Red Cells and Anaemia Flashcards
What are the substances needed to make a red blood cell?
Metals: Iron, copper, cobalt, manganese
Vitamins: B12, folic acid, thiamine, Vit.B6, C,E
Amino acids
Hormones: Erythropoietin, GM-CSF, androgens, thyroxine, SCF
What is the cell called that is the precursor to a red blood cell?
Reticulocyte
Why do men have a higher Hg than women?
They have more androgen which is one of the hormones that drives red cell production
Where does RBC breakdown happen?
Occurs in the reticuloendothelial system
Macrophages in Spleen, liver, lymph nodes, lungs etc
What happens to haem during breakdown?
Turned to unconjugated bilirubin
What is hereditary spherocytosis?
Congenital autosomal recessive anaemia
Defects in the different structural proteins mean that the red cell is spherical in shape so they are removed faster by the extravascular reticuloendothelial system than they would be if biconcave
What is the presentation of hereditary spherocytosis?
Breaking down faster so more bilirubin-jaundice
Enlarged spleen larger as have to work harder to remove haem
Higher levels of bilirubin can precipitate out into gallbladder and cause stones
Variable presentation, depending on which protein is affected
Anaemia symptoms
What is the normal life span of an RBC?
120 days
What is the management of hereditary spherocytosis?
Folic acid (increased requirements) Transfusion Splenectomy-If remove spleen then the red cells might last longer, destroyed less readily, last resort
What are three other disorders of the red blood cell’s membrane?
Hereditary Elliptocytosis-form elliptocytes
Hereditary Pyropoikilocytosis-cells are different shapes and sizes
South East Asian Ovalocytosis-oval shaped cells and usually relatively benign
What is G6PD deficiency?
Cells vulnerable to oxidative damage due to affecting of the enzyme Glucose 6 Phosphate Dehydrogenase
Confers protection against malaria so most common in malarial areas
X Linked so affects males and there are female carriers
Cells are blistered and broken on a blood smear and cells fragment in the circulation and die
Intravascular haemolysis- cells bursting in the circulation, free haemoglobin which makes the urine darker
What can precipitate a G6PD deficiency presentation?
Drug, broad bean or infection precipitated jaundice and anaemia
What is the Bohr effect?
Bohr effect means haemoglobin will give up oxygen when needed so in acidosis, hyperthermia and hypercapnia and the graph will shift to the right
What are the three types of haemoglobin and what chains are they made up of?
Haemoglobin A- two alpha chains and two beta
Haemoglobin A2- two alpha chains and two delta
Foetal haemoglobin- two alpha chains and two gamma
What is thalassaemia?
Reduced or absent globin chain production
Alpha plus and alpha zero thalassaemias
If both parents are alpha zero carriers then child can’t make any foetal Hg in utero so incompatible with life
What is sickle cell disease?
Autosomal recessive condition
Mutations leading to structurally abnormal globin chain
Usually a point mutation in a beta gene
In low O2 tension get polymerisation of abnormal haemoglobin and crystallises so red cells sickle. So red cells are made normal but only when low O2 (which happens physiologically) does it sickle which is irreversible. Sickle Hg has lower O2 affinity so gives up O2 more easily but will get haemolysis as abnormal shape
What are the possible complications of sickle cell disease?
Attributed to vasoocclusive tissue damage Painful Vaso-occlusive crises Bone pain Chest Crisis Stroke Increased infection risk Hyposplenism Chronic haemolytic anaemia Gallstones Aplastic crisis Sequestration crises Spleen Liver Dactylitis
What is an aplastic crisis?
high red cell turnover, if virus attacks then red cells dip (only last a week) as switches off red cell production which causes severe anaemia, which can present as slap cheek in children Aplastic anaemia (AA) is defined by pancytopenia with hypocellular marrow and no abnormal cells
What is the management of sickle cell disease?
Acute Events Hydration Oxygenation Prompt treatment of infection Analgesia Opiates NSAIDs Life long prophylaxis Vaccination Penicillin (and malarial) prophylaxis Folic acid Blood Transfusion Hydroxycarbamide increases Haemoglobin F production which doesn’t sickle Bone marrow transplantation Gene therapy
What is the presentation of beta thalassaemia major?
Severe anaemia Present at 3-6 months of age Expansion of ineffective bone marrow Bony deformities Splenomegaly Growth retardation “Hair on end” appearance on scans seen on skull due to bone marrow expansion
What is the management of thalassaemia?
Chronic transfusion support - 4-6 weekly
Normal growth and development
Iron overloading from transfusions needs to be managed with Iron chelation therapy
Bone marrow transplant is curative
What defects in haem formation causes what kind of anaemias?
Defects in mitochondrial steps of haem synthesis result in sideroblastic anaemia
Defects in cytoplasmic steps result in porphyrias
What are the reference ranges for haemoglobin in men and women?
Male 12-70 (140-180)
Male >70 (116-156)
Female 12-70 (120-160)
Female >70 (108-143)
What are some underlying causes of anaemia?
Evidence of bleeding Menorrhagia Dyspepsia, PR bleeding Symptoms of malabsorption Diarrhoea Weight loss Jaundice Splenomegaly/Lymphadenopathy Pregnancy Coeliac disease Diet deficiency
What are MCV and MCH?
MCV = Mean cell volume (cell size) MCH = Mean cell haemoglobin (cell colour)
What are the three morphological descriptions of anaemia?
Microcytic and hypochromic
Normocytic and normochromic
Macrocytic
What can be the underlying cause of a microcytic and hypochromic anaemia and what should the investigations be?
Iron deficiency anaemia Thalassaemia Secondary anaemia Sideroblastic anaemia Do a serum ferritin and if low then could be iron deficiency anaemia and if normal then could be thalassaemia or secondary anaemia
What can be the underlying cause of a normocytic and normochromic anaemia and what should the investigations be?
Haemolytic anaemia
Bone marrow tumour
A reticulocyte count indicates if the bone marrow is normal, if low then could be a bone marrow tumour or aplastic anaemia or a secondary anaemia, if high then could be a haemolysing anaemia or acute blood loss
What can be the underlying cause of a macrocytic anaemia and what should the investigations be?
B12 or folate deficiency
Bone marrow tumour
Do a B12 and folate levels, if normal then do reticulocyte count to look at bone marrow
What is secondary anaemia?
Iron levels are normal but being used inefficiently to make blood. Ferritin goes up with CRP if active inflammatory process, so can mask an anaemia. “Anaemia of chronic disease” 70% normochromic normocytic 30% hypochromic microcytic Defective iron utilisation Increased hepcidin in inflammation Ferritin often elevated Identifiable underlying disease Infection, inflammation, malignancy
What are some intra and extravascular haemolytic anaemias?
Intravascular- Mechanical eg.artificial valve
Severe infection/DIC
PET/HUS/TTP
G6PD enzyme deficiency
Extravascular- Auto-immune haemolytic anaemia
Hereditary spherocytosis
What test can be used to tell if an acquired haemolytic anaemia is immune (extravascular) or non immune (intravascular)?
Coomb’s test
Take patient’s blood in blood transfusion lab
In lab add anti-globulin antibody and cross links red cells, so they agglutinate in the tubes
Tells you that antibodies are on surface of the cell and there is an immune cause to the anaemia-immune mediated anaemia
If negative then not immune mediated
What is the management for haemolytic anaemia?
Support marrow function Folic acid Correct cause Immunosuppression if autoimmune Steroids Treat trigger eg.CLL, Lymphoma Remove site of red cell destruction Splenectomy Treat sepsis, leaky prosthetic valve, malignancy etc. if intravascular Consider transfusion
What are megaloblastic anaemias?
Megaloblastic anaemia is B12 or folate deficiency
What are some non-megaloblastic causes of macrocytic anaemia?
Myelodysplasia (bone marrow cancer)
Marrow infiltration
Drugs
What are the causes of B12 deficiency anaemia?
If problem with stomach or terminal ileum or diet deficiency then can have low B12
Or get antibodies against intrinsic factor which affects binding-pernicious anaemia
What are the causes of a folate deficiency anaemia?
Dietary Increased requirements (haemolysis) GI pathology (eg.coeliac disease)
What is the management of megaloblastic anaemias?
Replace vitamin
B12 deficiency
B12 intramuscular injection
Loading dose then 3 monthly maintenance
Folate deficiency
Oral folate replacement
Ensure B12 normal if neuropathic symptoms, Check B12 before giving folate as can make neuropathy worse, so give both until get results
What are some causes other than anaemia for a macrocytosis?
Alcohol Drugs -Methotrexate, Antiretrovirals, hydroxycarbamide Disordered liver function Hypothyroidism Myelodysplasia
