Anaemia Flashcards
Anaemia definition
reduction of total circulating red cell mass below normal limits - reduces oxygen carrying capacity of blood
reduced oxygen carrying capacity of blood could lead to
tissue hypoxia
etiological clues to anaemia (3)
red cell size, shape, degree of haemoglobinisation
3 red cell sizes
normocytic, microcytic, macrocytic
2 degrees of haemoglobinisation
normochromic, hypochromic
microcytic and hypochromic anaemia suggest
haemoglobin synthesis disorder
macrocytic anaemia suggests
maturation in bone marrow abnormalities
leg ulcers suggest
sickle cell anaemia
bone deformities suggest
thalassaemia major
jaundice suggests
haemolytic anaemia
koilonychia (spoon-shaped nails) suggests
iron deficiency anaemia
3 features of haemolytic anaemias
premature destruction and short life span RBCs, accumulation of breakdown material, elevated erythropoietin and rate of erythropoiesis
cause of extravascular haemolytic anaemia
alterations which make RBCs less deformable
causes of intravascular haemolytic anaemia (4)
mechanical injury, complement fixation, intracellular parasites, exogenous toxic factors
3 signs of extravascular haemolytic anaemia
anaemia, splenomegaly, jaundice (bilirubin)
3 signs of intravascular haemolytic anaemia
anaemia, jaundice (bilirubin), haemoglobinaemia
process extravascular haemolytic anaemia
can’t navigate splenic pulp > red cell sequestration > phagocytosis within cords > some escapes
process intravascular haemolytic anaemia
large amount Hb free from lysed cells > bound to HAPTOglobin > rapidly cleared by phagocytes > Hb oxidised to METHEMOglobin (brown) > some passes in urine
Jaundice is from
iron build up in kidney > bilirubin
genetics of sickle cell disease
maturation in 6th codon of beta globin > replacement of glutamate residue with valine residue
in sickle cell disease, glutamate residue is replace with
valine residue
haemoglobin type of sickle cell sufferers
HbS
HbS heterozygous phenotype
sickle cell trait
sickle cell trait protects against
malaria
sickle cell trait symptoms
asymptomatic
sickle cell disease and trait most common in people of what descent
african
3 major pathological manifestations of sickle cell anaemia
chronic haemolysis, microvascular occlusions, tissue damage
4 variables affecting sickling
interaction of HbS with other types of Hb in cell, mean cell Hb concentration, transit time of red cells through microvascular beds, intracellular pH
sickle cell trait, percentage HbS and HbA
HbS = 40%, HbA = 60%
HbA interferes with
HbS polymerisation
RBCs of people with sickle cell TRAIT do not sickle unless under what conditions
hypoxic conditions
intracellular what facilitates sickling
dehydration
intracellular dehydration facilitates sickling because
increases mean cell Hb conc.
transit times slow where (3)
spleen, bone marrow, inflamed vascular beds
why might vascular beds be inflamed
increased adhesion molecules
sickle red cells express higher than normal amounts of what
adhesion molecules
decrease in pH reduced Hb affinity for what
oxygen
reduced Hb oxygen affinity increases fraction of
deoxygenated HbS
low pH increases tendency of
sickling
sickle cell disease, splenomegaly can be seen in
children
autosplenectomy seen in
adults with sickle cell disease
progressive hypoxic tissue damage leads to
autosplenectomy
how does sickling damage RBCs
HbS polymers grow > herniate membrane > influx calcium ions into RBC > efflux potassium ions and water > dehydration > increased density and rigidity
sickle cell - damage to RBCs - influx of
calcium ions
sickle cell - damage to RBCs - efflux of
potassium ions and water
sickle cell is a form of what type of anaemia
haemolytic
vaso-occlusive crises
episodes of infarction causing sever pain in affected region
vaso-occlusive crises common in what tissue
bone
chronic hypoxia in sickle cell responsible for
impaired growth and development
sickle cell prognosis improved by (4)
DNA synthesis inhibitor drugs, bone marrow transplants, prophylactic antibiotics, blood transfusions
HbA has which 4 chains
2 alpha, 2 beta
HbA alpha chains genes on chromosome
16
HbA beta gene on chromosome
11
thalassaemia consequences are from
Hb deficiency and excess of other globin chain
thalassaemia CARRIERS are protected against
Malaria
how many HbA alpha chain genes
2
how many HbA beta chain genes
1
two categories of beta thalassaemias
beta 0 and beta positive
beta zero thalassaemia mutations associated with
absent beta globin synthesis
beta positive thalassaemia mutations associated with
reduced beta globin synthesis
most common cause of beta positive thalassaemia
splicing mutations
most common cause of beta zero thalassaemia
chain terminator mutations
mutations associated with beta positive thalassaemia
promotor region mutations (and splicing mutations)
beta thalassaemia is (2)
hypochromic, microcytic
two beta thalassaemia alleles
beta thalassaemia major
one beta thalassaemia allele
beta thalassaemia minor
beta thalassaemia minor is (2)
asymptomatic, microcytic
beta thalassaemia major manifests when
6-9 months after birth (hbF–>HbA)
major red cell Hb in beta thalassaemia major
HbF
blood transfusion needed or death as child in
beta thalassaemia major
bony prominences enlarged and distorted in
beta thalassaemia major
only cure for beta thalassaemia major is
bone marrow transplant
in newborns with alpha thalassaemia (hydrops fetalis), excess unpaired gamma globin chains form gamma 4 tetramers known as
haemoglobin barts
in order children and adults with alpha thalassaemia, excess beta globin chains form beta 4 tetramers known as
HbH
haemolysis and ineffective erythropoiesis less severe than
beta thalassaemia
most common cause of reduced alpha chain synthesis and therefore alpha thalassaemia
gene deletion
silent carrier state alpha thalassaemia
deletion of single alpha globin gene allele
symptoms of silent carrier state alpha thalassaemia
asymptomatic
silent carrier state alpha thalassaemia cell type
microcytic (slight)
deletion of two alpha globin gene alleles
alpha thalassaemia trait
deletion of two alpha globin gene alleles from single chromosome
asian
deletion of two alpha globin gene alleles from two different chromosomes
african
alpha thalassaemia trait cell type
microcytic
symptoms of alpha thalassaemia trait
asymptomatic
deletion of 3 alpha globin gene alleles
haemoglobin H disease (HbH disease)
HbH disease most common in which populations
asian
in HbH tetramers of what form
beta globin
HbH has what kind of affinity for oxygen
very high
deletion of all four alpha globin gene alleles
hydrops fetalis
barts have what type of affinity for oxygen
very high
hydrops fetalis have life long dependency on
blood transfusion
only possible cure for hydrops fetalis
bone marrow transplant
vitamin B12 deficiency anaemia is what type of anaemia (2)
megaloblastic, macrocytic
pernicious anaemia
vitamin B12 deficiency anaemia resulting from inadequate gastric production / defective function of INTRINSIC FACTOR
most common cause of vitamin B12 deficiency anaemia
long-standing malabsorption
3 types of antibody found in pernicious anaemia
parietal canalicular, blocking, binding antibodies
spinal cord disease associated with which anaemia
vitamin B12 deficiency anaemia
treatment for vitamin B12 deficiency anaemia
hydroxycobalamin (vitamin B12)
median age of diagnosis of pernicious anaemia
60
folate deficiency anaemia very similar to vitamin B12 deficiency anaemia other than
no neurological abnormalities
treatment for folate deficiency anaemia
oral folic acid
most common cause of anaemia worldwide
iron deficiency anaemia
percentage of world affected by iron deficiency anaemia
30%
most common cause iron deficiency anaemia (developed world)
blood loss
most common cause iron deficiency anaemia (developing world)
nutritional deficiencies
iron absorbed where
duodenum
cell type in iron deficiency anaemia (2)
microcytic, hypochromic
long standing anaemia leads to
spooning of fingernails
conditions carrying increased likelihood of iron deficiency (4)
pregnancy, adolescence, periods of rapid growth, intermittent history of blood loss
