ITS BOARDS Flashcards
define hypo proliferative anaemia
bone marrow contains an inadequate number of red cell precursors (erythroblasts)
define ineffective erythropoiesis
despite normal or increased numbers of bone marrow erythroblasts, they produces a reduced number of normal cells
define haemolytic/haemorrhagic anaemia
shortened red cell survival
what are the most common causes of anaemia
inflammation
iron deficiency
acute bleeding
what are less common causes of anaemia
disorders of bone marrow stroma
disorders of stem cells
maturation disorders
haemolytics anaemias
when might a bone marrow biopsy aid diagnosis and why
when retic count is low, it may help differentiate between hypo proliferative and maturation disorders
why is bone marrow biopsy not indicated if retic count is high
the marrow is clearly capable of producing cells, but they are not surviving normally in circulation
in what types of anaemia is the retic count high
haemolytic
haemorrhagic
in what types of anaemia is the retic count low
hypoproliferative
maturation disorders
what are reticulocytes
young red blood cells that have been formed by extrusion of the erythroblast nucleus
why do retics stain slightly blue
they contain RNA/ribosomes
what is the normal percentage of retics in blood
1%
retic count increases in proportion to
the amount of erythropoiesis in the bone marrow
what dye is used to stain reticulocytes
brilliant cresyl blue
what is a more accurate measure of red cell production in anaemia; retic percentage or absolute retic count
the absolute retic count
the percentage will be skewed as there is a reduced number of red cells
what can cause decreased production of Hb or red cells
iron deficiency anaemia
megaloblastic anaemia
aplastic anaemia
what can cause premature loss or destruction of red cells
haemolytic anaemias (autoimmune, inherited red cell defects) bleeding
where is the majority of iron in the body located
in red cells (Hb)
what are the three main compartments of body iron
iron stores
transport iron
red cell iron
how is iron stored
ferritin
how is iron transferred in the plasma and why
transferrin
must be bound to a protein to prevent oxidative damage
what is the best measure of iron supply tot tissues
total iron binding capacity
saturation of the serum transferrin
how many iron molecules can bind to each transferrin molecule
2
what type of iron is present in the diet
ferric (Fe3+)
how is iron status assessed
functional iron in red cells (Hb)
storage iron in the form of ferritin
what are the levels of iron stores, iron supply to tissues and red cell iron if there is reduced intake or increased loss of iron
iron stores: reduced
iron supply to tissues: normal
red cell iron: normal
what are the levels of iron stores, iron supply to tissues and red cell iron if iron stores are depleted
iron stores: reduced
iron supply to tissues: reduced
red cell iron: normal
what are the levels of iron stores, iron supply to tissues and red cell iron if iron deficient erythropoiesis is occurring
iron stores: reduced
iron supply to tissues: reduced
red cell iron: reduced
what are the common causes of iron deficiency in developing and developed countries
developing countries
- blood loss (GI bleeding)
- diet
developed countries
- rapid growth (infants, young children, adolescents)
- women of childbearing age (menstrual blood loss, pregnancy)
what are the clinical effects of iron deficiency
anaemia
epithelial abnormalities
impaired lymphocyte function and immune response
what epithelial abnormalities are associated with iron deficiency
buccal mucosal atrophy gastro mucosal atrophy post cricoid web koilonychia angular cheilitis
what is the basic structure of Hb
4 globin molecules; 2 alpha, 2 beta
4 haem molecules
what mutation causes sickle cell anaemia
substitution of valine for glutamic acid at codon 6 or beta globin gene
(point mutation in beta gene)
what types of Hb can be produced in homozygotic sickle cell
HbS
variable amount of HbF
what causes red cell sickling
intracellular dehydration
what is the molecular structure of HbS
a2bs2
what are clinical features of sickle cell anaemia
anaemia
painful crises
rarely aplastic crises, stroke, priapism
how do painful crises occur in sickle cell
sickled red cells produce microvascular obstruction and ischaemia
crises precipitated by cold, infection, dehydration
how many alpha genes are there in each cell
4
what genotypes can result in heterozygotic alpha thalassaemia
single gene deletion (a-/aa)
two gene deletion (–/aa)
what clinical features are present in single/two gene deletion alpha thalassaemia
no clinical features
what does a three alpha gene deletion cause
HbH disease with chronic haemolysis
what are HbH molecules
beta chan tetramers (ie contain no alpha globin chains)
what is hydrops fetalis
four alpha gene deletion
lethal
what are signs of heterozygotic beta thalassaemia
high HbA2
low MCV
increased red cell count
clinically asymptomatic
which Hb molecules are present in homozygotic beta thal
no HbA
mostly HbF
some HbA2
what does does precipitation of alpha-globin in erythroid cells produce in beta thal
ineffective erythropoiesis and extra medullary haematopoiesis
what is meant by beta thal trait
heterozygotic carriers of the mutation but with no symptoms
how are haemoglobin disorders screened for
neonatal: heel prick/cord blood
preconceptual: in at risk populations
antenatal: selective
what are complications of extra medullary haematopoiesis
enlargement of other bones eg maxilla, frontal bossing
iron accumulation
what are causes of haemolysis
hereditary (enzymatic, membrane disorder, globin disorder)
acquired (immune, non-immune)
what are causes of immune haemolysis
autoimmune spherocytic
alloimmune: haemolytic disease of the newborn
ABO mismatch transfusion
what are causes of non-immune acquired haemolysis
mechanical (prosthetic heart valve, DIC)
infection (malaria)
chemical/physical (oxidative stress, burns)
membrane: liver disease
what are diagnostic tests for haemolysis
direct Coombs test (detects antibodies bound to RBCs)
osmotic fragility (increased membrane fragility is spherocytosis)
G6PD enzyme activity screening test (quantitates production of NADPH)
what are causes of inherited haemolysis
enzymes (G6PD)
membrane defects (spherocytosis, ellipocytosis)
