Anaemia + B12 and folate metabolism Flashcards
what is anaemia
a haemoglobin concentration lower than the normal range
how can body adjust to the lower concentration of haemoglobin
- increasing cardiac stroke volume to increase blood supply to tissues
- increase concentration of 2,3-bisphosphoglycerate to promote oxygen dissociation
signs of anaemia
- pallor
- tachycardia
- systolic flow murmur
- tachypnoea
- hypotension
specific signs associated with cause of anaemia
- koilonychia (spoon shaped nails) - iton deficiency
- angular stomatitis (inflammation of corners of mouth) - iron deficiency
- glossitis (inflammation + depapillation of tongue) - B12 deficiency
- abnormal facial bone development (expansion of haemopoietic tissue at young age) - thalassaemia
symptoms of anaemia
- shortness of breath
- palpitations
- headaches
- claudication
- angina
- weakness + lethargy
- confusion
life cycle of an erythrocyte
bone marrow (production)
peripheral RBC (function)
reticuloendothelial system (removal)
why might anaemia develop
production
- reduced or dysfunctional erythropoiesis
- abnormal haem synthesis
- abnormal globin chain synthesis
function
- abnormal structure
- mechanical damage
- abnormal metabolism
removal
- excessive bleeding
- increased removal by reticuloendothelial system
classifications of anaemia
- macrocytic
- microcytic
- normocytic
role of erythropoietin (EPO) in hormonal control of erythropoiesis
- pericytes in kidney sense hypoxia and produce EPO
- EPO binds to receptors on erythroblasts in bone marrow and stimulates red cell production
- increased number of RBC
- high blood oxygen acts as negative feedback
reduced or dysfunctional erythropoesis
- chronic kidney disease - lack of response in haemostatic loop or insufficient production of EPO
- marrow unable to respond to EPO - after chemotherapy, ionising radiation, autoimmunity, infection with parvovirus
- marrow infiltrated by cancer cells or fibrous tissue - normal haemopoietic cells reduced
- anaemia of chronic disease - iron not made available to marrow for RBC production
- myelodysplastic syndromes - abnormal clones of marrow stem cells limit capacity to make red and white cells
defects in haemoglobin synthesis
- deficiency in iron, vitamin B12 and folate - lower RBC production as they’re key for Hb synthesis
- mutations in genes encoding globin chain proteins - thalassaemias (alter amount) and sickle cell disease (alter function)
what is sideroblastic anaemia
body has enough iron but unable to use it to produce haemoglobin
what is megaloblastic anaemia
- most common cause of macrocytic anaemia
- erythrocytes large and show oval morphology
- due to deficiency of vitamin B12 and folate as red cell precursors can’t synthesise DNA and divide so nuclear maturation and cell division lag behind cytoplasm development
- large red cell precursors with large nuclei and open chromatin
haemolytic anaemia
destruction of RBCs in blood vessels or spleen faster than they can be replaced
acquired damage to RBCs
- microangiopathic haemolytic anaemias from mechanical damage - shear stress e.g. defective heart valve, cells snagging on fibrin strands e.g. disseminated intravascular coagulation
- heat damage from severe burns - dehydrates RBCs
- osmotic damage
inherited causes of RBC damage
- e.g. hereditary spherocytosis
- mutations in genes coding for proteins involved in interactions between plasma membrane and cytoskeleton
- cells less flexible and more easily damaged
- break up in circulation or removed more quilky by RES
inherited causes of RBC damage
- hereditary spherocytosis
- glucose-6-phosphate dehydrogenase deficiency
hereditary spherocytosis
- RBCs spherical instead of having biconcave shape
- defective cell membrane proteins making them more fragile and easily damaged
- break up in circulation or removed more quicly by RES
defects in red cell metabolism
G6PDH deficiency
- NADPH limited so lower GSH
- more susceptible to oxidative damage
- lipid peroxidation and protein damage lead to haemolysis
- Heinz bodies recognised by RES and removed
pyruvate kinase deficiency
- red cells become deficient in ATP so haemolysis
- lack mitochondria so depend on glycolysis for energy production
autoimmune haemolytic anaemia
- autoantibodies bind to proteins on RBC membrnae causing RBCs to be targeted and destroyed
- diseases like lupus, lymphomas, HIV
- some medications like penicilin
excessive bleeding
acute blood loss
- injury
- surgery
- childbirth
- ruptured blood vessel
chronic bleeding
- heavy menstrual bleeding
- repeated nosebleeds
- haemorrhoids
- occult GI bleeding
- kidney or bladder tumours
chronic NSAID use
- aspirin, ibuprofen, naproxen
- treatment of conditions with pain and inflammation
- induces GI bleeding via inhibtion of COX activity and direct cytotoxic effects on epithelium
