Anaemia Flashcards
define anaemia
the reduction in the haemoglobin concentration in the blood ie when hb falls below reference range for age and sex of an idividual
how is the reference range obtained
from a representative sample of healthy individuals in whom iron deficiency has been excluded
what are the mechanisms of anaemia
blood loss decreased red cell survival impairment of red cell formation- insufficient or ineffective erythropoiesis pooling of blood in spleen increased plasma volume in pregnancy
what can cause impaired red cell formation
deficiency of essential haematinics
chronic disorders eg infection, renal disease
marrow infiltration eg carcinoma
endocrine deficiency
myelotoxic agents - cause aplastic anaemia
miscellaneous- myelodysplasia. thalassaemia syndromes
what is the distribution of iron in the body
found in plasma and all cells
ionised iron is toxic- most iron is contained in the harm moiety in Hb, myoglobin and cytochrome or is bound to a protein e.g. ferretin, transferrin or haemosiderin.
the total iron in a healthy adult is 2-5g. approximate 2g in red cell mass
0.15g in myoglobin in muscle and respiratory enzymes.
the remainder is stored in macrophages of spleen and BM and in Kupffer and parenchymal cells of the liver.
iron stores 0-1g
what are the two forms of iron storage
ferritin
haemosiderin
what is ferritin
ferritin is an iron storage. it is water soluble adn consists of a protein shell containing up to 4500 atoms of iron ( not stainable by PERLS reaction)
what is haemosiderin
an iron storage. is insoluble and consists of ferritin aggregates which have lost part of their protein shell, it can be stained by PERLS reaction
what is the dynamic state of body iron
iron is continually circulated bound to transerffin.
most of iron comes from destruction of red cells (20mls per day = 20 mg iron)
further 5 mg comes from iron stores adn iron absorption in the GI tract
plasma iron is removed by erythropoietic tissue in BM- some goes to other dividing cells.
halftime for passage of iron is 50-110 minutes depends on plasma irpn concentration
how is iron absorbed
present in food (mainly meat)
ferric iron must be reduced to ferrous form before it can be absorbed.
ascorbic acid promotes absorption of non haem iron because it is a reducing agent and can form a complex with the iron that is readily absorbed
iron entering the gut is passed either to transferrin or to apoferritin to form ferritin
transfer of iron is in response to iron requirements
how is iron lost
iron is highly conserved. no specific excretion mechanisms- some iron is lost when gut and skin cells exfoliate
what are the three stages of iron depletion that lead to iron deficiency anaemia (IDA)
depletion of iron stores- supply to tissues not diminished, no anaemia
further depletion of iron stores- reduced iron supply to tissues
IDA - fall in hb and ida blood picture ie microcytic hypochromic anaemia.
iron depletion without anaemia is more common than IDA
what are the causes of iron deficiency
reduced iron stored at birth due to prematurity
inadequate intake - prolonged breast or bottle feeding, vegetarian diet, poverty
increased requirement: pregnancy or lactation
blood loss
malabsorption
chronic intravascular haemolysis (rare)
what are the symptoms of IDA
malaise fatigue faintness/ dizziness lack of concentration palpitations shortness of breath
what are the haematological findings for IDA
FBC- HB,MCV and MCH low MCHC may be low but tends to fall later
Blood film microcytic hypochromic red cell picture with pencil cells +/- target cellsone marrow stained with PERLS shows no iron stores
Serum iron is < 9g/dl
Low serum ferritin
Transferrin and transferrin saturation rise in IDA
Increased Transferrin receptors in IDA
what is the treatment for IDA
oral administration of anhydrous ferrous sulphate
min response is 2g/dl rise in 3 weeks
if there is no response check for, non compliance, intolerance to ferrous sulphate (use ferrous gluconate), malabsorption syndrome, bleeding, Vit B12/folate deficiency or wrong inital diagnosis ?thalassaemia
what are hereditary haemolytic anaemias
they are anaemia that are inherited
those haemolytic anaemias which are the result of intrinsic red cell defects
what is sickle cell anaemia
is a group of disorders in which the sickle B globin gene is inherited.
homozygous HbSS is the most common but also doubly heterozygous HbSC and HbS Bthal cause sickling disease
due to substitution Beta 6 glutamic acid for valine
HbS (22s ) is insoluble and forms crystals at low oxygen tensions
what is Visceral sequestration crises
caused by sickling in organs and pooling of blood
exacerbates anaemia
acute sickle chest syndrome is the most common casue of death post puberty- presents with dyspnoae, falling PO2, chest pain and pulmonary infiltrates on Xray- treatment is oxygen, analgesia, exchange transfusion and ventilation if required.
hepatic, girdle and splenic crises may all lead to severe ilness requiring exchange transfusions
splenic sequestration is most common in infants, presents with enlarged spleen, abdo pain adn falling Hb
attacks tend to be recurrent, splenectomy may be advised.
what is aplastic crises
may occur as a result of infection with parvo virus or by folate deficiency
characterised by sudden fall in Hb
fall in reticulocytes
usually require transfusion
haemolytic crises (increased rate of haemolysis) show fall in Hb but there s a reticulocytosis
name of some other clinical features
ulcers of lower legs- due to vascular stasis and local ischaemia
splenomegally in infancy- - size reduces in later life due to infarcts
chronic liver damage due to infarcts
pigment gallstones
kidneys vulnerable to infarctions of the medulla with papillary necrosis
what would be the laboratory findings with HHA
Hb usually 6-9g/dl- low in comparison to symptoms of anaemia.
Sickle cells and target cells occur in blood (maybe Howell jolly bodies if splenectomy or autosplenectomy has occurred)
Screening tests for HbS are positive
Hb electrophoresis or HPLC shows HbS and HbF (5-15%) bands with no HbA (unless transfused)
what is the sickle solubility test
screening test based on the decreased solubility of HbS in conditions of reduced oxygen concentration.
mixture of blood containing HbS and a reducing solution will give a turbid solution.
normal Hb will give a clear solution
positive and negative controls should be run with each test
wash resuspended (to 50%) red cells should be used to:
remove the effects of plasma proteins
to avoid false negative results due to low Hb (HbS <20% can giv ean equivocal result or false negative)
any positive S test result should be confirmed by another method eg electrophoresis or HPLC
what is HPLC
high performance liquid chromatography
what is involved in HPLC
used for the separation and determination of the relative percentages of normal and adnormal haemoglobins
uses the binding properties of the target substances to a solid phase (the column) for the seperation process.
the different types of Hb normal and adnormal are eluted from the column using a buffer gradient
the individual components of the lysed blood will seperate according to their charge
the %age of each type of haemoglobin is proportional to the area under the peak (this is calculated automatically by semi automated and automated HPLC systems)
adnormal peaks should be confirmed by a second method (eg s test or IEF if not S)
what is the treatment HHA
avoid factors which percipitate crises folic acid good nutrition pneumococcal and haemophilus vaccines crises treat with rest, rehydration warmth, analgesia, antibiotics if infection
care needed in pregnancy and in analgesia
transfusion- aim to suppress HbS production
Hydroxyurea increases HbF levels which protects against sickling (not to be used in pregnancy)
stem cell transplantation (mortality rate <10% but only for severe cases)
what is sickle cell trait
benign condition
red cells appear normal on blood film, unless reduced oxygen levels
25-45% of total Hb
haematuria most common symptom- thought to be caused by minor infarcts of renal papillae
care must be taken during anaesthesia, pregnancy and high altitudes
important to screen antenatak patients for sickle trait (and partners if mother HbAS)
if both parents have sickle cell trait there is a 1 in 4 chance of the body having sickle cell disease.
