Haematology - Blood Cell Abnormalities

Question 1

Leukaemia - general

Answer 1

Bone marrow disease, cancer because of mutation in precursor of myeloid/lymphoid cell

Question 2

Leukaemia - mutations

Answer 2

growth/survival advantage in primitive cell due to mutations -> clone -> replacing of normal cells; mutations in proto-oncogenes + tumor suppressor genes, germline mutations can be beneficial (evolution) but somatic rarely are (can be neutral or positively harmful, in latter apoptosis or cancer), random or because of mutagen exposure, older = more likely for enough spontaneous/induced mutations

Question 3

Leukaemia - classification

Answer 3

abnormal cells circulate and migrate into various tissues so unlike solid tumours = acute/chronic rather than malignant/benign (acute = profound pathological effects, death in at most months)

Question 4

Leukaemia - abnormal behavior of leukaemic clone

Answer 4

growth independent of growth factors, continued proliferation without maturation, failure to undergo apoptosis

Question 5

Leukaemia - nature of mutation

Answer 5

Determines leukaemia nature, acute = mutations in transcription factor genes (abnormality in cell maturation but continue to proliferate = accumulation of primitive blast cells (lympho-/myeloblasts))

Question 6

Leukaemia - CML

Answer 6

Activation of signalling pathways (fusion protein BCR-ABL1 encoded by A(9;22) Philadelphia chromosome) so cells proliferate without growth factors but maturation still occurs so effect less severe

Question 7

Leukaemia - CLL and ALL

Answer 7

CLL Unknown, mainly elderly; ALL mainly children

Question 8

Leukaemia - symptoms

Answer 8

Direct effects of leukaemic cell proliferation (bone pain, hepatomegaly, splenomegaly, lymphadenopathy (mainly in lymphoid ones)), indirect (replacement of normal bone marrow with leukaemic ones = anemia, thrombocytopenia, neutropenia), clinical features = fatigue + lethargy + pallor (anemia), fever + infections (neutropenia), petachiae (puntini rossi) + bruising (thrombocytopenia)

Question 9

Leukaemia - investigations

Answer 9

Full blood count and film, cytometry (profile of surface markers expressed ie to distinguish between B and T cells), cytogenetic/molecular genetic analysis from bone marrow sample

Question 10

Anemia - general

Answer 10

Reduction in [Hb], RBC count and Hct

Question 11

Anemia - mechanisms

Answer 11

Reduced RBC production by bone marrow, blood loss, haemolysis, increased RBC pooling in splenomegaly

Question 12

Anemia - microcytic

Answer 12

Usually associated to hypochromia, iron deficiency (1), chronic disease (2), thalassemia (3)(1 and 2 = reduced haem synthesis, 3 = reduced globin synthesis)

Question 13

Anemia - of chronic disease (ACD)

Answer 13

Usually inflammatory aspect to underlying disease, rheumatoid arthritis + autoimmune disease + malignancy + kidney disease + infections (ie TB and HIV), cytokines like TNF alpha and interleukins in chronic disease = decrease in epo production and prevent normal Fe flow from duodenum to RBCs (both mediated by hepcidicin), treating ACD with iron replacement therapy (as with iron deficiency anemia) will not help and should be avoided because there is plenty of storage iron, control underlying disease or if not possible -> epo treatment

Question 14

Reticulocyte count

Answer 14

Expose living red cells to new methylene blue that stains higher RNA content (polychromasia also has pink from haemoglobin), high = response to haemolytic anemia + recent blood loss + treatment with iron and vitamin B12 and folic acid, low = reduced RBC output by bone marrow