Anaemia Flashcards
definition of anaemia
reduced total red cell mass
where does red cell production take place in adults
bone marrow
what is the bone marrows response to anaemia
Increased RBC production- reticulocytosis
what are reticulocytes
red cells that have just left the bone marrow
larger than average red cells
still have RNA remnants
stain purple/deeper red as a result
what are the 2 ways anaemia can be classified
pathophysiology
morphological characteristics
what are the two categories of anaemia pathophysiology
Decreased production (low reticulocyte count) Increased loss or destruction of red cells (high reticulocyte count)
causes of decreased RBC production
hypoproliferative- reduced amount of erythropoiesis e.g. chronic kidney disease, aplastic anaemia
Maturation abnormality- erythropoiesis present but ineffective
name some maturation abnormalities that cause decreased RBC production
Cytoplasmic defects: impaired haemoglobinisation (results in small cells)
Nuclear defects: impaired cell division (results in big cells)
what causes loss/destruction of RBCs
bleeding
haemolysis
what is a useful tool in distinguishing cytoplasmic and nuclear defects
mean cell volume
how can anaemia be classified by morphology
MCV low = microcytic
MCV high = macrocytic
what should you consider if MCV is low
problems with haemoglobinisation (cytoplasmic defect)
what should you consider if MCV is high
problems with maturation
where does haemoglobin synthesis occur
in the cytoplasm
what is needed to make Hb
globins
Haem: porphyrin ring, Iron (Fe 2+)
what does the inability to make Hb result in
small, pale red cells with a low Hb content
Microcytic (small) and hypochromic (lacking in colour)
causes of hypochromic, microcytic anaemia
Haem deficiency Globin deficiency (thalassaemia)
what 2 states can iron exist in the body
Fe2+ - ferrous iron
Fe3+ ferric iron
why iron important
oxygen transport- Hb, myoglobin
Electron transport- mitochondrial production of ATP
What does iron generate
free radicals
where is most of the iron in our bodies found
in the haemoglobin
how is iron stored in the body
as ferritin in tissues, mainly the liver and macrophages
what is circulating iron bound to
transferrin
how can we assess iron status: functional, transported and storage
functional: Hb
Transported: serum iron, transferrin, transferrin saturation
Storage iron: serum ferritin
function of transferrin
takes iron from donor tissues (macrophages, hepatocytes) to tissues expressing transferrin receptors
how many binding sites for iron does transferrin have
2
what does % saturation of transferrin with iron measure
iron supply
what does changes in transferrin suggest when reduced/increased
Reduced in iron deficiency and anaemia of chronic disease
Increased in genetic haemachromatosis
what does low ferritin indicate
iron deficiency
causes of iron deficiency
not eating enough
blood loss (usually GI- tumours, ulcers, NSAIDs)
Malabsorption (coeliac disease)
Menorrhagia (>60mls)
where is iron absorbed in the bowel
duodenum
consequences of negative iron imbalance
- exhaustion of iron stores
- iron deficient erythropoiesis - falling red cell MCV
- Microcytic anaemia
- Epithelial changes e.g. koilonychia
what is important to remember about iron deficiency anaemia
it is a symptom not a diagnosis- needs investigating
what is macrocytic anaemia
anaemia where red cells have a larger than normal mean cell volume
what is a megaloblast
an abnormally large nucleated red cell precursor with an immature nucleus
what are megaloblastic anaemias characterised by
defects in DNA synthesis and nuclear maturation with preservation of RNA and Hb synthesis
consequences of megaloblastic changes
while the cytoplasm has developed and become mature enough to divide, the nucleus is still immature
Leads to a bigger than normal red cell precursor
in summary, what causes the larger cell size in megaloblastic anaemia
cell failure to become smaller
what causes megaloblastic anaemia
B12 deficiency
Folate deficiency
Drugs
Rare inherited abnormalities
why does a lack of B12/folate cause megaloblastic anaemia
B12 and folate are essential co-factors for nuclear maturation
They enable chemical reactions that provide enough nucleosides for DNA synthesis
what cycle is B12 responsible for
methionine cycle
what cycle is folate responsible for
folate cycle
what does the methionine cycle produce
s-adenosyl methionine, a methyl donor to DNA, RNA, proteins, lipids, folate intermediates
what is the folate cycle important for
nucleoside synthesis (e.g. uridine to thymidine conversion)
what is the pathway of B12 absorption
- comes as cobalamin (Cbl) in meat/eggs
- acid in the stomach makes Cbl separate and bind to hepatocorrin (HC)
- Intrinsic factor (IF) formed in the stomach
- they all travel together in the gut
- pancreas raises the pH causing Cbl to separate from HC
- Cbl now binds to IF
- Cbl-IF binds to cubulin receptors in the distal bowel (ileum)
- Cbl transported into the blood vessels
causes of B12 deficiency
dietary (e.g. vegan) pernicious anaemia atrophic gastritis chronic pancreatitis coeliac disease crohns disease
what are dietary folates converted to and where are they absorbed
converted to mono glutamate
absorbed in the jejunum
how long do body stores of B12 and folate last
B12- 2-4 years
Folate- 4 months
causes of folate deficiency
inadequate intake
malabsorption (coeliac, crohns)
Excess utilisation (haemolytic, pregnancy, malignancy)
drugs (anti-convulsants)
features of B12/Folate deficiency
symptoms/signs of anaemia (fatigue, dyspnoea, headache, palpitations)
weight loss, diarrhoea, infertility, jaundice, developmental problems
what symptom is specific to B12 deficiency
neurological problems:
- posterior/dorsal column abnormalities
- neuropathy
- dementia
- Psychiatric manifestations
what spinal problem is seen in B12 deficiency
subacute combined degeneration of the spinal cord
what is pernicious anaemia
autoimmune condition which results in destruction of gastric parietal cells
these cells produce intrinsic factor– results in intrinsic factor deficiency with B12 malabsorption and deficiency
what conditions are associated with pernicious anaemia
atrophic gastritis, hypothyroidism, vitiligo, Addison’s disease
blood results seen in pernicious anaemia
Macrocytic anaemia (red cells large + low)
Pancytopenia (all cells low)
Macrovalocytes (enlarged, oval shaped erythrocytes)
Hypersegmented neutrophils
What should be checked in pernicious anaemia
Serum folate and B12
Autoantibodies:
anti gastric-parietal cells: autoimmune gastritis
Anti-intrinsic factor
treatment of megaloblastic anaemia
Treat the cause
For pernicious anaemia- vit B12 injections for life
Folic acid 5mg oral daily
what is injections of vitamin b12 called
hydroxycobalamin
what are causes of macrocytosis split into
Genuine: megaloblastic/non-megaloblastic
Spurious
Non-megaloblastic causes of macrocytosis
Alcohol
Liver disease
Hypothyroidism
(these may not be associated with anaemia)
Marrow failure: Myelodysplasia, Myelomo, Aplastic anaemia
what is meant by megaloblastic anaemia
inhibition of DNA synthesis during RBC production
When DNA synthesis is impaired, it leads to continuing cell growth without division, which presents as macrocytosis
what is spurious macrocytosis
The size of the mature read cell is normal but the MCV is high
causes of spurious macrocytosis
Increase in reticulocyte numbers as marrow responds to acute blood loss or RBC break down
Cold-agglutinins (abnormal proteins that cause clumping of RBC)
If the reticulocyte count is raised, what should you consider
haemorrhage
haemolysis
if the reticulocyte count is low in a macrocytosis, what investigation should be done next
serum B12 + Folate
If serum B12 and/or folate is high, what causes should be considered
Myelodysplasia
Myeloma
Aplastic anaemia
If serum B12 and/or folate is low, what is the likely diagnosis
megaloblastic anaemia
why can liver disease cause a low platelet count
leads to hypersplenism – increased destruction
what can people with pernicious anaemia present with
mild jaundice due to intramedullary haemolysis
why do people get jaundice in pernicious anaemia
Red cells die prematurely in the bone marrow
Haemoglobin and lactate dehydrogenase (LDH) are released from dead red cells
Haemoglobin is converted to bilirubin
what can complicate severe megaloblastic anaemia
pancytopenia
What are the two headings for classifications of anaemia
Decreased production (would see reticulocytopenia) Increased loss or destruction of RBCs (would see reticulocytosis)
what is seen in increased haemolysis of RBCs
Increased unconjugated serum bilirubin
Increased urinary urobilinogen
Result is anaemia + jaundice, sometimes with splenomegaly
commonest cause of hypo chromatic microcytic anaemia
iron deficiency
what is the platelet count in iron deficiency anaemia
low
other less common causes of microcytic anaemia
Thalassaemia
investigation of thalassaemia
electrophoresis
HPLC
nutritional causes of macrocytic anaemia
B12 deficiency Folate deficiency (This causes megaloblastic anaemia)
causes of macrocytic anaemia
myelodysplasia myeloma aplastic anaemia reticulocytosis cold agglutinins
when can you see a macrocytosis without anaemia
alcohol
liver disease
hypothyroid
what are the causes of normochromatic normocytic anaemia
Acute blood loss/early iron deficiency Hypoproliferative: -Chronic diseases - Anaemia of renal failure -Hypothyroidism - Marrow failure
How is EPO production affected in renal failure
It decreases
what is the big differentiating factor for anaemia caused by iron deficiency and anaemia of chronic disease
Iron deficiency = reduced ferritin
Chronic disease = normal/increased ferritin
