Red Cells Flashcards
What is anaemia?
Reduction in red cells or their haemoglobin
What are some aetiologies of anaemia?
Blood loss
Increased destruction
Lack of production
Defective production
Do erythrocytes have nuclei?
No
What are the most important vitamins for red blood cell formation?
B12
Folic acid
What happens when red cells get old?
Macrophages from spleen, gut, lymph etc. recognise old red cells and eliminate them
How are red cells broken down?
Globin amino acids
Iron from haem reutilised
Some haem broken into bilirubin
What form will circulating bilirubin be in when it results from liver problems?
Conjugated
What from will circulating bilirubin be in when it results from red blood cell breakdown?
Unconjugated
Where are genetic defects causing congenital anaemias?
Red cell membrane
Metabolic pathways
In haemoglobin
What is the clinical presentation of hereditary spherocytosis?
Anaemia
Jaundice (Unconjugated circulating bilirubin)
Splenomegaly
Pigment gallstones
How is hereditary spherocytosis treated?
Folic acid (increased requirements)
Transfusion
Splenectomy if very severe anaemia
What are the 2 main roles of enzymes for metabolic pathways in red cells?
Glycolysis
Pentose phosphate shunt
Where are the problems usually in red cell enzyme issues?
G6P dehydrogenase (G6PD) Pyruvate kinase
What is G6PD?
Glucose 6 phosphate dehydrogenase
Protects red cell proteins from oxidative damage
Why are males mostly affected by G6DP deficiency?
X linked
Men only have one X chromosome which is mutated
Females have another X chromosome with a normal gene so less likely to be affected
How does G6PD deficiency present?
Anaemia Neonatal jaundice (from infection or drugs) Splenomegaly Pigment gallstones Haemolysis
What triggers haemolysis in G6DP deficiency?
Infection Acute illness Fava beans (broad beans) Antimalarials Aspirin Other drugs
What does pyruvate kinase deficiency do?
Reduced ATP
Increased 2,3-DPG
Cells rigid
What is reduced or absent globin chain production called?
Thalassaemia
What are some mutations leading to structurally abnormal globin chains?
HbS (Sickle cell) disease HbC HbD HbE HbO Arab
What is Sickle cell disease?
Normal alpha chain Point mutations in 2 beta chains where Glu replaced by Val in beta chains Deoxygenated Haemolysed
What does sickle cell disease do?
Endothelial activation Promotion of inflammation Coagulation activation Dysregulation of vasomotor tone by vasodilator mediators (NO) Vasal occlusion
How might sickle cell disease present in multiple systems?
Painful vaso-occlusive crises (bone)
Chest crisis when lungs affected
Stroke
Gallstones due to haemolysis
Does sickle cell increase infection risk?
Yes
Why is folic acid used to treat anaemias?
Increased demand due to red cell breakdown
How might severe anaemia affect babies?
Present at 3-6 months of age Expansion of ineffective bone marrow Bony deformities Splenomegaly Growth retardation
How are young children treated for thalassaemia?
Iron chelation therapy
Desferrioxamine infusions
Bone marrow transplantation
How can sickle cell cause vaso-occlusion?
Endothelial activation
Promotion of inflammation
Coagulation activation
Dysregulation of vasomotor tone by vasodilator mediators (NO)
What are the main components of life-long sickle cell disease prophylaxis?
Vaccination Penicillin Folic acid Bone marrow transplant Gene therapy
How do we manage acute events of sickle cell disease?
Hydration Oxygenation Prompt treatment of infection Analgesia Blood transfusion
What is a drug used to manage sickle cell disease?
Hydroxycarbamide
What is a thalassaemia?
Reduced or absent globin chain production
How might severe anaemia resulting from beta thalassaemia major present?
Present at 3-6 months of age Expansion of ineffective bone marrow Bony deformities (hair-on-end x-ray appearance) Splenomegaly Growth retardation
What are the 3 main causes of inherited anaemias?
Red cell membrane defect
Red cell metabolism defect (enzyme problem)
Haemoglobin production defect
What are some factors influencing normal range of Hb levels?
Age Sex Ethnic origin Time of day Time to analysis
Do men or women have higher Hb?
Men
How does anaemia usually present?
Tiredness Pallor SOB Ankle swelling Dizziness Chest pain
What might indicate malabsorption as a cause of anaemia?
Diarrhoea
Weight loss
What are red cell indices?
Mean cell haemoglobin (MCH)
Mean cell volume (MCV)
Can give morphological description of anaemia and indicate cause
Which test could be used to determine morphology of anaemia?
Blood film
What blood film result is affected in hypochromic, microcytic anaemia?
Serum ferritin
What blood film result is affected in normochromic, normocytic anaemia?
Reticulocyte count
What blood film result is affect in macrocytic anaemia?
B12
Folate
Bone marrow
What are the possible fates of absorbed iron?
Bound to mucosal ferritin and sent off
OR
Transported across basement membrane by ferroporin
How is iron transported in plasma?
Bound to transferrin
How is iron stored?
As ferritin
Mainly in liver
Which part of the GI tract absorbs iron?
Duodenum
What is the most common cause of anaemia?
Iron deficiency
What are some clinical features of iron deficiency?
Hypochromic microcytic cells
Koilonychia
Atrophic tongue
Angular cheilitis
What are the main causes of iron deficiency?
GI blood loss
Menorrhagia
Malabsorption
What would increased reticulocyte count indicate?
Acute blood loss
Haemolysis
What would normal/low reticulocyte count indicate?
Secondary anaemia
Hypoplasia
Marrow infiltration
What are some possible causes of secondary anaemia?
Infection
Inflammation
Malignancy
What is the mechanism of haemolytic anaemia?
Accelerated red cell destruction (retics)
What are some congenital causes of haemolytic anaemia?
Hereditary spherocytosis
G6PD deficiency
Haemoglobinopathy
What are some acquired causes of haemolytic anaemia?
Auto-immune
Mechanical (artificial valve)
Severe infection
What does the direct antiglobulin test do?
Detect antibody or complement on red cell membrane
If positive then HA is immune mediated
What kind of anaemia is associated with CLL or drugs?
Warm autoimmune haemolytic anaemia
What kind of anaemia is associated with CHAD, infections and lymphoma?
Cold autoimmune haemolytic anaemia
What kind of anaemia is associated with a transfusion reaction?
Alloantibody haemolytic anaemia
What are schistocytes?
Red cell fragments on blood film
Indicate intravascular haemolysis
What are some necessary blood tests if you think a patient is haemolysing?
FBC Reticulocyte count Blood film Serum bilirubin LDH Serum haptoglobin Direct Antiglobulin Test
How do we support marrow function in haemolytic anaemia?
Folic acid
How do we treat autoimmune haemolytic anaemias?
Steroids Treat trigger (CLL, lymphoma etc.)
What is a possible role of surgery in haemolytic anaemia?
Remove site of red cell destruction
E.g. splenectomy
What kind of anaemia is indicated by B12 and folate deficiency?
Megaloblastic macrocytic anaemia
What kind of anaemia is indicated by myelodysplasia, marrow infiltration and drugs?
Non-megaloblastic macrocytic anaemia
How might megaloblastic anaemia present?
Lemon yellow tinge
Bilirubin
LDH
What is the most common cause of B12 deficiency in Western populations?
Pernicious anaemia
How is megaloblastic anaemia treated?
Replace B12 by IM injection
Oral folate replacement
What is the most common enzymopathy?
G6PD deficiency
