231 - Anaemia

Question 1

what are the precursors to haematopoietic Stem Cells called (derived from aortic/gonadal/mesonephros region mesoderm in embryo)

Answer 1

Haemangioblasts - also become endothelium

Question 2

what do haemopoietic stem cells do?

Answer 2

reside in the bone marrow and other haemopoietic tissue and are the precursors to all blood cells - lymphoid progenitor (B,T and NK) and myeloid progenitor (RBC, platelets, monocytes,macrophages , neutrophils, etc). Proliferate/self renew in response to healing, blood loss, infection to maintain constant levels in tissue driven by growth factors

Question 3

what growth factors act on what haemopoeitic cells?

Answer 3

• haemopoeitc stem cells - stem cell factor incr stem cell production, IL-3 incr myeloid progenitor cell production
• Early multipotential cells - granulocyte montocyte colony stimulating factor(G_MCSF) stimulates monocyte and granulocyte production from myeloid progenitors
• Late progenitor cells - Erythropoietin (EPO) produced from kidneys due to low pO2 acc. RBC production, thrombopoietin (TPO) from liver and kidneys acc conversion of megakaryocytes to platelets, granulocyte colony stimulating factor (G-CSF) acc production of neutrophils

Question 4

what are reticulocytes?

Answer 4

immature RBC with nucleus still intact - released when marrow working hard eg blood loss

Question 5

what plasma proteins does plasma contain?

Answer 5

Albumin, globulin, fibrinogen

Question 6

where are the sites of haematopoiesis in foetus, children and adults?

Answer 6

• foetus - yolk sac until 3m, then liver and spleen 3-6m then bone marrow from 6m
• children - bone marrow mostly - long bones initially important then central bones
• adults - bone marrow of ribs, sternum, vertebrae and pelvis. long bones, spleen and liver may resume in times of high demand or leukaemia

Question 7

what does bone marrow consist of?

Answer 7

• bone trabeculae/osteoblasts/clasts,cytes
• collagen
• fat spaces
• arterioles, sinusoids and venules
• haemopoietic cells

Question 8

how can haemopoiesis be assessed?

Answer 8

• FBC - bone marrow function (reticulocyte no), vascular system integrity, plasma vol and content, impact of spleen
• bone marrow aspiration - fine needle removes fluid for exam of cell ratios and levels of maturation
• bone marrow biopsy via trephine - bore collects core for exam of architecture, hypocellularity (fat spaces)

Question 9

how can anaemia be classed?

Answer 9

• primary - congenital or immune - failure of production

* secondary - acquired - increased destruction

Question 10

what is idiopathic thrombocytopaenia (immune throbocytopaenic purpura)?

Answer 10

autoantibodies opsonise platelets which are lysed in spleen. causes incr in megakaryocytes, petechiae and purpura. Triggered by heparin, quinine

Question 11

what is hereditary spherocytosis?

Answer 11

mutation of genes responsible for RBC membrane proteins causing stiff spherical RBCs which don’t fit capilllaries and lyse easily

Question 12

what is aplastic anaemia?

Answer 12

autoimmune suppression of marrow stem cells triggered by radiation, viruses or drugs and causes pancytopaenia

Question 13

what is anaemia of chronic renal failure?

Answer 13

renal failure causes low erythropoietin resulting in low no of RBCs

Question 14

what is anaemia of chronic disease?

Answer 14

incr inflammatory cytokines lead to RBC precursor inhibition and decr iron availability. Done by release of hepcidin in the liver which decr fe absorbtion and release from stores

Question 15

what is pernicious anaemia?

Answer 15

autoimmune attack against gastric parietal cells causing decr intrinsic factor production - schilling test determines whether low B12 due to malabsorption or in terminal ileum or low intrinsic factor

Question 16

what is acute myeloid leukaemia?

Answer 16

clonal proliferation of primitive (abnormal) progenitor cell filling the bone marrow and then enters blood. Causes anaemia, neutropaenia and thrombocytopaenia. -chemo

Question 17

what is acute lymphoblastic leukaemia?

Answer 17

clonal proliferation of primitive lymphoblasts causing bone marrow failure. most common malignant childhood disease -chemo

Question 18

what is chronic myeloid leukaemia?

Answer 18

genetic mutation (Philadelphia translocation) caused abnormal tyrosine kinase producing proliferation and reduced apoptosis of granulocyte cells. Causes hypercatabolic symptoms, leucocytosis

Question 19

what is chronic lymphocytic leukaemia?

Answer 19

clonal proliferation of Bcells leading to decr Ig and decr immunity, lymphadenopathy. in elderly and no treatment reqd

Question 20

what is lymphoma?

Answer 20

proliferation of malignant lymphocytes originating in lymph organs leaving solid depositions in lymph glands/spleen/organs. Causes fever, night sweats and weight loss (cytokines), lymphadenopathy/splenomegaly. Hodgkins - reed Sternberg cells (giant B cells with double nuclei)

Question 21

what is myelodysplasia?

Answer 21

malignant dysplastic changes in blood and marrow myeloid lines which may become leukaemia

Question 22

what causes myeloproliferative disorders?

Answer 22

mutations of eg EPO receptor and myeloid cells become independent of EPO. Causes polycythaemia, thrombocythaemia, myelofibrosis (incr collagen in marrow)

Question 23

what is the precursor to an RBC called and what stimulates its differentiation?

Answer 23

pronormoblast and stimulated by erythropoietin

Question 24

what does the production of RBCs require?

Answer 24

• progenitors - stem cells, erythropoietin and stimulating factors
• haemoglobin - requires Fe and normal Hb synthesis. Deficiency causes microcytic anaemia as cells remain in BM until they have enough Hb - more division and smaller cells. Seen by glossitis, angular stomatitis, koilonychia
• DNA production - requires folate and vit B12 for DNA synthesis. Deficiency causes macrocytic anaemia as not enough DNA made for reg mitosis - less division, larger
• Normal protein/membrane synthesis

Question 25

what are the causes of decreased bone marrow production?

Answer 25

• stem cell defects/dysfunction - intrinsic stem cell aplasia/abnormalities. extrisin drugs, virus, chem, radiation
• hypoproliferation - renal insuficiency - decr EPO
• marrow infiltration - marrow spaces reduced by cancers, fibrosis
• nutritional deficiencies - fe, folate, B12, protein

Question 26

what are the causes of excess peripheral loss in anaemia?

Answer 26

• bleeding - GIT, UGT
• haemolysis (Intrinsic) - abnormal haemoglobins (sickle cell, thalasaemia (globin chains)) and membrane protein defects (spherocytoses/eliptocytoses)
• haemolysis (extrinsic)- autoimmune reactions, hyperslenism, microangiopathic disorders (TTP, DIC), infections (malaria, clostridia)

Question 27

how does the ABO blood group system work?

Answer 27

• O - H protein has no sugar residues and non antigenic
  *A - H protein has A sugar residue by A-transferase enzyme and is antigenic (A antigen)
  *B - H protein has B sugar residue by B-transferase enzyme and is antigenic (B antigen)
  antibodies to A and B antigens naturally occur in persons who lack those antigens on their blood cells (anti-A/B IgM etc)

Question 28

What happens when a Rh D -ve person is exposed to Rh D antigen?

Answer 28

antiD IgG formed. Can occur in transfusion or labour if foetus is Rh +ve and blood mixes. Only problem for next foetus if RH+ve

Question 29

who are universal blood donors and recipients?

Answer 29

• Group O RhD-ve universal RBC donor and universal plasma recipient
• Group AB RHD +ve universal RBC recipient and universal plasma donor