Anaemia Flashcards
What is haemoglobin made up of?
Polyphyrin, haem + Fe atom and 4 polypeptide chains forming globin
What chains form HbA?
2 alpha and 2 beta
What chains form HbA2?
2 alpha and 2 delta - present in small amounts
What chains form HbF?
2 alpha and 2 gamma
What causes a left shift in the O2 dissociation curve?
An increase in pH or a decrease in temp, CO2, 2,3DPG
Causes HIGHER O2 affinity so less O2 delivery
What causes a right shift in O2 dissociation curve?
Decrease in pH or an increase in temp, CO2, 2,3DPG
Causes LOWER O2 affinity so high O2 delivery
Give an example of a Hb with a left shifted curve and conditions in which there is a right shifted curve.
Left = HbF
Right = Methaemoglobin - Fe3+ prevents O2 binding
Sickle cell HbS
Why don’t Sickle cell patients present as breathless?
O2 is more readily supplied due to the right shift allowing release of O2 more readily.
What is the function of 2,3DPG?
As O2 is released, beta chains pull apart and 2,3DPG binds within to further decrease the affinity of O2 and increase O2 delivery = right shift effect
Where is Hb synthesised?
Mitochondria
What is the definition and classification of anaemia?
A reduction in Hb concentration accompanied by reduced RBC count and packed cell volume/Haematocrit.
Males <130g.L
Females <115g.L
What is relative polycythemia and what may cause it?
A reduced plasma volume which elevates Hb concentration and masks anaemia e.g. Dehydration
What state may lead to apparent anaemia?
Pregnancy - Plasma volume increases and reduces the concentration of Hb
What happens to Hb at altitude?
Hb concentration increases to increase O2 transport due to the reduced availability in the atmosphere
What happens to O2 carrying capacity when Hb concentration changes?
Remains the same
What is the definition of O2 carrying capacity?
The amount of O2 that will bind to a Hb unit in blood.
What are the SYMPTOMS of anaemia?
Fatigue, SoB, palpitations, angina, drowsiness, headache
What are the SIGNS of anaemia?
Angular stomatitis (Mouth)
Koilonychia (nail spooning)
Conjunctiva pallor
=Iron deficiency
How can anaemia be classified?
Based on size of RBC and mean cell volume = Micro, normo, macro
Based on the cause = Reduced production, poor function, increased destruction
What type of conditions cause macrocytic anaemia?
DEFICIENCIES and DESTRUCTION
What type of conditions cause microcytic anaemia?
Conditions that directly affect Hb
What type of conditions cause normocytic anaemia?
Blood loss and all other causes
List the causes of macrocytic anaemia.
B12 and folate deficiency
EPO deficiency - Liver diseases and hypothyroidism
HSC reduction - myelodysplasia and aplastic anaemia
Haemolysis
Why does B12 and folate deficiency results in macrocytic anaemia?
Impairs production resultingin megaloblastic anaemia due to the release of immature RBCs.
B12 is absorbed in terminal ileum bound to IF from parietal cells so caused by Gastrectomy or pernicious anaemia (AI on Parietal) = IF deficiency
Diet
Intestinal malabsorption e.g. Crohn’s
What causes B12 deficiency?
B12 is absorbed in terminal ileum bound to IF from parietal cells so caused by Gastrectomy or pernicious anaemia (AI on Parietal) = IF deficiency
Diet
Intestinal malabsorption e.g. Crohn’s
What causes a folate deficiency?
Folate is absorbed in the duodenum and jejunum so is caused by
Diet
malabsorption e.g. Coeliac
What are the consequences of a reduced EPO and how does this arise?
Alcoholism leads to liver disease which results in reduced EPO production.
This fails to stimulate growth of thyroid tissue resulting in HYPOTHYROIDISM.
How does hypothyroidism present haematologically?
Macrocytosis in absence of anaemia. Lack of thyroid hormones fails to stimulate the growth of RBCs, so RBC stay enlarged.
What is Aplastic anaemia?
BM failure - HSC reduction shuts down blood cell production due to viruses such a Hep B, toxic drugs and radiation.
Requires BM transplant
What is Myelodyplasia?
BM wear and tear preventing maturation of precursors. Pre-leukaemic state.
What are the causes of haemolysis?
- Chronic haemolytic anaemia due to a G6PD deficiency, an X linked condition that is exacerbated by drugs, infection and fava beans.
- AI - Ig against RBC
- Hereditary spherocytosis - Ankyrin and spectrin mutations producing sphere shaped RBC
How can AI be detected?
+ve Coomb’s test
How does hereditary spherocytosis present?
Increase bilirubin due to increase Hb release and increased reticulocytes = Increased MCV
How is hereditary spherocytosis treated?
Splenectomy as destruction occurring within the circulation/intravascular
Why does MCV increases?
Failure in RBC production leads to the release of immature precursors such as reticulocytes which are larger cells.
What are the causes of normocytic anaemia?
Acute blood loss
Anaemia of chronic disease
Mixed deficiency anaemia
Ineffective erythropoeisis
What is anaemia of chronic disease?
Chronic inflammation, in conditions such as RA or TB, leads to increased expression of HEPCIDIN due to IL-6. This suppresses ferroportin-1 expression to inhibit the absorption of iron in the duodenum and inhibits release of iron from ferritin
When will acute blood loss present?
After 24hrs
What is mixed deficiency anaemia?
Malabsorption of iron, B12 and folate
How does ineffective erythropoeisis occur?
A reduction in EPO production due to chemotherapy or chronic renal disease
What causes microcytic anaemia?
Iron deficiency
Sickle cell
Siberoblastic anaemia
Thalasaemia
How does iron deficiency present haematologically? How can it be treated?
Deficiency can result from diet or CHRONIC blood loss (GIT or menorrhagia).
Reduced serum ferritin and increased transferrin. Investigate bledding with barium study or endoscopy.
Treat with iron tablets or ferrous sulphate tablets in blood loss.
What is thalasaemia?
A Hb defect caused by an autorecessive condition. Results in an alpha and beta globin imbalance during erythropoeisis and results in haemolysis. Haematopoeisis may begin to occur outside of the BM.
How is thalasaemia treated? What are the complications of this?
Repeated blodd transfusions to cause RBC overload and shut down the BM. May cause iron overload which should be treated with desferrioxamine.
What is sickle cell anaemia?
An autoressive mutation in beta globin causing chain polymerisation and deformity of RBC during deoxygenated state. Results in chronic haemolysis and vaso-occlusive crisis
What is sideroblastic anaemia?
BM produces ringed sideroblasts in place of RBC. Can be caused by drugs or congenital defect.
What is displacement?
Cells present in the BM that are foreign to the environment
What defines the macro and micro boundaries?
Macro >100
Micro <80
Normo = 80-96
What is relative polycythemia?
Decreased plasma volume increasing RBC concentration e.g. dehydration or plasma loss from burns
What is absolute polycythemia?
Increased RBC mass.
Primary - raised RBC in BM e.g. polcythemia vera
Secondary - raised EPO e.g. hypoxic conditions such as altitude and lung disease
What is the consequence of polycythemia?
THROMBOSIS
What is polycythemia?
Haematocrit >55% due to rise in RBC, WBC and platelets
What is erythrocytosis?
An increase in RBC line only
