Red Cells Flashcards
What is anaemia?
Reduction in red cells or their haemoglobin content
What substances are required for red cell production?
Iron, copper, cobalt, manganese
B12, folic acid, thiamine
Amino acids
Erythropoietin, androgens, thyroxine, SCF
What is the typically lifespan of red blood cells?
120 days
What are red blood cells broken down into?
Globin
Haem > bilirubin
What is the function of skeletal proteins?
Maintain red cell shape and deformability
What can occur if there are skeletal protein defects?
Increased cell destruction
What structural proteins are defected in hereditary spherocytosis?
Ankyrin Alpha Spectrin Beta Spectrin Band 3 Protein 4.2
What is the clinical presentation of hereditary spherocytosis?
Anaemia
Jaundice (neonatal)
Splenomegaly
Pigment gallstones
What is the treatment for hereditary spherocytosis?
Folic acid
Transfusion
Splenectomy
What is the function of the pentose phosphate shunt?
Protects from oxidative damage
What is the function of glucose 6 phosphate dehydrogenase?
Protects red cell proteins from oxidative damage
If G6PD deficiency is X linked, who is affected?
Affects males
Female carriers
What is the clinical presentation of G6PD deficiency?
Neonatal jaundice
Drug, broad bean or infection precipitated jaundice or anaemia
Splenomegaly
Pigment gallstones
What drugs can cause G6PD deficiency?
Antimalarials Sulphonamides and sulphones Antibacterials Analgesics Antihelminthics Vitamin K analogues
What occurs in pyruvate kinase deficiency?
Reduced ATP
Increased 2,3-DPG
Cells rigid
What is the clinical presentation of pyruvate kinase deficiency?
Anaemia
Jaundice
Gallstones
What is the basic function of haemoglobin?
Oxygen to tissues
Carbon dioxide to lungs
What is the composition of haemoglobin?
Haem molecule
2 alpha chains
2 beta chains
What is the composition of sickle haemoglobin?
Haem molecule
2 alpha chains
2 beta (sickle) chains
What are the consequences of HbS polymerisation?
Haemolysis, endothelial activation, promotion of inflammation, coagulation activation, vaso occlusion
What are the complications of sickle cell disease?
Acute chest syndrome
Stroke
Pain episodes attributed to vasoocclusive tissue damage
What is the clinical presentation of sickle cell disease?
Painful bone and chest vaso-occlusive crises
Stroke
Hyposplenism
Chronic haemolytic anaemia (gallstones, aplastic crises)
Spleen and liver sequestration crises
What is the management of a chest crises?
Respiratory support Antibiotics IV fluids Analgesia Transfusion
What is the clinical presentation of chest crises?
Chest pain
Fever
Worsening hypoxia
Infiltrates on CXR
What is the life long prophylaxis for sickle cell disease?
Vaccination
Penicillin (and malarial) prophylaxis
Folic acid
What is the treatment for acute events due to sickle cell disease?
Hydration Oxygenation Prompt treatment of infection Analgesia (opiates, NSAIDs) Blood transfusion Disease modifying drugs (hydroxycarbimide) Bone marrow transplantation Gene therapy
What are thalassaemias?
Reduced or absent globin chain production
Mutation or deletion of alpha or beta genes
What are the clinical features of beta thalassaemia major?
Present at 3-6 months of age Expansion of ineffective bone marrow Bony deformities Splenomegaly Growth retardation
What is the treatment for beta thalassaemia major?
Chronic transfusion support 4-6 weekly
Iron chelation therapy (desferrioxamine infusions, oral deferasirox)
Bone marrow transplantation (curative)
What causes sideroblastic anaemia?
Defects in mitochondrial steps of harm synthesis
What factors influence the normal range of Hb?
Age Sex Ethnic origin Time of day sample taken Time to analysis
What is the Hb reference range for males under 70?
140-180
What is the Hb reference range for males over 70?
116-156
What is the Hb reference range for females under 70?
120-160
What is the Hb reference range for females over 70?
108-143
What are the general clinical features of anaemia?
Tiredness Breathlessness Swelling of ankles Dizziness Chest pain
What are the symptoms of anaemia with an underlying cause of bleeding?
Menorrhagia
Dyspepsia, PR bleeding
What are the symptoms of anaemia related to malabsorption?
Diarrhoea
Weight loss
What measurement are used when investigating red cells?
Mean cell volume (MCV)
Mean cell haemoglobin (MCH)
Where is hepcidin produced and what is its function?
Made in hepatocytes
Blocks ferroportin, reducing intestinal iron absorption
What are the clinical features of iron deficiency?
Koilonychia
Angular cheilitis
Atrophic tongue
What are the causes of iron deficiency?
GI blood loss (worms)
Menorrhagia
Malabsorption (gastrectomy, coeliac disease)
What is the treatment for iron deficiency anaemia?
Diet Ulcer therapy Surgery if bleeding Oral iron supplements Transfusion
What is a positive direct antiglobin test an indicator of?
Immune mediated haemolytic anaemia
What is a negative direct antiglobin test an indicator of?
Non-immune mediated haemolytic anaemia
What is the management of haemolytic anaemia?
Folic acid
Immunosuppression if autoimmune
Remove site of red cell destruction (splenectomy)
Treat sepsis, leaky prosthetic valve, malignancy if intravascular
What are the causes of B12 deficiency?
Pernicious anaemia
Gastric/ileal disease
What are the causes of folate deficiency?
Dietary Increased requirements (haemolysis) GI pathology (coeliac disease)
What is the treatment for megaloblastic anaemia?
Replace vitamin
B12 IM injection
Oral folate replacement
What are the other causes of macrocytosis?
Alcohol Drugs (methotrexate, ART, hydroxycarbamide) Disordered liver function Hypothyroidism Myelodysplasia
What does the “Bohr effect” on an oxygen dissociation curve take into account?
Acidosis
Hyperthermia
Hypercapnia
What is sickle cell?
Mutations leading to structurally abnormal global chain
What is homozygous alpha zero thalassaemia?
No alpha chains
Hydrops fettles incompatible with life
What is thalassaemia major?
No beta chains
Transfusion dependent anaemia
What are the possibly morphological descriptions of cells within anaemia?
Hypochromic microcytic (little and pale cells)
Normochromic normocytic
Microcytic (big cells)
What does serum ferritin indicate?
Measurement of the body’s iron stores
What would a low serum ferritin indicate?
Iron deficiency anaemia
What would a normal or increased serum ferritin indicate?
Thalassaemia
Secondary anaemia
Sideroblastic anaemia
Where is ferritin mostly found?
Liver
What are the investigations for iron deficiency anaemia?
Endoscopy
Barium studies
What are the causes of haemolytic anaemia?
Hereditary spherocytosis (HS) Enzyme deficiency (G6PD deficiency) Haemoglobinopathy (HbSS) Auto-immune haemolytic anaemia Mechanical eg.artificial valve Severe infection Drugs
How would you know if a patient is haemolysing?
FBC, reticulocyte count, blood film
Serum bilirubin high, LDH high
Serum haptoglobin low
What are the features of pernicious anaemia?
Antibodies against intrinsic factor and gastric parietal cells
Malabsorption of dietary B12
