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Flashcards in 231 - Anaemia Deck (29):
1

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

Haemangioblasts - also become endothelium

2

what do haemopoietic stem cells do?

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

3

what growth factors act on what haemopoeitic cells?

*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

4

what are reticulocytes?

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

5

what plasma proteins does plasma contain?

Albumin, globulin, fibrinogen

6

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

*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

7

what does bone marrow consist of?

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

8

how can haemopoiesis be assessed?

*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)

9

how can anaemia be classed?

*primary - congenital or immune - failure of production
*secondary - acquired - increased destruction

10

what is idiopathic thrombocytopaenia (immune throbocytopaenic purpura)?

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

11

what is hereditary spherocytosis?

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

12

what is aplastic anaemia?

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

13

what is anaemia of chronic renal failure?

renal failure causes low erythropoietin resulting in low no of RBCs

14

what is anaemia of chronic disease?

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

15

what is pernicious anaemia?

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

16

what is acute myeloid leukaemia?

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

17

what is acute lymphoblastic leukaemia?

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

18

what is chronic myeloid leukaemia?

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

19

what is chronic lymphocytic leukaemia?

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

20

what is lymphoma?

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)

21

what is myelodysplasia?

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

22

what causes myeloproliferative disorders?

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

23

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

pronormoblast and stimulated by erythropoietin

24

what does the production of RBCs require?

*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

25

what are the causes of decreased bone marrow production?

*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

26

what are the causes of excess peripheral loss in anaemia?

*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)

27

how does the ABO blood group system work?

* 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)

28

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

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

29

who are universal blood donors and recipients?

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