Anaemia

Question 1

define anaemia

Answer 1

the reduction in the haemoglobin concentration in the blood ie when hb falls below reference range for age and sex of an idividual

Question 2

how is the reference range obtained

Answer 2

from a representative sample of healthy individuals in whom iron deficiency has been excluded

Question 3

what are the mechanisms of anaemia

Answer 3

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

Question 4

what can cause impaired red cell formation

Answer 4

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

Question 5

what is the distribution of iron in the body

Answer 5

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

Question 6

what are the two forms of iron storage

Answer 6

ferritin

haemosiderin

Question 7

what is ferritin

Answer 7

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)

Question 8

what is haemosiderin

Answer 8

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

Question 9

what is the dynamic state of body iron

Answer 9

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

Question 10

how is iron absorbed

Answer 10

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

Question 11

how is iron lost

Answer 11

iron is highly conserved. no specific excretion mechanisms- some iron is lost when gut and skin cells exfoliate

Question 12

what are the three stages of iron depletion that lead to iron deficiency anaemia (IDA)

Answer 12

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

Question 13

what are the causes of iron deficiency

Answer 13

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)

Question 14

what are the symptoms of IDA

Answer 14

malaise
fatigue
faintness/ dizziness
lack of concentration
palpitations
shortness of breath

Question 15

what are the haematological findings for IDA

Answer 15

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

Question 16

what is the treatment for IDA

Answer 16

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

Question 17

what are hereditary haemolytic anaemias

Answer 17

they are anaemia that are inherited

those haemolytic anaemias which are the result of intrinsic red cell defects

Question 18

what is sickle cell anaemia

Answer 18

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 (22s ) is insoluble and forms crystals at low oxygen tensions

Question 19

what is Visceral sequestration crises

Answer 19

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.

Question 20

what is aplastic crises

Answer 20

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

Question 21

name of some other clinical features

Answer 21

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

Question 22

what would be the laboratory findings with HHA

Answer 22

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)

Question 23

what is the sickle solubility test

Answer 23

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

Question 24

what is HPLC

Answer 24

high performance liquid chromatography

Question 25

what is involved in HPLC

Answer 25

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)

Question 26

what is the treatment HHA

Answer 26

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)

Question 27

what is sickle cell trait

Answer 27

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.