Red Cells

Question 1

what is anaemia?

Answer 1

Reduction in red cells or their haemoglobin content

Question 2

describe rbc production in marrow

Answer 2

hemocytoblast stem cell –> commited cell –> erythroblasts –> nucleus leaves giving a reticulocyte –> erythrocyte

Question 3

sustances required for rbc production

Answer 3

Fe, Cu, Co, Mg, B12, folic acid, thiamine, B6, C, E, amino acids, epo, csf, androgens, thyroxine

Question 4

red cell breadown

Answer 4

Occurs in the reticuloendothelial system, Macrophages in Spleen, liver, lymph nodes, lungs etc, Normal red cell lifespan 120 days - Globin, Amino acids –reutilised, Haem , Iron-recycled into haemoglobin, Haem – biliverdin  bilirubin, Bilirubin – bound to albumin in plasma, From red cell breakdown -unconjugated

Question 5

what does a rbc contain?

Answer 5

Hb, Enzymes, membrane (3 areas of RBC where there can be issues)

Question 6

features of congenital anaemias

Answer 6

Genetic defects described: In red cell membrane, In metabolic pathways (Enzymes), In haemoglobin
Most reduce red cell survival: Result in haemolysis, Carrier states often “silent”, Prevalence varies geographically

Question 7

Hereditary Spherocytosis - what are the most common forms of autosomal dominant Defects in 5 different structural proteins described

Answer 7

Ankyrin, Alpha Spectrin, Beta Spectrin, Band 3, Protein 4.2

Question 8

clinical px of hereditary spherocytosis

Answer 8

Anaemia, Jaundice (neonatal), Splenomegaly, Pigment gallstones

Question 9

Tx

Answer 9

Folic acid (increased requirements), Transfusion, Splenectomy if anaemia very severe

Question 10

enzyme pathways rbc uses

Answer 10

Glycolysis - to provide engery, pentose phosphate shunt - protects from oxidative damage

Question 11

G6PD (Glucose 6 Phosphate Dehydrogenase)

Answer 11

Protects red cell proteins (Haemoglobin) from oxidative damage: Produces NADPH - Vital for reduction of glutathione
Reduced glutathione scavenges and detoxifies reactive oxygen species

Question 12

G6PD (Glucose 6 Phosphate Dehydrogenase) Deficiency…

Answer 12

Commonest disease causing enzymopathy in the world: Many genetic variants
Cells vulnerable to oxidative damage
Confers protection against malaria: Most common in malarial areas
X Linked: Affects males, Female carriers

Question 13

what types of cells are found in G6PD deficiency?

Answer 13

Blister cells, bite cells

Question 14

G6PD Px

Answer 14

Variable degrees of anaemia, Neonatal Jaundice, Splenomegaly, Pigment Gallstones.

Question 15

what precipitates haemolysis?

Answer 15

Drug, broad bean (fava beans) or infection precipitated jaundice and anaemia, Intravascular haemolysis, Haemoglobinuria

Question 16

Hb structure

Answer 16

fe, with a porphorin complex around it, 4 haem molecules, 2 beta and 2 alpha chains

Question 17

how does Hb bind O2 - type of curve and how it changes?

Answer 17

(sigmoid curve - easier binding the more O2 already attatched), Shifts as a compensatory mechanism: “Bohr effect”, Acidosis, Hyperthermia, Hypercapnia, HbF – higher O2 affinity than HbA.

Question 18

types of Hb and proportions?

Answer 18

Hb A – 97% (2 alpha chains and 2 beta chains)
Hb A2 – 2% (2 alpha and 2 delta)
Hb F – 1% (2 alpha and 2 gamma)

Question 19

inherited Haemoglobinopathies

Answer 19

Reduced or absent globin chain production - Thalassaemia (alpha α, Beta β, delta δ, gamma γ)

Question 20

point mutaitons leading to structurally abnormal globin chain examples…

Answer 20

HbS (Sickle cell ), HbC, HbD, HbE, HbO Arab……

Question 21

SICKLE CELL genetic type?

Answer 21

Autosomal Recessive, 1 in 4 chance of having affected child, 1 in 2 chance of being a carrier or “trait

Question 22

what point mutaiton is there in sickle cell disease?

Answer 22

GLUTAMINE replaced by VALINE in the beta chains. Point mutation

Question 23

consequences of HbS polymerisation

Answer 23

Red cell injury, cation loss, dehydration –> Haemolysis
Endothelial activation, Promotion of inflammation, Coagulation activation, Dysregulation of vasomotor tone by vasodilator mediators (NO)–> Vaso-occlusion

Question 24

Clinical Px of Sickle cell disease

Answer 24

Painful Vaso-occlusive crises - BONE CRISIS, ACUTE CHEST CRISIS/SYNDROME (rapid onset chest pain, progression rapidly, hypoxia, cough, bilateral lung infiltrates) , Stroke, Increased infection risk - Hyposplenism, Chronic haemolytic anaemia - Gallstones, Aplastic crisis, Sequestration crises - Spleen (autoinfarction of the spleen), Liver

Question 25

Ix for sickle cell disease

Answer 25

Blood film - Sickle shaped cells. Features of splenic atrophy, moderate anaemia onm FBC

Question 26

Acute Mx of sickle cell disease

Answer 26

Hydration, Oxygenation, Prompt treatment of infection (Antibiotics), Analgaesia (Opiates, NSAIDs), Blood transfusion (Alloimmunisation or Iron overload), Folic acid.
Disease modifying drugs - Hydroxycarbamide/ Bone marrow transplantation/ Gene therapy

Question 27

Life long Mx

Answer 27

Vaccination, Penicillin - given for prophylaxis due to encapsulated bacteria, (and malarial), Folic acid.

Question 28

THALASSAEMIAS - causes/ outline…

Answer 28

Reduced or absent globin chain production, Mutations or deletions e.g. In alpha genes (alpha thalassaemia), you need at least 2 out of the 4 possible available alpha chains from parents to be compatible with life. Loss of one or more lapha genes gives alpha thalassaemia)

Question 29

thalassaemias - spectrum of clinical severity…

Answer 29

Homozygous alpha zero thalassaemia (α0/α0 ) - No alpha chains  = Hydrops Fetalis –incompatible with life - intrauterine death.
Beta thalassaemia major (Homozygous beta thalassaemia) - No  beta chains = Transfusion dependent anaemia
Non-transfusion dependent thalassaemia – “Intermedia” - Range of genotypes eg.HbE/beta thal, HbH disease
Thalassaemia minor (common) - “Trait” or carrier state, Hypochromic microcytic red cell indices

Question 30

beta thalassaemia major Px

Answer 30

Severe anaemia - Present at 3-6 months of age, jaundice, leg ulcers, recurrent infections.
Expansion of ineffective bone marrow, Bony deformities = frontal bossing of the skull, Splenomegaly, hepatomegaly, Growth retardation, Life expectancy untreated or with irregular transfusions <10 years

Question 31

with beta thalassaemia major what is seen on blood films?

Answer 31

target cells, nucleated red cells.

Question 32

Beta Thalassaemia major Tx

Answer 32

Chronic BLOOD TRANSFUSION support - 4-6 weekly, Normal growth and development, BUT - Iron overloading may occur, Death in 2nd or 3rd decades due to heart/liver/endocrine failure if iron loading untreated. SO GIVE Iron chelation therapy - s/c AND desferrioxamine infusions (desferal), Oral deferasirox (exjade).
Good adherence to chelation – life expectancy near normal: Requires regular monitoring, Ferritin and MRI scans
Bone marrow transplantation-curative

Question 33

Rare defects in haem sysnthesis…

Answer 33

Defects in mitochondrial steps of haem synthesis result in sideroblastic anaemia, ALA synthase mutations, Hereditary, Aquired – (most common) a form of myelodysplasia, Defects in cytoplasmic steps result in porphyrias.