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NMF: Haematology > Haemopoiesis, anaemia + haemolysis > Flashcards

Haemopoiesis, anaemia + haemolysis Flashcards

1
Q

Where does haematopoeisis occur in a fetus?

A

yolk sac then liver and spleen

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2
Q

Where does haematopoeisis occur in an adult?

A

bone marrow of the axial skeleton (skull, ribs, sternum, pelvis, prox femur)

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3
Q

Which cells develop from the lymphoid lineage?

A
  • lymphocytes: B cells, T cells, NK cells - dendrites
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4
Q

Which cells develop from the myeloid lineage?

A
  • granulocytes: neutrophils, basophils, eosinophils - platelets - erythrocytes - macrophages - dendritic cells - mast cells
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5
Q

Which myeloid cells target tissues?

A

macrophages mast cells dendritic cells

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6
Q

give the pathway for erythropoiesis

A

haemocytoblast proerythroblast early erythroblast late erythroblast reticulocyte mature erythrocyte

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7
Q

At what stage of erythropoeisis is/are a) the nucleus lost? b) ribosomes lost?

A

a) when reticulocyte is formed b) when mature erythrocyte is formed

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8
Q

How is erythopoeitin produced?

A

in kidneys cells have a signalling molecule called hypoxia-inducible factor which needs oxygen to be broken down in hypoxia this doesn’t happen so the signal is sent to increase production of erythopoeitin

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9
Q

Where are erythrocytes destroyed?

A

in the spleen by macrophages

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10
Q

What are the specialised antigens on rbc called?

A

agglutinatagens

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11
Q

In microcytic anaemia where is the problem?

A

the cytoplasm - impaired haemoglobin

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12
Q

In macrocytic anaemia where is the problem?

A

the nucleus - impaired cell division

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13
Q

Causes of microcytic anaemia

A

iron deficiency anaemia of chronic disease thalassaemia lead poisoning

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14
Q

How does lead poising affect blood results?

A

microcytic microchromic due to its effect on porphyrin ring synthesis

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15
Q

Causes of macrocytic anaemia

A

b12/folate deficiency drug-induced alcohol hypothyroid pregnancy

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16
Q

What is the most common cause of macrocytosis?

A

alcohol

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17
Q

Where does platelet production occur?

A

platelets bud off from megakaryocytes in the bone marrow

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18
Q

What do neutrophils do?

A

immediate line of defence

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19
Q

What do eosinophils do?

A

fight parasitic infections, involved in hypersensitiviy

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20
Q

What does a monocyte become in tissues?

A

macrophage

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21
Q

name the a) oxidised version b) reduced version of iron

A

a) Fe3+ = ferric (more positive because it has lost an electron and oxidation is loss) b) Fe2+ = ferrous

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22
Q

In red cell destruction what does a) globin b) heme become?

A

a) amino acids b) iron recycled, porphyrin becomes unconjugated bilirubin

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23
Q

Which pathway generates ATP and NADH? why?

A

Ebden-Meyerhof ATP needed for Na-K pump to maintain osmotic pressure NADH prevents Fe2+ oxidation

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24
Q

How do we prevent free radicals from damaging the erythrocyte?

A

hexose monophosphate shunt generates NADPH that maintains glutathione (an antioxidant capable of donating electrons)

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25
Q

Which enzyme is the rate-limiting step in the pathway that prevents oxidative damage?

A

glucose-6-phosphate dehydrogenase (G6PD)

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26
Q

What chains make up a) fetal haemoglobin? b) adult haemoglobin?

A

a) 2 alpha, 2 gamma b) 2 alpha, 2 beta

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27
Q

Which effect moves the oxygen dissociation curve to the

a) left?
b) right?

A

a) Haldane
b) Bohr

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28
Q

What is the Haldane effect?

A

decreased affinity for CO2 at the lungs results in CO2 release

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29
Q

What is the Bohr effect?

A

decreased affinity for oxygen at the tissues results in oxygen release

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30
Q

Which factors influence the Haldane effect?

A

increased pH

decreased DPG

decreased temperature

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31
Q

Which factors influence the Bohr effect?

A

CADET face right:

inc CO2,

acid,

inc DPG,

exercise

inc temperature

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32
Q

Which protein measures

a) iron supply?
b) iron storage?

A

a) transferrin saturation
b) ferritin

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33
Q

What is megaloblastic macrocytic anaemia?

A

Defect in the maturation of the nucleus means that their isn’t enough division (cells aren’t getting smaller) happening so the cell has the contents of more cells the cells might be larger but daughter cells apoptose more so there are fewer

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34
Q

What does reticulocytosis occur in response to ?

A

acute blood loss or haemolysis

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35
Q

In b12 absorption which protein

a) binds in the stomach to stop it being destroyed by acid?
b) binds in the duuodenum so it can be absorbed

A

a) r binder
b) intrinsic factor

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36
Q

Where is b12 absorbed?

A

distal small bowel - ilium

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37
Q

What is the master iron regulator and how does it work?

A

hepcidin inhibits ferroportin

38
Q

SE of oral iron supplements

A

Abdominal pain constipation bloating diarrhoea black stools

39
Q

Why can B12 deficiency present with neurological symptoms?

A

may affect methyl donor on myelin sheath makes prone to present with neurological problems

40
Q

What is pernicious anaemia?

A

auto-immune condition affecting gastric mucosa (intrinsic factor, parietal and gastric cells) causing vitamin B12 malabsorption associated with hypothyroid and other autoimmune conditions

41
Q

How are haemoglobinopathies usually inherited?

A

autosomal recessive

42
Q

What type of anaemia is seen in thalassaemia and why?

A

microcytic hypochromic anaemia problem with globin chains causes ineffective erythopoeisis and lots of red cells undergo apoptosis

43
Q

What happpens if you lose 1 or 2 alpha chains?

A

A thal trait - no treatment if asymptomatic

44
Q

What happens if you lose 3/4 alpha chains?

A

you have HbH disease as there is an excess of beta chains that form tetramers that cant carry oxygen may need transfusions

45
Q

What happens if you have no working alpha chains?

A

Hb Barts hydrops fetalis (most severe) no adult hb usually incompatible with life

46
Q

How does alpha thalassaemia come about?

A

1/2/3/4 of alpha genes knocked out

47
Q

How does beta thalassaemia come about?

A

point mutations in the gene

48
Q

how do we illustrate there being reduced beta synthesis and absent beta synthesis?

A

B+ = reduced B0 = absent

49
Q

If one of the two beta genes is reduced or absent how will it present?

A

beta thalassaemia trait - asymptomatic - low MCV - normal Hb

50
Q

if both the mother and father have beta thalassaemia trait what is the chance of beta thal major in the child?

A

1/4

51
Q

What is beta thal intermedia?

A

2 x reduced 1x reduced, 1 x absent - moderate - occasional transfusions

52
Q

What is beta thal major?

A

no beta chain synthesis - severe - life-long transfusions - extramedullary haematopoeisis –> hepatosplenomegaly, skeletal changes, organ damage

53
Q

What are sickling disorders?

A

a structural variant of haemoglobin which polymerises in low oxygen to distort the RBC and damage its membrane

54
Q

How do we illustrate a) sickle trait? b) sickle cell anaemia?

A

a) HbAS b) HbSS

55
Q

features of sickle cell anaemia

A

episodes of crisis in hypoxia, dehydration, infection…

chronic haemolysis

hyposplenism

56
Q

How do you manage sickle cell anaemia?

A

avoid triggers of crisis

opiates, fluids, rest, oxygen, antibiotics, transfusion if severe crisis

folic acid and hydroxycarbamide

if hyposplenic –> prophylactic penicillin

57
Q

First sign of haemolysis

A

jaundice

58
Q

is haemolytic anaemia compensated ?

A

no rate of red cell destruction exceeds the bone marrow’s capacity to make new cells

59
Q

How can we detect haemolysis?

A

reticulocyte count breakdown products

60
Q

In which type of haemolysis is there excess bilirubin?

A

extravascular: due to release of protoprophyrin

61
Q

What products are seen in intravascular haemolysis?

A

abnormal process = abnormal products eg haemosiderin and haemoglobin in urine

62
Q

Causes of intravascular haemolysis

A
  • prosthetic heart valve
  • ABO incompatible transfusion reaction
  • G6PD deficiency
  • falciparum malaria
  • Paroxysmal nocturnal hemoglobinuria (PNH)
  • Thrombotic thrombocytopenic purpura
  • cold autoimmune haemolytic anaemia
63
Q

Causes of extravascular haemolysis

A
  • Delayed transfusion reaction
  • Warm autoimmune hemolytic anemia
  • Hereditary spherocytosis
  • Hypersplenism
64
Q

Which type of AIHA is

a) IgG?
b) IgM?

A

a) warm
b) cold

65
Q

Which type of autoimmune haemolytic anaemia results in intravascular haemolysis?

A

cold

66
Q

What does hypersegmented nuclei on a blood film indicate?

A

macrocytic vitamin B12/folate deficiency

67
Q

When does reticulocytosis manifest after an acute bleed?

A

1-2 days

68
Q

Is acute transfusion reaction IgG or IgM?

A

IgG

69
Q

Causes of raised platelets (thrombocytosis)

A

primary - bone marrow problem

secondary - trauma, surgery, splenectomy, active infection, iron deficiency, anaemia, malignancy (LEGO C lung endometrial GI oesophageal colorectal)

70
Q

In a patient who is deficient in both b12 and folate, which do you replace first?

A

b12

71
Q

How do patients on haemodialysis maintain adequate haemoglobin?

A

treatment with erythropoietin

72
Q

What usually causes an aplastic crisis in sickle cell disease? How does it present?

A

parovirus B19

sudden fall in haemoglobin

73
Q

aplastic crisis + symptoms

A

transfuse

74
Q

risk factors for TTP

A

obesity

pregnancy

female

african

75
Q

What happens to ferritin levels in anaemia of chronic disease?

A

increased

76
Q

When is TIBC increased?

A

iron-deficiency

pregnancy

77
Q

Which drugs can cause aplastic anaemia?

A

Phenytoin

Chloramphenicol

Cytotoxics

Sulphonamides

78
Q

Treat acute transfusion reaction

A

generous fluid resuscitation and termination of the transfusion

79
Q

Acutely swollen and painful fingers is a sign of what disease?

A

dactylitis is a sign of sickle cell anaemia

80
Q

Diagnose sickle cell anaemia

A

haemoglobin performance liquid chromatopgraphy

81
Q

What blood results would you expect in vitamin D deficiency

A
  • increase parathyroid hormone
  • low calcium
  • low phosphate
  • high ALP
82
Q

Which diagnosis is most likely with the following blood results

Low Hb, low white cells and low platelets ?

A

pancytopenia –> aplastic anaemia

83
Q

What causes sickle cell disease?

A

point mutation in the globin gene

84
Q

92 year old woman who is breathless after receiving a 4 unit red cell transfusion for chronic anaemia.

A

Transfusion associated circulatory overload

85
Q

48 year old man becoming breathlessness two hours after an infusion of fresh frozen plasma.

A

Transfusion related acute lung injury

86
Q

Which pathway is the most common form of glycolysis?

A

Ebden-Meyerhoff

87
Q

What is glutathione?

A

an antioxidant capable of donating electrons

88
Q

Name a small molecule with high affinity for oxygen

A

2,3-BPG

89
Q

gastric resection + peripheral neuropathy

A

B12 deficiency

90
Q

Young female, spenomegaly, intermittent mild jaundice, gallstones and father had a splenectomy as a child

A

hereditary spherocytosis

NMF: Haematology (8 decks)

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