Anaemia Flashcards
definition of anaemia
reduced total red cell mass
- Hb concentration is a surrogate marker
where does red cell production take place
bone marrow
what is the bone marrows response to anaemia
Increase red cell production-
Reticulocytosis
what are reticulocytes
Red cells that have just left the bone marrow
Larger than average red cells
Still have remnants of protein making machinery (RNA)
Stain purple/deeper red as a consequence
what are the 2 ways we classify anaemia
pathophysiology
morphological characteristics
what are the two subcategories of pathophysiology
decreased production (low reticulocyte count)
increased loss/destruction of RBC (high reticulocyte count)
what can cause decreased production of RBC
Hypoproliferative – reduced amount of erythropoiesis
e.g. chronic kidney disease, aplastic anemia
Maturation abnormality – erythropoiesis present but ineffective
what type of maturation abnormalities cause problems in the production of RBC
Cytoplasmic defects: impaired haemoglobinisation (result in small cells)
Nuclear defects: impaired cell division. (result in big cells)
what causes a loss/destruction of RBC
Bleeding
Haemolysis
how can an anaemia be classified by morphology
MCV low = microcytic
MCV high = macrocytic
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 and hypochromic
what causes a hypo chromic microcytic anaemia
haem deficiency
- lack of iron
globin deficiency
- thalassaemia
what two states can iron exist in in the body
Fe2+ = ferrous iron
Fe3+ = ferric iron
why is iron essential
Oxygen transport
- Hb, myoglobin
Electron transport
- Mitochondrial production of ATP
what does iron generate
free radicals
where is most of our body’s iron
in the haemoglobin
how is iron stored in the body
as ferritin in tissues, mainly the liver
and as ferritin in macrophages
what is circulating iron bound to
transferrin
what do the macrophages do with ferritin
feed it to red cell precursors
how can we assess iron - functional, transported and storage
functional
- Hb
transported
- serum iron
- transferrin
- transferrin saturation
storage
- serum ferritin
what does transferrin do
takes iron from donor tissues (macrophages, intestinal cells and hepatocytes) to tissues expressing transferrin receptors (esp erythroid marrow)
what does measuring transferrin show
iron supply
what does changes in transferrin suggest when reduced/increased
reduced in iron deficiency
reduced in anaemia of chronic disease
increased in genetic haemachromatosis
what does serum ferritin show and what does low ferritin mean
storage of iron
low ferritin = iron deficiency
what blood results are seen in iron deficiency
low Hb i.e. anaemia
low serum ferritin i.e. reduced storage iron
what are causes of iron deficiency
not eating enough
blood loss (usually GI - tumours, ulcers, NSAIDs)
malabsorption (coeliac disease)
menorrhagia (>60ml)
where is iron absorbed in the bowel
duodenum
what are the consequences of a negative iron balance
- Exhaustion of iron stores (in the liver)
- Iron deficient erythropoiesis
- Falling red cell MCV - Microcytic Anaemia
- Epithelial changes
- koilonychia (spoon nails)
- angular stomatitis
what is important to remember about iron deficiency anaemia
it is a Sx and requires Ix for an underlying cause
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 haemoglobin synthesis
what are the consequences of megaloblastic changes
While the cytoplasm has developed and become mature (and big) enough to divide, the nucleus is still immature
causes a bigger than normal red cell precursor
so in summary, what causes a 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 or 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 is B12 and folate responsible for
B12 = methionine cycle
folate = 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
what is the pathway of B12 absorption
1 - comes as cobalamin in meat/eggs
2 - acid in the stomach makes Cbl separate and bind to Hepatocorrin (HC)
3 - intrinsic factor formed in the stomach
4 - they all travel together in the gut
5 - pancreas raises the pH causing Cbl to separate from HC
6 - Cbl now binds to IF
7 - Cbl-IF binds to Cubulin recptors in the distal bowel (ileum)
8 - Cbl transported into the blood vessels by TC
causes of vitamin B12 deficiency
Dietary (e.g. vegan) Pernicious anaemia Atrophic gastritis Chronic pancreatitis Coeliac disease Crohn's disease
what are dietary folates converted to and where are they absorbed
converted to monoglutamate
absorbed in jejunum
how long do body stores of B12 and folate last
B12 = 2-4 years Folate = 4 months
what are causes of folate deficiency
Inadequate intake
malabsorption (Coeliac, Crohn’s)
Excess utilisation (haemolysis, pregnancy, malignancy)
Drugs (anticonvulsants)
features of B12/folate deficiency
Symptoms/signs of anaemia
weight loss, diarrhoea, infertility
Sore tongue, jaundice
Developmental problems
what Sx 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 cord
what is pernicious anaemia
Autoimmune condition with resulting destruction of gastric parietal cells (which produce intrinsic factor)
what is pernicious anaemia associated with
atrophic gastritis and personal or family history of other autoimmune disorders (eg. Hypothyroidism, vitiligo, Addison’s disease)
what blood results are seen in PA
Macrocytic anaemia (red cells low)
Pancytopenia (all cells low) in some patients
macrovalocytes (enlarged, oval-shaped erythrocytes)
hypersegmented neutrophils (normally 3-5 nuclear segments)
what should be checked in PA
Serum folate and B12
Auto-antibodies (anti gastric-parietal cells and anti-intrinsic factor)
what is the Tx of megaloblastic anaemia
treat the cause
for PA = vitamin B12 injections for life
folic acid 5mg per day
what is injections of vitamin B12 called
hydroxycobalamin
what are causes of a macrocytosis split into
genuine
- megaloblastic
- non-megaloblastic
spurious
what are non-megaloblastic causes of macrocytosis
- alcohol
- liver disease
- hypothyroidism
(these 3 might not be associated with anaemia)
marrow failure - myelodysplasia - myeloma - aplastic anaemia (all associated with 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 red cell is NORMAL, but the MCV is measured as being high
what are causes of a spurious macrocytosis
- increase in reticulocyte number as a marrow response to acute blood loss or RBC breakdown
- cold-agglutinins [abnormal proteins that cause clumping of RBC]
if the reticulocyte is raised what should you consider
haemorrhage
haemolysis
why can liver disease cause a low platelet count
lead to hypersplenism»_space; increased destruction
if the reticulocyte count is low in a macrocytosis what investigation should be done next
serum B12 and/or folate level
if serum B12 and/or folate is high what should be considered
myelodysplasia
myeloma
aplastic anaemia
what can people with PA present with
mildly jaundiced
- due to intramedullary haemolysis
why do people get jaundice in PA
Red cells die prematurely in the marrow
Haemoglobin and lactate dehydrogenase (LDH) are released from dead red cells
Haemoglobin converted to bilirubin
what can complicated severe megaloblastic anaemia
pancytopenia
what are the two headings for classification of anaemia
Decreased production (would see reticulocytopenia)
Increased loss or destruction of red cells (reticulocytosis)
what does it mean when there is a reticulocytosis
red cell production is increased
what are causes for a macrocytic anaemia
myelodysplasia myeloma aplastic anaemia reticulocytosis cold agglutinins
B12 and folate deficiency
when can you see a macrocytosis without anaemia
alcohol
liver disease
hypothyroidism
what are causes of a normochromic normocytic anaemia
Acute blood loss/early iron deficiency
Anaemia of renal failure
Hypothyroidism
Marrow failure
what do we get an anaemia in chronic kidney disease
Epo production decreases which normally stimulates erythropoiesis by bone marrow
what is the big differentiating factor for anaemia caused by iron deficiency and anaemia of chronic disease
Iron deficiency = ferritin reduced
chronic disease = ferritin normal/increased
how is the marrow in B12/folate deficiency
hypercellular
what is the platelet number in iron deficiency anaemia
low
how is thalassaemia Ix
electrophoresis
HPLC
