Anaemia Flashcards
anaemia definition
red total RBC mass
what are the 2 possible pathophysiologies of anaemia
increased destruction of RBCs eg bleeding, haemolysis
decreased production of RBCs
what is the problem in microcytic anaemias
there is a problem with the haemoglobin production
either heme problem or globin problem
microcytic anaemia, potential causes of haem deficiency caused by iron deficiency (4)
low dietary intake
anaemia of chronic disease
malabsorption
blood loss
microcytic anaemia, cause of globin deficiency
thalassaemia
most common cause of microcytic anaemia
who gets it
low iron dietary intake
veggie/vegans
microcytic anaemia, potential causes of haem deficiency not caused by iron deficiency (2)
porphyrin synthesis problem - lead poisoning
genetic
pneumonic for remembering causes of microcytic anaemia
find the small cell
Fe deficiency - diet, malabsorption, blood loss, anaemia of chronic disease
Thalassaemia
Sideroblastic anaemia (don’t need to know)
anaemia of Chronic disease
relative iron deficiency anaemia
eat ‘enough’ iron but not enough for body eg pregnant, children
absolute iron deficiency anaemia
don’t eat enough iron
what is anaemia of chronic disease
when you have enough iron intake but cant use it
second most common cause of anaemia after iron deficiency
anaemia of chronic disease
causes of anaemia of chronic disease
malignancy
infection
inflammatory (eg rheumatoid arthritis)
in anaemia of chronic disease, the cause of the problem is due to increased inflammatory cytokines, what does this then lead to the production of
what does this do
hepcidin
inhibits release of iron from duodenum = decreased Hb production in bone marrow = anaemia
NOTE inflammatory cytokines also decrease EPO from kidneys and directly inhibit erythropoiesis in bone marrow, but above is the main mechanism
example of chronic condition with malabsorption of iron
coeliac
causes of blood loss that can cause anaemia (3)
GI bleed
haematuria
menorrhagia
cause of porphyrin synthesis problem = haem deficiency = anaemia
lead poisoning
globin deficiency
thalassaemia
why does haemoglobin deficiency cause MICROCYTIC anaemia
bone marrow still makes RBCs, they just contain less Hb than normal = smaller with less Hb (low MCV)
is haemogllobin deficiency hypo or hyperchromic anaemia
hypochromic - less Hb than normal RBCs
when do people present with symptoms in microcytic anaemia
late stage
once microcytic anaemia has been diagnosed, what do you want to measure to diagnose cause
serum ferritin
if low = iron deficiency cause
if high = globin problem (thalassaemia)
iron deficiency anaemia diagnosed (microcytic anaemia with low serum ferritin), what do you do
prescribe fe2+ supplements (ferrous fumarate)
AND investigate cause further for blood loss - FOB, endoscopy etc
what blood component will be increased in microcytic anaemia
why
platelets = thromobocytosis
bone marrow compensates for decreased RBCs = tries to make more, platelets come from same precursor
pencil/rod cells
iron deficiency anaemia
reticulocyte count in microcytic anaemia
low - bc not enough components to make RBCs in the first place
reticulocytes are only high in increased destruction where the bone marrow wants to get the RBCs out as soon as possible
side effect of ferrous fumarate
constipation
what is the expected response after starting iron supplements for microcytic anaemia
what may cause a lesser response
7-10g/L Hb rise per week
poor compliance (SEs) underlying problem eg bleed
cause of macrocytic anaemia (2 types)
megaloblastic - defects in DNA synthesis
non megaloblastic - liver disease, alcohol, hypothyroidism, bone marrow failure
cause of macrocytosis that doesn’t cause anaemia
alcohol
causes of megaloblastic macrocytic anaemia
B12 deficiency
folate deficiency
cytotoxic drugs eg methotrexate
pneumonic for megaloblastic anaemia causes
cant be fucked
cytotoxic drugs eg methotrexate
B12 deficiency
folate deficiency
causes of B12 deficiency causing megaloblastic microcytic anaemia (3)
vegan diet - B12 comes form animal products
eating disorder
pernicious anaemia
PPIs
definition of megaloblastic anaemia
DNA synthesis problem = cell maturation problems = megaloblasts formed (precursor cells)
failure of normal maturation
autoimmune cause of macrocytic anaemia
pernicious anaemia
PMH/Fx of autoimmune conditions or hypothyroid
develops anaemia
pernicious anaemia
how does pernicious anaemia cause B12 deficiency (and hence anaemia)
autoimmune destruction of gastric parietal cells = intrinsic factor deficiency = B12 malabsorption = B12 deficiency
folate deficiency causes
poor intake - alcoholics, eating disorder
malabsorption - coeliac, crohns
drugs
which drug causes folate deficiency
phenytoin (anticonvulsant)
which 2 substances are important in nuclear maturation
what does this cause
B12 and folate
abnormal cell division = premature stop = makes macrocytes
what DNA base is the folate cycle crucial in forming
thymidine (T)
where is B12 normally absorbed
ileum (distal bowel)
THINK: B12 = wants to get passed T12 = far away = distal bowel
what things bind to B12 when its broken down in the stomach to take it to the distal bowel (ileum)
protein R
intrinsic factor
where is folate normally absorbed
jejunum (proximal bowel)
THINK: not B12 so no need to get passed T12 = can be absorbed proximally
what is RNA, cytoplasm and haemoglobin synthesis like in macrocytic anaemia
all normal
the only problem is DNA synthesis = reduced maturation
how do megaloblasts look in comparison to normal RBCs
what RBC precursor are they similar to, whats the only difference
larger
has an immature nucleus
look similar to normoblasts/erythroblasts, just have an immature nucleus (erythroblasts = normal nucleus)
what happens to the majority of the megaloblasts produced in megaloblastic anaemia
apoptosis in the bone marrow (bc theyre faulty RBCs)
= intramedulary haemolysis (break down of RBCs)
= jaundice
where does hameolysis happen in megaloblastic anaemia
intramedullary - in the bone marrow
due to apoptosis of megaloblasts (immature RBCs)
what happens to a minority of the megaloblasts produced in megaloblastic anaemia
some survive = hence seen in blood count = anaemia
what happens to normal RBCs as they mature
how is this differnet for megaloblasts
they get smaller
megaloblasts have faulty NDA = unable to undergo cell division = big cells = hence cause macrocytic anaemia
beefy red tongue
megaloblastic macrocytic anaemia (B12/folate deficiency/cytotoxic drugs)
what cells seen on blood film are characteristic of megaloblastic macrocytic anaemia
macroovalocytes
hypersegmented nucleus of neutrophils
tear drop RBCs
hypersegmented nucleus of neutrophils
megaloblastic macrocytic anaemia
macroovalocytes
megaloblastic macrocytic anaemia
tear drop RBCs
megaloblastic macrocytic anaemia
investigations after diagnosis of megaloblastic macrocytic anaemia
B12 levels
folate levels
anti-gastric-parietal cell AND anti-intrinsic factor autoantibodies - for pernicious anaemia
coeliac antibodies
management of B12 deficiency causing megaloblastic macrocytic anaemia
what special consideration is needed if caused by pernicious anaemia
IM hydroxycobalamin
for life - if pernicious anemia
for 3 months and reassess - if dietary problem
management of folate deficiency causing megaloblastic macrocytic anaemia
folic acid 5mg daily
apart from megaloblastic causes of macrocytic anaemia, what are the other causes (4)
alcohol
liver disease
hypothyroidism
bone marrow failure
how does hypothyroidism cause non-megaloblastic macrocytic anaemia
reduced EPO from kidney = anaemia
also link with pernicious anaemia, but don’t worry too much lol
how does the blood film differ between megaloblastic macrocytic anaemia and non-megaloblastic macrocytic anaemia
megaloblastic macrocytic anaemia = macroovalocytes, hypersegmented nucleus of neutrophils, tear drop RBCs
investigations once non-megaloblastic macrocytic anaemia diagnosed (find cause)
LFTs
TFTs
alcohol history
bone marrow biopsy
false causes of macrocytosis (when MCV is high but mature red cells are actually the normal size)
reticulocytosis
autoimmune haemolytic anaemia - clumping of RBCs = get picked up as one not several
what blood results do you look at for ?anaemia
what are each looking for
Hb - to confirm anaemia
MCV - to see if macrocytic or macrocytic
serum ferritin - if microcytic, to look at iron deficiency cause
blood film (MCH) - if macrocytic, for hypersegmented neutrophils and macroovalocytes = megaloblastic cause
B12/folate - if macrocytic for B12/folate deficiency
autoantibodies for pernicious anaemia - if macrocytic
main presentation of anaemia
fatigue
female anaemia Hb
<120 g/L
male anaemia Hb
<130 g/L
what does haematocrit measure (not used in UK)
problems with this
% of whole blood that is RBCs
blood loss causing anaemia = % will still be the same, even though low RBC (bc total blood volume is reduced)
O2 sats in anaemia
pO2 sats in anaemia
probs 99% bc the heamoglobin that is going around is fully saturated, just isn’t much of the haemoglobin itself
pO2 also probs normal bc same amount of oxygen is entering the blood from the lungs (what pO2 measures) just isn’t much going round
high platelets (thrombocytosis)
microcytic anaemia - bc bone marrow is trying to compensate for decreased RBC production, and platelets and RBCs have the same precursor cell
is serum ferritin or transferrin preferred
why
serum ferritin - measure of iron stores, not just circulating iron
when do you blood transfuse for anaemia
only if symptomatic and <70g/L
which type of anaemia do you see reactive changes in
what are reactive changes
anaemia of chronic disease
neutrophilia (high neutrophils)
thrombocytosis (high platelets)
haemolysis definition
premature destruction of RBCs <3 months
most common cause of haemolysis
autoimmune haemolytic anaemia
what are the 2 types of autoimmune haemolytic anaemia
what does this mean
cold and warm autoantibody
cold - happens in cold weather
warm - happens in warm weather
which autoantibody is warm autoimmune haemolytic anaemia associated with
IgG
THINK: when you go to Ghana (warm) = IgG
which autoantibody is cold autoimmune haemolytic anaemia associated with
IgM
THINK: when you go to Moscow (cold) = IgM
is warm or cold autoimmune hemolytic anaemia more common
warm (IgG)
what does positive coombs mean when testing for types of haemolysis
immune cause of haemolysis
blood film of autoimmune hemolytic anaemia (2)
spherocytes
reticulocytes
differentials of spherocytes (2)
how do you tell the difference (investigation)
autoimmune hameolytic anaemia
hereditary spherocytosis
do coombs test - positive in autoimmune haemolytic anaemia bc immune
what does presence of reticulocytes mean
haemolysis (or haemorrhage) has occurred and bone marrow trying to compensate
management of autoimmune haemolytic anaemia
steroids or immunosuppression bc autoimmune
what antibody is associated with extravascular haemolysis as a result of ABO incompatibility
is it an immediate or a delayed reaction
IgG (THINK: igM = iMMediate, so igG must be delayed)
delayed - bc blood transfusion initially goes to blood vessels, then moves out of vessels (hence extravascular)
what antibody is associated with intravascular haemolysis as a result of ABO incompatibility
is it an immediate or a delayed reaction
IgM (THINK: igM = iMMediate)
immediate - bc in the vessels (that’s where the blood transfusion goes)
haemolysis associated with mechanical/leaking heart valves
microangiopathic haemolytic anaemia (MAHA)
hereditary causes of haemolysis (2)
hereditary spherocytosis
G6PD deficiency
blood film of hereditary spherocytosis
spherocytes - sphere shaped RBs instead of biconcave
inheritance pattern of hereditary spherocytosis
autosomal dominant
why are spherocytes susceptible to haemolysis
spherical shape means they get stuck in blood vessels = early deconstruction (haemolysis)
are spherocytes hypo or hyperchromic
hyperchromic, loss of central pallor (the dip in the middle when RBCs are biconcave)
what happens to bone marrow (hyper or hypo plasia) in haemolysis
bone marrow hyperplasia to compensate for haemolysis
tries to make more RBCs fast!!
the presence of which cell is classic of haemolysis
reticulocytes - immature RBCs (still have RNA), bone marrow just fires out whatever it can make (whether theyre mature or not) to try and compensate for anaemia)
spleen in hereditary spherocytosis
splenomegaly
complication of bone marrow hyperplasia in spherocytosis
short stature
skin in extravascular haemolysis
likely jaundice from excess bilirubin breakdown after haemolysis
intravascular = not jaundice bc break down of RBCs in circulation = Hb excreted in urine (not broken down)
management of hereditary spherocytosis
folic acid - in encourage normal RBC production
splenectomy - sometimes in children
which drug can alter RBC metabolism and cause hemolysis
dapsone
which hereditary cause of abnormal haemoglobin can result in haemolysis
sickle cell anaemia
difference between reticulocytes and RBCs
reticulocytes still have RNA = premature RBCs
reticulocytes are larger and more purple
why does presence of reticulocytes cause macrocytosis
bc they are classed as the ‘same’ as RBCs but are larger = macrocytosis
are most causes of haemolysis intravascular or extravascular
what does this mean
extravascular
haemolysis happens in the liver/spleen
which causes of haemolysis are intravascular (3)
immediate ABO incompatibility (IgM mediated)
microangiopathic haemolytic anaemia (MAHA) - mechanical/leaking heart valves
G6PD deficiency
when haemolysis happens inside the blood vessels (intravascular haemolysis) what breakdown product forms
how is it excreted
how can you tell if this has happened or not
schistocytes
free haemoglobin in circulation
excreted in urine (haemoglobinuria)
urine turns black on standing
what blood film finding occurs in G6PD deficiency causing intravascular haemolysis
Heinz bodies
investigations for hemolysis
Hb - anaemia
blood film - reticulocytes, spherocytes, Heinz bodies
direct coombs test - for immune cause
what is the most common anaemia in children
iron deficiency anaemia
the normal physiological response to which chronic condition can cause high RBCs
why
COPD
if hypoxia = EPO made from kidneys = increased RBC production
causes for iron overload
hereditary haemochromatosis
repeated RBC transfusion
what is the problem in hereditary haemochromatosis that results in increased iron
decreased hepcidin synthesis = increased iron absorption
occurs over years
transferrin levels in hereditary haemochromatosis
> 50% (normal 20-30%)
management of hereditary haemochromatosis
weekly venesection for life (take blood off them)
complications of untreated hereditary haemochromatosis
end organ damage = BAD
management of iron overload caused by repeated RBC transfusion
iron chelating durgs eg desferrioxamine
NOT venesection (like hereditary haemachromatosis) bc they need the Hb, just not the Iron
microcytic anaemia with target cells
thalassaemia
microcytic anaemia with rod cells
iron deficiency anaemia
