Haematology Flashcards
1
Q
Where do all blood cell types originate
A
Bone marrow
2
Q
What type of stem cells are blood cell types derived from
A
pluripotent haematopoietic stem cells
3
Q
What type of stem cells do the pluripotent stem give rise to
A
Lymphoid stem cells
Multipotent myeloid stem cells
4
Q
What do multipotent myeloid stem cells form
A
Erythrocytes
Granulocytes
Megakaryocytes
5
Q
What do Lymphoid stem cells form
A
T-cells
B-cells
NK-cells
6
Q
What are the cell types that go to form erythrocytes
A
Multipotent myeloid stem cell
Proerythroblast
Erythroblasts
Erythrocytes
7
Q
What are cell characteristics of a blast cell
A
LARGE nuclei and small amounts of cytoplasm
8
Q
What is the colour of undifferentiated cells under microscope
A
Blue/purple
9
Q
What is the colour of differentiated cells under microscope
A
Pink
10
Q
What is the process of producing red blood cells
A
Erythropoiesis
11
Q
What hormone increases erythropoiesis
Where is is produced
What stimulates erythropoietin production
A
Erythropoietin
Kidneys
Hypoxia
12
Q
Where is hypoxia detected
A
Kidneys
13
Q
What is the action of erythropoietin
A
Increases bone marrow activity
14
Q
Which cell types produce erythropoietin (x2)
A
90% Juxtatubular cells
10% Hepatocyte and interstitial cells
15
Q
How, where and when are erythrocytes destroyed
A
Phagocytosis, spleen, 120 days after production
16
Q
In absence of nucleus, what property do erythrocytes possess
A
Extensive cytoskeleton to wriggle through capillary walls
17
Q
Why do red blood cells die after 120 days?
A
As they get older they become less flexible and less able to squeeze through the wall so they get held up in the spleen and destroyed
18
Q
Anisocytosis
A
red cells show more variation in SIZE than is normal
19
Q
Poikilocytosis
A
red cells show more variation in SHAPE than is normal
20
Q
What can be used as a reference for erythrocyte size
A
Lymphocytes (Normally a red cell is a bit smaller than a lymphocyte)
21
Q
Hypochromia
A
Normal red cells have about ONE THIRD of the diameter that is pale
This means that in hypochromia, the red cells appear much paler in the middle
Definition of hypochromia: the cells have a larger area of central pallor than normal
22
Q
What does hypochromia result in
A
This results from a lower haemoglobin content and concentration and a flatter cell
Red cells in hypochromia are described as being hypochromic
Hypochromia and Microcytosis often go together
23
Q
Hyperchromia
A
Definition: the cells LACK central pallor
This can occur because they are thicker than normal or because their shape is abnormal
Cells that have hyperchromia can be described as hyperchromatic or hyperchromic
24
Q
What are the two types of hyperchromatic cells?
A
Spherocytes
Irregularly Contracted Cells
25
Describe characteristics of spherocytes
They are approximately spherical in shape
They have a round regular outline and lack central pallor
They result from the loss of cell membrane without the loss of an equivalent amount of cytoplasm
This means that the cell is forced into a spherical form
You get spherocytes in hereditary spherocytosis
NOTE: not all the red blood cells will be spherical
26
Characteristics of Irregularly Contracted Cells
Irregular in outline and smaller than normal cells
They have also lost their central pallor
They usually result from oxidant damage to the cell membrane and to the haemoglobin
This helps to narrow down the diagnoses
27
Polychromasia
An increased blue tinge to the cytoplasm of a red cell
28
What causes polychromasia
As red cells mature they go from being dark blue to pink
The blue tinge to the cells in polychromasia indicates that the cells are young
Reticulocytes are red blood cells that are slightly younger than the proper mature cells
These reticulocytes can be stained with methylene blue
29
Where would you see polychromasia
in a patient with reticulocytosis
30
What does anaemia and reticulocytosis mean diagnostically
shows that the bone marrow is capable of making new cells
31
Target Cells
Cells with an accumulation of haemoglobin in the middle of the central pallor
32
When do target cells occurr
Obstructive jaundice
Liver disease
Haemoglobinopathies
Hyposplenism
33
Elliptocytes
These are eliptical in shape
34
When do elliptocytes occurr
Hereditary Elliptocytosis
Iron Deficiency (cells are elliptical and hypochromic)
35
Sickle Cells
Sickle cells are sickle shaped
36
When do sickle cells occurr
They result from the polymerisation of haemoglobin S when it is present in a high concentration
37
schistocytes or Fragments
These don't look like full cells
They are small pieces of red blood cells
They indicate that a red cell has fragmented
The fragments do still tend to have the red cell colour and sometimes even the central pallor - its just the shape that is different
38
Rouleaux
These are stacks of red cells
They resemble a pile of coins
They result from alterations in the plasma proteins
The plasma protein levels are increased and are pushing the cells together
39
Agglutinates
These form irregular clumps rather than tidy stacks seen in rouleaux
They usually result from antibodies on the cell surface
These antibodies make the red cells stick to each other
40
Howell-Jolly Body
This is a nuclear remnant in a red cell
Commonest cause: lack of splenic function
The spleen should remove these tiny remaining bits of nuclear material
This is seen in the blood film as a very precise and distinct dot
Platelets overlying red cells have a little bit of fuzziness
41
White Cells
Multipotent haematopoietic stem cells can also give rise of myeloblasts, which in turn can give rise to granulocytes and monocytes
For the differentiation in these cell lineages you need cytokines: G-CSF, M-CSF, GM-CSF and various interleukins
42
Normal granulocyte maturation
```
Myeloblast
promyelocyte
myelocyte
band form
neutrophil
```
43
Neutrophils
The neutrophil survives 7-10 hours in the circulation before migrating into the tissues
Its main function is defence against infection
It phagocytoses and kills microorganisms
44
Eosinophils
Spends less time in the circulation than neutrophils
Its main function is defence against PARASITIC infection
It only has TWO lobes in its nucleus
45
Basophils
These have a role in ALLERGIC RESPONSES
In basophils there are often so many dark blue dots that you don't even see the nucleus
46
Monocytes
These spend several days in the circulation
They are large cells with a kidney bean shaped nucleus
Monocytes migrate to the tissues where they develop into macrophages and other specialised cell types that have a phagocytic function
Macrophages also store and release IRON
47
Platelets
Multipotent haematopoietic stem cells can also give rise to megakaryocytes and then to platelets
Platelets survive about 10 days in the circulation
If someone takes aspirin then it will destroy part of the function of all the platelets and the wont start working properly again for another 10 days when the platelets are replenished
Platelets have a role in primary haemostasis
Platelets contribute phospholipid, which promotes blood coagulation
48
Lymphocytes
The lymphoid stem cell gives rise to B cells, T cells and NK cells
Lymphocytes recirculate to the lymph nodes and other tissues and then back to the blood stream
The intravascular life span of lymphocytes is very variable
49
Leucocytosis
too many white cells
50
Leucopenia
too few white cells
51
Neutrophilia
too many neutrophils
52
Neutropenia
too few neutrophils
53
Lymphocytosis
too many lymphocytes
54
Eosinophilia
too many eosinophils
55
Thrombocytosis
too many platelets
56
Thrombocytopenia
too few platelets
57
Erythrocytosis
lots of red blood cells
58
Reticulocytosis
lots of reticulocytes
59
Lymphopenia
decrease in the number of lymphocytes
60
Atypical Lymphocyte
They are normally small and round with a large nucleus and little cytoplasm
Sometimes you get atypical lymphocytes that have a large and very visible nucleus with loads of really faint cytoplasm
When people see a huge nucleus they expect it to be a blast but these cells have a lot of cytoplasm too
NOTE: these are totally typical of having a viral infection - this is seen in glandular fever (infectious mononucleosis)
61
Left Shift
Left shift means that there is an increase in non-segmented neutrophils or that there are neutrophil precursors in the blood
62
Describe the process of left shift
You normally start off with a big cell with a big nucleus and then you get lots of granules appearing
Then the nucleus gets smaller and smaller and start to segment
One of the first steps in segmenting is that it becomes a slightly more squashed looking nucleus that has more of a band shape and then it starts to segment
If someone's blood film has a lot of these band form neutrophils then you say that there has been a left shift
Normally, you don't see many band forms
63
What does left shift indicate
Left shift suggest that you are fighting an infection because it shows that the bone marrow is chucking out lots of lymphocytes
64
Toxic Granulation
Toxic granulation is the heavy granulation of neutrophils
65
What causes toxic granulation
It results from infection, inflammation and tissue necrosis
This is also a feature of normal pregnancy
66
Hypersegmented Neutrophil
This means there is an increase in the average number of neutrophil lobes or segments
It usually results from a lack of vitamin B12 or folic acid
67
What is the initial response to injury
Vessel constriction (small vessels)
68
Two stages of the formation of an unstable platelet plug
Platelet adhesion to the damaged vessel wall
Platelet aggregation
69
What stabilises the unstable primary platelet plug
Fibrin
70
Functions of the endothelium?
Blood-tissue barrier, synthesis of PgI2, thrombomodulin, vWF, Plasminogen Activating Factors
71
How do endothelial cells prevent coagulation
The endothelial cells create a barrier between the blood and the procoagulant subendothelial structures
72
How do endothelial cells aid coagulation
they produce components that are important in haemostasis:
Prostacyclin
Thrombomodulin
Von Willebrand Factor
Plasminogen Activator (these actually dissolute clots)
73
Where do platelets originate
megkaryocytes
74
Describe the maturation of megakaryocytes
The megakaryocyte undergoes a maturation process in the bone marrow leading to granulation - this is important for the formation of platelets
Platelets then break off from the cytoplasm of the megakaryocyte
75
Approximately how many platelets does one megakaryocyte form
4000
76
Describe the structure of a platelet
No nucleus, granulated microtubules and actomyosin,
77
What receptors does a platelet have
glycoprotein receptors, thrombin receptors
78
What is contained within alpha granules
Factor V and von Willebrand factor
79
Describe steps in the formation of a platelet plug. Draw a diagram to show steps.
Subendothelial structures get exposed
This exposes collagen in various forms. Platelets can bind to the collagen in TWO ways:
Von Willebrand Factor can bind to the collagen at the site of damage and unfolds so that it can capture the platelets via glycoprotein 1b receptors
The platelets can bind directly to the collagen via glycoprotein 1a receptors
These adhesive reactions are passive - it is a mechanism of recruiting the platelet to the site of damage but the platelet itself has NOT been activated
Once the platelets have been recruited and the receptors have been engaged - the receptors signal inside the cell to release the ADP from the storage granules and to synthesise thromboxane
Once these agents are released they bind to receptors on the surface of the platelets and activate them - making them change shape and release its storage granules
The platelets aggregate and form a haemostatic plug
Once the platelets have been activated, glycoprotein 2b/3a receptors become available which can bind to fibrinogen and helps the platelets clump together
The glycoprotein 2b/3a receptors are important therapeutic targets
So aggregation takes place once the platelet has been activated and additional receptors become available on the surface of the platelets
Platelets can also be activated by THROMBIN which is generated in coagulation
80
Prostacyclin synthesis (Endothelial cells)
Membrane phospholipid -> Arachidonic Acid -> Endoperoxides (PGG2, PGH2) -> Prostacyclin
81
Thromboxane synthesis (platelets)
Membrane phospholipid -> Arachidonic Acid -> Endoperoxides (PGG2, PGH2) -> Thromboxane
82
What enzyme converts phospholipids to arachidonic acid
phospholipase
83
What is the function of thromboxane
Vasoconstrictor and Thromboxane is a potent inducer of platelet aggregation
ADP and thromboxane are generated by the activated platelet
84
When is prostacyclin synthesised
Prostacyclin is an important regulator of haemostasis that is constantly synthesised by endothelial cells
85
What is Aspirin
ASPIRIN IS A COX INHIBITOR, irrreversible action on platelets
86
What are common targets of anti platelet therapy
ADP is important in activating the platelets so that they express these glycoprotein 2b/3a receptors
COX1 is the cyclooxygenase enzymes present in platelets
87
Aspirin
Cox-1 nhibitor
88
clopidogrel, prasugrel
ADP receptor antagonist
89
Abciximab (antibody), tirofiban (small molecule), eptifibatide
GPIIb/IIIa antagonists
90
Which is the most reliable ADP receptor antagonist
Prasugrel
91
What are tests to monitor platelet function
Platelet count - MOST IMPORTANT (used for thrombocytopaenia)
Bleeding time
Platelet aggregation
92
What's the normal range of platelets
150-400 x 109/L
93
What is autoimmune thrombocytopenia
This is where autoimmune antibodies remove the platelets from the circulation. Autoimmune thrombocytopenia can give rise to purpura, multiple bruises and ecchymoses
94
How does leukaemia cause thrombocytopenia
Leukaemia - the bone marrow is populated with leukaemic cells so it crowds out the megakaryocytes so the platelets aren't produced in sufficient numbers
95
How does bleeding time work
Bleeding time used to be a popular test years ago when there was little concern for patients and use of invasive tests
You make an incision in the patient's arm and you monitor the interaction between the platelets and the vessel wall
This is difficult to study without an invasive test
96
What is platelet aggregation
Platelet Aggregation is used extensively
The platelets are stimulated with ADP/thromboxane/collagen to study their function
This is used to diagnose platelet diseases e.g. von Willebrand disease
We're unlikely to use bleeding time and aggregation tests on the ward, platelet count is the most important one
97
Where is vWF produced
endothelial cells and megakaryocytes
98
where is factor V produced
megakaryoctes
99
Which clotting factor is associate with tissue factor?
F7a
100
Which clotting factor stablilises fibrin to crosslinked fibrin
F13a
