3.Anaemia Flashcards
Definition:
as a reduction of red cell mass,
but typically is described in terms of the haemoglobin concentration,
whose normal range in adult males is quoted as
between 130–180 g l–1,
and in adult females 115–160 g
reference data do vary between laboratories but encompass the 95% of adults who are
within two standard deviations of the mean
Causes
Causes: there are only three ways in which red cell mass will decrease:
through blood loss;
because of red cell destruction, usually by haemolysis;
and by failure of red cell production.
Within these three broad categories, however, there lie a myriad of causes
Red cell los
Red cell loss:
Obvious causes include
surgical,
civilian and military trauma,
ruptured aneurysms (typically abdominal aortic),
ruptured spleen,
burns,
ruptured ectopic pregnancy,
antepartum and
postpartum haemorrhage
placental abruption, placenta praevia, uterine atony).
Red cell destruction
Red cell destruction: there are both congenital and acquired causes of haemolysis
Congenital causes include
hereditary spheroctytosis,
haemoglobinopathies such as sickle cell disease,
and erythrocytic metabolic disorders such as
glucose-6-phosphate dehydrogenase deficiency.
acquired causes are
infection (such as mycoplasma, malaria, clostridia);
autoimmiune conditions such as autoimmune haemolytic anaemia itself,
Rheumatoid arthritis and systemic lupus erythematosus;
paroxysmal nocturnal haemoglobinuria
in which haemolysis is secondary to complement activation;
HELLP syndrome in pregnancy
haemolysis, elevated liver enzymes and low platelets).
Failure of red cell production
: common
nutritional causes include
lack of dietary iron,
generalized malnutrition,
vitamin B12 and folate deficiency.
Erythropoiesis is suppressed by the uraemia of chronic renal impairment
and is reduced, partially or even completely in
some myelodysplastic and myeloproliferative disorders
Erythropoiesis
: red cell precursors from pluripotent stem cells are produced in the
bone marrow and are released into the circulation as reticulocytes
(so named because they contain a reticular matrix of rRNA).
Within 24–48 hours these mature into erythrocytes and then remain viable for about 120 days.
Red cell production is under the influence of erythropoietin (EPO),
produced mainly in the kidney by interstitial cells in peritubular capillaries of the renal cortex.
EPO stimulates the production of erythroblasts,
which are stem cells that are committed to becoming erythrocytes.
It also stimulates angiogenesis and has an anti-apoptotic action.
Recombinant EPO can be used to raise haematocrit;
legitimately in patients and illegitimately in
athletes seeking to enhance performance.
As a separate effect it also increases the time to exhaustion.
It has a relatively short elimination half-life of 4–13 hours after
intravenous administration and can be detected in blood and urine.
The rate at which the haematocrit will increase depends on the indication for the drug and the
dose regimen employed.
Compensatory responses to anaemia
In chronic anaemia, there is the same imperative to maintain
oxygen delivery to the tissues but without the shifts of fluid between compartments
and without activation of the rapid humoral responses.
Cardiac output increases as do the production of erythropoietin
(which can rise by several hundred times)
the stimulation of erythropoiesis.
This may have little impact on the haematocrit,
depending on the cause underlying the anaemia.
Haemoglobin-oxygen affinity decreases so as to offload more oxygen,
and tissue oxygen extraction also increases.
Red cell morphology
: It would be unreasonable to expect a detailed account of the
numerous abnormal forms of erythrocytes,
but the commoner ones are outlined here
in the event that a simple description may be required from you as part of the overall
discussion.
The normal red blood cell is a biconcave, anuclear structure between
6 and 8 μm in diameter and with a volume of between 80 and 95 fl (this varies with
different laboratory reference values).
Of the many morphological abnormalities described,
the commoner ones include
Morphology of cell
microcytosis and hypochromia (typically due to iron deficiency anaemia);
macrocytosis typically associated with megaloblastic anaemia
due to vitamin B12 and folate deficiency,
liver disease and some myelodysplastic syndromes;
target cells with a dark centre with high haemoglobin content
(liver disease, haemoglobinopathies);
spherocytes, which are microcytic and circular
(haemolysis, post-transfusion);
tear drop cells, whose appearance is as described and which may be seen in severe anaemias; sickle cells, as in the anaemia of the same name; and schistocytes, which are fragmented cells seen after haemolytic processes and in severe coagulopathies
Oral iron supplementation:
the largest reservoir of iron in the body is in blood,
which contains around 500 mg in each 1,000 ml.
Otherwise iron is stored in ferritin complexes which
are most numerous in the liver, bone marrow and spleen.
Total body iron is variously quoted as around 5 mg kg–1 in females and up to 10 mg kg–1 in males.
Other sources quote a typical value in a healthy subject in the developed
world of 4–6 g.
Depleted iron stores can usually be corrected by oral iron, which is
inexpensive, effective and safe.
It is, however, associated with a number of low-level
gastrointestinal side effects,
including nausea, disturbed bowel function and epigastric
discomfort.
Absorption is increased if iron is in the ferrous form within an
acidic medium and so may be reduced in patients whose gastric pH is reduced by
proton pump inhibitors or histamine H2 receptor antagonists.
Iron metabolism is regulated by hepcidin,
a polypeptide produced in the liver which controls absorption
across the gut by inhibiting ferroportin (the iron export channel on gut
enterocytes) and which also controls iron export from macrophages.
If hepcidin concentrations are elevated,
which happens in response to various inflammatory
processes, then iron absorption from the gut will fall.
Effective repletion of iron stores is also reduced by compounds present in some foods which bind iron and prevent absorption.
These include phosphates and phytates
(for example in whole
grains, legumes and nuts) as well as all calcium-containing foods and liquids.
The maximal rate of elemental iron absorption after oral administration is around
25 mg daily.
Intravenous iron supplementation
: in contrast to oral iron, intravenous iron can replenish body iron stores after a single infusion, depending on the deficit.
Its use is indicated in those who either cannot tolerate or absorb oral iron.
These would include some pregnant women,
individuals with malabsorption syndromes and those
who have undergone bariatric surgery such as gastric bypass procedures and sleeve
gastrectomy.
Its effectiveness is not in doubt, and meta-analysis of controlled trials of
oral versus intravenous iron has shown a lower frequency of blood transfusion in the
intravenous group.
Dose regimens
although dose calculation tables are available which take into
account factors such as body weight and haemoglobin concentration,
it is more common to give a dose of 1,000 mg
(higher doses confer no clinical benefit). This
would be sufficient for the initial treatment of an iron deficit of 500–1,000 mg.
Side effects of intravenous iron:
anaphylactic reactions are very rare although possible,
as are non-allergic and non-life-threatening reactions such as urticaria
and lumbo-nuchal discomfort.
The incidence of these is quoted as <1%.
Patients with inflammatory arthropathies may experience exacerbations during treatment and may require pretreatment with increased doses of glucocorticoid.
The mechanism
underlying these exacerbations is not clear. Iron is a substrate for bacterial
growth and so should theoretically be avoided in those with active infection. In
practice the risks are generally considered to be low.
