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Clinical Immunology and Haematology > Normal Haematopoiesis > Flashcards

Normal Haematopoiesis Flashcards

1
Q

What are the sites of haematopoiesis in humans?

A

Yolk sac
Liver and spleen
Bone marrow (in adults this is the central skeleton, proximal ends of femur).

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2
Q

What part of the bone marrow creates red blood cells

A

Red bone marrow

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3
Q

When do we find stem cells?

A

Bone marrow

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4
Q

what can stem cells develop into?

A

Red cells
White cells
Platelets

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5
Q

Multipotent haematopoitic stem cells can differentiate into what 2 types of cells?

A

Common myeloid progenitor and common lymphiod progenitor

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6
Q

What cells can the common myeloid progenitor differentaite into?

A

Erythrocytes, mast cells, myeloblasts, megokaryocytes

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7
Q

What can myeloblasts divide into?

A

Basophil, neutrophil, eosinophil, monocyte.

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8
Q

Where do macrophages come from?

A

Monocytes

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9
Q

What can lymphoid progenitors divide into?

A

Natural killer cells and small lymphocytes

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10
Q

What are the subcategories of small lymphocytes?

A

T-lymphocytes and B lymphocytes

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11
Q

Where do plasma cells develop from?

A

B lymphocytes

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12
Q

What can totipotent stem cells give rise to?

A

Intraembryonic and extraembryonic structures

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13
Q

Are stem cells capable of self renewal?

A

Yes

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14
Q

How do stem cells become self renewal?

A

They give rise to two daughter cells, one will stay as a stem cell the other will differentiation intp a specialised cells

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15
Q

How would you diagnose abnormalities in the blood?

A

Bone marrow examinations

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16
Q

Do blood cells become more or less identifiable as they develop?

A

More

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17
Q

Why dont red blood cells have nuclei?

A

They need more room to carry haemoglobin and oxygen around the body

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18
Q

Do HSC’s create niches and if so why?

A

Yes because they need to survive, it also helps them differentiate

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19
Q

How do cells make a niche?

A

Through extrinsic and intrinsic signalling pathways

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20
Q

Examples of the extrinsic signalling used to make a niche (what do growth factors help with?)

A

Growth factors which help cell survival, proliferation, differentiation, maturation and activation

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21
Q

Examples of the extrinsic signalling used to make a niche (what do adhesion molecules help with?)

A

Interactions with the extracellular matrix.

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22
Q

What are examples of intrinsic signalling to help with differentiation?

A

transcription factors

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23
Q

Growth factors can help create specifical lineages, for example what growth factor regulates erythropoiesis?

A

Renal erythropoietin which is stimulated by tissue oxygen

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24
Q

What growth factors encourage white cell growth (myelopoiesis) for granulocytes, macrophages and eosinophils?

A

Granulocytes = G-CSF
Macrophages - M-CSF
Eosinophils - IL-5

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25
Q

What growth factor encourages platelet differentiation (thrombopoiesis) and is part fo the feedback method to control platelet count?

A

Thrombopoietin from the liver

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26
Q

What does the normal peripheral blood (full blood count) tell you?

A

Gives you different values of peripheral blood. This includes, haemoglobin, RBC, Haematocrit (amount of blood which is actually cells), MCV, reticulocyte (immature cells), neutrophils, lymphocytes, eosinophils, monocytes, basophils and platelets

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27
Q

What conditions could arise from having too many of a type of cells?

A

Erythrocytosis - too many red cells
Leucocytosis - too many white cells
Thrombocytosis - too many platelets

All end in cytosis

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28
Q

What conditions could arise from having too little of a type of cells?

A

Anaemia - too little red blood cells
Leucopenia - too little white blood cells
Thrombocytopenia - too little platelets
Pancytopenia - too little of everything

All end in cytopenia (apart from anaemia)

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29
Q

Can cytosis and cytopenias be caused by malignancys and non-malignant diseases?

A

yes

30
Q

Why is pancytopenia common in malignant disease?

A

The malignancy invades the entirety of the bone marrow pushing all the blood cells into the peripheral blood

31
Q

What are myeloproliferative disorders?

A

These are too many cells caused by a malignancy

32
Q

What can cause benign erythrocytosis?

A

Smoking, alcohol, altitude, lung disease

33
Q

What can cause benign leucocytosis?

A

Infection, inflammation

34
Q

What can cause benign thrombocytosis?

A

Iron deficiency, infection

35
Q

What are some ways to can get cytopenias?

A

This is a failure of production which can be inhertied or acquired, general or specific, primary (primary bone marrow disorder) or secondary (e.g infection is worse, sepsis).

36
Q

what causes cytopenias?

A

Excessive loss or consumption of cells. For example a massive bleed or a an autoimmune consumption (the body is attacking its own cells).

37
Q

Does anaemia cause less oxygen to be in the body?

A

Yes

38
Q

Symptoms of anaemia?

A

Lethargy, breathlessness, chest pain, headache, dizziness, pallor.

39
Q

Can some people function with very low haemoglobin levels?

A

Yes if it happens slowly their body can adjust.

40
Q

What type of leucopenia are doctors most worried about and is most common?

A

Neutropenia (neutrophils are too low)

41
Q

What are symptoms of leucopenia?

A

Recurrant bacterial skin infections, mouth ulcers, overwhelming sepsis and more unusual infections.

42
Q

What are symptoms of thrombocytopenia?

A

Bruising, gum bleeding, nose bleeds, petechiae (rash), rash as back of mouth (normally due to a brain bleed) and prolonged bleeding from cuts.

43
Q

What are erythrocytes main function?

A

carry oxygen around the body

44
Q

Do RBC’s have osmotic equilibrium and flexable membranes?

A

yes

45
Q

What blood cells survive the longest in the blood?

A

red blood cells (3 months)

46
Q

How is haemoglobin made up?

A

Has 4 globin chains (in adults this is HbA alpha 2 and beta 2) (infants this is alpha 2 and gamma 2 chains). These are linked to 4 haem moieties - iron and protoporphyrin which can bind to oxygen

47
Q

What can cause anaemia?

A

Blood loss

48
Q

What types of illnesses can cause anaemia through reducing RBC production?

A

Iron deficiency (most common) , B12/folate deficiency, malignancy and thalassaemia ()

49
Q

How does an iron deficiency cause anaemia

A

Haem needs iron to bind oxygen and when there is less iron in the body there is less haem.

50
Q

How does B12 and folate deficiency cause Anaemia?

A

These are needed for DNA synthesis and lack of this means RBC’s cannot be produced

51
Q

What are haemotinics?

A

Iron, B12 and folate as these are the most common causes of anaemia

52
Q

What is thalassaemia?

A

Inherited defects of haemoglobin synthesis

53
Q

What diseases cause anaemia through increased RBC production?

A

Haemolysis (e.g. autoimmune diseases) and sickle cell disease.

54
Q

What causes iron deficiency?

A
  • Chronic blood loss such as menstruation or gastrointenstinal bleeding (common in older people as it is more common for them to get bowel cancer than younger people)
  • Diet (vegetarian, vegan, toddlers)
  • Malabsorption (coeliac disease, gastric surgery)
  • Increased requirements (pregnancy, growth).
55
Q

Can you spot iron deficiency anaemia?

A

Yes - cells will be paler and smaller, there is also pencil cells which is common in iron deficiency anaemia.

56
Q

What causes Megaloblastic anaemia?

A

Defective DNA synthesis causing the RBC’s being produced to grow significantly larger and not divide.

57
Q

What is the most common cause of megaloblastic anaemia?

A

B12/ folate dificiency which would then need to be tested for and replaced.

58
Q

Megaloblastic anaemia - Macrocytic anaemia (increased MCV) shows you what on the blood film?

A

Oval macrocytes, neutropenia with hypersegmented neutrophils, thrombocytopenia (low platelet levels), Reduced reticulocytes (young cells) and large red cells

59
Q

What causes a folate deficiency?

A
  • Dietary sources usually include green vegtables and therefore inadequate intake (e.g. vegans),
  • malabsorption (e.g. coeliac disease),
    excess consumption (pregnancy)
  • drugs (e.g. anticonvulsants).
60
Q

What causes vitamin B12 deficiency?

A
  • B12 is found in meat, dairy and fish and therefore not eating enough could give you the deficiency (e.g. vegans)
  • Autoimmune diseases such as pernicious anaemia (B12 needs factors to be absorbed - these factors come from the pernicous cells in the stomach and pernicious anaemia is when the pernicious cells are reduced).
  • Malabsorption (e.g. gastric or ileal surgery - comes from the pernicious cell idea (these are lost in surgery)).
61
Q

What is Haemolytic anaemia

A

When red cells are destroyed and can be either inherited or acquired

62
Q

What are biochemical sign of haemolytic anaemia?

A

Spherocytes or fragments, anaemia and reticulocytosis, raised bilirubin and LDH.

63
Q

What can hereditary haemolytic anaemia cause?

A

Membrane and cytoskeleton defects (spherocytosis, elliptocytosis)
Issues with enzymes (Defective RBC metabolism (G6PD, pyruvate kinase deficiency))
Haemoglobin (Haemoglobinopathies (sickle cells, thalassemia))

64
Q

What would you see on a blood film of hereditary spherocytosis

A

More spherical red blood cells, paler red blood cells.

65
Q

What causes autoimmune haemolysis (AIHA)?

A

Antibody starts to be produced in the body against the bodies RBC.

66
Q

What tests would you use and expected results when suspecting AIHA?

A

Direct coombs/antiglobulin test which would test positive. This tests to see if RBC’s are coated in immunoblobin or complement in vivo after spinning and washing the blood.

67
Q

Where are Haemoglobinopathies more common in and why?

A

Africe, asia and the mediterranean as they have a selective advantage over malaria (someone with this cannot get malaria) and this is why it is more passed on through generations.

68
Q

What is thalassemia?

A

Reduced rate of synthesis of normal globin chain and haemolysis

69
Q

What is sickle cell disease?

A

When abnormal haemoglobin is synthesised which causes haemolysis and vaso-occlusive complications.

70
Q

What would you see on a blood film showing thalassemia?

A

Red cells are smaller and paler (similar to iron deficiency but more pronounced and iron will be normal).

71
Q

What would you see on a blood film for sickle cell disease?

A

All blood cells are sickle cells.

Clinical Immunology and Haematology (25 decks)

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