
A
- Autosomal recessive condition
- Most people have 4 alpha globin chains - α+ thal trait (missing one)
- Homozygous α+ thal trait (missing two, one on each allele)
- α0 thal trait (missing two α, both on same allele)
- HbH disease (missing three) - α thal major (missing four, incompatible with life in utero)
- Management:
- Monitoring of FBC
- Monitoring for complications
- Blood transfusions
- Splenectomy
- Bone marrow transplant
15
Q
- What are problems with beta globin chains?
A
- Beta thalassaemia (missing B genes – should have 2) trait isn’t pathogenic but leads to small red cells.
- Beta thalassaemia minor patients are carriers (one abnormal, one normal)
- Beta thalassaemia intermedia (patients have two defective genes, one defective and one deletion) - requires occasional blood transfusions
- Beta thalassaemia major is an AR disorder where the body is unable to make adult haemoglobin (HbA) leading to significant dyserythropoeises - requires regular transfusions, iron chelation and splenectomy. Bone marrow transplant can be curative.
- Main problem with this is it leads to iron deficiency.
