Red Cells Flashcards
what is anaemia?
Reduction in red cells or their haemoglobin content
describe rbc production in marrow
hemocytoblast stem cell –> commited cell –> erythroblasts –> nucleus leaves giving a reticulocyte –> erythrocyte
sustances required for rbc production
Fe, Cu, Co, Mg, B12, folic acid, thiamine, B6, C, E, amino acids, epo, csf, androgens, thyroxine
red cell breadown
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
what does a rbc contain?
Hb, Enzymes, membrane (3 areas of RBC where there can be issues)
features of congenital anaemias
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
Hereditary Spherocytosis - what are the most common forms of autosomal dominant Defects in 5 different structural proteins described
Ankyrin, Alpha Spectrin, Beta Spectrin, Band 3, Protein 4.2
clinical px of hereditary spherocytosis
Anaemia, Jaundice (neonatal), Splenomegaly, Pigment gallstones
Tx
Folic acid (increased requirements), Transfusion, Splenectomy if anaemia very severe
enzyme pathways rbc uses
Glycolysis - to provide engery, pentose phosphate shunt - protects from oxidative damage
G6PD (Glucose 6 Phosphate Dehydrogenase)
Protects red cell proteins (Haemoglobin) from oxidative damage: Produces NADPH - Vital for reduction of glutathione
Reduced glutathione scavenges and detoxifies reactive oxygen species
G6PD (Glucose 6 Phosphate Dehydrogenase) Deficiency…
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
what types of cells are found in G6PD deficiency?
Blister cells, bite cells
G6PD Px
Variable degrees of anaemia, Neonatal Jaundice, Splenomegaly, Pigment Gallstones.
what precipitates haemolysis?
Drug, broad bean (fava beans) or infection precipitated jaundice and anaemia, Intravascular haemolysis, Haemoglobinuria
Hb structure
fe, with a porphorin complex around it, 4 haem molecules, 2 beta and 2 alpha chains
how does Hb bind O2 - type of curve and how it changes?
(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.
types of Hb and proportions?
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)
inherited Haemoglobinopathies
Reduced or absent globin chain production - Thalassaemia (alpha α, Beta β, delta δ, gamma γ)
point mutaitons leading to structurally abnormal globin chain examples…
HbS (Sickle cell ), HbC, HbD, HbE, HbO Arab……
SICKLE CELL genetic type?
Autosomal Recessive, 1 in 4 chance of having affected child, 1 in 2 chance of being a carrier or “trait
what point mutaiton is there in sickle cell disease?
GLUTAMINE replaced by VALINE in the beta chains. Point mutation
consequences of HbS polymerisation
Red cell injury, cation loss, dehydration –> Haemolysis
Endothelial activation, Promotion of inflammation, Coagulation activation, Dysregulation of vasomotor tone by vasodilator mediators (NO)–> Vaso-occlusion
Clinical Px of Sickle cell disease
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
Ix for sickle cell disease
Blood film - Sickle shaped cells. Features of splenic atrophy, moderate anaemia onm FBC
Acute Mx of sickle cell disease
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
Life long Mx
Vaccination, Penicillin - given for prophylaxis due to encapsulated bacteria, (and malarial), Folic acid.
THALASSAEMIAS - causes/ outline…
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)
thalassaemias - spectrum of clinical severity…
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
beta thalassaemia major Px
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
with beta thalassaemia major what is seen on blood films?
target cells, nucleated red cells.
Beta Thalassaemia major Tx
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
Rare defects in haem sysnthesis…
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.
