Blood Cell Abnormalities Flashcards
What is anaemia?
A reduction in the amount of haemaglobin in a given volume of blood, below what would be expected in comparison with a healthy subject of the same age and gender
What are the four mechanisms of anaemia?
PPLS Production - reduced production of RBC Pooling - RBC may pool in the spleen Loss - RBCs may be lost due to blood loss Survival - reduced survival of RBCs
What is meant by microcytic RBCs
Smaller than usual - normally hypochromic and can therefore be identified by their larger area of central pallor
What causes microcytic anaemia?
Occurs either due to a loss of HAEM or GLOBIN
HAEM loss = due to iron deficiency
GLOBIN loss = thalassemia
What causes an iron deficiency?
Heavy menstruation, diet, malabsorption,
What is macrocytic anaemia?
When the red blood cells are larger than normal
What causes megaloblastic anaemia?
Deficiency of folate or B12 - cells are continuing to divide by cannot synthesize the DNA therefore just keep growing
What causes macrocytosis?
Abnormal haematopoiesis - red cell precursors continue to make Hb and other proteins but do not divide properly
How to diagnose megaloblastic anaemia?
Bone marrow examination
Causes of normocytic anaemia?
Recent blood loss - trauma, gastrointestinal bleed
Failure of production
Pooling of RBC in spleen
What is splenic sequestration?
When sickle cells get trapped in the spleen, leading to hyposplenism and the spleen not functioning properly
What is polycythemia?
Too many red cells in circulation
What causes polycythemia?
Blood doping or transfusions
Increased EPO - can be appropriate or inappropriate
What is pseudo polycythemia?
When you have a reduced plasma volume, so it looks like the RBCs take up a larger proportion of the blood colume
What causes a reduced plasma volume?
Dehydration
What is leukemia?
A cancer arising as a result of a mutation in a precursor of myeloid or lymphocyte cells
How is leukemia different to other cancer?
The cells involved circulate in the blood so invasion / metastasis doesn’t apply here
What are the four types of leukemia?
Acute Lymphoblastic Leukemia
Chronic Lymphocytic Leukemia
Acute Myeloid Leukemia
Chronic Myeloid Leukemia
What does acute mean in the context of leukemia?
Profound pathological affects, fatal in days
What does chronic mean in the context of leukemia?
Takes years to be fatal
What genes are mutations in to cause leukemia?
Proto-oncogenes and tumour suppressor genes
What are the three I’s of leukemic clones?
Immortal, independent and immature
What does the abnormal behavior of leukemia clones include?
growth without the need for growth factors
Proliferation without maturation
Failure to undergo normal cell death
What are some causes of leukemogenic mutations?
Irradiation eg X Rays
Chemicals eg Benzene
Anti cancer drugs
Cigarette smoke
What is the difference between AML and CML?
In AML - there is failure of production of end cells
In CML - there is too much production of end cells
What happens in AML?
There is too many immature myeloblasts in the bone marrow - cells continue to divide but cannot nature. Failure of production of end cells like neutrophils, basophils etc
What happens in CML?
Too many mature cells end cells - reduced apoptosis so end cells do no die
What is hepatomegaly?
Increased liver size
What disease characteristics does leukemia lead to?
Enlarged liver, enlarged spleen (splenomegaly), lymphomegaly (enlarged lymph nodes), thymic enlargement (if lymphoid leukemia)
What is thrombocytopenia?
Lack of platelets - can arise from leukemia
What mutation causes CML?
Translocation between chromosome 9 and chromosome 22, forming the BCR-ABL1 gene which gives the cell a growth and survival advantage
What happens in CML?
Increase in ALL GRANULOCYTES and their precursors = splenomegaly
What can CML be inhibited by?
Specific tyrosine kinase inhibitors - inhibits the tyrosine kinase which the BCR-ABL1 protein makes which stops the bone marrow from making abnormal cells
What is ALL?
Acute lymphoblastic anaemia - replacement of normal bone marrow cells with lymphoblasts
What can ALL cause?
Thrombocytopenia, anaemia
Which leukemia occurs more commonly in children?
ALL
How to treat ALL?
Supportive - give them the cells they are missing
Chemithearoy
An aspiring bodybuilder repeatedly takes steroid injections during his training for a competition. What could occur as a result? And why?
Polycythaemia - repeated steroid injections increase testosterone levels which acts on the kidney to increase erythrocyte production, leading to polycythaemia
What can increase the risk of leukaemia?
Increased chromosomal breaks, inability to repair DNA normally
What are some identifyable causes of leukaemogenic mutations?
Irradiation
Anti-cancer drugs
Cigarette Smoke
Chemicals eg benzene
In Chronic Myeloid Leukaemia, cells become independant of external signals. What affect does this have?
There are changes seen in the interactions with the stroma and reduced apoptosis
What types of genes are affected to cause chronic myeloid leukaemia?
Genes encoding proteins in signalling pathways between a cell surface receptor and the nucleus eg membrane receptor
Why is there a build up of immature cells (myeloblasts) in the bone marrow and in the blood?
Cells continue to proliferate but no longer mature
Mutations in what genes usually cause Acute Myeloid Leukaemia?
Mutations in transcription factors for multiple genes causing profoundly disturbed cell behaviour
What are the haematological features of Acute lymphoblastic Leukaemia?
Thrombocytopenia, replacement of normal bone marrow cells by lymphoblasts, neutropenia, normochromic and normocytic anaemia
What are five supportive treatments for acute lymphoblastic leukaemia?
red cells, platelets, antibiotics, intrathecal chemotherapy, systematic chemotherapy
