Week 1 Flashcards
What are the 3 different mechanisms of action of Erythropoietin?
- Early release of reticulocytes.
- Inhibition of apoptosis
- Reduce processing time of blood cells. (released faster)
RBC’s consist of how many globin chains and how many pairs?
4 globin chains and 2 pairs.
Each globin has how many heme groups?
1
Does ferrous iron (Fe2+) combine irreversibly or reversibly with oxygen?
reversibly
Majority of RBC natural death occurs in the ________.
Spleen - extravascular macrophage mediated haemolysis.
When it comes to investigating haemolysis what are you looking for?
increased RBC destruction, increased RBC produciton, evidence of damaged RBC’s
Where does Intravascular and extravascular haemolysis take place?
Intravascular - within blood vessels
Extravascular - outside the blood vessels
Haemoglobinaemia (increased plasma Hb) decreased haptoglobin, increase plasma bilirubin (unconjugated, haemoglobinuria, haemosiderinuria (iron in renal tubules) are all evidence of extravascular RBC destruction or intravascular RBC destruction?
Intravascular
What is the normal way of removing majority of senescent RBC’s?
macrophage mediated (extravascular) haemolysis
Increased extravascular destruction can happen when RBC’s have abnormal markers and are removed. What are 3 examples of abnormal markers on RBC’s?
heinz bodies
intracellular parasites
immunoglobulins
What would be seen on a blood film if a macrophage ingested only part of RBC membrane?
Spherocyte - Remainder membrane seals gap with ↓ content
Is this evidence of intravascular or extravascular RBC destruction? increased urobilinogen (urine), increased plasma bilirubin, increased stercobilinogen (faecal) decreased haptoglobin.
Extravascular
What do intrinsic and extrinsic RBC defects refer to.
Intrinsic - in the RBC itself
Extrinsic - the environment surrounding the RBC
Give 3 examples of intrinsic defects.
Membrane abnormalities (eg. spherocytosis) Enzymopathies( G6PD deficiency) haemoglobinopathies (sickle cell, thalassemias)
What are some laboratory findings for hereditary spherocytosis?
Anaemia = yes normally Retic = normally increased MCV & MCH = normal MCHC = increased Blood film = spherocytes RDW= increased
List 3 other tests to determine hereditary spherocytosis
- DAT
- Osmotic fragility test
- Autohaemolysis test
What does a neg DAT mean?
No Antibody/s bound to RBC
What DAT result would you expect in a patient with hereditary spherocytosis?
Neg
What does the DAT determine?
If RBC’s have been sensitised in vivo. Is there an antibody bound to the RBC
Describe the osmotic fragility test.
RBC’s are added to increasing hypotonic NaCl solutions. H2O enters cell until equilibrium is achieved. Cell swells until membrane cannot withhold the pressure
In the osmotic fragility test what would you expect a patient with hereditary spherocytosis to have?
RBC lysis beginning earlier in lower concentrations of the hypotonic NaCl solutions.
Describe an autohaemolysis test.
RBC are incubated in own plasma. RBC’s lyse gradually. (5% after 48 hours) more if glucose is added
What would the result of an autohaemolysis test be in a patient with hereditary spherocytosis?
haemolysis is much greater after 48hr (10-50% lysis)
Is eliptocytosis and ovalocytosis more common in malria endemic areas?
Yes
What are 2 most common enzymopathies?
G6PD - deficiency
Pyruvate Kinase deficieny.
List three triggers of oxidative stress?
- Infection (most common)
- Some drugs
- Fava beans
What are Heinz bodies and how do you visualise Heinz bodies?
Denatured Hb seen with a supravital stain eg. crystal violet
Haemoglobinopathies are all due to mutations in what?
Gene mutation
Haemoglobinopathy that has a structural defect is
Sickle cell disease = quality of Hb
Haemoglobinopathy that has a reduced rate of synthesis
Thalassemia = defect in quantity
Describe why a patient with sickle cell disease might experience joint pain
Sickle RBC’s are less soluble & less deformable, more fragile, leads to haemolysis, leads to vessel occlusion leading to infarct. Increase susceptibility to infection.
List other screening tests for sickle cell disease.
- Hb electrophoresis
2. Haemoglobin solubility test
What would be the difference between sickle cell trait and sickle cell anemia on an electrophoresis test?
Sickle cell anemia would be all HbS. Sickle cell trait would HbS plus another Hb beta chain.
What is the most severe form of Thalassemia?
Beta thal major
Would the MCV be low or high in a patient with Thalassemia?
Low
Blood film of a patient with thalassemia could include.
Target Cells Elliptocytes other poikilocytes basophilic stippling nucleated RBC (major thal)
Alloantibodies means
Antibodies to foreign
Autoantibodies means
Antibodies to self
Besides malaria what are some other causes of non-immune RBC haemolysis?
Drugs, chemicals, venoms, burns
What are the two types of Auto antibody?
Warm autoimmune (most common) Cold agglutinins
WARM AUTOimmune Haemolytic Anaemia (WAIHA) is what Ig class?
IgG
Normal age group for WARM AUTOimmune Haemolytic Anaemia (WAIHA) is
under 4 and over 40
What is the Ig class for COLD Agglutinin Disease (CAD)
IgM (4 degrees optimal)
What can be a source of foreign Ag to cause ALLO immune Haemolytic Anaemia?
Blood transfusions
How is Drug-Induced Immune Haemolytic Anaemia different to drug-induced haemolytic Anaemia?
in DIIHA drug us absorb to the RBC = immune complex - Ab is porduce against it - DAT will be positive
List 3 conditions with small RBC’s and briefly discuss why the RBC’s are smaller
Thalassemia minor - reduced synthesis of the globin chain of hemoglobin
iron deficiency - disruption of iron supply
Sideroblastic anemia
List 3 conditions with large RBC’s and briefly discuss why the RBC’s are larger
Megaloblastic anaemia
Alcoholism
Pernicious anaemia
What is the most common cause of microcytic anemia?
iron deficiency
