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HDT 2.1 > Haemotopoiesis and Anaemia > Flashcards

Haemotopoiesis and Anaemia Flashcards

1
Q

what does normal blood contain?

A
  • platelets for clotting
  • red cells for oxygen transport
  • white cells; lymphocytes and granulocytes (immunity and response to infection)
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2
Q

what types of white cells are there?

A

lymphoid cells

  1. T cells
  2. B cells
  3. NK cells

myeloid cells

  1. monocytes
  2. granulocytes; basophils and neutrophils and eosinophils
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3
Q

what is the life span of platelets and how are they removed?

A

8-12 days and are removed by macrophages in the spleen and liver

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4
Q

what can low levels of platelets cause?

A

easy bruising and haemorrhage

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5
Q

what do platelets contain that control clotting?

A

they have granules instead of a nucleus and these granules secrete substances that control clotting and the breakdown of a blood clot

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6
Q

what do neutrophils do and where do they live?

A

neutrophils engulf and destroy bacteria; they are phagocytic
they can live in blood for a few hours then migrate into tissues where they can live for 4-5 days

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7
Q

what are eosinophils and basophils?

A

eosinophils are parasite infections but not phagocytic

both are allergy and atopy related

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8
Q

what is the role of monocytes and what immunity are they involved with?

A

innate immunity
they are phagocytic - engulf and destroy dead cells, bacteria, fungi and protozoa

they can migrate from blood into tissues and become macrophages

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9
Q

where are T cells, B cells and NK cells produced?

A

T cells- early progenitor from bone marrow but migrates and develops in thymus
B cells develop in the bone marrow; exit as naive cells
NK cells develop in the bone marrow; they are natural killer cells

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10
Q

what are the other cells that are produced by haematopoiesis?

A 
dendritic cells
- antigen presenting cells
mast cells
- produced in bone marrow
- mature in tissues
- produce histamine; respond to allergy
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11
Q

what are the values for normal levels of red cells, platelets, neutrophils and lymphocytes? what are the lifespans?

A 
red cells: 4.5-6.5 x1012/L
120 days 
platelets: 150-400 x 109/L
in blood< 48 hours
neutrophils: 2.5-7.5 x 109/L (larger than eosinophil count which is larger than basophil count)
8-12 days
lymphocytes: 1.5-3.5 x109/L
years
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12
Q

what occurs when you have too little/few of platelets, neutrophils red cells etc.

A

too few; cytopenia

too many; cytosis

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13
Q

how long do platelet and erythrocyte transfusions last? how long do haemotopoietic stem cells last?

A

platelet transfusions: lasts 1 month
erythrocyte transfusions: lasts few days

stem cells transplants should last for life

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14
Q

what is haemotopoiesis? when does it start

A

regulated blood cell production

  • tissues can respond rapidly to increase cell production
  • starts 17 days after fertilisation and occurs for life
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15
Q

how do leukaemia and lymphoma malignancies occur?

A
  • leukaemia= malignancy of haemotopoietic cells arise in marrow and spread to involve the blood and spleen and lymph nodes
  • lymphoma= malignancy of lymphoid cells arise in lymph nodes and the spleen which then go on to spread to involve the blood and bone marrow
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16
Q

how are myelomas caused and myeloproliferative disease and myelodysplasia?

A

myeloma= malignancy of plasma cells

myeloproliferative disease and myelodysplasia= neoplastic chronic abnormal myeloid proliferation

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17
Q

how can maturation arrest cause acute leukaemia?

A
  • due to the proliferation of immature cells
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18
Q

what can happen to cells when there’s no maturation arrest

A

there will be an over-production of mature cells

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19
Q

what type of myeloid and lymphoid leukaemia’s are there?

A

myeloid

  • AML; acute myeloblastic leukaemia
  • CML; chronic myeloid leukaemia

lymphoid

  • ALL; acute lymphoblastic leukaemia
  • CLL; chronic lymphocytic leukaemia
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20
Q

what is a stem cell?

A
  • can divide indefinitely to
    1) replenish itself
    2) give rise to specialised, differentiated cells
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21
Q

HS cells are pluripotent. True or False?

A

false- they are multipotent

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22
Q

embryonic cells are pluripotent. True or false?

A

true; they can differentiate into any type of cell in the body

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23
Q

what are the sites of haematopoiesis?

A

foetus
infants; bone marrow and virtually all bones
adults; bone marrow- axial skeleton

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24
Q

how can you evaluate haematopoiesis in a patient?

A

you can do a bone marrow biopsy

  • the patient is under local anaesthetic
  • this involves the iliac crest
  • sample taken from the hip bone
  • for children the sample is taken from the sternum
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25
Q

what are tools for identifying haematopoietic cells?

A

cell markers

- each cell has a unique profile of markers and so have different functions - lineage, maturation, function, activation

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26
Q

what is CD?

A

cluster of differentiation

- a internationally standardised nomenclature for cell markers

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27
Q

how can different cells be identified?

A

by monoclonal antibodies to cell markers= immunophenotyping

- look at cell surface markers

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28
Q

what is the process of stem cells becoming mature blood cells?

A

starts of as a stem cell and then undergoes maturation to become a progenitor.
a progenitor then becomes a precursor which matures into a mature blood cells

some stem cells undergo self-renewal to produce more stem cells

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29
Q

what is the development from progenitors into cells?

A
  1. multipotent progenitors; MPP
  2. oligopotent progenitors; CLP, MEP, GM
  3. lineage committed progenitors; monocytes, pro-T, pro-B, pro-NK
  4. mature cells; b-cells, macrophages, granulocytes
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30
Q

what effects on cell does growth factors/ cytokines have in haematopoiesis?

A
  • proliferation; splitting of an early cell into multiple
  • maturation- early cell matures
  • functional activation; activation of phagocytosis, secretion from late cell
  • suppression of apoptosis
  • differentiation
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31
Q

what are the main growth factors?

A
  • Granulocyte-CSF/ G-CSF
  • Erythropoietin/Epo
  • Thrombopoeitin / TPO
  • Interleukins/ IL
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32
Q

how is erythropoiesis controlled?

A

by negative feedback
short-term it is controlled by Epo which will be induced through hypoxic conditions and stimulate proliferation of the CFU-E progenitors

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33
Q

what is the pre-cursor before erythrocyte?

A

reticulocyte

- has a extruded nucleus but still has RNA so can still make haemoglobin

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34
Q

how can erythropoietin be used clinically?

A

can be used as subset injections
the aim is to improve anaemia

can be used in

1) some cases of myelodysplasia; low blood cell count
2) patients receiving chemotherapy
3) Jehovah’s Witness (blood loss)

35
Q

what are the stages of monocyte maturation?

A

monoblast -> promonocyte -> monocyte

occurs by marrow staining

36
Q

how are growth factors used clinically?

A

G-CSF subcut injections; stimulates cells to come out of bone marrow into peripheral circulation and can be given daily

used for

1) primary or secondary prevention of infections in neutropenic patients
2) to mobilise stem cells into peripheral blood for stem cell harvests for stem cell transplants; take cells directly from bone marrow

37
Q

where do platelets arise from? and how are they regulated?

A

from the cytoplasm of megakaryocytes in bone marrow

they are regulated by thrombopoietin (TPO)

38
Q

what are the TPO receptor agonists?

A

1) romiplostim; subcut injection
2) eltrombopag; oral

licensed use- refractory immune thrombocytopenia
potential uses
- aplastic anaemia
- thrombocytopenia in post chemotherapy

39
Q

what is the blood composition made up of?

A

55% is the plasma; electrolytes, hormones, nutrients, plasma proteins
45% is the Buffy coat; white cells, platelets, red cells

40
Q

what units are used for Hb blood count?

A

g/L

41
Q

what are the functions of the red cells?

A
  • carry oxygen to tissues and return carbon dioxide from tissues to lungs
  • gas exchange is achieved through protein Hb
42
Q

how many group in Hb?

A

4 haem groups - iron atom

when in a reduced state the Fe2+ binds to oxygen

43
Q

what are the components of haemoglobin?

A 
multi-subunit protein (tetramer)
- 2 alpha and 2 beta subunits
Heme 
- one per subunit 
- an iron atom 
- carries o2
44
Q

what is anaemia?

A

anaemia means a reduction in red cell number

- many diff types of anaemia

45
Q

what is the criteria for red cell count in anaemia patients?

A

<130 g/L in men
<120 g/L in women

reduction in Hb conc, red cell count or haematocrit

46
Q

what are the signs and symptoms of anaemia?

A
  • depends how severe
    1) decreased oxygen delivery to tissues
    2) hypovolaemia (with acute bleeding)
    common ones:
  • exertion dyspnoea
  • fatigue
  • palpitations
  • headache
    -angina and intermittent claudication

compensatory mechanisms include:

  • increase stroke volume and HR
  • increased oxygen extraction by tissues
47
Q

what are the causes of anaemia?

A
  1. reduced red cell production
  2. increased red cell destruction
  3. blood loss
48
Q

what diseases cause reduced red cell production?

A
  1. lack of haematinics; iron B12, folate and this leads to further decrease production
  2. bone marrow disorders
  3. bone marrow suppression; decreases WBC and platelet production
  4. reduced EPO production
  5. anaemia of chronic disease
49
Q

what can cause increased red cell destruction?

A
  1. inherited haemolytic anaemias; sickle cell disease

2. acquired haemolytic anaemias ; jaundice

50
Q

what occurs with a patient who has jaundice as a result of RBC destruction ?

A

get high levels of unconsecrated bilirubin due to RBC being broken down

51
Q

how to interpret results to find cause of anaemia?

A

look at the Hb level and see if its below the normal range

see if the MCV is low high or normal and this will indicate the cause and next steps

52
Q

what can be seen from blood film tests?

A

can see the changes in the red cell size and shape and this points towards the type of anaemia
changes in WBC can indicate leukaemia

53
Q

how can you classify anaemia?

A

based on the MCV:

  • microcytic (iron deficiency) LOW MCV
  • macrocrytic ( B12 or folate deficiency) HIGH MCV
  • normocytic (anaemia of chronic disease) NORMAL MCV
  • hameatinic deficiencies
  • haemolytic anaemia
54
Q

how do humans conserve iron?

A

by recycling it from senescent red cells

55
Q

what is the total body iron?

A

3000-4000mg

56
Q

what is the daily iron requirement for erythropoiesis?

A

20mg

57
Q

who is at risk from iron deficiency?

A
  • infants
  • young women
  • men ands women from GI blood loss
  • children and adults with coeliac disease
58
Q

for an adult with angular stomatitis, what would changes in the blood film look like?

A
  • Hb 75g/L
  • MCV 68fl (80-89)
  • MCH 22pg (27-32)
  • WBC normal
  • platelets normal or raised

blood film may show pencil cells

59
Q

how can assessment of a patients iron status be done and what can be used?

A
  • most hospitals use serum ferritin in place of the serum ion and iron-binding capacity
  • all tests are difficult to interpret in presence of inflammation or malignancy
  • transferrin saturation may be helpful in diagnosing iron deficiency in patients with cancer
60
Q

what processes can occur with normal or high ferritin?

A
  1. liver dysfunction: ferritin is released when hepatocytes are damaged
  2. increased haem turnover: haemolysis and trauma
  3. inflammatory lesions: malignancy, infection and inflammation
61
Q

what medical history aspects should you look when assessing iron deficiency?

A
  • on aspirin?
  • an GI blood loss
  • family history of anaemia
  • chronic diseases
  • thin underweight individuals
  • coeliac disease
62
Q

how do you refer men and women for iron deficiency?

A
  • > in young women you assume the cause is menstrual blood loss unless there is a clear indication
  • > in a male you refer the patient to the GI unit for an endoscopy and colonoscopy
63
Q

how can you treat iron deficiency?

A
  • is ferrous sulphate better
  • how well tolerated are the tablets
  • can you manoeuvre the diet and increase absorption?
64
Q

what warnings and points are there to consider with treatment of iron deficiency?

A
  • incidence of side effects is high
  • 200mg ads is excessive
  • slow release preparations are illogical
  • vitaminC or alcohol with a meal can increase absorption
  • IV iron useful in genuine intolerance
  • iron meant to be taken on an empty stomach
65
Q

what kind of anaemia can chronic disease cause? what are the causes?

A 
- causes mild microcytic and normocytic anaemia 
causes 
- malignancy 
- rheumatological diseases 
- chronic infection
  • severity of anaemia reflects disease activity
66
Q

with anaemia what can inflammatory cytokines cause?

A
  • iron utilisation

- impaired red cell production

67
Q

for chronic disease anaemia what would blood film, ferritin, iron, TIBC and sTfR- ferritin ratio?

A 
blood film; normocytic, normochromic
ferritin; normal or raised
iron; low
TIBC; low 
ratio; <1
68
Q

for early iron deficiency what would blood film, ferritin, iron, TIBC and sTfR- ferritin ratio?

A 
blood film; hypo chromic mild anisocytosis
ferritin; normal or low
iron; low
TIBC; raised 
ratio; >2
69
Q

how long should red cells usually survive for?

A

120 days

patient will be pale and jaundiced and bone marrow can compensate for reduction in red cells

70
Q

what does the reticulocyte count reflect and what does a low/high count indicate?

A
  • reflects the bone marrows response to anaemia
  • low count indicates bone hypoplasia
  • high count indicates marrow is still responding so there’s an issue of destruction of RBC
71
Q

what is bone marrow hypoplasia?

A

bone marrow struggles to produce RBC

72
Q

what is the test for autoantibodies?

A

Coombs test

73
Q

what does it mean if the spleen is enlarged for RBC?

A

breaking down more RBC in reticular endothelium cells

this can lead to hypersplenism

74
Q

what is the first line treatment for AIHA? second line?

A

prednisolone 1mg/kg together with folic acid

second line includes azathioprine, ciclosporin

75
Q

what can having microcytic anaemia lead to?

A
  1. haematinic deficiency
  2. myelodysplasia
  3. liver disease
  4. Hypothyroidism
76
Q

what are the causes of vitamin B12 deficiency?

A

nutritional- strict vegans
autoimmune- addisonian pernicious anaemia; body produces antibodies against intrinsic factor which is the key component of B12 absorption
GI- gastric or terminal ileal problems

77
Q

where is the absorptions sites for Vitamin B12 and folate?

A

B12- terminal ileum

folate- duodenum and jejunum

78
Q

for B12 or folate deficiency what would typical blood film changes look like?

A

Hb- 63g/L
MCV- 118fl
WBC- normal or low
platelets- normal or low

79
Q

how would you typically investigate macrocytic anaemia?

A
  • check B12 and folate levels
  • GPs may check thyroid function
  • blood films may shown signs of myelodysplasia
80
Q

what is myelodysplasia?

A

its seen to be a variety of clonal marrow abnormalities, usually with a macrocytic anaemia
- treated by regular transfusions but some respond to EPO

81
Q

what is the process of finding out the cause of anaemia if seen MCV is sent o be low?

A

low= microcytic

  • look at ferritin levels
  • if patient is Fe deficient then establish cause
  • if fe is normal then it is anaemia of chronic disease or hemoglobinopathy
82
Q

what is the process of finding out the cause of anaemia if seen MCV is sent to be high?

A

high= macrocytic
measure b12 and folate levels
if they are normal then find obvious cause or cause is not obvious so consider bone marrow
is it low establish the cause

83
Q

what is the process of finding out the cause of anaemia if seen MCV is sent to be normal?

A

normal= normocytic
look at relic count
if high then cause is hemolysis or blood loss so look at b12 or folate levels
if low then it is due to marrow or renal failure or is anaemia of chronic disease

HDT 2.1 (11 decks)

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