red cells Flashcards
substances require for production
iron copper cobalt manganese B12 folic acid thiamine Vit B6 CE aminoacids Erythropoietin, GM-CSF Thyroxine, androgen
Red cell breakdown
occurs in the reticuloendothelial system macropahges in spleen liver lymph nodes 120 days Globin AA reutilised Haem Iron recycled Haem- biliverdin- bilirubin
genetic defects
in red cell membrane
in metabolic pathways
in haemoglobin
skeletal proteins
responsible for maintaining red cell shape and deformability
defects can lead to increased cell destruction
most common membrane disorder
hereditary spherocytosis autosomal dominant defects in 5 different structural proteins -Ankyrin -Alpha Spectrin -Beta Spectrin -Band 3 -Protein 4.2
clinical presentation
anaemia jaundice splenomegaly pigment gallstones treatment folic acid transfusion splenectomy
rare membrane disorders
hereditary elliptocytosis
hereditary pyropoikilocytosis
red cell enzymes
glycolysis
provides energy
Pentose Phosphate shunt
-protects from oxidative damage
Glucose 6 phosphate deficiency
commones disesse cusing enzymopathy in the world Oxidative damage confers protection against malaria X Linked affects males female carriers
G6PD defieciency
blister/ bite cells clinical features variable anaemia neonatal jaundice splenomegaly pigment gallstones drug broad bean or infection precipated jaundice and anaemia \: intravascular hemolysis if sick red cell count can be infected
pyruvate kinase deficiency
reduced ATP increased 2 3 DPG anaemia jaundice gallstone
4 alpha genes
chromosome 16 ( 2 from one parent)
2 Beta genes
chromosome 11
normal adult
HbA -97
Hb A2 -2
Hb F -1
sickle cell disease
point mutation in beta chain Glu replaced by Val
crystal form through deoxygenation tension
hemolysis
coagulation activation
dysregulation of vasomotor tone by vasodilator mediators
->
vaso- occlusion
presentation
stroke, brain sickling in lungs, bone early childhood sickling in spleen auto infarction- hyposplenic Bone pain presentation abnormal spleen immunity low high red cell turnover, parvovirus severe anaemia requiring transfusion sequestraion crises- enlarged liver spleen
painful crisis
severe pain often requires opiates -Analgesia should be given within 30 mins of presentation -Effective analgesia by 1hour - Avoid pethidine Hydration Oxygen Consider antibiotics
management
Life long prophylaxis Vaccination Penicillin (and malarial) prophylaxis Folic acid Acute Events Hydration Oxygenation Prompt treatment of infection Analgaesia Opiates NSAIDs - Blood transfusion
disease modifying drugs
hydroxycarbamide
blood transfusion
episodic or chronic
alloimmunisation
iron overload
thalassemia
reduced or absent globin chain
mutations or deletions
beta thalassaemia major
severe anaemia -presents at 3-6 months expansion of ineffective bone marrow bony deformities splenomegaly growth retardation
chronic transfusion
iron overloading
death in 2nd or 3rd decades due to heart/ liver/ endocrine failure if iron loading not treated
beta thalassemia ajor treatment
iron chelation therapy
bone marrow transplant
defects in haem synthesis
defects in mitochondrial
causes sideroblastic anaemia
defects in cytoplasmic result in porphyrias
factors affecting normal range
age sex ethnic origin time of day time of analysis
clinical features
feel tired pallor breathlessness swelling of ankles dizziness chest pain
morphological description
hypochromic microcytic, normochromic normocytic
macrocytic
red cell indices
blood film
hypochromic microcytic
serum ferritin
normochromic normocytic
reticulocyte count
macrocytic
B 12/folate
bone marrow
serum ferritin
low iron deficiency normal increased thalassaemia secondary anaemia sideroblastic anaemia
iron metabolism
absorbed iron bound to mucosal ferritin and sloughed off or transported
transported across the basement membrane by ferroportin
Then - bound to transferrin in plasma
Stored as Ferritin - mainly in liver
role of hepcidin
Iron absorbed in duodenum - Fe2+ > Fe3+
Transported from enterocytes and macrophages by ferroportin
Transported in plasma bound to transferrin
Stored in cells as ferritin
hepcidin synthesised in hepatocytes in response to ↑iron levels and inflammation – blocks ferroportin so reduces intestinal iron absorption and mobilisation from reticuloendothelial cells
reticulocyte count
increased Acute blood loss Haemolysis normal/low Secondary anaemia Hypoplasia Marrow infiltration
secondary anaemia
70% normochromic normocytic 30% hypochromic microcytic Defective iron utilisation increased hepcidin in inflammation frritin often eleveated
acquired (HA)
autoimmune hemolytic anaemia
mechanical valve
PreEclampsia T/ HUS/ TTP
cogenital
Hereditary spherocytosis (HS) Enzyme deficiency (G6PD deficiency) Haemoglobinopathy (HbSS)
Acquired
immune- extravascular
non immune- mostly intravascular
immune haemolysis
warm auto antibody autoimmune drugs CLL cold autoantibody CHAD infections lymphoma Alloantibody transfusion reaction
Schistocytes
bad
haematinics
B12/folate
ferritin in microcytic
megaloblastic
B12 deficiency
Folate deficiency
