red cells

Question 1

what is the process of RBC differentiation ?

Answer 1

1. haemocytoblast
2. proerythroblast
3. erythroblast
4. normoblast
5. reticulocyte
6. erythrocyte

Question 2

what substances are required for RBC production ?

Answer 2

metals - iron, copper, cobalt, manganese
vitamins - B12, folic acid, thiamine, B6, C, E
amino acids
hormones - erythropoietin, GM-CSF, androgens, thyroxine

Question 3

how are RBCs broken down ?

Answer 3

occurs in reticuloendothelial system - macrophages in spleen, liver, nodes
normal RBC life 120 days

globin amino acids are reutilised
haem - iron recycled, haem group becomes bilirubin

bilirubin bound to albumin in plasma

Question 4

what is hereditary spherocytosis ?

Answer 4

autosomal dominant condition

red cells are spherical, get removed from circulation

Question 5

what structural proteins are defective in hereditary spherocytosis ?

Answer 5

ankyrin
alpha spectrin
beta spectrin
band 3
protein 4.2

Question 6

what is the clinical presentation of hereditary spherocytosis ?

Answer 6

anaemia
splenomegaly
pigment gallstones
jaundice - neonatal

Question 7

what is the treatment of hereditary spherocytosis ?

Answer 7

folic acid
transfusion
splenectomy

Question 8

what are some other rare membrane disorders ?

Answer 8

hereditary elliptocytosis
hereditary pyropoikilocytosis
south east asian ovalocytosis

Question 9

what are the 2 key red cell enzyme systems ?

Answer 9

glycolysis - provides energy

pentose phosphate shunt - protects from oxidative damage

Question 10

what is G6PD ?

Answer 10

commonest enzymopathy

X-linked

glucose 6 phosphate dehydrogenase deficiency - protects haemoglobin from oxidative damage
most common in malaria areas

Question 11

what is seen on blood films of G6PD deficiency ?

Answer 11

blister cells

bite cells

Question 12

how does G6PD present ?

Answer 12

variable anaemia
splenomegaly
pigment gallstones
jaundice - neotnatal

drug, broad bean or infection precipitate jaundice or anaemia - haemolysis, haemoglobinuria

Question 13

what drugs can trigger haemolysis in G6PD deficiency ?

Answer 13

antimalarials - quinine
sulphonamides
antibiotics - nitrofuratoin
analgesics - aspirin
antihelminthics - B-naphthol
miscellaneous - vit K, methyl blue

Question 14

what are other rare enzyme deficiencies ?

Answer 14

pyruvate kinase deficiency, reduced ATP, rigid cells

Question 15

what factors cause Hb to have a lower affinity to O2 ?

Answer 15

acidosis
hyperthermia
hypercapnia

HbF has higher affinity for O2 then HbA

Question 16

what is the makeup for adult haemoglobin ?

Answer 16

2 alpha chains - 4 alpha genes Chr16
2 beta chains - 2 beta genes Chr11

2% - HbA2 delta chains
HbF - gamma chains

Question 17

what are the haemoglobinopathies ?

Answer 17

thalassaemia - reduced or absent chain production
sickle cell - structurally abnormal Hb

all autosomal recessive

Question 18

what is the makeup of HbS ?

Answer 18

2 alpha chains

2 beta sickle chains - point mutation

Question 19

what is the pathophysiology of sickle cell disease ?

Answer 19

cells polymerise in response to insult, cation loss, dehydration - haemolysis occurs

endothelial activation, promotion of inflammation, coagulation activation, dysregulation of vasomotor tone

vaso-occlusion

Question 20

what are clinical presentations of sickle cell disease ?

Answer 20

painful vaso-occlusive crisis - bone, chest, stroke

increased infection risk - hyposplenism
chronic haemolytic anaemia - gallstones, aplastic crisis
sequestration crisis - liver, spleen

Question 21

how do you treat a sickle cell painful crisis ?

Answer 21

analgesia in 30 mins - opiates
avoid pethidine

hydration
O2
antibiotics ?

Question 22

how do you manage sickle cell disease ?

Answer 22

life long - vaccine, penicillin prophylaxis, folic acid

acute - hydrate, O2, analgesia, prompt infection treatment, blood transfusion

hydroxycarbamide
bone marrow transplant
gene therapy

Question 23

what is thalassaemia ?

Answer 23

reduced or absent chain production
mutations or deletion
either alpha or beta genes

chronic haemolysis and anaemia

Question 24

what are the different types of thalassaemia ?

Answer 24

homozygous alpha zero thalassaemia - no alpha chains, hydrops fetalis - incompatible with life

beta thalassaemia major - no beta chains, transfusion dependent anaemia

non-transfusion dependent thalassaemia - range of genotypes

thalassaemia minor - trait/carrier state, hypochromic, microcytic red cells

Question 25

what are features of beta thalassaemia major ?

Answer 25

severe anaemia 
presents 3-6 months
expansion of ineffective bone marrow
bony deformities
splenomegaly 
growth retardation

life expectancy without regular treatment <10 years

Question 26

how do you treat beta thalassaemia major ?

Answer 26

chronic transfusion 4-6 weekly
normal growth and development
iron overloading can cause death in 2nd/3rd decade if untreated - iron chelation therapy

Question 27

what are rare defects in haem synthesis ?

Answer 27

defect in mitochondrial steps of haem synthesis results in sideroblastic anaemia
ALA synthase mutations
hereditary
acquired form of myelodysplase

defects in cytoplasmic steps result in prophyrias