Red cells (anaemia) 1 Flashcards
Define anaemia and give the normal ranges in men and women
Reduction in the number of red cells or their haemoglobin content
RBCs = 4-5 (x1012/L)
Male haemoglobin = 135-170 g/L
Female haemoglobin = 120-160 g/L
As with all blood cells, RBCs are derived from haematopoietic stem cells (hemocytoblast)
Where are RBCs produced?
What substances are required for them to form?
Produced in bone marrow and require…
Metals - Iron, copper, cobalt, manganese
Vitamins - B12, Folic acid, thiamine, B6, C, E
Amino acids
Hormones - Erythropoietin, GM-CSF, androgens, thyroxine
What are the stages of red cell maturation?
Hemocytoblast
Proerythroblast
Early erythroblast
Late erythroblast
Normoblast
Reticulocyte
Erythrocyte
At which stage is the nucleus ejected from the developing red blud cell
Normoblast
Once ejected, it becomes a reticulocyte which still contains some RNA and occasionally can be found in the peripheral circulation
How long do RBCs survive in the blood?
How are these geriatric RBCs removed from the blood?
RBC lifespan = 120 days
Old RBCs are removed from the blood by the reticuloendothelial system
This is just macrophages in the Spleen, liver, lymph nodes, lungs etc
How is haemoglobin broken down once RBCs have reached senescence and been removed from the bloodstream?
Firstly in the reticuloendothelial system, Globin is removed, leaving Haem (Fe + porphyrin ring)
Haem is then broken down and the iron from it is reutilized
The remaining porphyrin ring is broken down into bilirubin
The end product of haemoglobin breakdown is bilirubin
What happens to bilirubin?
Bilirubin is transported - in its unconjugated form - in plasma bound to albumin
It is transported to the liver
Once in the liver, bilirubin is conjugated to form bilirubin glucorinide
How is bilirubin excreted from the body?
In the urine - as urobilinogen
In the stool - as stercobilinogen
Which proteins associated with the membrane of RBCs are important for maintaining their shape and structure?
(these are often called skeletal proteins)
Band 3
Ankyrin
alpha spectrin
beta spectrin
Congenital anaemias are caused by defects in what areas?
Defects of the:
Red cell membrane
Red cell enzymes (metabolic problems)
Haemoglobin itself
What condition is characterised by a dysfunctional red blood cell cytoskeleton, leading to a spherical RBC?
What proteins are implicated?
Is it autosomal recessive or dominance
Hereditary spherocytosis
Autosomal dominant (most forms)
Mutations in genes for:
- ankyrin
- alpha spectrin
- beta spectrin
- band 3
- protein 4.2
How would a patient with hereditary spherocytosis present?
What condition can this often be confused with (ie a differential)?
Variable clinical presentation as theres lots of types of HSphero
- Anaemia symptoms
- Failure to thrive
- Jaundice (neonatal)
- Splenomegaly
- Pigment gallstones (gallstones made from bilirubin)
HSphero is very similar in presentation to Gilbert syndrome (which is a kinda very mild jaundice) & also G6PD deficiency
How is hereditary spherocytosis treated?
Folic acid - mild
Transfusion - in acute haemolytic crisis
Splenectomy - if very severe anaemia
Aside from hereditary spherocytosis, what are the other red cell membrane disorders?
Hereditary elliptocytosis
Hereditary pyropoikilocytosis
South East Asian ovalocytosis
What are the main metabolic processes (pathways) in red cells?
Glycolytic pathway (glycolysis) - to provide energy
Pentose-phosphate shunt - to protect from oxidative damage
What metabolic defects can affect red blood cells?
Defects in…
G6PD - Glucose 6-phosphate dehydrogenase:
- G6PD is involved in preventing oxidative damage
- most common enzymopathy in the world
- X linked - so affects males, females are carriers
Pyruvate kinase
How does G6PD affect the blood?
Causes episodes of excess haemolysis in the circulation
“Blister” cells or “Bite” cells
How does G6PD deficiency present?
Variable clinical presentation:
- variable degrees of anaemia
- neonatal jaundice
- splenomegaly
- pigment gallstones
Episode(s) of anaemia and jaundice:
- Intravascular haemolysis (blister cells)
- haemoglobinuria
What precipitates haemolytic crises in patients with G6PD deficiency?
Drugs - eg anti-malarials (primaquine, pamaquine)
Broad beans (Fava beans)
Infection
Acute illness - eg DKA
Describe the normal structure of haemoglobin?
Polypeptide chains & haem:
2 alpha chains
2 beta chains
4 haem molecules - which contain 1 iron atom each
The oxygen dissociation curve shows how the affinity of haemoglobin for oxygen changes as partial pressure increases
The curve can ‘shift’ left or right under different envrionmental conditions - ‘Bohr effect’
In which direction does the curve shift in:
a) Exercise or acidosis
b) Hypothermia
c) Hypercapnia
a) Exercise/acidosis:
* Right shift - at same ppO2, more oxygen is released to tissues
b) Hypothermia = Left shift
c) Hypercapnia = Right shift
How does fetal haemoglobin (HbF) compare to normal haemoglobin?
How does haemoglobin content in kuds differ from adults?
HbF has a higher affinity for oxygen and lower partial pressures (LEFT SHIFTED)
This would mean that less oxygen is released to tissues at the same ppO2 experienced outside
To compensate - yung bois have more haemoglobin and are technically polycythaemic
Give an overview of how you inherit your haemoglobin genes
Haemoglobin A (97% adult DNA) - aabb:
- 4 alpha genes on chr16 - 2 from each parent
- 2 beta genes on chr11 - 1 from each parent
Hb A2 (2% adult DNA) - aadeltadelta:
- 2 delta genes - 1 from each parent - Chr11
Hb F (1% adult DNA) - aagammagamma:
- 4 gamma genes - 2 from each parent - Chr11
What is meant by a haemoglobinopathy
Inherited abnormalities of haemoglobin synthesis
Can either be:
Reduced/absent production = Thalassaemia
Mutations leading to abnormal structure - eg HbS (sickle cell)
