What are the primary causes of anaemia?
- Anaemia is caused by a reduced number of red blood cells in circulation or a decreased amount of haemoglobin in the red blood cells.
- This results in reduced levels of oxygen delivery to tissues.
- In some cases, this can lead to confusion, thirst and loss of consciousness.
- Anaemia may be significant before a patient appears pale.
What are the signs of anaemia?
- Pallor (especially of the conjunctiva).
- Tachycardia (pulse rate over 100 beats per minute).
- Glossitis (swollen and painful tongue - reasonably specific for vitamin B12 deficiency)
- Koilonychia (spoon nails - reasonably specific for iron deficiency).
- Dark urine (in haemolytic anaemia).
What are the symptoms of anaemia?
- Decreased work capacity, fatigue, lethargy
- Weakness, dizziness, palpitations
- Shortness of breath (especially on exertion).
- 'Tired all the time'
- In children: decreased IQ, poor concentration & sleepiness.
Rarely: headaches, tinnitus, taste disturbance.
More severe symptoms: Jaundice, splenomegaly, hepatomegaly, angina, cardiac failure, fever.
What form of anaemia would be indicative in dark urine?
What are the aetiological casses of anaemia?
Give an overview of the process of Erythropoiesis
Regulated by stem cell cytokines:
- SCF, IL-3 & TPO
What are conditions that affect specifically erythropoiesis in the bone marrow?
They are termed pure red cell aplasia (PRCA).
Most common PRCA is Diamond-Blackfan anaemia.
What is Pancytopenia?
Pancytopenia is a condition that affects other cell types in addition to RBCs (including white cells and platelets).
What is the common hallmark of Diamond-Blackfan anaemia?
- Reduced proliferation of erythroblasts
What is the difference between accquired and secondary PRCA?
Primary - idiopathic - where no clear cause can be identified or secondary (accquired as a result to exposure to a pathogenic agent such as a drug or infection).
How can you get anaemia from changes in the bone marrow?
How else can pancytopenia manifest from changes in the bone marrow?
What are the causes of haemolytic anaemia?
- They are caused by the premature destruction (reduced lifespan of 120 days) of functional erythrocytes either by extrinsic or intrinsic mechanisms.
- Anaemia will develop if the bone marrow is unable to match the destruction of erythrocytes by production of new cells.
- Erythrocyte destruction usually occurs through 2 broadly different reasons:
1. There is nothing fundamentally wrong with the erythrocyte, but they are destroyed by external pathological processes, such as drugs, toxins, auto-antibodies or infection.
2. There is something intrinsically wrong with the erythrocyte so it is destroyed. This can be due to damage, absence of certain enzymes or abnormal types of haemoglobin.
What are Alloantibodies?
Alloantibodies are produced in response to the immune recognition of foreign erythrocytes that have been introduced via a blood transfusion or due to pregnancy (following the mixing of maternal and foetal blood at delivery)
What is haemolytic disease of the newborn (HDN)?
- HDN develops in a foetus, when the IgG molecules produced by the mother pass through the placenta.
- Amongst these antibodies are some which attack antigens on the red blood cells in the foetal circulation, breaking down and destroying cells.
- This foetal disease ranges from mild to very severe, and foetal death from heart failure can occur.
- When the disease is moderate or severe, many erythroblasts (immature red blood cells) are present in the foetal blood.
What are the causes of Auto-Immune haemolytic anaemia (AIHA)
- Autoantibodies are found when a patient's immune system produces antibodies that recognise their own erythrocytes as foreign and mediate their destruction.
- Idiopathic AIHA accounts for approximately 50% of cases. Secondary AIHA can result from many other illnesses.
- The most common causes of secondary AIHA include lymphoproliferative disorders (e.g. chronic lymphocytic leukaemia, lymphoma) and other autoimmune disorders (e.g. systemic lupus erythrematosus, rheumatoid arthiritis, sceroderma, croh's disease, ulcerative colitis).
- Drug induced AIHA, though rare, can be caused by a number of drugs, including alpha-methyldopa and penicillin. The drug binds to the macromolecules on the surface of the RBCs and acts as an antigen.
- Antibodies are produced against the RBCs which leads to complement activation. This is one type of 'penicillin allergy'.
In blood films, what are shistocytes?
They are fragments parts of a red blood cell. Irregularly shaped and jagged. They result from fragmented destruction of red blood cells.
What are spherocytes?
Some cells are termed very small and termed micro-spherocytes.
What are nucleated erythrocytes?
A red cell with a nucleus that is usually lysed.
What are Haemoglobinopathy's?
Haemoglobinopathies are autosomal co-dominant genetic defects resulting in abnormal structure of one of the globin chains of the haemoglobin molecules.
Sickle cell anaemia is one of the most common haemoglobinopathies.
What are the causes of sickle-cell anaemia?
Sickle cell anaemia is attributed to mutations in the beta-globin gene.
Sickle cell erythrocytes are an abnormal shape, which affects their passage through the circularatory system, their ability to carry O2 and increased haemolysis.
Sickle cell anaemia can cause vaso-occlusive crises (vessel blockage), visceral sequestration crisis, aplastic and haemolytic crises.
Describe the structure of haemoglobin
- Haemoglobin is an iron-containing protein made in the erythrocyte cytoplasm.
- It is designed to absorb O2 from areas of high O2 content (lungs) and release it where O2 levels are low (tissues).
- Haemoglobin contains a protein part (globin) and a complex non-protein part (haem).
- The haem group contains iron which binds to O2 and the globin part consists of 4 globin subtypes.
Each erythrocyte contains 640 million haemoglobin molecules.
What vitamins and minerals are needed for erythropoiesis?
Vitamin B12, B6 and Folic Acid.
What causes iron-deficiency anaemia?
The essential micronutrients, irons, vitamins, b12 and b6 and folic acid, are required for various steps in regulating erythrocyte function, especially for the metabolism of haem.
- These micronutrients are obtained in the diet so malnutrition is likely to cause different types of anaemia. An apparently adequate diet may still lead to disease as essential micronutrients may fail to be absorbed due to abnormalities of the intestines (malabsorption).
Each molecule of haemoglobin must have an atom of iron to which O2 can bind to in the lungs. Therefore a lack of iron directly impacts the amount of O2 that can be transported to the tissues.
What would you see in the blood film of someone with iron-deficient anaemia?
- Iron deficiency is characterised by hypochromic (pale) microcytes (small).
- RBCs seem to be 'empty' with a lack of staining in the centre of the cell.
- RBCs are also significantly smaller (compare the size of RBCs to the white blood cell in the normal film).
- Hypochromic (pale) microcytes (small) RBCs
What are the daily iron requirements for an individual?
What intestinal factors contribute to reduced iron absorption?
What are the sources of iron?
- Dark green leafy vegetables
- Iron-fortified cereals
- Whole grains
- Iron Tablets
What factors can make iron absorption difficult?
- Tea and Coffee
- Proton Pump Inhibitors (PPIs)
- Wholegrain cereals (phytic acid).
What are the characteristics of sideroblastic anaemia?
- Sideroblastic anaemia is characterised not by a lack of iron, but its failure to be incorporated into haem in the erythrocyte percursor cells.
- There are various forms of sideroblastic anaemia that are the consequence of mutations or deletions of genes regulating the expression of key enzymes involved in haem synthesis.
- A consequence of the failure to incorporate iron into the correct areas, results in the formation of iron-rich mitochondria which surround the nucleus of the erythrocyte percurorsor as granules.
- These cells are termed 'Sideroblasts'
What is haem and where does it come from?
Haem is a complex molecule synthesised in the cytoplasm and mitochondria of erythrocyte progenitor cells.
Vitamins B6 and B12/folate are key regulators of haem production. Conseqently, deficiencies in these vitamins have significant effects or erythrocyte functions.
- Isolated B6 deficiency is rare. However, B12/folate deficiency is relatively common.
What is the function of ALA synthase?
- In mitochondria.
- Isoform of B12
- Involved in formation of haemoglobin.
What vitamin is required for the production of Succinyl CoA?
What vitamins are required for the formation of Protoporphyrinogen oxidase?
- B6 and B12
What vitamins are required for the formation fo Coprohyrinogen-oxidative decarboxylase?
- Vitamin B6 and B12
What are the progenitor cells in erythropoiesis?
What is the HCT (haematocrit)?
- Volume of red blood cells in blood.
- Normally 40% in men and 31% in women.
What form of anaemia would you expect to find in microcytic anaemia, if RBC count is high?
- Thalassemias (alpha and beta thalassemias)
What would you find in microcytic anaemia if RBC is low?
- Iron-deficiency anaemia
- Lead poisoning
- Anaemia of chronic inflammation
- Sideroblastic anaemia
What forms of anaemia are normocytic?
- Hemolytic anaemia
- Bone marrow disorders
- Acute Blood Loss
- Anaemias of chronic disease
What are the causes of macrocytic anaemia?
- Vitamin B12 deficiency
- Folic acid deficiency
- Liver disease